TREA

COMPOSITIONS FOR THE TREATMENT OF DISEASE

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Information

  • Patent Application
  • 20200165630
  • Publication Number
    20200165630
  • Date Filed
    April 28, 2017
    7 years ago
  • Date Published
    May 28, 2020
    4 years ago
Information
Abstract
The invention provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody-like polypeptides, for the prevention and/or treatment of diseases and/or disorders.
Description
REFERENCE TO THE SEQUENCE LISTING

The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing file, entitled 20571302PCTSL.txt, was created on Apr. 28, 2017, and is 14,209,554 bytes in size. The information in electronic format of the Sequence Listing is incorporated herein by reference in its entirety.


FIELD OF THE INVENTION

The invention relates to compositions and methods for vectored antibody delivery (VAD).


BACKGROUND OF THE INVENTION

Antibody-based therapies have been developed for a wide variety of diseases, disorders and conditions, including infectious and non-infectious diseases. The U.S. Food and Drug Administration (FDA) has approved antibodies for treatment of cancers, autoimmune and immune system disorders, ocular diseases, nervous system diseases, inflammations, and infections, amongst many others. Naturally, antibodies are components of the adaptive immune response and they function by recognizing specific foreign antigens and stimulating humoral immunity responses. As a consequence, antibodies may be applied to the treatment, prevention, management, diagnosis and research of diseases, disorders and/or conditions.


Antibodies have relatively short half-lives and this presents an ongoing and long-felt challenge for antibody-based therapies. In order to achieve a sufficiently high concentration of an antibody for long lasting therapeutic effects, antibody therapies are traditionally delivered by repeated administration, e.g. by multiple injections. This dosing regimen results in an inconsistent level of antibody throughout the treatment period, limited efficiency per administration, high cost of administration and consumption of the antibody. Hence, there remains a need in the art for delivery of antibodies and antibody-based therapeutics through alternative routes or modalities of administration.


One such alternative route of administration is by expression vector (e.g. plasmid or viral vector), including but not limited to, adeno-associated viral vectors (AAVs). Adeno-associated viral vectors are widely used in gene therapy approaches due to a number of advantageous features. As dependoparvoviruses, AAV are non-replicating in infected cells and therefore not associated with any known disease. Further, AAVs may be introduced to a wide variety of host cells, do not integrate into the genome of the host cell, and are capable of infecting both quiescent and dividing cells. AAVs transduce non-replicating and long-lived cells in vivo, resulting in long term expression of the protein of interest. Further, AAVs can be manipulated with cellular and molecular biology techniques to produce non-toxic particles carrying a payload encoded in the AAV viral genome that can be delivered to a target tissue or set of cells with limited or no side-effects. Given the foregoing, the use of AAVs for vectored antibody delivery (VAD) would allow for longer lasting efficacy, fewer dose treatments, and more consistent levels of the antibody throughout the treatment period.


In vectored antibody delivery (VAD) an AAV is used as the delivery modality for a nucleic acid sequence encoding the antibody, which results in in vivo expression of the encoded payload, e.g., functional antibody.


The mechanism underlying VAD is thought to proceed through the following steps. First the AAV vector enters the cell via endocytosis, then escapes from the endosomal compartment and is transported to the nucleus wherein the viral genome is released and converted into a double-stranded episomal molecule of DNA by the host. The transcriptionally active episome results in the expression of encoded antibodies that may then be secreted from the cell into the circulation. VAD may therefore enable continuous, sustained and long-term delivery of antibodies administered by a single injection of an AAV particle.


Previous studies of an AAV-mediated antibody technique known as vectored immunoprophylaxis (VIP) have focused on neutralization of human immunodeficiency virus (HIV) (see, e.g. Johnson et al., 2009, Nature Med., 15, 901-906, Saunders et al., 2015, J. Virol., 89(16), 8334-8345, Balasz et al., 2012, Nature 481, 81-84, the contents of which are incorporated herein by reference in their entirety). Balasz et al. reported a long-term, even lifelong, expression of monoclonal antibody at high concentration from a single intramuscular administration in mice that resulted in full protection against HIV infection. AAV-mediated VIP has also been demonstrated against influenza strains (see, e.g. Balasz et al. Nat. Biotechnol., 2013, 31(7):647-52) and Plasmodium falciparum, a sporozoite causing malaria infection (see, e.g. Deal at al., 2014, PNAS, 111 (34), 12528-12532), as well as cancer, RSV and drug addiction (see, e.g. review by Schnepp and Johnson, Microbiol. Spectrum 2(4), 2014). Though promising, these studies emphasize efforts to merely prevent disease. There still remains a need for improved methods of prevention, and new antibody-mediated therapies for research, diagnosis, and treatment of disease.


The present invention addresses this need by providing novel AAV particles having viral genomes engineered to encode antibodies and antibody-based compositions and methods of using these constructs (e.g., VAD) for the treatment, prevention, diagnosis and research of diseases, disorders and/or conditions. The present invention further embraces optimized AAV particles for delivery of nucleic acids (e.g., viral genomes) encoding antibodies and antibody-based compositions to a subject in need thereof.


SUMMARY OF THE INVENTION

The invention provides AAV particles comprising a capsid and a viral genome, said viral genome comprising at least one inverted terminal repeat (ITR) region and a payload region, said payload region comprising a regulatory sequence operably linked to at least a first nucleic acid segment, said first nucleic acid segment encoding one or more polypeptides given in Tables 3-42, variants and fragments thereof. The capsid of the AAV particle may be any of the serotypes described herein and/or described in Table 1.


In one aspect, the first nucleic acid segment may encode one or more polypeptides such as, but not limited to, an antibody heavy chain, an antibody light chain, a linker, and combinations thereof. The first nucleic acid segment may encode one or more polypeptides which is humanized. As a non-limiting example, the first nucleic acid segment encodes from 5′ to 3′, an antibody heavy chain, a linker, and an antibody light chain. As another non-limiting example, the first nucleic acid segment encodes from 5′ to 3′, an antibody light chain, a linker, and an antibody heavy chain. As yet another non-limiting example, the first nucleic acid segment encodes one or more antibody heavy chains. As yet another non-limiting example, the first nucleic acid segment encodes one or more antibody light chains.


In one aspect, the first nucleic acid segment encodes an antibody, having at least 95% identity to any of the sequences of Tables 3-42 (SEQ ID NO: 2948-9220).


In one aspect, the regulatory sequence may comprise a promoter such as but not limited to, human elongation factor 1α-subunit (EF1α), cytomegalovirus (CMV) immediate-early enhancer and/or promoter, chicken β-actin (CBA) and its derivative CAG, 1(glucuronidase (GUSB), or ubiquitin C (UBC). Tissue-specific expression elements can be used to restrict expression to certain cell types such as, but not limited to, muscle specific promoters, B cell promoters, monocyte promoters, leukocyte promoters, macrophage promoters, pancreatic acinar cell promoters, endothelial cell promoters, lung tissue promoters, astrocyte promoters, or nervous system promoters which can be used to restrict expression to neurons, astrocytes, or oligodendrocytes.


In one aspect, the linker in the viral genome is selected from one or more of the linkers given in Table 2.


In one aspect, the AAV particles described herein may comprise a viral genome which is single stranded.


In one aspect, the AAV particles described herein may comprise a viral genome which is self-complementary.


In one aspect, the AAV particles described herein may comprise a viral genome comprising at least one intron sequence.


In one aspect, the AAV particles described herein may comprise a viral genome comprising at least one stuffer sequence to adjust the length of the viral genome to increase efficacy and/or efficiency.


In one aspect, the AAV particles described herein may comprise at least one region which has been codon optimized. As a non-limiting example, the viral genome may be codon optimized. As another non-limiting example, the first nucleic acid segment is codon-optimized.


In one aspect, the AAV particles described herein may comprise a viral genome with 2 ITR regions. At least one of the ITR regions may be derived from the same or different parental serotype of the capsid. As a non-limiting example, at least one ITR region is derived from AAV2.


In one aspect, the AAV particles comprise a viral genome which comprises a second nucleic acid segment. The second nucleic acid segment may encode an aptamer, siRNA, saRNA, ribozyme, microRNA, mRNA or combination thereof.


In one aspect, the AAV particles comprise a viral genome which comprises a second nucleic acid segment encoding an siRNA designed to target the mRNA that encodes the target of the antibody encoded by the first nucleic acid segment.


In one aspect, the AAV particles comprise a viral genome which comprises a second nucleic acid segment encoding a microRNA, the microRNA is selected to target the mRNA that encodes the target of the antibody encoded by the first nucleic acid segment.


In one aspect, the AAV particles comprise a viral genome which comprises a second nucleic acid segment encoding an mRNA, the mRNA encodes one or more peptides inhibitors of the same target of the antibody encoded by the first nucleic acid segment.


In one aspect, the AAV particles comprise a viral genome which comprises a third nucleic acid segment. The third nucleic acid segment may encode a nuclear export signal, a polynucleotide or polypeptide which acts as a regulator of expression of the viral genome in which it is encoded, a polynucleotide or polypeptide which acts as a regulator of expression of the payload region of the viral genome in which it is encoded and/or a polynucleotide or polypeptide which acts as a regulator of expression of the first nucleic acid segment of the payload region of the viral genome in which it is encoded.


The invention provides AAV particles comprising a capsid and a viral genome, said viral genome comprising at least one inverted terminal repeat (ITR) region and a payload region comprising a regulatory sequence operably linked to at least a first nucleic acid segment, the first nucleic acid segment encoding a bispecific antibody derived from any of the sequences listed in Tables 3-42 or portions or fragments thereof.


The invention provides methods of producing a functional antibody in a subject in need thereof, comprising administering to a subject the AAV particles described herein. The level or amount of the functional antibody in the target cell or tissue after administration to the subject may be from about 0.001 ug/mL to 100 mg/mL. The functional antibody may be encoded by a single first nucleic acid segment of a viral genome within the AAV particle. The functional antibody may be encoded by two different viral genomes, the two different viral genomes may be packaged in separate capsids.


The invention provides a pharmaceutical composition comprising an AAV particle described herein in a pharmaceutically acceptable excipient. As a non-limiting example, the pharmaceutically acceptable excipient is saline. As a non-limiting example, the pharmaceutically acceptable excipient is 0.001% pluronic in saline.


The invention provides methods of producing a functional antibody in a subject in need thereof, comprising administering to a subject the AAV particles described herein by a delivery route such as, but not limited to, enteral (into the intestine), gastroenteral, epidural (into the dura mater), oral (by way of the mouth), transdermal, intracerebral (into the cerebrum), intracerebroventricular (into the cerebral ventricles), epicutaneous (application onto the skin), intradermal, (into the skin itself), subcutaneous (under the skin), nasal administration (through the nose), intravenous (into a vein), intravenous bolus, intravenous drip, intra-arterial (into an arter.), intramuscular (into a muscle), intracardiac (into the heart), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intraparenchymal (into brain tissue), intraperitoneal, (infusion or injection into the peritoneum), intravesical infusion, intravitreal. (through the eye), intracavernous injection (into a pathologic cavity) intracavitary (into the base of the penis), intravaginal administration, intrauterine, extra-amniotic administration, transdermal (diffusion through the intact skin for systemic distribution), transmucosal (diffusion through a mucous membrane), transvaginal, insufflation (snorting), sublingual, sublabial, enema, eye drops (onto the conjunctiva), or in ear drops, auricular (in or by way of the ear), buccal (directed toward the cheek), conjunctival, cutaneous, dental (to a tooth or teeth), electro-osmosis, endocervical, endosinusial, endotracheal, extracorporeal, hemodialysis, infiltration, interstitial, intra-abdominal, intra-amniotic, intra-articular, intrabiliar, intrabronchial, intrabursal, intracartilaginous (within a cartilage), intracaudal (within the cauda equine), intracisternal (within the cisterna magna cerebellomedularis), intracorneal (within the cornea), dental intracoronal, intracoronary (within the coronary arteries), intracorporus cavernosum (within the dilatable spaces of the corporus cavernosa of the penis), intradiscal (within a disc), intraductal (within a duct of a gland), intraduodenal (within the duodenum), intradural (within or beneath the dura), intraepidermal (to the epidermis), intraesophageal (to the esophagus), intragastric (within the stomach), intragingival (within the gingivae), intraileal (within the distal portion of the small intestine), intralesional (within or introduced directly to a localized lesion), intraluminal (within a lumen of a tube), intralymphatic (within the lymph), intramedullary (within the marrow cavity of a bone), intrameningeal (within the meninges), intramyocardial (within the myocardium), intraocular (within the eye), intraovarian (within the ovary), intrapericardial (within the pericardium), intrapleural (within the pleura), intraprostatic (within the prostate gland), intrapulmonary (within the lungs or its bronchi), intrasmal (within the nasal or periorbital sinuses), intraspinal (within the vertebral column), intrasynovial (within the synovial cavity of a joint), intratendinous (within a tendon), intratesticular (within the testicle), intrathecal (within the cerebrospinal fluid at any level of the cerebrospinal axis), intrathoracic (within the thorax), intratubular (within the tubules of an organ), intraturnor (within a tumor), intratympanic (within the aurus media), intravascular (within a vessel or vessels), intraventricular (within a ventricle), iontophoresis (by means of electric current where ions of soluble salts migrate into the tissues of the body), irrigation (to bathe or flush open wounds or body cavities), laryngeal (directly upon the larynx), nasogastric (through the nose and into the stomach), occlusive dressing technique (topical route administration which is then covered by a dressing which occludes the area), ophthalmic (to the external eye), oropharyngeal (directly to the mouth and pharynx), parenteral, percutaneous, periarticular, pendural, perineural, penodontal, rectal, respiratory (within the respiratory tract by inhaling orally or nasally for local or systemic effect), retrobulbar (behind the pons or behind the eyeball), soft tissue, subarachnoid, subconjunctival, submucosal, topical, transplacental (through or across the placenta), transtracheal (through the wall of the trachea), transtympanic (across or through the tympanic cavity), ureteral (to the ureter), urethral (to the urethra), vaginal, caudal block, diagnostic, nerve block, biliary perfusion, cardiac perfusion, photophoresis and spinal.


The invention provides methods of treating and/or preventing a disease or disorder in a subject comprising administering to the subject an AAV particle described herein. The administration may be at a prophylactically effective dose such as, but not limited to, from about 1 ug/mL to about 500 ug/mL of expressed polypeptide or 1×10e4 to 1×10e16 VG/mL from the pharmaceutical composition. The pharmaceutical composition may be administered at least once. The pharmaceutical composition may be administered daily, weekly, monthly or yearly. The pharmaceutical composition may be co-administered as part of a combination therapy.


The invention provides methods of producing an antibody in a subject by administering the AAV particles described herein, where the antibody is not a virus neutralizing antibody.


The invention provides methods of producing an antibody in a subject by administering the AAV particles described herein, where the antibody is not an HIV or HCV virus neutralizing antibody.





BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of various embodiments of the invention.



FIG. 1 is a schematic of vectored antibody delivery.



FIG. 2 is a schematic of a viral genome of the invention.



FIG. 3 is a schematic of payload regions FIG. 3 discloses SEQ ID NO: 9221.





DETAILED DESCRIPTION OF THE INVENTION
I. Compositions of the Invention

According to the present invention, compositions for delivering functional antibodies and/or antibody-based compositions by adeno-associated viruses (AAVs) are provided. AAV particles of the invention may be provided via any of several routes of administration, to a cell, tissue, organ, or organism min vivo, ex vivo or in vitro.


As used herein, an “AAV particle” is a virus which comprises a viral genome with at least one payload region and at least one inverted terminal repeat (ITR) region.


As used herein. “viral genome” or “vector genome” refers to the nucleic acid sequence(s) encapsulated in an AAV particle. Viral genomes comprise at least one payload region encoding polypeptides of the invention, e.g., antibodies, antibody-based compositions or fragments thereof.


As used herein, a “payload” or “payload region” is any nucleic acid molecule which encodes one or more polypeptides of the invention. At a minimum, a payload region comprises nucleic acid sequences that encode an antibody, an antibody-based composition, or a fragment thereof, but may also optionally comprise one or more functional or regulatory elements to facilitate transcriptional expression and/or polypeptide translation.


The nucleic acid sequences and polypeptides disclosed herein may be engineered to contain modular elements and/or sequence motifs assembled to enable expression of the antibodies or antibody-based compositions of the invention. In some embodiments, the nucleic acid sequence comprising the payload region may comprise one or more of a promoter region, an intron, a Kozak sequence, an enhancer or a poly adenylation sequence. Payload regions of the invention typically encode antibodies or antibody based compositions, which may include an antibody heavy chain domain, an antibody light chain domain, both antibody heavy and light chain domains, or fragments of the foregoing in combination with each other or in combination with other polypeptide moieties. In some cases, payload regions may also encode one or more linkers or joining regions between antibody heavy and light chain domains or fragments. The order of expression, structural position, or concatemer count (heavy chain, light chain, or linker) may be different within or among different payload regions. The identity, position and number of linkers expressed by payload regions may also vary.


The payload regions of the invention may be delivered to one or more target cells, tissues, organs or organisms within the viral genome of an AAV particle.


Adeno-Associated Viruses (AAVs) and AAV Particles

Viruses of the Parvoviridae family are small non-enveloped icosahedral capsid viruses characterized by a single stranded DNA genome. Parvovindae family viruses consist of two subfamilies: Parovirinae, which infect vertebrates, and Densovinnae, which infect invertebrates. Due to its relatively simple structure, easily manipulated using standard molecular biology techniques, this virus family is useful as a biological tool. The genome of the virus may be modified to contain a minimum of components for the assembly of a functional recombinant virus, or viral particle, which is loaded with or engineered to express or deliver a desired payload, which may be delivered to a target cell, tissue, organ, or organism.


The parvoviruses and other members of the Parvoviridae family are generally described in Kenneth I. Berns, “Parvoviridae: The Viruses and Their Replication,” Chapter 69 in FIELDS VIROLOGY (3d Ed. 1996), the contents of which are incorporated by reference in their entirety.


The Parvoviridae family comprises the Dependovirus genus which includes adeno-associated viruses (AAV) capable of replication in vertebrate hosts including, but not limited to, human, primate, bovine, canine, equine, and ovine species.


The AAV vector genome is a linear, single-stranded DNA (ssDNA) molecule approximately 5,000 nucleotides (nt) in length. The AAV viral genome can comprise a payload region and at least one inverted terminal repeat (ITR) or ITR region. ITRs traditionally flank the coding nucleotide sequences for the non-structural proteins (encoded by Rep genes) and the structural proteins (encoded by capsid genes or Cap genes). While not wishing to be bound by theory, an AAV viral genome typically comprises two ITR sequences. The AAV vector genome comprises a characteristic T-shaped hairpin structure defined by the self-complementary terminal 145 nt of the 5′ and 3′ ends of the ssDNA which form an energetically stable double stranded region. The double stranded hairpin structures comprise multiple functions including, but not limited to, acting as an origin for DNA replication by functioning as primers for the endogenous DNA polymerase complex of the host viral replication cell.


In addition to the encoded heterologous payload, AAV vectors may comprise the viral genome, in whole or in part, of any naturally occurring and/or recombinant AAV serotype nucleotide sequence or variant. AAV variants may have sequences of significant homology at the nucleic acid (genome or capsid) and amino acid levels (capsids), to produce constructs which are generally physical and functional equivalents, replicate by similar mechanisms, and assemble by similar mechanisms. Chiorini et al., J. Vir. 71: 6823-33(1997); Srivastava et al., J. Vir. 45:555-64 (1983), Chiorini et al., J. Vir. 73:1309-1319 (1999); Rutledge et al., J. Vir. 72:309-319 (1998); and Wu et al., J. Vir. 74: 8635-47 (2000), the contents of each of which are incorporated herein by reference in their entirety.


In one embodiment, AAV particles of the present invention are recombinant AAV viral vectors which are replication defective, lacking sequences encoding functional Rep and Cap proteins within their viral genome. These defective AAV vectors may lack most or all parental coding sequences and essentially carry only one or two AAV ITR sequences and the nucleic acid of interest for delivery to a cell, a tissue, an organ or an organism.


In one embodiment, the viral genome of the AAV particles of the present invention comprise at least one control element which provides for the replication, transcription and translation of a coding sequence encoded therein. Not all of the control elements need always be present as long as the coding sequence is capable of being replicated, transcribed and/or translated in an appropriate host cell. Non-limiting examples of expression control elements include sequences for transcription initiation and/or termination, promoter and/or enhancer sequences, efficient RNA processing signals such as splicing and polyadenylation signals, sequences that stabilize cytoplasmic mRNA, sequences that enhance translation efficacy (e.g., Kozak consensus sequence), sequences that enhance protein stability, and/or sequences that enhance protein processing and/or secretion.


According to the present invention. AAV particles for use in therapeutics and/or diagnostics comprise a virus that has been distilled or reduced to the minimum components necessary for transduction of a nucleic acid payload or cargo of interest. In this manner, AAV particles are engineered as vehicles for specific delivery while lacking the deleterious replication and/or integration features found in wild-type viruses.


AAV vectors of the present invention may be produced recombinantly and may be based on adeno-associated virus (AAV) parent or reference sequences. As used herein, a “vector” is any molecule or moiety which transports, transduces or otherwise acts as a carrier of a heterologous molecule such as the nucleic acids described herein.


In addition to single stranded AAV viral genomes (e.g., ssAAVs), the present invention also provides for self-complementary AAV (scAAVs) viral genomes scAAV vector genomes contain DNA strands which anneal together to form double stranded DNA. By skipping second strand synthesis, scAAVs allow for rapid expression in the cell.


In one embodiment, the AAV particle of the present invention is an scAAV.


In one embodiment, the AAV particle of the present invention is an ssAAV.


Methods for producing and/or modifying AAV particles are disclosed in the art such as pseudotyped AAV vectors (PCT Patent Publication Nos. WO200028004; WO200123001; WO2004112727; WO 2005005610 and WO2005072364, the content of each of which is incorporated herein by reference in its entirety).


AAV particles may be modified to enhance the efficiency of delivery. Such modified AAV particles can be packaged efficiently and be used to successfully infect the target cells at high frequency and with minimal toxicity. In some embodiments, the capsids of the AAV particles are engineered according to the methods described in US Publication Number US 20130195801, the contents of which are incorporated herein by reference in their entirety.


In one embodiment, the AAV particles comprising a payload region encoding the polypeptides of the invention may be introduced into mammalian cells.


AAV Serotypes

AAV particles of the present invention may comprise or be derived from any natural or recombinant AAV serotype. According to the present invention, the AAV particles may utilize or be based on a serotype selected from any of the following AAV1, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4, AAV4-4, AAV5, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9, AAV9.11, AAV9.13, AAV9.16, AAV9.24, AAV9.45, AAV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3, AAV24.1, AAV27.3, AAV42.12, AAV42-1b, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42-10, AAV42-11, AAV42-12, AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAV1-7/rh.48, AAV1-8/rh.49, AAV2-15/rh.62, AAV2-3/rh.61, AAV2-4/rh.50, AAV2-5/rh.51, AAV3.1/hu.6, AAV3.1/hu.9, AAV3-9/rh.52, AAV3-11/rh.53, AAV4-8/r11.64, AAV4-9/rh.54, AAV4-19/rh.55, AAV5-3/rh.57, AAV5-22/rh.58, AAV7.3/hu.7, AAV16.8/hu.10, AAV16.12/hu.11, AAV29.3/bb.1, AAV29.5/bb.2, AAV106.1/hu.37, AAV114.3/hu.40, AAV127.2/hu.41, AAV127.5/hu.42, AAV128.3/hu.44, AAV130.4/hu.48, AAV145.1/hu.53, AAV145.5/hu.54, AAV145.6/hu.55, AAV161.10/hu.60, AAV161.6/hu.61, AAV33.12/hu.17, AAV33.4/hu.15, AAV33.8/hu.16, AAV52/hu.19, AAV52.1/hu.20, AAV58.2/hu.25, AAVA3.3, AAVA3.4, AAVA3.5, AAVA3.7, AAVC1, AAVC2, AAVC5, AAV-DJ, AAV-DJ8, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.1, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.12, AAVH6, AAVLK03, AAVH-1/hu.1, AAVH-5/hu.3, AAVLG-10/rh.40, AAVLG-4/rh.38, AAVLG-9/hu.39, AAVN721-8/rh.43, AAVCh.5, AAVCh.5Ra, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5R1, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6, AAVhu.1, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.11, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44R1, AAVhu44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48R1, AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.14/9, AAVhu.t 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.13R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54. AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64R1, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74, AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhE1.1, AAVhEr1.5, AAVhER1.14, AAVhEr1.8, AAVhEr1.16, AAVhEr1.18, AAVhEr1.35, AAVhEr1.7, AAVhEr1.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T, AAV-PAEC, AAV-LK01, AAV-LK02, AAV-1LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV-LK09, AAV-LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV-LK15, AAV-LK16, AAV-LK17, AAV-LK18, AAV-LK19, AAV-PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV-PAEC12, AAV-2-pre-mniRNA-101, AAV-8h, AAV-8b, AAV-h, AAV-b, AAV SM 10-2, AAV Shuffle 100-1, AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100-2, AAV SM 10-1, AAV SM 10-8, AAV SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.11, AAVhu.53, AAV4-8/rh.64, AAVLG-9/hu.39, AAV54.5/hu.23, AAV54.2/hu.22, AAV54.7/hu.24, AAV54.1/hu.21, AAV54.4R/hu.27, AAV46.2/hu.28, AAV46.6/hu.29, AAV128.1/hu.43, true type AAV (ttAAV), UPENN AAV10, Japanese AAV10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr-7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-E1, AAV CBr-E2, AAV CBr-E3, AAV CBr-E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CBr-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2, AAV CHt-3, AAV CHt-6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt-P1, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-B1, AAV CKd-B2, AAV CKd-B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV Ckd-B7, AAV Ckd-B8, AAV CKd-H1, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd-H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd-N9, AAV CLg-F1, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg-F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1, AAV CLv1-1, AAV Clv1-10, AAV CLv1-2, AAV CLv-12, AAV CLv1-3, AAV CLv-13, AAV CLv1-4, AAV Clv1-7, AAV Clv1-8, AAV Clv1-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-D1, AAV CLv-D2, AAV CLv-D3, AAV CLv-D4, AAV Clv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CL-E1, AAV CL-K1, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv-M1, AAV CLv-M11, AAV CLv-M2, AAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv-R1, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv-R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-1, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4, AAV5, AAVF1/HSC1, AAVF11/HSC11, AAVF12/HSC12, AAVF13/HSC13, AAVF14/HSC14, AAVF15/HSC15, AAVF16/HSC16, AAVF17/HSC17, AAVF2/HSC2, AAVF3/HSC3, AAVF4/HSC4, AAVF5/HSC5, AAVF6/HSC6, AAVF7/HSC7, AAVF8/HSC8, AAVF9/HSC9, PHP.B. PHP.A, G2B-26, G2B-13, TH1.1-32 and/or TH1.1-35 and variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Publication No. US20030138772, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV1 (SEQ ID NO: 6 and 64 of US20030138772), AAV2 (SEQ ID NO: 7 and 70 of US20030138772), AAV3 (SEQ ID NO: 8 and 71 of US20030138772), AAV4 (SEQ ID NO: 63 of US20030138772), AAV5 (SEQ ID NO-114 of US20030138772), AAV6 (SEQ ID NO: 65 of US20030138772), AAV7 (SEQ ID NO: 1-3 of US20030138772), AAV8 (SEQ ID NO: 4 and 95 of US20030138772), AAV9 (SEQ ID NO: 5 and 100 of US20030138772), AAV10 (SEQ ID NO: 117 of US20030138772), AAV11 (SEQ ID NO-118 of US20030138772), AAV12 (SEQ ID NO: 119 of US20030138772), AAVrh10 (amino acids 1 to 738 of SEQ ID NO: 81 of US20030138772), AAV16.3 (US20030138772 SEQ ID NO. 10), AAV29.3/bb.1 (US20030138772 SEQ ID NO: 11), AAV29.4 (US20030138772 SEQ ID NO:12), AAV29.5/bb.2 (US20030138772 SEQ ID NO: 13), AAV1.3 (US20030138772 SEQ ID NO: 14), AAV13.3 (US20030138772 SEQ ID NO: 15), AAV24.1 (US20030138772 SEQ ID NO: 16), AAV27.3 (US20030138772 SEQ ID NO: 17), AAV7.2 (US20030138772 SEQ ID NO: 18), AAVC1 (US20030138772 SEQ ID NO: 19), AAVC3 (US20030138772 SEQ ID NO: 20), AAVC5 (US20030138772 SEQ ID NO: 21), AAVF1 (US20030138772 SEQ ID NO: 22), AAVF3 (US20030138772 SEQ ID NO: 23), AAV F5 (US20030138772 SEQ ID NO: 24), AAVH6 (US20030138772 SEQ ID NO: 25), AAVH2 (US20030138772 SEQ ID NO: 26), AAV42-8 (US20030138772 SEQ ID NO: 27), AAV42-15 (US20030138772 SEQ ID NO: 28), AAV42-5b (US20030138772 SEQ ID NO: 29), AAV42-1b (US20030138772 SEQ ID NO: 30), AAV42-13 (US20030138772 SEQ ID NO: 31), AAV42-3a (US20030138772 SEQ ID NO: 32), AAV42-4 (US20013138772 SEQ ID NO: 33), AAV42-5a (US20030138772 SEQ ID NO: 34), AAV42-10 (US20030138772 SEQ ID NO: 35), AAV42-3b (US20030138772 SEQ ID NO: 36), AAV42-11 (US20030138772 SEQ ID NO: 37), AAV42-6b (US20030138772 SEQ ID NO: 38), AAV43-1 (US20030138772 SEQ ID NO: 39), AAV43-5 (US20030138772 SEQ ID NO: 40), AAV43-12 (US20030138772 SEQ ID NO: 41), AAV43-20 (US20030138772 SEQ ID NO: 42), AAV43-21 (US20030138772 SEQ ID NO: 43), AAV43-23 (US20030138772 SEQ ID NO: 44), AAV43-25 (US20030138772 SEQ ID NO: 45), AAV44.1 (US20030138772 SEQ ID NO: 46), AAV44.5 (US20030138772 SEQ ID NO: 47), AAV223.1 (US20030138772 SEQ ID NO: 48), AAV223.2 (US20030138772 SEQ ID NO: 49), AAV223.4 (US20030138772 SEQ ID NO: 50), AAV223.5 (US20030138772 SEQ ID NO: 51), AAV223.6 (US20030138772 SEQ ID NO: 52), AAV223.7 (US20030138772 SEQ ID NO: 53), AAVA3.4 (US20030138772 SEQ ID NO: 54), AAVA3.5 (US20030138772 SEQ ID NO: 55), AAVA3.7 (US20030138772 SEQ ID NO: 56), AAVA3.3 (US20030138772 SEQ ID NO: 57), AAV42.12 (US20030138772 SEQ ID NO: 58), AAV44.2 (US20030138772 SEQ ID NO: 59), AAV42-2 (US20030138772 SEQ ID NO: 9), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Publication No. US20150159173, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV2 (SEQ ID NO: 7 and 23 of US20150159173), rh20 (SEQ ID NO: 1 of US20150159173), rh32/33 (SEQ ID NO: 2 of US20150159173), rh39 (SEQ ID NO: 3, 20 and 36 of US20150159173), rh46 (SEQ ID NO: 4 and 22 of US20150159173), rh73 (SEQ ID NO: 5 of US20150159173), rh74 (SEQ ID NO: 6 of US20150159173), AAV6.1 (SEQ ID NO:29 of US20150159173), rh.8 (SEQ ID NO: 41 of US20150159173), rh.48.1 (SEQ ID NO: 44 of US20150159173), hu.44 (SEQ ID NO: 45 of US20150159173), hu.29 (SEQ ID NO: 42 of US20150159173), hu.48 (SEQ ID NO: 38 of US20150159173), rh54 (SEQ ID NO:49 of US20150159173), AAV2 (SEQ ID NO: 7 of US20150159173), cy.5 (SEQ ID NO: 8 and 24 of US20150159173), rh.10 (SEQ ID NO: 9 and 25 of US20150159173), rh.13 (SEQ ID NO: 10 and 26 of US20150159173), AAV1 (SEQ ID NO: 11 and 27 of US20150159173), AAV3 (SEQ ID NO: 12 and 28 of US20150159173), AAV6 (SEQ ID NO: 13 and 29 of US20150159173), AAV7 (SEQ ID NO: 14 and 30 of US20150159173), AAV8 (SEQ ID NO: 15 and 31 of US20150159173), hu.13 (SEQ ID NO: 16 and 32 of US20150159173), hu.26 (SEQ ID NO: 17 and 33 of US20150159173), hu.37 (SEQ ID NO: 18 and 34 of US20150159173), hu.53 (SEQ ID NO: 19 and 35 of US20150159173), rh.43 (SEQ ID NO: 21 and 37 of US20150159173), rh2 (SEQ ID NO: 39 of US20150159173), rh.37 (SEQ ID NO: 40 of US20150159173), rh.64 (SEQ ID NO: 43 of US20150159173), rh.48 (SEQ ID NO: 44 of US20150159173), ch 5 (SEQ ID NO: 46 of US20150159173), rh.67 (SEQ ID NO: 47 of US20150159173), rh.58 (SEQ ID NO: 48 of US20150159173), or variants thereof including, but not limited to Cy5R1, Cy5R2, Cy5R3, Cy5R4, rh.13R, rh.37R2, rh.2R, rh.8R, rh.48.1, rh.48.2, rh.48.12, hu.44R1, hu.44R2, hu.44R3, hu.29R, ch.5R1, rh64R1, rh64R2, AAV6.2, AAV6.1, AAV6.12, hu.48R1, hu.48R2, and hu.48R3.


In some embodiments, the AAV serotype may be, or have, a sequence as described in U.S. Pat. No. 7,198,951, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV9 (SEQ ID NO: 1-3 of U.S. Pat. No. 7,198,951), AAV2 (SEQ ID NO: 4 of U.S. Pat. No. 7,198,951), AAV1 (SEQ ID NO: 5 of U.S. Pat. No. 7,198,951), AAV3 (SEQ ID NO: 6 of U.S. Pat. No. 7,198,951), and AAV8 (SEQ ID NO: 7 of U.S. Pat. No. 7,198,951).


In some embodiments, the AAV serotype may be, or have, a mutation in the AAV9 sequence as described by N Pulicherla et al. (Molecular Therapy 19(6): 1070-1078 (2011), herein incorporated by reference in its entirety), such as but not limited to, AAV9.9, AAV9.11, AAV9.13, AAV9.16, AAV9.24, AAV9.45, AAV9.47, AAV9.61, AAV9.68, AAV9.84.


In some embodiments, the AAV serotype may be, or have, a sequence as described in U.S. Pat. No. 6,156,303, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV3B (SEQ ID NO: 1 and 10 of U.S. Pat. No. 6,156,303), AAV6 (SEQ ID NO: 2, 7 and 11 of U.S. Pat. No. 6,156,303), AAV2 (SEQ ID NO: 3 and 8 of U.S. Pat. No. 6,156,303), AAV3A (SEQ ID NO: 4 and 9, of U.S. Pat. No. 6,156,303), or derivatives thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Publication No US20140359799, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV8 (SEQ ID NO:1 of US20140359799), AAVDJ (SEQ ID NO: 2 and 3 of US20140359799), or variants thereof.


In some embodiments, the serotype may be AAVDJ or a variant thereof, such as AAVDJ8 (or AAV-DJ8), as described by Grimm et al. (Journal of Virology 82(12): 5887-5911 (2008), herein incorporated by reference in its entirety). The amino acid sequence of AAVDJ8 may comprise two or more mutations in order to remove the heparin binding domain (HBD). As a non-limiting example, the AAV-DJ sequence described as SEQ ID NO: 1 in U.S. Pat. No. 7,588,772, the contents of which are herein incorporated by reference in their entirety, may comprise two mutations: (1) R587Q where arginine (R; Arg) at amino acid 587 is changed to glutamine (Q; Gin) and (2) R590T where arginine (R; Arg) at amino acid 590 is changed to threonine (T; Thr). As another non-limiting example, may comprise three mutations: (1) K406R where lysine (K; Lys) at amino acid 406 is changed to arginine (R; Arg), (2) R587Q where arginine (R; Arg) at amino acid 587 is changed to glutamine (Q; Gln) and (3) R590T where arginine (R; Arg) at amino acid 590 is changed to threonine (T; Thr).


In some embodiments, the AAV serotype may be, or have, a sequence of AAV4 as described in International Publication No. WO1998011244, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to AAV4 (SEQ ID NO: 1-20 of WO1998011244).


In some embodiments, the AAV serotype may be, or have, a mutation in the AAV2 sequence to generate AAV2C9 as described in International Publication No. WO2014144229 and herein incorporated by reference in its entirety.


In some embodiments, the AAV serotype may be, or have, a sequence as described in International Publication No. WO2005033321, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to AAV3-3 (SEQ ID NO:217 of WO2005033321), AAV1 (SEQ ID NO: 219 and 202 of WO2005033321), AAV106.1/hu.37 (SEQ ID No: 10 of WO2005033321), AAV114.3/hu.40 (SEQ ID No: 11 of WO2005033321), AAV127.2/hu.41 (SEQ ID NO:6 and 8 of WO2005033321), AAV128.3/hu.44 (SEQ ID No. 81 of WO2005033321), AAV130.4/hu.48 (SEQ ID NO: 78 of WO2005033321), AAV145.1/hu.53 (SEQ ID No: 176 and 177 of WO2005033321), AAV145.6/hu.56 (SEQ ID NO: 168 and 192 of WO2005033321), AAV16.12hu.11 (SEQ ID NO: 153 and 57 of WO2005033321), AAV16.8/hu.10 (SEQ ID NO: 156 and 56 of WO2005033321), AAV61.10hu.60 (SEQ ID No-170 of WO2005033321), AAV161.6/hu.61 (SEQ ID No: 174 of WO2005033321), AAV1-7/rh.48 (SEQ ID NO: 32 of WO2005033321), AAV1-8/rh.49 (SEQ ID NOs: 103 and 25 of WO2005033321), AAV2 (SEQ ID NO: 211 and 221 of WO2005033321), AAV2-15rh.62 (SEQ ID No: 33 and 114 of WO2005033321), AAV2-3/rh.61 (SEQ ID NO: 21 of WO2005033321), AAV2-4/rh.50 (SEQ ID No: 23 and 108 of WO2005033321), AAV2-5/rh.51 (SEQ ID NO: 104 and 22 of WO02005033321), AAV3.1/hu.6 (SEQ ID NO: 5 and 84 of WO20 (5033321), AAV3.4/hu.9 (SEQ ID NO: 155 and 58 of WO2005033321), AAV3-11/rh.53 (SEQ ID NO: 186 and 176 of WO2005033321), AAV3-3 (SEQ ID NO: 200 of WO2005033321), AAV33.12/hu.17 (SEQ ID NO:4 of WO2005033321), AAV33.4/hu.15 (SEQ ID No: 50 of WO2005033321), AAV33.8/hu.16 (SEQ ID No: 51 of WO2005033321), AAV3-9/rh.52 (SEQ ID NO: 96 and 18 of WO2005033321), AAV4-19/rh.55 (SEQ ID NO: 117 of WO2005033321), AAV4-4 (SEQ ID NO: 201 and 218 of WO2005033321), AAV4-9/rh.54 (SEQ ID NO: 116 of WO2005033321), AAV5 (SEQ ID NO: 199 and 216 of WO2005033321), AAV52.1/hu.20 (SEQ ID NO: 63 of WO2005033321), AAV52hu.19 (SEQ ID NO:133 of WO2005033321), AAV5-22/rh.58 (SEQ ID No: 27 of WO2005033321), AAV5-3/rh.57 (SEQ ID NO: 105 of WO2005033321), AAV5-3/rh.57 (SEQ ID No. 26 of WO2005033321), AAV58.2hu.25 (SEQ ID No: 49 of WO2005033321), AAV6 (SEQ ID NO: 203 and 220 of WO2005033321), AAV7 (SEQ ID NO: 222 and 213 of WO20050333321), AAV7.3/hu.7 (SEQ ID No: 55 of WO2005033321), AAV8 (SEQ ID NO: 223 and 214 of WO02005033321), AAVH-1/hu.1 (SEQ ID No: 46 of WO2005033321), AAVH-5/hu.3 (SEQ ID No:44 of WO2005033321), AAVhu.11 (SEQ ID NO: 144 of WO2005033321), AAVhu.10 (SEQ ID NO: 156 of WO2005033321), AAVhu.1 (SEQ ID NO: 153 of WO20050333321), AAVhu.12 (WO2005033321 SEQ ID NO: 59), AAVhu.13 (SEQ ID NO: 129 of WO2005033321), AAVhu.14AAV9 (SEQ ID NO: 123 and 3 of WO2005033321), AAVhu.15 (SEQ ID NO: 147 of WO2005033321), AAVhu.16 (SEQ ID NO: 148 of WO02005033321), AAVhu.17 (SEQ ID NO: 83 of WO02005033321), AAVhu.18 (SEQ ID NO: 149 of WO2005033321), AAVhu.19 (SEQ ID NO: 133 of WO205033321), AAVhu.2 (SEQ ID NO:143 of WO2005033321), AAVhu.20 (SEQ ID NO:134 of WO2005033321), AAVhu.21 (SEQ ID NO: 135 of WO2005033321), AAVhu.22 (SEQ ID NO: 138 of WO2005033321), AAVhu.23.2 (SEQ ID NO: 137 of WO20050333321), AAVhu.24 (SEQ ID NO: 136 of WO2005033321), AAVhu.25 (SEQ ID NO: 146 of WO2005033321), AAVhu.27 (SEQ ID NO: 140 of WO2005033321), AAVhu.29 (SEQ ID NO: 132 of WO2005033321), AAVhu.3 (SEQ ID NO: 145 of WO20050333321), AAVhu.31 (SEQ ID NO: 121 of WO2005033321), AAVhu.32 (SEQ ID NO: 122 of WO2005033321), AAVhu.34 (SEQ ID NO. 125 of WO2005033321), AAVhu.35 (SEQ ID NO: 164 of WO2005033321), AAVhu.37 (SEQ ID NO: 88 of WO2005033321), AAVhu.39 (SEQ ID NO: 102 of WO2005033321), AAVhu.4 (SEQ ID NO: 141 of WO2005033321), AAVhu.40 (SEQ ID NO: 87 of WO2005033321), AAVhu.41 (SEQ ID NO: 91 of WO2005033321), AAVhu.42 (SEQ ID NO: 85 of WO2005033321), AAVhu.43 (SEQ ID NO:160 of WO2005033321), AAVhu.44 (SEQ ID NO-144 of WO2005033321), AAVhu.45 (SEQ ID NO: 127 of WO2005033321), AAVhu.46 (SEQ ID NO. 159 of WO2005033321), AAVhu.47 (SEQ ID NO: 128 of WO2005033321), AAVhu.48 (SEQ ID NO:157 of WO2005033321), AAVhu.49 (SEQ ID NO:189 of WO2005033321), AAVhu.51 (SEQ ID NO: 190 of WO2005033321), AAVhu.52 (SEQ ID NO: 191 of WO2005033321), AAVhu.53 (SEQ ID NO: 186 of WO2005033321), AAVhu.54 (SEQ ID NO: 188 of WO205033321), AAVhu.55 (SEQ ID NO: 187 of WO2005033321), AAVhu.56 (SEQ ID NO-192 of WO2005033321), AAVhu.57 (SEQ ID NO:193 of WO2005033321), AAVhu.58 (SEQ ID NO: 194 of WO2005033321), AAVhu.6 (SEQ ID NO: 84 of WO2005033321), AAVhu.60 (SEQ ID NO: 184 of WO2005033321), AAVhu.61 (SEQ ID NO: 185 of WO2005033321), AAVhu.63 (SEQ ID NO: 195 of WO2005033321), AAVhu.64 (SEQ ID NO: 196 of WO2005033321), AAVhu.66 (SEQ ID NO: 197 of WO2005033321), AAVhu.67 (SEQ ID NO: 198 of WO2005033321), AAVhu.7 (SEQ ID NO: 150 of WO2005033321), AAVhu.8 (WO2005033321 SEQ ID NO: 12), AAVhu.9 (SEQ ID NO: 155 of WO2005033321), AAVLG-10/rh.40 (SEQ ID No: 14 of WO2005033321), AAVLG-4/rh.38 (SEQ ID NO: 86 of WO2005033321), AAVLG-4/rh.38 (SEQ ID No: 7 of WO2005033321), AAVN721-8/rh.43 (SEQ ID NO:163 of WO2005033321), AAVN721-8/rh.43 (SEQ ID No: 43 of WO2005033321), AAVpi.1 (WO2005033321 SEQ ID NO: 28), AAVpi.2 (WO2005033321 SEQ ID NO: 30), AAVpi.3 (WO2005033321 SEQ ID NO: 29), AAVrh.38 (SEQ ID NO: 86 of WO2005033321), AAVrh.40 (SEQ ID NO: 92 of WO2005033321), AAVrh.43 (SEQ ID NO: 163 of WO2005033321), AAVrh.44 (WO2005033321 SEQ ID NO: 34), AAVrh.45 (WO2005033321 SEQ ID NO: 41), AAVrh.47 (WO2005033321 SEQ ID NO: 38), AAVrh.48 (SEQ ID NO: 115 of WO2005033321), AAVrh.49 (SEQ ID NO: 103 of WO2005033321), AAVrh.50 (SEQ ID NO: 108 of WO2005033321), AAVrh.51 (SEQ ID NO: 104 of WO2005033321), AAVrh.52 (SEQ ID NO: 96 of WO2005033321), AAVrh.53 (SEQ ID NO: 97 of WO2005033321), AAVrh.55 (WO2005033321 SEQ ID NO: 37), AAVrh.56 (SEQ ID NO: 152 of WO20050333321), AAVrh.57 (SEQ ID NO: 105 of WO2005033321), AAVrh.58 (SEQ ID NO: 106 of WO2005033321), AAVrh.59 (WO2005033321 SEQ ID NO: 42), AAVrh.60 (WO2005033321 SEQ ID NO: 31), AAVrh.61 (SEQ ID NO: 107 of WO2005033321), AAVrh.62 (SEQ ID NO: 114 of WO2005033321), AAVrh.64 (SEQ ID NO: 99 of WO2005033321), AAVrh.65 (WO2005033321 SEQ ID NO: 35), AAVrh.68 (WO2005033321 SEQ ID NO: 16), AAVrh.69 (WO2005033321 SEQ ID NO: 39), AAVrh.70 (WO2005033321 SEQ ID NO: 20), AAVrh.72 (WO2005033321 SEQ ID NO: 9), or variants thereof including, but not limited to, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVcy.6, AAVrh.12, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.25/42 15, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.14. Non-limiting examples of variants include SEQ ID NO: 13, 15, 17, 19, 24, 36, 40, 45, 47, 48, 51-54, 60-62, 64-77, 79, 80, 82, 89, 90, 93-95, 98, 100, 101, 109-113, 118-120, 124, 126, 131, 139, 142, 151, 154, 158, 161, 162, 165-183, 202, 204-212, 215, 219, 224-236, of WO2005033321, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the AAV serotype may be, or have, a sequence as described in International Publication No. WO2015168666, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAVrh8R (SEQ ID NO: 9 of WO2015168666), AAVrh8R A586R mutant (SEQ ID NO: 10 of WO2015168666), AAVrh8R R533A mutant (SEQ ID NO: 11 of WO2015168666), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in U.S. Pat. No. 9,233,131, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAVhE1.1 (SEQ ID NO:44 of U.S. Pat. No. 9,233,131), AAVhEr1.5 (SEQ ID NO:45 of U.S. Pat. No. 9,233,131), AAVhER1.14 (SEQ ID NO:46 of U.S. Pat. No. 9,233,131), AAVhEr1.8 (SEQ ID NO:47 of U.S. Pat. No. 9,233,131), AAVhEr1.16 (SEQ ID NO:48 of U.S. Pat. No. 9,233,131), AAVhEr1.18 (SEQ ID NO:49 of U.S. Pat. No. 9,233,131), AAVhEr1.35 (SEQ ID NO:50 of U.S. Pat. No. 9,233,131), AAVhEr1.7 (SEQ ID NO:51 of U.S. Pat. No. 9,233,131), AAVhEr1.36 (SEQ ID NO:52 of U.S. Pat. No. 9,233,131), AAVhEr2.29 (SEQ ID NO:53 of U.S. Pat. No. 9,233,131), AAVhEr2.4 (SEQ ID NO:54 of U.S. Pat. No. 9,233,131), AAVhEr2.16 (SEQ ID NO:55 of U.S. Pat. No. 9,233,131), AAVhEr2.30 (SEQ ID NO:56 of U.S. Pat. No. 9,233,131), AAVhEr2.31 (SEQ ID NO:58 of U.S. Pat. No. 9,233,131), AAVhEr2.36 (SEQ ID NO:57 of U.S. Pat. No. 9,233,131), AAVhER1.23 (SEQ ID NO:53 of U.S. Pat. No. 9,233,131), AAVhEr3.1 (SEQ ID NO:59 of U.S. Pat. No. 9,233,131), AAV2.5T (SEQ ID NO:42 of U.S. Pat. No. 9,233,131), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Patent Publication No. US20150376607, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV-PAEC (SEQ ID NO: 1 of US20150376607), AAV-LK01 (SEQ ID NO:2 of US20150376607), AAV-LK02 (SEQ ID NO:3 of US20150376607), AAV-LK03 (SEQ ID NO:4 of US20150376607), AAV-LK04 (SEQ ID NO:5 of US20150376607), AAV-LK05 (SEQ ID NO:6 of US20150376607), AAV-LK06 (SEQ ID NO:7 of US20150376607), AAV-LK07 (SEQ ID NO:8 of US20150376607), AAV-LK08 (SEQ ID NO:9 of US20150376607), AAV-LK09 (SEQ ID NO:10 of US20150376607), AAV-LK10 (SEQ ID NO: 11 of US20150376607), AAV-LK11 (SEQ ID NO: 12 of US20150376607), AAV-LK12 (SEQ ID NO: 13 of US20150376607), AAV-LK13 (SEQ ID NO:14 of US20150376607), AAV-LK14 (SEQ ID NO:15 of US20150376607), AAV-LK15 (SEQ ID NO:16 of US20150376607), AAV-LK16 (SEQ ID NO:17 of US20150376607), AAV-LK17 (SEQ ID NO:18 of US20150376607), AAV-LK8 (SEQ ID NO:19 of US20150376607), AAV-LK19 (SEQ ID NO:20 of US20150376607), AAV-PAEC2 (SEQ ID NO:21 of US20150376607), AAV-PAEC4 (SEQ ID NO:22 of US20150376607), AAV-PAEC6 (SEQ ID NO:23 of US20150376607), AAV-PAEC7 (SEQ ID NO:24 of US20150376607), AAV-PAEC8 (SEQ ID NO:25 of US20150376607), AAV-PAEC11 (SEQ ID NO:26 of US20150376607), AAV-PAEC12 (SEQ ID NO:27, of US20150376607), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in U.S. Pat. No. 9,163,261, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV-2-pre-miRNA-101 (SEQ ID NO: 1 U.S. Pat. No. 9,163,261), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Patent Publication No. US20150376240, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV-8h (SEQ ID NO: 6 of US20150376240), AAV-8b (SEQ ID NO: 5 of US20150376240), AAV-h (SEQ ID NO: 2 of US20150376240), AAV-b (SEQ ID NO: 1 of US20150376240), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Patent Publication No. US20160017295, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV SM 10-2 (SEQ ID NO: 22 of US20160017295), AAV Shuffle 100-1 (SEQ ID NO: 23 of US2016017295), AAV Shuffle 100-3 (SEQ ID NO: 24 of US20160017295), AAV Shuffle 100-7 (SEQ ID NO: 25 of US20160017295), AAV Shuffle 10-2 (SEQ ID NO: 34 of US20160017295), AAV Shuffle 10-6 (SEQ ID NO: 35 of US20160017295), AAV Shuffle 10-8 (SEQ ID NO: 36 of US20160017295), AAV Shuffle 100-2 (SEQ ID NO: 37 of US20160017295), AAV SM 10-1 (SEQ ID NO: 38 of US20160017295), AAV SM 10-8 (SEQ ID NO: 39 of US20160017295), AAV SM 100-3 (SEQ ID NO: 40 of US20160017295), AAV SM 100-10) (SEQ ID NO: 41 of US20160017295), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in United States Patent Publication No. US20150238550, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, BNP61 AAV (SEQ ID NO: 1 of US20150238550), BNP62 AAV (SEQ ID NO: 3 of US20150238550), BNP63 AAV (SEQ ID NO: 4 of US20150238550), or variants thereof.


In some embodiments, the AAV serotype may be or may have a sequence as described in United States Patent Publication No. US20150315612, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAVrh.50 (SEQ ID NO: 108 of US20150315612), AAVrh.43 (SEQ ID NO: 163 of US20150315612), AAVrh.62 (SEQ ID NO. 114 of US20150315612), AAVrh.48 (SEQ ID NO: 115 of US20150315612), AAVhu.19 (SEQ ID NO:133 of US20150315612), AAVhu.11 (SEQ ID NO: 153 of US20150315612), AAVhu.53 (SEQ ID NO: 186 of US20150315612), AAV4-8/rh.64 (SEQ ID No: 15 of US20150315612), AAVLG-9/hu.39 (SEQ ID No: 24 of US20150315612), AAV54.5/hu.23 (SEQ ID No: 60 of US20150315612), AAV54.2/hu.22 (SEQ ID No. 67 of US20150315612), AAV54.7/hu.24 (SEQ ID No: 66 of US20150315612), AAV54.1/hu.21 (SEQ ID No:65 of US20150315612), AAV54.4R/hu.27 (SEQ ID No: 64 of US20150315612), AAV46.2/hu.28 (SEQ ID No: 68 of US20150315612), AAV46.6hu.29 (SEQ ID No: 69 of US20150315612), AAV128.1/hu.43 (SEQ ID No:80 of US20150315612), or variants thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in International Publication No. WO2015121501, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, true type AAV (ttAAV) (SEQ ID NO: 2 of WO2015121501. “UPenn AAV10” (SEQ ID NO: 8 of WO2015121501), “Japanese AAV10” (SEQ ID NO: 9 of WO2015121501), or variants thereof.


According to the present invention, AAV capsid serotype selection or use may be from a variety of species. In one embodiment, the AAV may be an avian AAV (AAAV). The AAAV serotype may be, or have, a sequence as described in U.S. Pat. No. 9,238,800, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAAV (SEQ ID NO: 1, 2, 4, 6, 8, 10, 12, and 14 of U.S. Pat. No. 9,238,800), or variants thereof.


In one embodiment, the AAV may be a bovine AAV (BAAV). The BAAV serotype may be, or have, a sequence as described in U.S. Pat. No. 9,193,769, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, BAAV (SEQ ID NO: 1 and 6 of U.S. Pat. No. 9,193,769), or variants thereof. The BAAV serotype may be or have a sequence as described in U.S. Pat. No. 7,427,396, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, BAAV (SEQ ID NO: 5 and 6 of U.S. Pat. No. 7,427,396), or variants thereof.


In one embodiment, the AAV may be a caprine AAV. The caprine AAV serotype may be, or have, a sequence as described in U.S. Pat. No. 7,427,396, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, caprine AAV (SEQ ID NO: 3 of U.S. Pat. No. 7,427,396), or variants thereof.


In other embodiments, the AAV may be engineered as a hybrid AAV from two or more parental serotypes. In one embodiment, the AAV may be AAV2G9 which comprises sequences from AAV2 and AAV9. The AAV2G9 AAV serotype may be, or have, a sequence as described in United States Patent Publication No. US2016017005, the contents of which are herein incorporated by reference in its entirety.


In one embodiment, the AAV may be a serotype generated by the AAV9 capsid library with mutations in amino acids 390-627 (VP1 numbering) as described by Pulicherla et al. (Molecular Therapy 19(6):1070-1078 (2011), the contents of which are herein incorporated by reference in their entirety. The serotype and corresponding nucleotide and amino acid substitutions may be, but is not limited to, AAV9.1 (G1594C; D5321HI), AAV6.2 (T1418A and T1436X; V473D and 1479K), AAV9.3 (T1238A; F413Y), AAV9.4 (T1250C and A1617T; F417S), AAV9.5 (A1235G, A1314T, A1642G, C1760T; Q412R, T548A, A587V), AAV9.6 (T1231A; F4111), AAV9.9 (G1203A, G1785T; W595C), AAV9.10 (A1500G, T1676C; M559T), AAV9.11 (A1425T, A1702C, A1769T; T568P, Q590L), AAV9.13 (A1369C, A1720T; N457H, T574S), AAV9.14 (T1340A, T1362C, T1560C, G1713A; L447H), AAV9.16 (A1775T; Q592L), AAV9.24 (T1507C, T1521G; W503R), AAV9.26 (A1337G, A1769C; Y446C, Q590P), AAV9.33 (A1667C; D556A), AAV9.34 (A1534G, C1794T; N512D), AAV9.35 (A1289T, TI 450, C1494T, A1515T, C1794A, G1816A; Q430L, Y484N, N98K, V6061), AAV9.40 (A1694T, E565V), AAV9.41 (A1348T, T1362C; T450S), AAV9.44 (A1684C, A1701T, A1737G; N562H, K567N), AAV9.45 (A1492T, C804T; N498Y, L602F), AAV9.46 (G1441C, T1525C, T1549G; G481R, W509R, L517V), 9.47 (G1241A, G1358A, A1669G, C1745T; S414N, G453D, K557E, T582I), AAV9.48 (C1445T, A1736T; P482L, Q579L), AAV9.50 (A1638T, C1683T, T1805A; Q546H, L602H), AAV9.53 (G1301A, A1405C, C1664T, G1811T; R134Q, S469R, A555V, G604V), AAV9.54 (C1531A, T1609A; L511I, L537M), AAV9.55 (T1605A; F535L), AAV9.58 (C1475T, C1579A; T492I, H527N), AAV.59 (T1336C; Y446H), AAV9.61 (A1493T; N4981), AAV9.64 (C1531A, A1617T; L511I), AAV9.65 (C1335T, T1530C, C1568A; A523D), AAV9.68 (C1510A; P504T), AAV9.80 (G1441A, G481R), AAV9.83 (C1402A, A1500T; P468T, E500D), AAV9.87 (T1464C, T1468C; S49(P), AAV9.90 (A1196T; Y399F), AAV9.91 (T1316G, A1583T, C1782G, T1806C; L439R, K5281), AAV9.93 (A1273G, A1421G, A1638C, C1712T, G1732A, A1744T, A1832T; S425G, Q474R, Q546H, P571L, G578R, T582S, D611V), AAV9.94 (A1675T; M559L) and AAV9.95 (T1605A; F535L).


In some embodiments, the AAV serotype may be, or have, a sequence as described in International Publication No. WO2016049230, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to AAVF1/HSC1 (SEQ ID NO: 2 and 20 of WO2016049230), AAVF2/HSC2 (SEQ ID NO: 3 and 21 of WO2016049230), AAVF3/HSC3 (SEQ ID NO: 5 and 22 of WO20160(49230), AAVF4/HSC4 (SEQ ID NO: 6 and 23 of WO2016049230), AAVF5/HSC5 (SEQ ID NO: 11 and 25 of WO2016049230), AAVF6/HSC6 (SEQ ID NO: 7 and 24 of WO2016049230), AAVF7/HSC7 (SEQ ID NO: 8 and 27 of WO2016049230), AAVF8/HSC8 (SEQ ID NO: 9 and 28 of WO20160(49230), AAVF9/HSC9 (SEQ ID NO: 10 and 29 of WO2016049230), AAVF11/HSC11 (SEQ ID NO: 4 and 26 of WO2016049230), AAVF12/HSC12 (SEQ ID NO: 12 and 30) of WO2016049230), AAVF13/HSC13 (SEQ ID NO: 14 and 31 of WO2016049230), AAVF14/HSC14 (SEQ ID NO: 15 and 32 of WO2016049230), AAVF15/HSC15 (SEQ ID NO: 16 and 33 of WO2016049230), AAVF16/HSC16 (SEQ ID NO: 17 and 34 of WO2016049230), AAVF177/HSC17 (SEQ ID NO. 13 and 35 of WO2016049230), or variants or derivatives thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in U.S. Pat. No. 8,734,809, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV CBr-E1 (SEQ ID NO: 13 and 87 of U.S. Pat. No. 8,734,809), AAV CBr-E2 (SEQ ID NO: 14 and 88 of U.S. Pat. No. 8,734,809), AAV CBr-E3 (SEQ ID NO: 15 and 89 of U.S. Pat. No. 8,734,809), AAV CBr-E4 (SEQ ID NO: 16 and 90 of U.S. Pat. No. 8,734,809), AAV CBr-E5 (SEQ ID NO: 17 and 91 of U.S. Pat. No. 8,734,809), AAV CBr-e5 (SEQ ID NO: 18 and 92 of U.S. Pat. No. 8,734,809), AAV CBr-E6 (SEQ ID NO:19 and 93 of U.S. Pat. No. 8,734,809), AAV CBr-E7 (SEQ ID NO: 20 and 94 of U.S. Pat. No. 8,734,809), AAV CBr-E8 (SEQ ID NO: 21 and 95 of U.S. Pat. No. 8,734,809), AAV CLv-D1 (SEQ ID NO: 22 and 96 of U.S. Pat. No. 8,734,809), AAV CLv-D2 (SEQ ID NO: 23 and 97 of U.S. Pat. No. 8,734,809), AAV CLv-D3 (SEQ ID NO: 24 and 98 of U.S. Pat. No. 8,734,809), AAV CLv-D4 (SEQ ID NO: 25 and 99 of U.S. Pat. No. 8,734,809), AAV CLv-D5 (SEQ ID NO: 26 and 100 of U.S. Pat. No. 8,734,809), AAV CLv-D6 (SEQ ID NO: 27 and 101 of U.S. Pat. No. 8,734,809), AAV CLv-D7 (SEQ ID NO: 28 and 102 of U.S. Pat. No. 8,734,809), AAV CLv-D8 (SEQ ID NO: 29 and 103 of U.S. Pat. No. 8,734,809, AAV CLv-E1 (SEQ ID NO: 13 and 87 of U.S. Pat. No. 8,734,809), AAV CLv-R1 (SEQ ID NO: 30 and 104 of U.S. Pat. No. 8,734,809), AAV CLv-R2 (SEQ ID NO: 31 and 105 of U.S. Pat. No. 8,734,809), AAV CLv-R3 (SEQ ID NO: 32 and 106 of U.S. Pat. No. 8,734,809), AAV CLv-R4 (SEQ ID NO: 33 and 107 of U.S. Pat. No. 8,734,809), AAV CLv-R5 (SEQ ID NO: 34 and 108 of U.S. Pat. No. 8,734,809), AAV CLv-R6 (SEQ ID NO: 35 and 109 of U.S. Pat. No. 8,734,809), AAV CLv-R7 (SEQ ID NO: 36 and 110 of U.S. Pat. No. 8,734,809), AAV CLv-R8 (SEQ ID NO: 37 and 111 of U.S. Pat. No. 8,734,809), AAV CL-R9 (SEQ ID NO: 38 and 112 of U.S. Pat. No. 8,734,809), AAV CLg-F1 (SEQ ID NO: 39 and 113 of U.S. Pat. No. 8,734,809), AAV CLg-F2 (SEQ ID NO: 40 and 114 of U.S. Pat. No. 8,734,809), AAV CLg-F3 (SEQ ID NO: 41 and 115 of U.S. Pat. No. 8,734,809), AAV CLg-F4 (SEQ ID NO: 42 and 116 of U.S. Pat. No. 8,734,809), AAV CLg-F5 (SEQ ID NO: 43 and 117 of U.S. Pat. No. 8,734,809), AAV CLg-F6 (SEQ ID NO: 43 and 117 of U.S. Pat. No. 8,734,809), AAV CLg-F7 (SEQ ID NO: 44 and 118 of U.S. Pat. No. 8,734,809), AAV CLg-F8 (SEQ ID NO: 43 and 117 of U.S. Pat. No. 8,734,809), AAV CSp-1 (SEQ ID NO: 45 and 119 of U.S. Pat. No. 8,734,809), AAV CSp-10 (SEQ ID NO: 46 and 120 of U.S. Pat. No. 8,734,809), AAV CSp-11 (SEQ ID NO: 47 and 121 of U.S. Pat. No. 8,734,809), AAV CSp-2 (SEQ ID NO: 48 and 122 of U.S. Pat. No. 8,734,809), AAV CSp-3 (SEQ ID NO: 49 and 123 of U.S. Pat. No. 8,734,809), AAV CSp-4 (SEQ ID NO: 50 and 124 of U.S. Pat. No. 8,734,809), AAV CSp-6 (SEQ ID NO: 51 and 125 of U.S. Pat. No. 734,809), AAV CSp-7 (SEQ ID NO-52 and 126 of U.S. Pat. No. 8,734,809), AAV CSp-8 (SEQ ID NO: 53 and 127 of U.S. Pat. No. 8,734,809), AAV CSp-9 (SEQ ID NO: 54 and 128 of U.S. Pat. No. 8,734,809), AAV CHt-2 (SEQ ID NO: 55 and 129 of U.S. Pat. No. 8,734,809), AAV CHt-3 (SEQ ID NO: 56 and 130 of U.S. Pat. No. 8,734,809), AAV CKd-1 (SEQ ID NO: 57 and 131 of U.S. Pat. No. 8,734,809), AAV CKd-10 (SEQ ID NO: 58 and 132 of U.S. Pat. No. 8,734,809), AAV CKd-2 (SEQ ID NO: 59 and 133 of U.S. Pat. No. 8,734,809), AAV CKd-3 (SEQ ID NO: 60 and 134 of U.S. Pat. No. 8,734,809), AAV CKd-4 (SEQ ID NO: 61 and 135 of U.S. Pat. No. 8,734,809), AAV CKd-6 (SEQ ID NO: 62 and 136 of U.S. Pat. No. 8,734,809), AAV CKd-7 (SEQ ID NO: 63 and 137 of U.S. Pat. No. 8,734,809), AAV CKd-8 (SEQ ID NO: 64 and 138 of U.S. Pat. No. 8,734,809), AAV CLv-1 (SEQ ID NO: 35 and 139 of U.S. Pat. No. 8,734,809), AAV CLv-12 (SEQ ID NO: 66 and 140 of U.S. Pat. No. 8,734,809), AAV CLv-13 (SEQ ID NO: 67 and 141 of U.S. Pat. No. 8,734,809), AAV CLv-2 (SEQ ID NO: 68 and 142 of U.S. Pat. No. 8,734,809), AAV CLv-3 (SEQ ID NO: 69 and 143 of U.S. Pat. No. 8,734,809), AAV CLv-4 (SEQ ID NO: 70 and 144 of U.S. Pat. No. 8,734,809), AAV CLv-6 (SEQ ID NO: 71 and 145 of U.S. Pat. No. 8,734,809), AAV CLv-8 (SEQ ID NO: 72 and 146 of U.S. Pat. No. 8,734,809), AAV CKd-B1 (SEQ ID NO: 73 and 147 of U.S. Pat. No. 8,734,809), AAV CKd-B2 (SEQ ID NO: 74 and 148 of U.S. Pat. No. 8,734,809), AAV CKd-B3 (SEQ ID NO: 75 and 149 of U.S. Pat. No. 8,734,809), AAV CKd-B4 (SEQ ID NO: 76 and 150) of U.S. Pat. No. 8,734,809), AAV CKd-B5 (SEQ ID NO: 77 and 151 of U.S. Pat. No. 8,734,809), AAV CKd-B6 (SEQ ID NO: 78 and 152 of U.S. Pat. No. 8,734,809), AAV CKd-B7 (SEQ ID NO: 79 and 153 of U.S. Pat. No. 8,734,809), AAV CKd-B8 (SEQ ID NO: 80 and 154 of U.S. Pat. No. 8,734,809), AAV CKd-H1 (SEQ ID NO: 81 and 155 of U.S. Pat. No. 8,734,809), AAV CKd-H2 (SEQ ID NO: 82 and 156 of U.S. Pat. No. 8,734,809), AAV CKd-H3 (SEQ ID NO: 83 and 157 of U.S. Pat. No. 8,734,809), AAV CKd-H4 (SEQ ID NO: 84 and 158 of U.S. Pat. No. 8,734,809), AAV CKd-H5 (SEQ ID NO: 85 and 159 of U.S. Pat. No. 8,734,809), AAV CKd-H6 (SEQ ID NO: 77 and 151 of U.S. Pat. No. 8,734,809), AAV CHt-1 (SEQ ID NO: 86 and 160 of 8734809), AAV CLv1-1 (SEQ ID NO: 171 of U.S. Pat. No. 8,734,809), AAV CLv1-2 (SEQ ID NO: 172 of U.S. Pat. No. 8,734,809), AAV CLv1-3 (SEQ ID NO: 173 of U.S. Pat. No. 734,809), AAV CLv1-4 (SEQ ID NO: 174 of U.S. Pat. No. 8,734,809), AAV Clv1-7 (SEQ ID NO: 175 of U.S. Pat. No. 8,734,809), AAV Clv1-8 (SEQ ID NO: 176 of U.S. Pat. No. 8,734,809), AAV Clv1-9 (SEQ ID NO: 177 of U.S. Pat. No. 8,734,809), AAV Clv-10 (SEQ ID NO: 178 of U.S. Pat. No. 8,734,809), AAV.VR-355 (SEQ ID NO: 181 of U.S. Pat. No. 8,734,809), AAV.hu.48R3 (SEQ ID NO: 183 of U.S. Pat. No. 8,734,809), or variants or derivatives thereof.


In some embodiments, the AAV serotype may be, or have, a sequence as described in International Publication No. WO02016065001, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to AAV CHt-P2 (SEQ ID NO: 1 and 51 of WO2016065001), AAV CHt-P5 (SEQ ID NO: 2 and 52 of WO2016065001), AAV CHt-P9 (SEQ ID NO: 3 and 53 of WO2016065001), AAV CBr-7.1 (SEQ ID NO: 4 and 54 of WO2016065001), AAV CBr-7.2 (SEQ ID NO: 5 and 55 of WO2016065001), AAV CBr-7.3 (SEQ ID NO: 6 and 56 of WO2016065001), AAV CBr-7.4 (SEQ ID NO: 7 and 57 of WO2016065001), AAV CBr-7.5 (SEQ ID NO: 8 and 58 of WO2016065001), AAV CBr-7.7 (SEQ ID NO: 9 and 59 of WO2016065001), AAV CBr-7.8 (SEQ ID NO: 10 and 60 of WO2016065001), AAV CBr-7.10 (SEQ ID NO: 11 and 61 of WO2016065001), AAV CKd-N3 (SEQ ID NO: 12 and 62 of WO2016065001), AAV CKd-N4 (SEQ ID NO: 13 and 63 of WO2016065001), AAV CKd-N9 (SEQ ID NO: 14 and 64 of WO2016065001), AAV CLv-L4 (SEQ ID NO: 15 and 65 of WO2016065001), AAV CLv-L5 (SEQ ID NO: 16 and 66 of WO2016065001), AAV CLv-L6 (SEQ ID NO: 17 and 67 of WO2016065001), AAV CLv-K1 (SEQ ID NO: 18 and 68 of WO2016065001), AAV CLv-K3 (SEQ ID NO: 19 and 69 of WO2016065001), AAV CLv-K6 (SEQ ID NO: 20 and 70 of WO2016065001), AAV CLv-M (SEQ ID NO: 21 and 71 of WO2016065001), AAV CLv-M11 (SEQ ID NO: 22 and 72 of WO2016065001), AAV CLv-M2 (SEQ ID NO: 23 and 73 of WO2016065001), AAV CLv-M5 (SEQ ID NO: 24 and 74 of WO2016065001), AAV CLv-M6 (SEQ ID NO: 25 and 75 of WO2016065001), AAV CLv-M7 (SEQ ID NO: 26 and 76 of WO2016065001), AAV CLv-M8 (SEQ ID NO: 27 and 77 of WO2016065001), AAV CLv-M9 (SEQ ID NO: 28 and 78 of WO2016065001), AAV CHt-P1 (SEQ ID NO: 29 and 79 of WO2016065001), AAV CHt-P6 (SEQ ID NO: 30 and 80 of WO2016065001), AAV CHt-P8 (SEQ ID NO: 31 and 81 of WO2016065001), AAV CHt-6.1 (SEQ ID NO: 32 and 82 of WO2016065001), AAV CHt-6.10 (SEQ ID NO: 33 and 83 of WO2016065001), AAV CHt-6.5 (SEQ ID NO: 34 and 84 of WO2016065001), AAV CHt-6.6 (SEQ ID NO: 35 and 85 of WO2016065001), AAV CHt-6.7 (SEQ ID NO: 36 and 86 of WO2016065001), AAV CHt-6.8 (SEQ ID NO: 37 and 87 of WO2016065001), AAV CSp-8.10 (SEQ ID NO: 38 and 88 of WO2016065001), AAV CSp-8.2 (SEQ ID NO: 39 and 89 of WO2016065001), AAV CSp-8.4 (SEQ ID NO: 40 and 90 of WO2016065001), AAV CSp-8.5 (SEQ ID NO: 41 and 91 of WO2016065001), AAV CSp-8.6 (SEQ ID NO: 42 and 92 of WO2016065001), AAV CSp-8.7 (SEQ ID NO: 43 and 93 of WO2016065001), AAV CSp-8.8 (SEQ ID NO: 44 and 94 of WO2016065001), AAV CSp-8.9 (SEQ ID NO: 45 and 95 of WO2016065001), AAV CBr-B7.3 (SEQ ID NO: 46 and 96 of WO2016065001), AAV CBr-B7.4 (SEQ ID NO: 47 and 97 of WO2016065001), AAV3B (SEQ ID NO: 48 and 98 of WO2016065001), AAV4 (SEQ ID NO: 49 and 99 of WO2016065001), AAV5 (SEQ ID NO: 50 and 100 of WO2016065001), or variants or derivatives thereof.


In one embodiment, the AAV may be a serotype selected from any of those found in Table 1.


In one embodiment, the AAV may comprise a sequence, fragment or variant thereof, of the sequences in Table 1.


In one embodiment, the AAV may be encoded by a sequence, fragment or variant as described in Table 1.









TABLE 1







AAV Serotypes









Serotype
SEQ ID NO
Reference Information












AAV1
1
US20150159173 SEQ ID NO: 11,




US2015 315612 SEQ ID NO: 202


AAV1
2
US20160017295 SEQ ID NO: 1US20030138772




SEQ ID NO: 64, US20150159173




SEQ ID NO: 27, US20150315612




SEQ ID NO: 219, US7198951 SEQ ID NO: 5


AAV1
3
US20030138772 SEQ ID NO: 6


AAV1.3
4
US20030138772 SEQ ID NO: 14


AAV10
5
US20030 38772 SEQ ID NO: 117


AAV10
6
WO20151501 SEQ ID NO: 9


AAV10
7
WO2015121501 SEQ ID NO: 8


AAV11
8
US20030138772 SEQ ID NO: 118


AAV12
9
US20030138772 SEQ ID NO: 119


AAV2
10
US20150159173 SEQ ID NO: 7, US20150315612 SEQ ID NO: 211


AAV2
11
US20030138772 SEQ ID NO: 70, US20150159173 SEQ ID NO: 23, US20150315612




SEQ ID NO: 221, US20160017295 SEQ ID NO: 2, US6156303 SEQ ID NO: 4,




US7198951 SEQ ID NO: 4, WO2015121501 SEQ ID NO: 1


AAV2
12
US6156303 SEQ ID NO: 8


AAV2
13
US20030138772 SEQ ID NO: 7


AAV2
14
US6156303 SEQ ID NO: 3


AAV2.5T
15
US9233131 SEQ ID NO: 42


AAV223.10
16
US20030138772 SEQ ID NO: 75


AAV223.2
17
US20030138772 SEQ ID NO: 49


AAV223.2
18
US20030138772 SEQ ID NO: 76


AAV223.4
19
US20030138772 SEQ ID NO: 50


AAV223.4
20
US20030138772 SEQ ID NO: 73


AAV223.5
21
US20030138772 SEQ ID NO: 51


AAV223.5
22
US20030138772 SEQ ID NO: 74


AAV223.6
23
US20030138772 SEQ ID NO: 52


AAV223.6
24
US20030138772 SEQ ID NO: 78


AAV223.7
25
US20030138772 SEQ ID NO: 53


AAV223.7
26
US20030138772 SEQ ID NO: 77


AAV29.3
27
US20030138772 SEQ ID NO: 82


AAV29.4
28
US20030138772 SEQ ID NO: 12


AAV29.5
29
US20030138772 SEQ ID NO: 83


AAV29.5
30
US20030138772 SEQ ID NO: 13


(AAVbb.2)




AAV3
31
US20150159173 SEQ ID NO: 12


AAV3
32
US20030138772 SEQ ID NO: 71, US2015019173 SEQ ID NO: 28,




US20160017295 SEQ ID NO: 3, US7198951 SEQ ID NO: 6


AAV3
33
US20030138772 SEQ ID NO: 8


AAV3.3b
34
US20030138772 SEQ ID NO: 72


AAV3-3
35
US20150315612 SEQ ID NO: 200


AAV3-3
36
US20150315612 SEQ ID NO: 217


AAV3a
37
US6156303 SEQ ID NO: 5


AAV3a
38
US6156303 SEQ ID NO: 9


AAV3b
39
US6156303 SEQ ID NO: 6


AAV3b
40
US6156303 SEQ ID NO: 10


AAV3b
41
US6156303 SEQ ID NO: 1


AAV4
42
US20140348794 SEQ ID NO: 17


AAV4
43
US20140348794 SEQ ID NO: 5


AAV4
44
US20140348794 SEQ ID NO: 3


AAV4
45
US20140348794 SEQ ID NO: 14


AAV4
46
US20140348794 SEQ ID NO: 15


AAV4
47
US20140348794 SEQ ID NO: 19


AAV4
48
US20140348794 SEQ ID NO: 12


AAV4
49
US20140348794 SEQ ID NO: 13


AAV4
50
US20140348794 SEQ ID NO: 7


AAV4
51
US20140348794 SEQ ID NO: 8


AAV4
52
US20140348794 SEQ ID NO: 9


AAV4
53
US20140348794 SEQ ID NO: 2


AAV4
54
US20140348794 SEQ ID NO: 10


AAV4
55
US20140348794 SEQ ID NO: 11


AAV4
56
US20140348794 SEQ ID NO: 18


AAV4
57
US20030138772 SEQ ID NO: 63, US20160017295 SEQ ID NO: 4,




US20140348794 SEQ ID NO: 4


AAV4
58
US20140348794 SEQ ID NO: 16


AAV4
59
US20140348794 SEQ ID NO: 20


AAV4
60
US20140348794 SEQ ID NO: 6


AAV4
61
US20140348794 SEQ ID NO: 1


AAV42.2
62
US20030138772 SEQ ID NO: 9


AAV42.2
63
US20030138772 SEQ ID NO: 102


AAV42.3b
64
US20030138772 SEQ ID NO: 36


AAV42.3B
65
US20030138772 SEQ ID NO: 107


AAV42.4
66
US20030138772 SEQ ID NO: 33


AAV42.4
67
US20030138772 SEQ ID NO: 88


AAV42.8
68
US20030138772 SEQ ID NO: 27


AAV42.8
69
US20030138772 SEQ ID NO: 85


AAV43.1
70
US20030138772 SEQ ID NO: 39


AAV43.1
71
US20030138772 SEQ ID NO: 92


AAV43.12
72
US20030138772 SEQ ID NO: 41


AAV43.12
73
US20030138772 SEQ ID NO: 93


AAV43.20
74
US20030138772 SEQ ID NO: 42


AAV43.20
75
US20030138772 SEQ ID NO: 99


AAV43.21
76
US20030138772 SEQ ID NO: 43


AAV43.21
77
US20030138772 SEQ ID NO: 96


AAV43.23
78
US20030138772 SEQ ID NO: 44


AAV43.23
79
US20030138772 SEQ ID NO: 98


AAV43.25
80
US20030138772 SEQ ID NO: 45


AAV43.25
81
US20030138772 SEQ ID NO: 97


AAV43.5
82
US20030138772 SEQ ID NO: 40


AAV43.5
83
US20030138772 SEQ ID NO: 94


AAV4-4
84
US20150315612 SEQ ID NO: 201


AAV4-4
85
US20150315612 SEQ ID NO: 218


AAV44.1
86
US20030138772 SEQ ID NO: 46


AAV44.1
87
US20030138772 SEQ ID NO: 79


AAV44.5
88
US20030138772 SEQ ID NO: 47


AAV44.5
89
US20030138772 SEQ ID NO: 80


AAV4407
90
US20150315612 SEQ ID NO: 90


AAV5
91
US7427396 SEQ ID NO: 1


AAV5
92
US20030138772 SEQ ID NO: 114


AAV5
93
US20160017295 SEQ ID NO: 5, US7427396 SEQ ID NO: 2,




US2015035612 SEQ ID NO: 216


AAV5
94
US20150315612 SEQ ID NO: 199


AAV6
95
US20150159173 SEQ ID NO: 13


AAV6
96
US20030138772 SEQ ID NO: 65, US20150159173 SEQ ID NO: 29,




US20160017295 SEQ ID NO: 6, US6156303 SEQ ID NO: 7


AAV6
97
US6156303 SEQ ID NO: 11


AAV6
98
US6156303 SEQ ID NO: 2


AAV6
99
US20150315612 SEQ ID NO: 203


AAV6
100
US20150315612 SEQ ID NO: 220


AAV6.1
101
US20150159173


AAV6.12
102
US20150159173


AAV6.2
103
US20150159173


AAV7
104
US20150159173 SEQ ID NO: 14


AAV7
105
US20150315612 SEQ ID NO: 183


AAV7
106
US20030138772 SEQ ID NO: 2, US20150159173 SEQ ID NO: 30,




US20150315612 SEQ ID NO: 181, US20160017295 SEQ ID NO:7


AAV7
107
US20030138772 SEQ ID NO: 3


AAV7
108
US20030138772 SEQ ID NO: 1, US20150315612 SEQ ID NO: 180


AAV7
109
US20150315612 SEQ ID NO: 213


AAV7
110
US20150315612 SEQ ID NO: 222


AAV8
111
US20150159173 SEQ ID NO: 15


AAV8
112
US20150376240 SEQ ID NO: 7


AAV8
113
US20030138772 SEQ ID NO: 4, US20150315612 SEQ ID NO: 182


AAV8
114
US20030138772 SEQ ID NO: 95, US20140359799 SEQ ID NO: 1,




US20150159173 SEQ ID NO: 31, US20160017295 SEQ ID NO: 8,




US7198951 SEQ ID NO: 7, US20150315612 SEQ ID NO: 223


AAV8
115
US20150376240 SEQ ID NO: 8


AAV8
116
US20150315612 SEQ ID NO: 214


AAV-8b
117
US20150376240 SEQ ID NO: 5


AAV-8b
118
US20150376240 SEQ ID NO: 3


AAV-8h
119
US20150376240 SEQ ID NO: 6


AAV-8h
120
US20150376240 SEQ ID NO: 4


AAV9
121
US20030138772 SEQ ID NO: 5


AAV9
122
US7198951 SEQ ID NO: 1


AAV9
123
US20160017295 SEQ ID NO: 9


AAV9
124
US20030138772 SEQ ID NO: 100, US7198951 SEQ ID NO: 2


AAV9
125
US7198951 SEQ ID NO: 3


AAV9
126
US7906111 SEQ ID NO: 3; WO2015038958 SEQ ID NO: 11


(AAVhu.14)




AAV9
127
US7906111 SEQ ID NO: 123; WO2015038958 SEQ ID NO: 2


(AAVhu.14)




AAVA3.1
128
US20030138772 SEQ ID NO: 120


AAVA3.3
129
US20030138772 SEQ ID NO: 57


AAVA3.3
130
US20030138772 SEQ ID NO: 66


AAVA3.4
131
US20030138772 SEQ ID NO: 54


AAVA3.4
132
US20030138772 SEQ ID NO: 68


AAVA3.5
133
US20030138772 SEQ ID NO: 55


AAVA3.5
134
US20030138772 SEQ. ID NO: 69


AAVA3.7
135
US20030138772 SEQ ID NO: 56


AAVA3.7
136
US20030138772 SEQ ID NO: 67


AAV29.3
137
US20030138772 SEQ ID NO: 11


(AA.Vbb.1)




AAVC2
138
US20030138772 SEQ ID NO: 61


AAVCh.5
139
US20150159173 SEQ ID NO: 46, US20150315612 SEQ ID NO: 234


AAVcy.2
140
US20030138772 SEQ ID NO: 15


(AAV13.3)




AAV24.1
141
US20030138772 SEQ ID NO: 101


AAVcy.3
142
US20030138772 SEQ ID NO: 16


(AAV24.1)




AAV27.3
143
US20030138772 SEQ ID NO: 104


AAVcy.4
144
US20030138772 SEQ ID NO: 17


(AAV27.3)




AAVcy.5
145
US20150115612 SEQ ID NO: 227


AAV7.2
146
US20030138772 SEQ ID NO: 103


AAVcy.5
147
US20030138772 SEQ ID NO: 18


(AAV7.2)




AAV16.3
148
US20030138772 SEQ ID NO: 105


AAVcy.6
149
US20030138772 SEQ ID NO: 10


(AAV16.3)




AAVcy.5
150
US20150159173 SEQ ID NO: 8


AAVcy.5
151
US20150159173 SEQ ID NO: 24


AAVCy.5R1
152
US20150159173


AAVCy.5R2
153
US20150159173


AAVCy.5R3
154
US20150159173


AAVCy.5R4
155
US20150159173


AAVDJ
156
US20140359799 SEQ ID NO: 3, US7588772 SEQ ID NO: 2


AAVDJ
157
US20140359799 SEQ ID NO: 2, US7588772 SEQ ID NO: 1


AAVDJ-8
158
US7588772; Grimm et al 2008


AAVDJ-8
159
US7588772; Grimm et al 2008


AAVF5
160
US20030138772 SEQ ID NO: 110


AAVH2
161
US20030138772 SEQ ID NO: 26


AAVH6
162
US20030138772 SEQ ID NO: 25


AAVhE1.1
163
US9233131 SEQ ID NO: 44


AAVhEr1.14
164
US9233131 SEQ ID NO: 46


AAVhEr1.16
165
US9233131 SEQ ID NO: 48


AAVhEr1.18
166
US9233131 SEQ ID NO: 49


AAVhEr1.23
167
US9233131 SEQ ID NO: 53


(AAVhEr2.29)




AAVhEr1.35
168
US9233131 SEQ ID NO: 50


AAVhEr1.36
169
US9233131 SEQ ID NO: 52


AAVhEr1.5
170
US9233131 SEQ ID NO: 45


AAVhEr1.7
171
US9233131 SEQ ID NO: 51


AAVhEr1.8
172
US9233131 SEQ ID NO: 47


AAVhEr2.16
173
US9233131 SEQ ID NO: 55


AAVhEr2.30
174
US9233131 SEQ ID NO. 56


AAVhEr2.31
175
US9233131 SEQ ID NO: 58


AAVhEr2.36
176
US9233131 SEQ ID NO: 57


AAVhEr2.4
177
US9233131 SEQ ID NO: 54


AAVhEr3.1
178
US9233131 SEQ ID NO: 59


AAVhu.1
179
US20150315612 SEQ ID NO: 46


AAVhu.1
180
US20150315612 SEQ ID NO: 144


AAVhu.10
181
US20150315612 SEQ ID NO: 56


(AAV16.8)




AAVhu.10
182
US20150315612 SEQ ID NO: 156


(AAV16.8)




AAVhu.11
183
US20150315612 SEQ ID NO: 57


(AAV16.12)




AAVhu.11
184
US20150315612 SEQ ID NO: 153


(AAV16.12)




AAVhu.12
185
US20150315612 SEQ ID NO: 59


AAVhu.12
186
US20150315612 SEQ ID NO: 154


AAVhu.13
187
US20150159173 SEQ ID NO: 16, US20150315612 SEQ ID NO: 71


AAVhu.13
188
US20150159173 SEQ ID NO: 32, US20150315612 SEQ ID NO: 129


AAVhu.136.1
189
US20150315612 SEQ ID NO: 165


AAVhu.140.1
190
US20150315612 SEQ ID NO: 166


AAVhu.140.2
191
US20150315612 SEQ ID NO: 167


AAVhu.145.6
192
US20150315612 SEQ ID No: 178


AAVhu.15
193
US20150315612 SEQ ID NO: 147


AAVhu.15
194
US20150315612 SEQ ID NO: 50


(AAV33.4)




AAVhu.156.1
195
US20150315612 SEQ ID No: 179


AAVhu.16
196
US20150315612 SEQ ID NO: 148


AAVhu.16
197
US20150315612 SEQ ID NO: 51


(AAV33.8)




AAVhu.17
198
US20150315612 SEQ ID NO: 83


AAVhu.17
199
US20150315612 SEQ ID NO: 4


(AAV33.12)




AAVhu.172.1
200
US20150315612 SEQ ID NO: 171


AAVhu.172.2
201
US20150315612 SEQ ID NO: 172


AAVhu.173.4
202
US20150315612 SEQ ID NO: 173


AAVhu.173.8
203
US20150315612 SEQ ID NO: 175


AAVhu.18
204
US20150315612 SEQ ID NO: 52


AAVhu.18
205
US20150315612 SEQ ID NO: 149


AAVhu.19
206
US20150315612 SEQ ID NO: 62


AAVhu.19
207
US20150315612 SEQ ID NO: 133


AAVhu.2
208
US20150315612 SEQ ID NO: 48


AAVhu.2
209
US20150315612 SEQ ID NO: 143


AAVhu.20
210
US20150315612 SEQ ID NO: 63


AAVhu.20
211
US20150315612 SEQ ID NO: 134


AAVhu.21
212
US20150315612 SEQ ID NO: 65


AAVhu.21
213
US20150315612 SEQ ID NO: 135


AAVhu.22
214
US20150315612 SEQ ID NO: 67


AAVhu.22
215
US20150315612 SEQ ID NO: 138


AAVhu.23
216
US20150315612 SEQ ID NO: 60


AAVhu.23.2
217
US20150315612 SEQ ID NO: 137


AAVhu.24
218
US20150315612 SEQ ID NO: 66


AAVhu.24
219
US20150315612 SEQ ID NO: 136


AAVhu.25
220
US20150315612 SEQ ID NO: 49


AAVhu.25
221
US20150315612 SEQ ID NO: 146


AAVhu.26
222
US20150159173 SEQ ID NO: 17, US20150315612 SEQ ID NO: 61


AAVhu.26
223
US20150159173 SEQ ID NO: 33, US20150315612 SEQ ID NO: 139


AAVhu.27
224
US20150315612 SEQ ID NO: 64


AAVhu.27
225
US20150315612 SEQ ID NO: 140


AAVhu.28
226
US20150315612 SEQ ID NO: 68


AAVhu.28
227
US20150315612 SEQ ID NO: 130


AAVhu.29
228
US20150315612 SEQ ID NO: 69


AAVhu.29
229
US20150159173 SEQ ID NO: 42, US20150315612 SEQ ID NO: 132


AAVhu.29
230
US20150315612 SEQ ID NO: 225


AAVhu.29R
231
US20150159173


AAVhu.3
232
US20150315612 SEQ ID NO: 44


AAVhu.3
233
US20150315612 SEQ ID NO: 145


AAVhu.30
234
US20150315612 SEQ ID NO: 70


AAVhu.30
235
US20150315612 SEQ ID NO: 131


AAVhu.31
236
US20150315612 SEQ ID NO: 1


AAVhu.31
237
US20150315612 SEQ ID NO: 121


AAVhu.32
238
US20150315612 SEQ ID NO: 2


AAVhu.32
239
US20150315612 SEQ ID NO: 122


AAVhu.33
240
US20150315612 SEQ ID NO: 75


AAVhu.33
241
US20150315612 SEQ ID NO: 124


AAVhu.34
242
US20150315612 SEQ ID NO: 72


AAVhu.34
243
US20150315612 SEQ ID NO: 125


AAVhu.35
244
US20150315612 SEQ ID NO: 73


AAVhu.35
245
US20150315612 SEQ ID NO: 164


AAVhu.36
246
US20150315612 SEQ ID NO: 74


AAVhu.36
247
US20150315612 SEQ ID NO: 126


AAVhu.37
248
US20150159173 SEQ ID NO: 34, US20150315612 SEQ ID NO: 88


AAVhu.37
249
US20150315612 SEQ ID NO: 10, US20150159173 SEQ ID NO: 18


(AAV106.1)




AAVhu.38
250
US20150315612 SEQ ID NO: 161


AAVhu.39
251
US20150315612 SEQ ID NO: 102


AAVhu.39
252
US20150315612 SEQ ID NO: 24


(AAVLG-9)




AAVhu.4
253
US20150315612 SEQ ID NO: 47


AAVhu.4
254
US20150315612 SEQ ID NO: 141


AAVhu.40
255
US20150315612 SEQ ID NO: 87


AAVhu.40
256
US20150315612 SEQ ID No: 11


(AAV114.3)




AAVhu.41
257
US20150315612 SEQ ID NO: 91


AAVhu.41
258
US20150315612 SEQ ID NO: 6


(AAV127.2)




AAVhu.42
259
US20150315612 SEQ ID NO: 85


AAVhu.42
260
US20150315612 SEQ ID NO: 8


(AAV127.5)




AAVhu.43
261
US20150315612 SEQ ID NO: 160


AAVhu.43
262
US20150315612 SEQ ID NO: 236


AAVhu.43
263
US20150315612 SEQ ID NO: 80


(AAV128.1)




AAVhu.44
264
US20150159173 SEQ ID NO: 45, US20150315612 SEQ ID NO: 158


AAVhu.44
265
US20150315612 SEQ ID NO: 81


(AAV128.3)




AAVhu.44R1
266
US20150159173


AAVhu.44R2
267
US20150159173


AAVhu.44R3
268
US20150159173


AAVhu.45
269
US20150315612 SEQ ID NO: 76


AAVhu.45
270
US20150315612 SEQ ID NO: 127


AAVhu.46
271
US20150315612 SEQ ID NO: 82


AAVhu.46
272
US20150315612 SEQ ID NO: 159


AAVhu.46
273
US20150315612 SEQ ID NO: 224


AAVhu.47
274
US20150315612 SEQ ID NO: 77


AAVhu.47
275
US20150315612 SEQ ID NO: 128


AAVhu.48
276
US20150159173 SEQ ID NO: 38


AAVhu.48
277
US20150315612 SEQ ID NO: 157


AAVhu.48
278
US20150315612 SEQ ID NO: 78


(AAV130.4)




AAVhu.48R1
279
US20150159173


AAVhu.48R2
280
US20150159173


AAVhu.48R3
281
US20150159173


AAVhu.49
282
US20150315612 SEQ ID NO: 209


AAVhu.49
283
US20150315612 SEQ ID NO: 189


AAVhu.5
284
US20150315612 SEQ ID NO: 45


AAVhu.5
285
US20150315612 SEQ ID NO: 142


AAVhu.51
286
US20150315612 SEQ ID NO: 208


AAVhu.51
287
US20150315612 SEQ ID NO: 190


AAVhu.52
288
US20150315612 SEQ ID NO: 210


AAVhu.52
289
US20150315612 SEQ ID NO: 191


AAVhu.53
290
US20150159173 SEQ ID NO: 19


AAVhu.53
291
US20150159173 SEQ ID NO: 35


AAVhu.53
292
US20150315612 SEQ ID NO: 176


(AAV145.1)




AAVhu.54
293
US20150315612 SEQ ID NO: 188


AAVhu.54
294
US20150315612 SEQ ID No: 177


(AAV145.5)




AAVhu.55
295
US20150315612 SEQ ID NO: 187


AAVhu.56
296
US20150315612 SEQ ID NO: 205


AAVhu.56
297
US20150315612 SEQ ID NO: 168


(AAV145.6)




AAVhu.56
298
US20150315612 SEQ ID NO: 192


(AAV145.6)




AAVhu.57
299
US20150315612 SEQ ID NO: 206


AAVhu.57
300
US20150315612 SEQ ID NO: 169


AAVhu.57
301
US20150315612 SEQ ID NO: 193


AAVhu.58
302
US20150315612 SEQ ID NO: 207


AAVhu.58
303
US20150315612 SEQ ID NO: 194


AAVhu.6
304
US20150315612 SEQ ID NO: 5


(AAV3.1)




AAVhu.6
305
US20150315612 SEQ ID NO: 84


(AAV3.1)




AAVhu.60
306
US20150315612 SEQ ID NO: 184


AAVhu.60
307
US20150315612 SEQ ID NO: 170


(AAV161.10)




AAVhu.61
308
US20150315612 SEQ ID NO: 185


AAVhu.61
309
US20150315612 SEQ ID NO: 174


(AAV161.6)




AAVhu.63
310
US20150315612 SEQ ID NO: 204


AAVhu.63
311
US20150315612 SEQ ID NO: 195


AAVhu.64
312
US20150315612 SEQ ID NO: 212


AAVhu.64
313
US20150315612 SEQ ID NO: 196


AAVhu.66
314
US20150315612 SEQ ID NO: 197


AAVhu.67
315
US20150315612 SEQ ID NO: 215


AAVhu.67
316
US20150315612 SEQ ID NO: 198


AAVhu.7
317
US20150315612 SEQ ID NO: 226


AAVhu.7
318
US20150315612 SEQ ID NO: 150


AAVhu.7
319
US20150315612 SEQ ID NO: 55


(AAV7.3)




AAVhu.71
320
US20150315612 SEQ ID NO: 79


AAVhu.8
321
US20150315612 SEQ ID NO: 53


AAVhu.8
322
US20150315612 SEQ ID NO: 12


AAVhu.8
323
US20150315612 SEQ ID NO: 151


AAVhu.9
324
US20150315612 SEQ ID NO: 58


(AAV3.1)




AAVhu.9
325
US20150315612 SEQ ID NO: 155


(AAV3.1)




AAV-LK01
326
US20150376607 SEQ ID NO: 2


AAV-LK01
327
US20150376607 SEQ ID NO: 29


AAV-LK02
328
US20150376607 SEQ ID NO: 3


AAV-LK02
329
US20150376607 SEQ ID NO: 30


AAV-LK03
330
US20150376607 SEQ ID NO: 4


AAV-LK03
331
WO2015121501 SEQ ID NO: 12, US20150376607 SEQ ID NO: 31


AAV-LK04
332
US20150376607 SEQ ID NO: 5


AAV-LK04
333
US20150376607 SEQ ID NO: 32


AAV-LK05
334
US20150376607 SEQ ID NO: 6


AAV-LK05
335
US20150376607 SEQ ID NO: 33


AAV-LK06
336
US20150376607 SEQ ID NO: 7


AAV-LK06
337
US20150376607 SEQ ID NO: 34


AAV-LK07
338
US20150376607 SEQ ID NO: 8


AAV-LK07
339
US20150376607 SEQ ID NO: 35


AAV-LK08
340
US20150376607 SEQ ID NO: 9


AAV-LK08
341
US20150376607 SEQ ID NO: 36


AAV-LK09
342
US20150376607 SEQ ID NO: 10


AAV-LK09
343
US20150376607 SEQ ID NO: 37


AAV-LK10
344
US20150376607 SEQ ID NO: 11


AAV-LK10
345
US20150376607 SEQ ID NO: 38


AAV-LK11
346
US20150376607 SEQ ID NO: 12


AAV-LK11
347
US20150376607 SEQ ID NO: 39


AAV-LK12
348
US20150376607 SEQ ID NO: 13


AAV-LK12
349
US20150376607 SEQ ID NO: 40


AAV-LK13
350
US20150376607 SEQ ID NO: 14


AAV-LK13
351
US20150376607 SEQ ID NO: 41


AAV-LK14
352
US20150376607 SEQ ID NO: 15


AAV-LK14
353
US20150376607 SEQ ID NO: 42


AAV-LK15
354
US20150376607 SEQ ID NO: 16


AAV-LK15
355
US20150376607 SEQ ID NO: 43


AAV-LK16
356
US20150376607 SEQ ID NO: 17


AAV-LK16
357
US20150376607 SEQ ID NO: 44


AAV-LKI7
358
US20150376607 SEQ ID NO: 18


AAV-LK17
359
US20150376607 SEQ ID NO: 45


AAV-LK18
360
US20150376607 SEQ ID NO: 19


AAV-LK18
361
US20150376607 SEQ ID NO: 46


AAV-LK19
362
US20150376607 SEQ ID NO: 20


AAV-LK19
363
US20150376607 SEQ ID NO: 47


AAV-PAEC
364
US20150376607 SEQ ID NO: 1


AAV-PAEC
365
US20150376607 SEQ ID NO: 48


AAV-PAEC11
366
US20150376607 SEQ ID NO: 26


AAV-PAEC11
367
US20150376607 SEQ ID NO: 54


AAV-PAEC12
368
US20150376607 SEQ ID NO: 27


AAV-PAEC12
369
US20150376607 SEQ ID NO: 51


AAV-PAEC13
370
US20150376607 SEQ ID NO: 28


AAV-PAEC13
371
US20150376607 SEQ ID NO: 49


AAV-PAEC2
372
US20150376607 SEQ ID NO: 21


AAV-PAEC2
373
US20150376607 SEQ ID NO: 56


AAV-PAEC4
374
US20150376607 SEQ ID NO: 22


AAV-PAEC4
375
US20150376607 SEQ ID NO: 55


AAV-PAEC6
376
US20150376607 SEQ ID NO: 23


AAV-PAEC6
377
US20150376607 SEQ ID NO: 52


AAV-PAEC7
378
US20150376607 SEQ ID NO: 24


AAV-PAEC7
379
US20150376607 SEQ ID NO: 53


AAV-PAEC8
380
US20150376607 SEQ ID NO: 25


AAV-PAEC8
381
US20150376607 SEQ ID NO: 50


AAVpi.1
382
US20150315612 SEQ ID NO: 28


AAVpi.1
383
US20150315612 SEQ ID NO: 93


AAVpi.2
384
US20150315612 SEQ ID NO: 30


AAVpi.2
385
US20150315612 SEQ ID NO: 95


AAVpi.3
386
US20150315612 SEQ ID NO: 29


AAVpi.3
387
US20150315612 SEQ ID NO: 94


AAVrh.10
388
US20150159173 SEQ ID NO: 9


AAVrh.10
389
US20150159173 SEQ ID NO: 25


AAV44.2
390
US20030138772 SEQ ID NO: 59


AAVrh.10
391
US20030138772 SEQ ID NO: 81


(AAV44.2)




AAV42.1B
392
US20030138772 SEQ ID NO: 90


AAVrh.12
393
US20030138772 SEQ ID NO: 30


(AAV42.1b)




AAVrh.13
394
US20150159173 SEQ ID NO: 10


AAVrh.13
395
US20150159173 SEQ ID NO: 26


AAVrh.13
396
US20150315612 SEQ ID NO: 228


AAVrh.13R
397
US20150159173


AAV42.3A
398
US20030138772 SEQ ID NO: 87


AAVrh.14
399
US20030138772 SEQ ID NO: 32


(AAV42.3a)




AAV42.5A
400
US20030138772 SEQ ID NO: 89


AAVrh.17
401
US20030138772 SEQ ID NO: 34


(AAV42.5a)




AAV42.5B
402
US20030138772 SEQ ID NO: 91


AAVrh.18
403
US20030138772 SEQ ID NO: 29


(AAV42.5b)




AAV42.6B
404
US20030138772 SEQ ID NO: 112


AAVrh.19
405
US20030138772 SEQ ID NO: 38


(AAV42.6b)




AAVrh.2
406
US20150159173 SEQ ID NO: 39


AAVrh.2
407
US20150315612 SEQ ID NO: 231


AAVrh.20
408
US20150159173 SEQ ID NO: 1


AAV42.10
409
US20030138772 SEQ ID NO: 106


AAVrh.21
410
US20030138772 SEQ ID NO: 35


(AAV42.10)




AAV42.11
411
US20030138772 SEQ ID NO: 108


AAVrh.22
412
US20030138772 SEQ ID NO: 37


(AAV42.11)




AAV42.12
413
US20030138772 SEQ ID NO: 113


AAVrh.23
414
US20030138772 SEQ ID NO: 58


(AAV42.12)




AAV42.13
415
US20030138772 SEQ ID NO: 86


AAVrh..24
416
US20030138772 SEQ ID NO: 31


(AAV42.13)




AAV42.15
417
US20030138772 SEQ ID NO: 84


AAVrh.25
418
US20030138772 SEQ ID NO: 28


(AAV42.15)




AAVrh.2R
419
US20150159173


AAVrh.31
420
US20030138772 SEQ ID NO: 48


(AAV223.1)




AAVC1
421
US20030138772 SEQ ID NO: 60


AAVrh.32
422
US20030138772 SEQ ID NO: 19


(AAVC1)




AAVrh.32/33
423
US20150159173 SEQ ID NO: 2


AAVrh.33
424
US20030138772 SEQ ID NO: 20


(AAVC3)




AAVC5
425
US20030138772 SEQ ID NO: 62


AAVrh.34
426
US20030138772 SEQ ID NO: 21


(AAVC5)




AAVF1
427
US20030138772 SEQ ID NO: 109


AAVrh.35
428
US20030138772 SEQ ID NO: 22


(AAVF1)




AAVF3
429
US20030138772 SEQ ID NO: 111


AAVrh.36
430
US20030138772 SEQ ID NO: 23


(AAVF3)




AAVrh.37
431
US20030138772 SEQ ID NO: 24


AAVrh.37
432
US20150159173 SEQ ID NO: 40


AAVrh.37
433
US20150315612 SEQ ID NO: 229


AAVrh.37R2
434
US20150159173


AAVrh.38
435
US20150315612 SEQ ID NO: 7


(AAVLG-4)




AAVrh.38
436
US20150315612 SEQ ID NO: 86


(AAVLG-4)




AAVrh.39
437
US20150159173 SEQ ID NO: 20, US20150315612 SEQ ID NO: 13


AAVrh.39
438
US20150159173 SEQ ID NO: 3, US20150159173 SEQ ID NO: 36,




US20150315612 SEQ ID NO: 89


AAVrh.40
439
US20150315612 SEQ ID NO: 92


AAVrh.40
440
US20150315612 SEQ ID No: 14


(AAVLG-10)




AAVrh.43
441
US20150315612 SEQ ID NO: 43, US20150159173 SEQ ID NO: 21


(AAVN721-8)




AAVrh.43
442
US20150315612 SEQ ID NO: 163, US20150159173 SEQ ID NO: 37


(AAVN721-8)




AAVrh.44
443
US20150315612 SEQ ID NO: 34


AAVrh.44
444
US20150315612 SEQ ID NO: 111


AAVrh.45
445
US20150315612 SEQ ID NO: 41


AAVrh.45
446
US20150315612 SEQ ID NO: 109


AAVrh.46
447
US20150159173 SEQ ID NO: 22, US20150315612SEQ ID NO: 19


AAVrh.46
448
US20150159173 SEQ ID NO: 4, US20150315612 SEQ ID NO: 101


AAVrh.47
449
US20150315612 SEQ ID NO: 38


AAVrh.47
450
US20150315612 SEQ ID NO: 118


AAVrh.48
451
US20150159173 SEQ ID NO: 44, US20150315612 SEQ ID NO: 115


AAVrh.48.1
452
US20150159173


AAVrh.48.1.2
453
US20150159173


AAVrh.48.2
454
US20150159173


AAVrh.48
455
US20150315612 SEQ ID NO: 32


(AAV1-7)




AAVrh.49
456
US20150315612 SEQ ID NO: 25


(AAV1-8)




AAVrh.49
457
US20150315612 SEQ ID NO: 103


(AAV1-8)




AAVrh.50
458
US20150315612 SEQ ID NO: 23


(AAV2-4)




AAVrh.50
459
US20150315612 SEQ ID NO: 108


(AAV2-4)




AAVrh.51
460
US20150315612 SEQ ID NO: 22


(AAV2-5)




AAVrh.51
461
US20150315612 SEQ ID NO: 104


(AAV2-5)




AAVrh.52
462
US20150315612 SEQ ID NO: 18


(AAV3-9)




AAVrh.52
463
US20150315612 SEQ ID NO: 96


(AAV3-9)




AAVrh.53
464
US20150315612 SEQ ID NO: 97


AAVrh.53
465
US20150315612 SEQ ID NO: 17


(AAV3-11)




AAVrh.53
466
US20150315612 SEQ ID NO: 186


(AAV3-11)




AAVrh.54
467
US20150315612 SEQ ID NO: 40


AAVrh.54
468
US20150159173 SEQ ID NO: 49, US20150315612 SEQ ID NO: 116


AAVrh.55
469
US20150315612 SEQ ID NO: 37


AAVrh.55
470
US20150315612 SEQ ID NO: 117


(AAV4-19)




AAVrh.56
471
US20150315612 SEQ ID NO: 54


AAVrh.56
472
US20150315612 SEQ ID NO: 152


AAVrh.57
473
US20150315612 SEQ ID NO: 26


AAVrh.57
474
US20150315612 SEQ ID NO: 105


AAVrh.58
475
US20150315612 SEQ ID NO: 27


AAVrh.58
476
US20150159173 SEQ ID NO: 48, US20150315612 SEQ ID NO: 106


AAVrh.58
477
US20150315612 SEQ ID NO: 232


AAVrh.59
478
US20150315612 SEQ ID NO: 42


AAVrh.59
479
US20150315612 SEQ ID NO: 110


AAVrh.60
480
US20150315612 SEQ ID NO: 31


AAVrh.60
481
US20150315612 SEQ ID NO: 120


AAVrh.61
482
US20150315612 SEQ ID NO: 107


AAVrh.61
483
US20150315612 SEQ ID NO: 21


(AAV2-3)




AAVrh.62
484
US20150315612 SEQ ID NO: 33


(AAV2-15)




AAVrh.62
485
US20150315612 SEQ ID NO: 114


(AAV2-15)




AAVrh.64
486
US20150315612 SEQ ID No: 15


AAVrh.64
487
US20150159173 SEQ ID NO: 43, US20150315612 SEQ ID NO: 99


AAVrh.64
488
US20150315612 SEQ ID NO: 233


AAVRh.64R1
489
US20150159173


AAVRh.64R2
490
US20150159173


AAVrh.65
491
US20150315612 SEQ ID NO: 35


AAVrh.65
492
US20150315612 SEQ ID NO: 112


AAVrh.67
493
US20150315612 SEQ ID NO: 36


AAVrh.67
494
US20150315612 SEQ ID NO: 230


AAVrh.67
495
US20150159173 SEQ ID NO: 47, US20150315612 SEQ ID NO: 113


AAVrh.68
496
US20150315612 SEQ ID NO: 16


AAVrh.68
497
US20150315612 SEQ ID NO: 100


AAVrh.69
498
US20150315612 SEQ ID NO: 39


AAVrh.69
499
US20150315612 SEQ ID NO: 119


AAVrh.70
500
US20150315612 SEQ ID NO: 20


AAVrh.70
501
US20150315612 SEQ ID NO: 98


AAVrh.71
502
US20150315612 SEQ ID NO: 162


AAVrh.72
503
US20150315612 SEQ ID NO: 9


AAVrh.73
504
US20150159173 SEQ ID NO: 5


AAVrh.74
505
US20150159173 SEQ ID NO: 6


AAVrh.8
506
US20150159173 SEQ ID NO: 41


AAVrh.8
507
US20150315612 SEQ ID NO: 235


AAVrh.8R
508
US20150159173, WO2015168666 SEQ ID NO: 9


AAVrh.8R
509
WO2015168666 SEQ ID NO: 10


A586R mutant




AAVrh.8R
510
WO2015168666 SEQ ID NO: 11


R533A mutant




BAAV
511
US9193769 SEQ ID NO: 8


(bovine AAV)




BAAV
512
US9193769 SEQ ID NO: 10


(bovine AAV)




BAAV
513
US9193769 SEQ ID NO: 4


(bovine AAV)




BAAV
514
US9193769 SEQ ID NO: 2


(bovine AAV)




BAAV
515
US9193769 SEQ ID NO: 6


(bovine AAV)




BAAV
516
US9193769 SEQ ID NO: 1


(bovine AAV)




BAAV
517
US9193769 SEQ ID NO: 5


(bovine AAV)




BAAV
518
US9193769 SEQ ID NO: 3


(bovine AAV)




BAAV
519
US9193769 SEQ ID NO: 11


(bovine AAV)




BAAV
520
US7427396 SEQ ID NO: 5


(bovine AAV)




BAAV
521
US7427396 SEC ID NO: 6


(bovine AAV)




BAAV
522
US9193769 SEQ ID NO: 7


(bovine AAV)




BAAV
523
US9193769 SEQ ID NO: 9


(bovine AAV)




BNP61 AAV
524
US20150238550 SEQ ID NO: 1


BNP61 AAV
525
US20150238550 SEQ ID NO: 2


BNP62 AAV
526
US20150238550 SEQ ID NO: 3


BNP63 AAV
527
US20150238550 SEQ ID NO: 4


caprine AAV
528
US7427396 SEQ ID NO: 3


caprine AAV
529
US7427396 SEQ ID NO: 4


true type
530
WO2015121501 SEQ ID NO: 2


AAV




(ttAAV)




AAAV
531
US9238800 SEQ ID NO: 12


(Avian AAV)




AAAV
532
US9238800 SEQ ID NO: 2


(Avian AAV)




AAAV
533
US9238800 SEQ ID NO: 6


(Avian AAV)




AAAV
534
US9238800 SEQ ID NO: 4


(Avian AAV)




AAAV
535
US9238800 SEQ ID NO: 8


(Avian AAV)




AAAV
536
US9238800 SEQ ID NO: 14


(Avian AAV)




AAAV
537
US9238800 SEQ ID NO: 10


(Avian AAV)




AAAV
538
US9238800 SEQ ID NO: 15


(Avian AAV)




AAAV
539
US9238800 SEQ ID NO: 5


(Avian AAV)




AAAV
540
US9238800 SEQ ID NO: 9


(Avian AAV)




AAAV
541
US9238800 SEQ ID NO: 3


(Avian AAV)




AAAV
542
US9238800 SEQ ID NO: 7


(Avian AAV)




AAAV
543
US9238800 SEQ ID NO: 11


(Avian AAV)




AAAV
544
US9238800 SEQ ID NO: 13


(Avian AAV)




AAAV
545
US9238800 SEQ ID NO: 1


(Avian AAV)




AAV Shuffle
546
US20160017295 SEQ ID NO: 23


100-1




AAV Shuffle
547
US20160017295 SEQ ID NO: 11


100-1




AAV Shuffle
548
US20160017295 SEQ ID NO: 37


100-2




AAV Shuffle
549
US20160017295 SEQ ID NO: 29


100-2




AAV Shuffle
550
US20160017295 SEQ ID NO: 24


100-3




AAV Shuffle
551
US20160017295 SEQ ID NO: 12


100-3




AAV Shuffle
552
US20160017295 SEQ ID NO: 25


100-7




AAV Shuffle
553
US20160017295 SEQ ID NO: 13


100-7




AAV Shuffle
554
US20160017295 SEQ ID NO: 34


10-2




AAV Shuffle
555
US20160017295 SEQ ID NO: 26


10-2




AAV Shuffle
556
US20160017295 SEQ ID NO: 35


10-6




AAV Shuffle
557
US20160017295 SEQ ID NO: 27


10-6




AAV Shuffle
558
US20160017295 SEQ ID NO: 36


10-8




AAV Shuffle
559
US20160017295 SEQ ID NO: 28


10-8




AAV SM
560
US20160017295 SEQ ID NO: 41


100-10




AAV SM
561
US20160017295 SEQ ID NO: 33


100-10




AAV SM
562
US20160017295 SEQ ID NO: 40


100-3




AAV SM
563
US20160017295 SEQ ID NO: 32


100-3




AAV SM 10-1
564
US20160017295 SEQ ID NO: 38


AAV SM 10-1
565
US20160017295 SEQ ID NO: 30


AAV SM 10-2
566
US20160017295 SEQ ID NO: 10


AAV SM 10-2
567
US20160017295 SEQ ID NO: 22


AAV SM 10-8
568
US20160017295 SEQ ID NO: 39


AAV SM 10-8
569
US20160017295 SEQ ID NO: 31


AAVF1/HSC1
570
WO2016049230 SEQ ID NO: 20


AAVF2/HSC2
571
WO2016049230 SEQ ID NO: 21


AAVF3/HSC3
572
WO2016019230 SEQ ID NO: 22


AAVF4/HSC4
573
WO2016049230 SEQ ID NO: 23


AAVF5/HSC5
574
WO2016049230 SEQ ID NO: 25


AAVF6/HSC6
575
WO2016049230 SEQ ID NO: 24


AAVF7/HSC7
576
WO2016049130 SEQ ID NO: 27


AAVF8/HSC8
577
WO2016049230 SEQ ID NO: 28


AAVF9/HSC9
578
WO2016049130 SEQ ID NO: 29


AAVF11/HSC11
579
WO2016049230 SEQ ID NO: 26


AAVF12/HSC12
580
WO2016049230 SEQ ID NO: 30


AAVF13/HSC13
581
WO2016049230 SEQ ID NO: 31


AAVF14/HSC14
582
WO2016049230 SEQ ID NO: 32


AAVF15/HSC15
583
WO2016049230 SEQ ID NO: 33


AAVF16/HSC16
584
WO2016049230 SEQ ID NO: 34


AAVF17/HSC17
585
WO2016049230 SEQ ID NO: 35


AAVF1/HSC1
586
WO2016049230 SEQ ID NO: 2


AAVF2/HSC2
587
WO2016049230 SEQ ID NO: 3


AAVF3/HSC3
588
WO2016049230 SEQ ID NO: 5


AAVF4/HSC4
589
WO2016049230 SEQ ID NO: 6


AAVF5/HSC5
590
WO2016049230 SEQ ID NO: 11


AAVF6/HSC6
591
WO2016049230 SEQ ID NO: 7


AAVF7/HSC7
592
WO2016049230 SEQ ID NO: 8


AAVF8/HSC8
593
WO2016049230 SEQ ID NO: 9


AAVF9/HSC9
594
WO2016049230 SEQ ID NO: 10


AAVF11/HSC11
595
WO2016049230 SEQ ID NO: 4


AAVF12/HSC12
596
WO2016049230 SEQ ID NO: 12


AAVF13/HSC13
597
WO2016049230 SEQ ID NO: 14


AAVF14/HSC14
598
WO2016049230 SEQ ID NO: 15


AAVF15/HSC15
599
WO2016049230 SEQ ID NO: 16


AAVF16/HSC16
600
WO2016049230 SEQ ID NO: 17


AAVF17/HSC17
601
WO2016049230 SEQ ID NO: 13


AAV CBr-E1
602
US8734809 SEQ ID NO: 13


AAV CBr-E2
603
US8734809 SEQ ID NO: 14


AAV CBr-E3
604
US8734809 SEQ ID NO: 15


AAV CBr-E4
605
US8734809 SEQ ID NO: 16


AAV CBr-E5
606
US8734809 SEQ ID NO: 17


AAV CBr-e5
607
US8734809 SEQ ID NO: 18


AAV CBr-E6
608
US8734809 SEQ ID NO: 19


AAV CBr-E7
609
US8734809 SEQ ID NO: 20


AAV CBr-E8
610
US8734809 SEQ ID NO: 21


AAV CLv-D1
611
US8734809 SEQ ID NO: 22


AAV CLv-D2
612
US8734809 SEQ ID NO: 23


AAV CLv-D3
613
US8734809 SEQ ID NO: 24


AAV CLv-D4
614
US8734809 SEQ ID NO: 25


AAV CLv-D5
615
US8734809 SEQ ID NO: 26


AAV CLv-D6
616
US8734809 SEQ ID NO: 27


AAV CLv-D7
617
US8734809 SEQ ID NO: 28


AAV CLv-D8
618
US8734809 SEQ ID NO: 29


AAV CLv-E1
619
US8734809 SEQ ID NO: 13


AAV CLv-R1
620
US8734809 SEQ ID NO: 30


AAV CLv-R2
621
US8734809 SEQ ID NO: 31


AAV CLv-R3
622
US8734809 SEQ ID NO: 32


AAV CLv-R4
623
US8734809 SEQ ID NO: 33


AAV CLv-R5
624
US8734809 SEQ ID NO: 34


AAV CLv-R6
625
US8734809 SEQ ID NO: 35


AAV CLv-R7
626
US8734809 SEQ ID NO: 36


AAV CLv-R8
627
US8734809 SEQ ID NO: 37


AAV CLv-R9
628
US8734809 SEQ ID NO: 38


AAV CLg-F1
629
US8734809 SEQ ID NO: 39


AAV CLg-F2
630
US8734809 SEQ ID NO: 40


AAV CLg-F3
631
US8734809 SEQ ID NO: 41


AAV CLg-F4
632
US8734809 SEQ ID NO: 42


AAV CLg-F5
633
US8734809 SEQ ID NO: 43


AAV CLg-F6
634
US8734809 SEQ ID NO: 43


AAV CLg-F7
635
US8734809 SEQ ID NO: 44


AAV CLg-F8
636
US8734809 SEQ ID NO: 43


AAV CSp-1
637
US8734809 SEQ ID NO: 45


AAV CSp-10
638
US8734809 SEQ ID NO: 46


AAV CSp-11
639
US8734809 SEQ ID NO: 47


AAV CSp-2
640
US8734809 SEQ ID NO: 48


AAV CSp-3
641
US8734809 SEQ ID NO: 49


AAV CSp-4
642
US8734809 SEQ ID NO: 50


AAV CSp-6
643
US8734809 SEQ ID NO: 51


AAV CSp-7
644
US8734809 SEQ ID NO: 52


AAV CSp-8
645
US8734809 SEQ ID NO: 53


AAV CSp-9
646
US8734809 SEQ ID NO: 54


AAV CHt-2
647
US8734809 SEQ ID NO: 55


AAV CHt-3
648
US8734809 SEQ ID NO: 56


AAV CKd-1
649
US8734809 SEQ ID NO: 57


AAV CKd-10
650
US8734809 SEQ ID NO: 58


AAV CKd-2
651
US8734809 SEQ ID NO: 59


AAV CKd-3
652
US8734809 SEQ ID NO: 60


AAV CKd-4
653
US8734809 SEQ ID NO: 61


AAV CKd-6
654
US8734809 SEQ ID NO: 62


AAV CKd-7
655
US8734809 SEQ ID NO: 63


AAV CKd-8
656
US8734809 SEQ ID NO: 64


AAV CLv-1
657
US8734809 SEQ ID NO: 65


AAV CLv-12
658
US8734809 SEQ ID NO: 66


AAV CLv-13
659
US8734809 SEQ ID NO: 67


AAV CLv-2
660
US8734809 SEQ ID NO: 68


AAV CLv-3
661
US8734809 SEQ ID NO: 69


AAV CLv-4
662
US8734809 SEQ ID NO: 70


AAV CLv-6
663
US8734809 SEQ ID NO: 71


AAV CLv-8
664
US8734809 SEQ ID NO: 72


AAV CKd-B1
665
US8734809 SEQ ID NO: 73


AAV CKd-B2
666
US8734809 SEQ ID NO: 74


AAV CKd-B3
667
US8734809 SEQ ID NO: 75


AAV CKd-B4
668
US8734809 SEQ ID NO: 76


AAV CKd-B5
669
US8734809 SEQ ID NO: 77


AAV CKd-B6
670
US8734809 SEQ ID NO: 78


AAV CKd-B7
671
US8734809 SEQ ID NO: 79


AAV CKd-B8
672
US8734809 SEQ ID NO: 80


AAV CKd-H1
673
US8734809 SEQ ID NO: 81


AAV CKd-H2
674
US8734809 SEQ ID NO: 82


AAV CKd-H3
675
US8734809 SEQ ID NO: 83


AAV CKd-H4
676
US8734809 SEQ ID NO: 84


AAV CKd-H5
677
US8734809 SEQ ID NO: 85


AAV CKd-H6
678
US8734809 SEQ ID NO: 77


AAV CHt-1
679
US8734809 SEQ ID NO: 86


AAV CLv1-1
680
US8734809 SEQ ID NO: 171


AAV CLv1-2
681
US8734809 SEQ ID NO: 172


AAV CLv1-3
682
US8734809 SEQ ID NO: 173


AAV CLv1-4
683
US8734809 SEQ ID NO: 174


AAV Clv1-7
684
US8734809 SEQ ID NO: 175


AAV Clv1-8
685
US8734809 SEQ ID NO: 176


AAV Clv1-9
686
US8734809 SEQ ID NO: 177


AAV Clv1-10
687
US8734809 SEQ ID NO: 178


AAV.VR-355
688
US8734809 SEQ ID NO: 181


AAV.hu.48R3
689
US8734809 SEQ ID NO: 183


AAV CBr-E1
690
US8734809 SEQ ID NO: 87


AAV CBr-E2
691
US8734809 SEQ ID NO: 88


AAV CBr-E3
692
US8734809 SEQ ID NO: 89


AAV CBr-E4
693
US8734809 SEQ ID NO: 90


AAV CBr-E5
694
US8734809 SEQ ID NO: 91


AAV CBr-e5
695
US8734809 SEQ ID NO: 92


AAV CBr-E6
696
US8734809 SEQ ID NO: 93


AAV CBr-E7
697
US8734809 SEQ ID NO: 94


AAV CBr-E8
698
US8734809 SEQ ID NO: 95


AAV CLv-D1
699
US8734809 SEQ ID NO: 96


AAV CLv-D2
700
US8734809 SEQ ID NO: 97


AAV CLv-D3
701
US8734809 SEQ ID NO: 98


AAV CLv-D4
702
US8734809 SEQ ID NO: 99


AAV CLv-D5
703
US8734809 SEQ ID NO: 100


AAV CLv-D6
704
US8734809 SEQ ID NO: 101


AAV CLv-D7
705
US8734809 SEQ ID NO: 102


AAV CLv-D8
706
US8734809 SEQ ID NO: 103


AAV CLv-E1
707
US8734809 SEQ ID NO: 87


AAV CLv-R1
708
US8734809 SEQ ID NO: 104


AAV CLv-R2
709
US8734809 SEQ ID NO: 105


AAV CLv-R3
710
US8734809 SEQ ID NO: 106


AAV CLv-R4
711
US8734809 SEQ ID NO: 107


AAV CLv-R5
712
US8734809 SEQ ID NO: 108


AAV CLv-R6
713
US8734809 SEQ ID NO: 109


AAV CLv-R7
714
US8734809 SEQ ID NO: 110


AAV CLv-R8
715
US8734809 SEQ ID NO: 111


AAV CLv-R9
716
US8734809 SEQ ID NO: 112


AAV CLg-F1
717
US8734809 SEQ ID NO: 113


AAV CLg-F2
718
US8734809 SEQ ID NO: 114


AAV CLg-F3
719
US8734809 SEQ ID NO: 115


AAV CLg-F4
720
US8734809 SEQ ID NO: 116


AAV CLg-F5
721
US8734809 SEQ ID NO: 117


AAV CLg-F6
722
US8734809 SEQ ID NO: 117


AAV CLg-F7
723
US8734809 SEQ ID NO: 118


AAV CLg-F8
724
US8734809 SEQ ID NO: 117


AAV CSp-1
725
US8734809 SEQ ID NO: 119


AAV CSp-10
726
US8734809 SEQ ID NO: 120


AAV CSp-11
727
US8734809 SEQ ID NO: 121


AAV CSp-2
728
US8734809 SEQ ID NO: 122


AAV CSp-3
729
US8734809 SEQ ID NO: 123


AAV CSp-4
730
US8734809 SEQ ID NO: 124


AAV CSp-6
731
US8734809 SEQ ID NO: 125


AAV CSp-7
732
US8734809 SEQ ID NO: 126


AAV CSp-8
733
US8734809 SEQ ID NO: 127


AAV CSp-9
734
US8734809 SEQ ID NO: 128


AAV CHt-2
735
US8734809 SEQ ID NO: 129


AAV CHt-3
736
US8734809 SEQ ID NO: 130


AAV CKd-1
737
US8734809 SEQ ID NO: 131


AAV CKd-10
738
US8734809 SEQ ID NO: 132


AAV CKd-2
739
US8734809 SEQ ID NO: 133


AAV CKd-3
740
US8734809 SEQ ID NO: 134


AAV CKd-4
741
US8734809 SEQ ID NO: 135


AAV CKd-6
742
US8734809 SEQ ID NO: 136


AAV CKd-7
743
US8734809 SEQ ID NO: 137


AAV CKd-8
744
US8734809 SEQ ID NO: 138


AAV CLv-1
745
US8734809 SEQ ID NO: 139


AAV CLv-12
746
US8734809 SEQ ID NO: 140


AAV CLv-13
747
US8734809 SEQ ID NO: 141


AAV CLv-2
748
US8734809 SEQ ID NO: 142


AAV CLv-3
749
US8734809 SEQ ID NO: 143


AAV CLv-4
750
US8734809 SEQ ID NO: 144


AAV CLv-6
751
US8734809 SEQ ID NO: 145


AAV CLv-8
752
US8734809 SEQ ID NO: 146


AAV CKd-B1
753
US8734809 SEQ ID NO: 147


AAV CKd-B2
754
US8734809 SEQ ID NO: 148


AAV CKd-B3
755
US8734809 SEQ ID NO: 149


AAV CKd-B4
756
US8734809 SEQ ID NO: 150


AAV CKd-B5
757
US8734809 SEQ ID NO: 151


AAV CKd-B6
758
US8734809 SEQ ID NO: 152


AAV CKd-B7
759
US8734809 SEQ ID NO: 153


AAV CKd-B8
760
US8734809 SEQ ID NO: 154


AAV CKd-H1
761
US8734809 SEQ ID NO: 155


AAV CKd-H2
762
US8734809 SEQ ID NO: 156


AAV CKd-H3
763
US8734809 SEQ ID NO: 157


AAV CKd-H4
764
US8734809 SEQ ID NO: 158


AAV CKd-H5
765
US8734809 SEQ ID NO: 159


AAV CKd-H6
766
US8734809 SEQ ID NO: 151


AAV CHt-1
767
US8734809 SEQ ID NO: 160


AAV CHt-P2
768
WO2016065001 SEQ ID NO: 1


AAV CHt-P5
769
WO2016065001 SEQ ID NO: 2


AAV CHt-P9
770
WO2016065001 SEQ ID NO: 3


AAV CBr-7.1
771
WO2016065001 SEQ ID NO: 4


AAV CBr-7.2
772
WO2016065001 SEQ ID NO: 5


AAV CBr-7.3
773
WO2016065001 SEQ ID NO: 6


AAV CBr-7.4
774
WO2016065001 SEQ ID NO: 7


AAV CBr-7.5
775
WO2016065001 SEQ ID NO: 8


AAV CBr-7.7
776
WO2016065001 SEQ ID NO: 9


AAV CBr-7.8
777
WO2016065001 SEQ ID NO: 10


AAV CBr-7.10
778
WO2016065001 SEQ ID NO: 11


AAV CKd-N3
779
WO2016065001 SEQ ID NO: 12


AAV CKd-N4
780
WO2016065001 SEQ ID NO: 13


AAV CKd-N9
781
WO2016065001 SEQ ID NO: 14


AAV CLv-L4
782
WO2016065001 SEQ ID NO: 15


AAV CLv-L5
783
WO2016065001 SEQ ID NO: 16


AAV CLv-L6
784
WO2016065001 SEQ ID NO: 17


AAV CLv-K1
785
WO2016065001 SEQ ID NO: 18


AAV CLv-K3
786
WO2016065001 SEQ ID NO: 19


AAV CLv-K6
787
WO2016065001 SEQ ID NO: 20


AAV CLv-M1
788
WO2016065001 SEQ ID NO: 21


AAV CLv-M11
789
WO2016065001 SEQ ID NO: 22


AAV CLv-M2
790
WO2016065001 SEQ ID NO: 23


AAV CLv-M5
791
WO2016065001 SEQ ID NO: 24


AAV CLv-M6
792
WO2016065001 SEQ ID NO: 25


AAV CLv-M7
793
WO2016065001 SEQ ID NO: 26


AAV CLv-M8
794
WO2016065001 SEQ ID NO: 27


AAV CLv-M9
795
WO2016065001 SEQ ID NO: 28


AAV CHt-P1
796
WO2016065001 SEQ ID NO: 29


AAV CHt-P6
797
WO2016065001 SEQ ID NO: 30


AAV CHt-P8
798
WO2016065001 SEQ ID NO: 31


AAV CHt-6.1
799
WO2016065001 SEQ ID NO: 32


AAV CHt-6.10
800
WO2016065001 SEQ ID NO: 33


AAV CHt-6.5
801
WO2016065001 SEQ ID NO: 34


AAV CHt-6.6
802
WO2016065001 SEQ ID NO: 35


AAV CHt-6.7
803
WO2016065001 SEQ ID NO: 36


AAV CHt-6.8
804
WO2016065001 SEQ ID NO: 37


AAV CSp-8.10
805
WO2016065001 SEQ ID NO: 38


AAV CSp-8.2
806
WO2016065001 SEQ ID NO: 39


AAV CSp-8.4
807
WO2016065001 SEQ ID NO: 40


AAV CSp-8.5
808
WO2016065001 SEQ ID NO: 41


AAV CSp-8.6
809
WO2016065001 SEQ ID NO: 42


AAV CSp-8.7
810
WO2016065001 SEQ ID NO: 43


AAV CSp-8.8
811
WO2016065001 SEQ ID NO: 44


AAV CSp-8.9
812
WO2016065001 SEQ ID NO: 45


AAV CBr-B7.3
813
WO2016065001 SEQ ID NO: 46


AAV CBr-B7.4
814
WO2016065001 SEQ ID NO: 47


AAV3B
815
WO2016065001 SEQ ID NO: 48


AAV4
816
WO2016065001 SEQ ID NO: 49


AAV5
817
WO2016065001 SEQ ID NO: 50


AAV CHt-P2
818
WO2016065001 SEQ ID NO: 51


AAV CHt-P5
819
WO2016065001 SEQ ID NO: 52


AAV CHt-P9
820
WO2016065001 SEQ ID NO: 53


AAV CBr-7.1
821
WO2016065001 SEQ ID NO: 54


AAV CBr-7.2
822
WO2016065001 SEQ ID NO: 55


AAV CBr-7.3
823
WO2016065001 SEQ ID NO: 56


AAV CBr-7.4
824
WO2016065001 SEQ ID NO: 57


AAV CBr-7.5
825
WO2016065001 SEQ ID NO: 58


AAV CBr-7.7
826
WO2016065001 SEQ ID NO: 59


AAV CBr-7.8
827
WO2016065001 SEQ ID NO: 60


AAV CBr-7.10
828
WO2016065001 SEQ ID NO: 61


AAV CKd-N3
829
WO2016065001 SEQ ID NO: 62


AAV CKd-N4
830
WO2016065001 SEQ ID NO: 63


AAV CKd-N9
831
WO2016065001 SEQ ID NO: 64


AAV CLv-L4
832
WO2016065001 SEQ ID NO: 65


AAV CLv-L5
833
WO2016065001 SEQ ID NO: 66


AAV CLv-L6
834
WO2016065001 SEQ ID NO: 67


AAV CLv-K1
835
WO2016065001 SEQ ID NO: 68


AAV CLv-K3
836
WO2016065001 SEQ ID NO: 69


AAV CLv-K6
837
WO2016065001 SEQ ID NO: 70


AAV CLv-M1
838
WO2016065001 SEQ ID NO: 71


AAV CLv-M11
839
WO2016065001 SEQ ID NO: 72


AAV CLv-M2
840
WO2016065001 SEQ ID NO: 73


AAV CLv-M5
841
WO2016065001 SEQ ID NO: 74


AAV CLv-M6
842
WO2016065001 SEQ ID NO: 75


AAV CLv-M7
843
WO2016065001 SEQ ID NO: 76


AAV CLv-M8
844
WO2016065001 SEQ ID NO: 77


AAV CLv-M9
845
WO2016065001 SEQ ID NO: 78


AAV CHt-P1
846
WO2016065001 SEQ ID NO: 79


AAV CHt-P6
847
WO2016065001 SEQ ID NO: 80


AAV CHt-P8
848
WO2016065001 SEQ ID NO: 81


AAV CHt-6.1
849
WO2016065001 SEQ ID NO: 82


AAV CHt-6.10
850
WO2016065001 SEQ ID NO: 83


AAV CHt-6.5
851
WO2016065001 SEQ ID NO: 84


AAV CHt-6.6
852
WO2016065001 SEQ ID NO: 85


AAV CHt-6.7
853
WO2016065001 SEQ ID NO: 86


AAV CHt-6.8
854
WO2016065001 SEQ ID NO: 87


AAV CSp-8.10
855
WO2016065001 SEQ ID NO: 88


AAV CSp-8.2
856
WO2016065001 SEQ ID NO: 89


AAV CSp-8.4
857
WO2016065001 SEQ ID NO: 90


AAV CSp-8.5
858
WO2016065001 SEQ ID NO: 91


AAV CSp-8.6
859
WO2016065001 SEQ ID NO: 92


AAV CSp-8.7
860
WO2016065001 SEQ ID NO: 93


AAV CSp-8.8
861
WO2016065001 SEQ ID NO: 94


AAV CSp-8.9
862
WO2016065001 SEQ ID NO: 95


AAV CBr-B7.3
863
WO2016065001 SEQ ID NO: 96


AAV CBr-B7.4
864
WO2016065001 SEQ ID NO: 97


AAV3B
865
WO2016065001 SEQ ID NO: 98


AAV4
866
WO2016065001 SEQ ID NO: 99


AAV5
867
WO2016065001 SEQ ID NO: 100


AAVPHP.B
868
WO2015038958 SEQ ID NO: 8 and 13; GenBankALU85156.1


or G2B-26




AAVPHP.B
869
WO2015038958 SEQ ID NO: 9


AAVG2B-13
870
WO2015038958 SEQ ID NO: 12


AAVTH1.1-32
871
WO2015038958 SEQ ID NO: 14


AAVTH1.1-35
872
WO2015038958 SEQ ID NO: 15









Each of the patents, applications and/or publications listed in Table 1 are hereby incorporated by reference in their entirety.


In one embodiment, the AAV serotype may be, or may have a sequence as described in International Patent Publication WO2015038958, the contents of which are herein incorporated by reference in their entirety, such as, but not limited to, AAV9 (SEQ ID NO: 2 and 11 of WO2015038958 or SEQ ID NO: 127 and 126 respectively herein), PHP.B (SEQ ID NO: 8 and 9 of WO2015038958, herein SEQ ID NO: 868 and 869), G2B-13 (SEQ ID NO: 12 of WO2015038958, herein SEQ ID NO: 870), G2B-26 (SEQ ID NO: 13 of WO2015038958, herein SEQ ID NO: 868 and 869), TH1.1-32 (SEQ ID NO: 14 of WO2015038958, herein SEQ ID NO: 871), TH1.1-35 (SEQ ID NO: 15 of WO2015038958, herein SEQ ID NO: 872) or variants thereof. Further, any of the targeting peptides or amino acid inserts described in WO2015038958, may be inserted into any parent AAV serotype, such as, but not limited to, AAV9 (SEQ ID NO: 126 for the DNA sequence and SEQ ID NO: 127 for the amino acid sequence). In one embodiment, the amino acid insert is inserted between amino acids 586-592 of the parent AAV (e.g., AAV9). In another embodiment, the amino acid insert is inserted between amino acids 588-589 of the parent AAV sequence. The amino acid insert may be, but is not limited to, any of the following amino acid sequences, TLAVPFK (SEQ ID NO: 1 of WO2015038958; herein SEQ ID NO: 873), KFPVALT (SEQ ID NO: 3 of WO2015038958, herein SEQ ID NO: 874), LAVPFK (SEQ ID NO: 31 of WO2015038958; herein SEQ ID NO: 875), AVPFK (SEQ ID NO: 32 of WO2015038958; herein SEQ ID NO: 876), VPFK (SEQ ID NO: 33 of WO02015038958; herein SEQ ID NO: 877), TLAVPF (SEQ ID NO: 34 of WO2015038958; herein SEQ ID NO: 878), TLAVP (SEQ ID NO: 35 of WO2015038958; herein SEQ ID NO: 879), TLAV (SEQ ID NO: 36 of WO2015038958; herein SEQ ID NO: 880), SVSKPFL (SEQ ID NO: 28 of WO2015038958; herein SEQ ID NO: 881), FTLTTPK (SEQ ID NO: 29 of WO2015038958; herein SEQ ID NO: 882), MNATKNV (SEQ ID NO: 30 of WO2015038958; herein SEQ ID NO: 883), QSSQTPR (SEQ ID NO: 54 of WO2015038958; herein SEQ ID NO: 884), ILGTGTS (SEQ ID NO: 55 of WO2015038958; herein SEQ ID NO: 885), TRTNPEA (SEQ ID NO: 56 of WO2015038958; herein SEQ ID NO: 886), NGGTSSS (SEQ ID NO:58 of WO2015038958; herein SEQ ID NO:887), or YTLSQGW (SEQ ID NO: 60 of WO2015038958; herein SEQ ID NO: 888). Non-limiting examples of nucleotide sequences that may encode the amino acid inserts include the following, AAGTITCCTGTGGKCGTTGACT (for SEQ ID NO: 3 of WO2015038958; herein SEQ ID NO: 889), ACYTTGGCGGTGCCTITYAAG (SEQ ID NO: 24 and 49 of WO2015038958; herein SEQ ID NO: 890), AGTGTGAGTAAGCCITIITG (SEQ ID NO: 25 of WO2015038958; herein SEQ ID NO. 891), TTACGTTGACGACGCCTAAG (SEQ ID NO: 26 of WO2015038958; herein SEQ ID NO:892), ATGAATGCTACGAAGAATGTG (SEQ ID NO: 27 of WO2015038958; herein SEQ ID NO: 893), CAGTCGTCGCAGACGCCTAGG (SEQ ID NO: 48 of WO2015038958; herein SEQ ID NO: 894), ATTCTGGGGACTCGGTACTTCG (SEQ ID NO: 50) and 52 of WO2015038958; herein SEQ ID NO: 895), ACGCGGACTAATCCTGAGGCT (SEQ ID NO-51 of WO2015038958; herein SEQ ID NO:896), AATGCiGGGGACTAGTAGTTCT (SEQ ID NO: 53 of WO2015038958; herein SEQ ID NO: 897), or TATACTTTGTCGCAGGGTTGG (SEQ ID NO: 59 of WO2015038958, herein SEQ ID NO: 898).


Viral Genome Component: Inverted Terminal Repeats (ITRs)

The AAV particles of the present invention comprise a viral genome with at least one ITR region and a payload region. In one embodiment, the viral genome has two ITRs. These two ITRs flank the payload region at the 5′ and 3′ ends. The ITRs function as origins of replication comprising recognition sites for replication. ITRs comprise sequence regions which can be complementary and symmetrically arranged. ITRs incorporated into viral genomes of the invention may be comprised of naturally occurring polynucleotide sequences or recombinantly derived polynucleotide sequences.


The ITRs may be derived from the same serotype as the capsid, selected from any of the serotypes listed in Table 1, or a derivative thereof. The ITR may be of a different serotype than the capsid. In one embodiment, the AAV particle has more than one ITR, In a non-limiting example, the AAV particle has a viral genome comprising two ITRs. In one embodiment, the ITRs are of the same serotype as one another. In another embodiment, the ITRs are of different serotypes. Non-limiting examples include zero, one or both of the ITRs having the same serotype as the capsid. In one embodiment both ITRs of the viral genome of the AAV particle are AAV2 ITRs.


Independently, each ITR may be about 100 to about 150 nucleotides in length. An ITR may be about 100-105 nucleotides in length, 106-110 nucleotides in length, 111-115 nucleotides in length, 116-120 nucleotides in length, 121-125 nucleotides in length, 126-130 nucleotides in length, 131-135 nucleotides in length, 136-140 nucleotides in length, 141-145 nucleotides in length or 146-150 nucleotides in length. In one embodiment, the ITRs are 140-142 nucleotides in length. Non-limiting examples of ITR length are 102, 140, 141, 142, 145 nucleotides in length, and those having at least 95% identity thereto


Viral Genome Component: Promoters

In one embodiment, the payload region of the viral genome comprises at least one element to enhance the transgene target specificity and expression (See e.g., Powell et al. Viral Expression Cassette Elements to Enhance Transgene Target Specificity and Expression in Gene Therapy, 2015; the contents of which are herein incorporated by reference in its entirety). Non-limiting examples of elements to enhance the transgene target specificity and expression include promoters, endogenous miRNAs, post-transcriptional regulatory elements (PREs, polyadenylation (PolyA) signal sequences and upstream enhancers (USEs), CMV enhancers and introns.


A person skilled in the art may recognize that expression of the polypeptides of the invention in a target cell may require a specific promoter, including but not limited to, a promoter that is species specific, inducible, tissue-specific, or cell cycle-specific (Parr et al., Nat. Med. 3:1145-9 (1997) the contents of which are herein incorporated by reference in their entirety).


In one embodiment, the promoter is deemed to be efficient when it drives expression of the polypeptide(s) encoded in the payload region of the viral genome of the AAV particle.


In one embodiment, the promoter is a promoter deemed to be efficient when it drives expression in the cell being targeted.


In one embodiment, the promoter drives expression of the polypeptides of the invention (e.g., a functional antibody) for a period of time in targeted tissues. Expression driven by a promoter may be for a period of 1 hour, 2, hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 3 weeks, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years or more than 10 years. Expression may be for 1-5 hours, 1-12 hours, 1-2 days, 1-5 days, 1-2 weeks, 1-3 weeks, 1-4 weeks, 1-2 months, 1-4 months, 1-6 months, 2-6 months, 3-6 months, 3-9 months, 4-8 months, 6-12 months, 1-2 years, 1-5 years, 2-5 years, 3-6 years, 3-8 years, 4-8 years or 5-10 years.


In one embodiment, the promoter drives expression of the polypeptides of the invention (e.g., a functional antibody) for at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, 19 years, 20 years, 21 years, 22 years, 23 years, 24 years, 25 years, 26 years, 27 years, 28 years, 29 years, 30 years, 31 years, 32 years, 33 years, 34 years, 35 years, 36 years, 37 years, 38 years, 39 years, 40 years, 41 years, 42 years, 43 years, 44 years, 45 years, 46 years, 47 years, 48 years, 49 years, 50 years, 55 years, 60 years, 65 years, or more than 65 years.


Promoters may be naturally occurring or non-naturally occurring. Non-limiting examples of promoters include viral promoters, plant promoters and mammalian promoters. In some embodiments, the promoters may be human promoters. In some embodiments, the promoter may be truncated.


Promoters which drive or promote expression in most tissues include, but are not limited to, human elongation factor 1α-subunit (EF1α), cytomegalovirus (CMV) immediate-early enhancer and/or promoter, chicken β-actin (CBA) and its derivative CAG, β glucuronidase (GUSB), or ubiquitin C (UBC). Tissue-specific expression elements can be used to restrict expression to certain cell types such as, but not limited to, muscle specific promoters, B cell promoters, monocyte promoters, leukocyte promoters, macrophage promoters, pancreatic acinar cell promoters, endothelial cell promoters, lung tissue promoters, astrocyte promoters, or nervous system promoters which can be used to restrict expression to neurons, astrocytes, or oligodendrocytes.


Non-limiting examples of muscle-specific promoters include mammalian muscle creatine kinase (MCK) promoter, mammalian desmin (DES) promoter, mammalian troponin I (TNNI2) promoter, and mammalian skeletal alpha-actin (ASKA) promoter (see, e.g. U.S. Patent Publication US 20110212529, the contents of which are herein incorporated by reference in their entirety).


Non-limiting examples of tissue-specific expression elements for neurons include neuron-specific enolase (NSE), platelet-derived growth factor (PDGF), platelet-derived growth factor B-chain (PDGF-β), synapsin (Syn), methyl-CpG binding protein 2 (MeCP2), Ca2+/calmodulin-dependent protein kinase II (CaM KII), metabotropic glutamate receptor 2 (mGluR2), neurofilament light (NFL) or heavy (NFH), β-globin minigene nβ2, preproenkephalin (PPE), enkephalin (Enk) and excitatory amino acid transporter 2 (EAAT2) promoters. Non-limiting examples of tissue-specific expression elements for astrocytes include glial fibrillary acidic protein (GFAP) and EAAT2 promoters. A non-limiting example of a tissue-specific expression element for oligodendrocytes includes the myelin basic protein (MBP) promoter.


In one embodiment, the promoter may be less than 1 kb. The promoter may have a length of 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 501), 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800 or more than 800 nucleotides. The promoter may have a length between 200-300, 200-400, 200-500, 200-60, 200-700, 200-800, 300-400, 300-500, 300-600, 300-700, 300-800, 400-500, 400-600, 400-700, 400-800, 500-600, 500-700, 500-800, 600-700, 600-800 or 700-800.


In one embodiment, the promoter may be a combination of two or more components of the same or different starting or parental promoters such as, but not limited to, CMV and CBA, Each component may have a length of 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800 or more than 800. Each component may have a length between 200-300, 200-400, 200-500, 200-600, 200-700), 200-800, 300-400, 300-500, 300-600, 300-700, 300-800, 400-500, 400-600, 400-700, 400-800, 500-600, 500-700, 500-800, 600-700, 600-800 or 700-800. In one embodiment, the promoter is a combination of a 382 nucleotide CMV-enhancer sequence and a 260 nucleotide CBA-promoter sequence.


In one embodiment, the viral genome comprises a ubiquitous promoter. Non-limiting examples of ubiquitous promoters include CMV, CBA (including derivatives CAG, CBh, etc.), EF-1α, PGK, UBC, GUSB (hGBp), and UCOE (promoter of HNRPA2B1-CBX3). Yu et al. (Molecular Pain 2011, 7-63, the contents of which are herein incorporated by reference in their entirety) evaluated the expression of eGFP under the CAG, EF1α, PGK and UBC promoters in rat DRG cells and primary DRG cells using lentiviral vectors and found that UBC showed weaker expression than the other 3 promoters and only 10-12% glial expression was seen for all promoters Soderblom et al. (E. Neuro 2015; the contents of which are herein incorporated by reference in its entirety) evaluated the expression of eGFP in AAV8 with CMV and UBC promoters and AAV2 with the CMV promoter after injection in the motor cortex. Intranasal administration of a plasmid containing a UBC or EF1a promoter showed a sustained airway expression greater than the expression with the CMV promoter (See e.g., Gill et al., Gene Therapy 2001, Vol. 8, 1539-1546; the contents of which are herein incorporated by reference in their entirety). Husain et al. (Gene Therapy 2009 the contents of which are herein incorporated by reference in its entirety) evaluated an HβH construct with a hGUSB promoter, a HSV-1LAT promoter and an NSE promoter and found that the HβH construct showed weaker expression than NSE in mouse brain. Passini and Wolfe (J. Virol. 2001, 12382-12392, the contents of which are herein incorporated by reference in its entirety) evaluated the long term effects of the HβH vector following an intraventricular injection in neonatal mice and found that there was sustained expression for at least 1 year. Low expression in all brain regions was found by Xu et al. (Gene Therapy 2001, 8, 1323-1332; the contents of which are herein incorporated by reference in their entirety) when NFL and NFH promoters were used as compared to the CMV-lacZ, CMV-luc, EF, GFAP, hENK, nAChR, PPE, PPE+wpre, NSE (0.3 kb), NSE (1.8 kb) and NSE (1.8 kb 4 wpre). Xu et al. found that the promoter activity in descending order was NSE (1.8 kb), EF, NSE (0.3 kb), GFAP, CMV, hENK, PPE, NFL and NFH. NFL is a 650 nucleotide promoter and NFH is a 920 nucleotide promoter which are both absent in the liver but NFH is abundant in the sensory proprioceptive neurons, brain and spinal cord and NFH is present in the heart. Scn8a is a 470 nucleotide promoter which expresses throughout the DRG, spinal cord and brain with particularly high expression seen in the hippocampal neurons and cerebellar Purkinje cells, cortex, thalamus and hypothalamus (See e.g., Drews et al. Identification of evolutionary conserved functional noncoding elements in the promoter region of the sodium channel gene SCN8A, Mamm Genome (2007) 18:723-731; and Raymond et al Expression of Alternatively Spliced Sodium Channel α-subunit genes, Journal of Biological Chemistry (2004) 279(44) 46234-46241; the contents of each of which are herein incorporated by reference in their entireties).


Any of promoters taught by the aforementioned Yu, Soderblom. Gill, Husamin, Passini, Xu, Drews or Raymond may be used in the present inventions.


In one embodiment, the promoter is not cell specific.


In one embodiment, the promoter is a ubiquitin c (UBC) promoter. The UBC promoter may have a size of 300-350 nucleotides. As a non-limiting example, the UBC promoter is 332 nucleotides.


In one embodiment, the promoter is a β-glucuronidase (GUSB) promoter. The CrUSB promoter may have a size of 350-400 nucleotides. As a non-limiting example, the GUSB promoter is 378 nucleotides.


In one embodiment, the promoter is a neurofilament light (NFL) promoter. The NFL promoter may have a size of 600-700 nucleotides. As a non-limiting example, the NFL promoter is 650 nucleotides.


In one embodiment, the promoter is a neurofilament heavy (NFH) promoter. The NFL promoter may have a size of 900-950 nucleotides. As a non-limiting example, the NFH promoter is 920 nucleotides.


In one embodiment, the promoter is a scn8a promoter. The scn8a promoter may have a size of 450-500 nucleotides. As a non-limiting example, the scn8a promoter is 470 nucleotides.


In one embodiment, the promoter is a phosphoglycerate kinase 1 (PGK) promoter.


In one embodiment, the promoter is a chicken β-actin (CBA) promoter.


In one embodiment, the promoter is a cytomegalovirus (CMV) promoter.


In one embodiment, the promoter is a liver or a skeletal muscle promoter. Non-limiting examples of liver promoters include human α-1-antitrypsin (hAAT) and thyroxine binding globulin (TBG). Non-limiting examples of skeletal muscle promoters include Desmin. MCK or synthetic C5-12.


In one embodiment, the promoter is a RNA pol III promoter. As a non-limiting example, the RNA pol III promoter is U6. As a non-limiting example, the RNA pol III promoter is H1.


In one embodiment, the viral genome comprises two promoters. As a non-limiting example, the promoters are an EF1α promoter and a CMV promoter.


In one embodiment, the viral genome comprises an enhancer element, a promoter and/or a 5′UTR intron. The enhancer element, also referred to herein as an “enhancer,” may be, but is not limited to, a CMV enhancer, the promoter may be, but is not limited to, a CMV. CBA. UBC, GUSB, NSE, Synapsin, MeCP2, and GFAP promoter and the 5′UTR/intron may be, but is not limited to, SV40, and CBA-MVM. As a non-limiting example, the enhancer, promoter and/or intron used in combination may be: (1) CMV enhancer. CMV promoter. SV40 5′UTR intron, (2) CMV enhancer, CBA promoter, SV 40 5′UTR intron, (3) CMV enhancer, CBA promoter, CBA-MVM 5′UTR intron; (4) UBC promoter; (5) GUSB promoter; (6) NSF promoter; (7) Synapsin promoter; (8) MeCP2 promoter and (9) GFAP promoter.


In one embodiment, the viral genome comprises an engineered promoter.


In another embodiment, the viral genome comprises a promoter from a naturally expressed protein.


Viral Genome Component: Untranslated Regions (UTRs)

By definition, wild type untranslated regions (UTRs) of a gene are transcribed but not translated. Generally, the 5′ UTR starts at the transcription start site and ends at the start codon and the 3′ UTR starts immediately following the stop codon and continues until the termination signal for transcription.


Features typically found in abundantly expressed genes of specific target organs may be engineered into UTRs to enhance the stability and protein production. As a non-limiting example, a 5′ UTR from mRNA normally expressed in the liver (e.g., albumin, serum amyloid A, Apolipoprotein A/B/E, transferrin, alpha fetoprotein, erythropoietin, or Factor VIII) may be used in the viral genomes of the AAV particles of the invention to enhance expression in hepatic cell lines or liver.


While not wishing to be bound by theory, wild-type 5′ untranslated regions (UTRs) include features which play roles in translation initiation. Kozak sequences, which are commonly known to be involved in the process by which the ribosome initiates translation of many genes, are usually included in 5′ UTRs. Kozak sequences have the consensus CCR(A/G)CCAUGG, where R is a purine (adenine or guanine) three bases upstream of the start codon (ATG), which is followed by another ‘G’.


In one embodiment, the 5′UTR in the viral genome includes a Kozak sequence.


In one embodiment, the 5′UTR in the viral genome does not include a Kozak sequence.


While not wishing to be bound by theory, wild-type 3′ UTRs are known to have stretches of Adenosines and Uridines embedded therein. These AU rich signatures are particularly prevalent in genes with high rates of turnover. Based on their sequence features and functional properties, the AU rich elements (AREs) can be separated into three classes (Chen et al, 1995, the contents of which are herein incorporated by reference in its entirety); Class I AREs, such as, but not limited to, c-Myc and MyoD, contain several dispersed copies of an AUUUA motif within U-rich regions. Class II AREs, such as, but not limited to, GM-CSF and TNF-a, possess two or more overlapping UUAUUUA(U/AXU/A) nonamers. Class III ARES, such as, but not limited to, c-Jun and Myogenin, are less well defined. These U rich regions do not contain an AUUUA motif. Most proteins binding to the AREs are known to destabilize the messenger, whereas members of the ELAV family, most notably HuR, have been documented to increase the stability of mRNA. HuR binds to AREs of all the three classes. Engineering the HuR specific binding sites into the 3′ UTR of nucleic acid molecules will lead to HuR binding and thus, stabilization of the message in vivo.


Introduction, removal or modification of 3′ UTR AU rich elements (AREs) can be used to modulate the stability of polynucleotides. When engineering specific polynucleotides, e.g., payload regions of viral genomes, one or more copies of an ARE can be introduced to make polynucleotides less stable and thereby curtail translation and decrease production of the resultant protein. Likewise, AREs can be identified and removed or mutated to increase the intracellular stability and thus increase translation and production of the resultant protein.


In one embodiment, the 3′ UTR of the viral genome may include an oligo(dT) sequence for templated addition of a poly-A tail.


In one embodiment, the viral genome may include at least one miRNA seed, binding site or full sequence, microRNAs (or miRNA or miR) are 19-25 nucleotide noncoding RNAs that bind to the sites of nucleic acid targets and down-regulate gene expression either by reducing nucleic acid molecule stability or by inhibiting translation. A microRNA sequence comprises a “seed” region, i.e., a sequence in the region of positions 2-8 of the mature microRNA, which sequence has perfect Watson-Crick complementarity to the miRNA target sequence of the nucleic acid.


In one embodiment, the viral genome may be engineered to include, alter or remove at least one miRNA binding site, sequence or seed region.


Any UTR from any gene known in the art may be incorporated into the viral genome of the AAV particle. These UTRs, or portions thereof, may be placed in the same orientation as in the gene from which they were selected or they may be altered in orientation or location. In one embodiment, the UTR used in the viral genome of the AAV particle may be inverted, shortened, lengthened, made with one or more other 5′ UTRs or 3′ UTRs known in the art. As used herein, the term “altered” as it relates to a UTR, means that the UTR has been changed in some way in relation to a reference sequence. For example, a 3′ or 5′ UTR may be altered relative to a wild type or native UTR by the change in orientation or location as taught above or may be altered by the inclusion of additional nucleotides, deletion of nucleotides, swapping or transposition of nucleotides.


In one embodiment, the viral genome of the AAV particle comprises at least one artificial UTRs which is not a variant of a wild type UTR.


In one embodiment, the viral genome of the AAV particle comprises UTRs which have been selected from a family of transcripts whose proteins share a common function, structure, feature or property.


Viral Genome Component: Polyadenylation Sequence

In one embodiment, the viral genome of the AAV particles of the present invention comprise at least one polyadenylation sequence. The viral genome of the AAV particle may comprise a poly adenylation sequence between the 3′ end of the payload coding sequence and the 5′ end of the 3′ITR


In one embodiment, the polyadenylation sequence or “polyA sequence” may range from absent to about 500 nucleotides in length. The polyadenylation sequence may be, but is not limited to, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, and 500) nucleotides in length.


In one embodiment, the polyadenylation sequence is 50-100 nucleotides in length.


In one embodiment, the polyadenylation sequence is 50-150 nucleotides in length.


In one embodiment, the polyadenylation sequence is 50-160 nucleotides in length.


In one embodiment, the polyadenylation sequence is 50-200 nucleotides in length.


In one embodiment, the polyadenylation sequence is 60-100 nucleotides in length.


In one embodiment, the polyadenylation sequence is 60-150 nucleotides in length.


In one embodiment, the polyadenylation sequence is 60-160 nucleotides in length.


In one embodiment, the polyadenylation sequence is 60-200) nucleotides in length.


In one embodiment, the polyadenylation sequence is 70-100 nucleotides in length.


In one embodiment, the polyadenylation sequence is 70-150 nucleotides in length.


In one embodiment, the polyadenylation sequence is 70-160 nucleotides in length.


In one embodiment, the polyadenylation sequence is 70-200 nucleotides in length.


In one embodiment, the polyadenylation sequence is 80-100 nucleotides in length.


In one embodiment, the polyadenylation sequence is 80-150 nucleotides in length.


In one embodiment, the polyadenylation sequence is 80-160 nucleotides in length.


In one embodiment, the polyadenylation sequence is 80-200 nucleotides in length.


In one embodiment, the polyadenylation sequence is 90-100 nucleotides in length.


In one embodiment, the polyadenylation sequence is 90-150 nucleotides in length.


In one embodiment, the polyadenylation sequence is 90-160 nucleotides in length.


In one embodiment, the polyadenylation sequence is 90-200 nucleotides in length.


Viral Genome Component: Linkers

Viral genomes of the invention may be engineered with one or more spacer or linker regions to separate coding or non-coding regions.


In one embodiment, the payload region of the AAV particle may optionally encode one or more linker sequences. In some cases, the linker may be a peptide linker that may be used to connect the polypeptides encoded by the payload region (i.e., light and heavy antibody chains during expression). Some peptide linkers may be cleaved after expression to separate heavy and light chain domains, allowing assembly of mature antibodies or antibody fragments. Linker cleavage may be enzymatic. In some cases, linkers comprise an enzymatic cleavage site to facilitate intracellular or extracellular cleavage. Some payload regions encode linkers that interrupt polypeptide synthesis during translation of the linker sequence from an mRNA transcript. Such linkers may facilitate the translation of separate protein domains (e.g., heavy and light chain antibody domains) from a single transcript. In some cases, two or more linkers are encoded by a payload region of the viral genome. Non-limiting examples of linkers that may be encoded by the payload region of an AAV particle viral genome are given in Table 2.









TABLE 2







Linkers









Linker No.
Description
SEQ ID NO





L1
Internal ribosome entry site (IRES)
 899


L2
Foot and month disease vims 2A (F2A)
 900


L3
Porcine teschovirus-1 virus 2A (P2A)
 901


L4
Furin cleavage site (F)
 902


L5
5xG4S (SEQ ID NO: 9221)
 903


L6
1,4-alpha-glucan-branching enzyme
CHP


L7
1,4-alpha-glucan-branching enzyme
 904


L8
1,4-beta-N-acetylmuramidase
FKK


L9
1,4-beta-N-acetylmuramidase
 905


L10
1,4-beta-N-acetylmuramidase
 906


L11
1,4-beta-N-acetylmuramidase
 907


L12
1,4-beta-N-acetylmuramidase
 908


L13
1,4-beta-N-acetylmuramidase
 909


L14
1,4-beta-N-acetylmuramidase
 910


L15
1,4-beta-N-acetylmuramidase
 911


L16
1,4-beta-N-acetylmuramidase
 912


L17
1,4-beta-N-acetylmuramidase
 913


L18
1,4-beta-N-acetylmuramidase
 914


L19
150aa long hypothetical transcriptional regulator
 915


L20
150aa long hypothetical transcriptional regulator
 916


L21
1-deoxy-D-xylulose 5-phosphate reductoisomerase
 917


L22
1-deoxy-D-xylulose 5-phosphate reductoisomerase
 918


L23
1-deoxy-D-xylulose 5-phosphate reductoisomerase
 919


L24
1-deoxy-D-xylulose 5-phosphate reductoisomerase
 920


L25
235aa long hypothetical biotin-[acetyl-CoA-carboxylase] ligase
 921


L26
235aa long hypothetical biotin-[acetyl-CoA-carboxylase] ligase
 922


L27
235aa long hypothetical biotin-[acetyl-CoA-carboxylase] ligase
 923


L28
2-dehydropantoate 2-reductase
 924


L29
2-dehydropantoate 2-reductase
 925


L30
2-dehydropantoate 2-reductase
 926


L31
2-dehydropantoate 2-reductase
 927


L32
2-dehydropantoate 2-reductase
 928


L33
2-dehydropantoate 2-reductase
 929


L34
2-dehydropantoate 2-reductase, putative
 930


L35
2-dehydropantoate 2-reductase, putative
 931


L36
4-alpha-glucanotransferase
 932


L37
4-alpha-glucanotransferase
 933


L38
4-alpha-glucanotransferase
 934


L39
4-diphosphocytidyl-2C-methyl-D-erythritol kinase
HAA


L40
4-diphosphocytidyl-2C-methyl-D-erythritol kinase
 935


L41
4-diphosphocytidyl-2C-methyl-D-erythritol kinase
 936


L42
4-diphosphocytidyl-2C-methyl-D-erythritol kinase
 937


L43
4-diphosphocytidyl-2C-methyl-D-erythritol kinase
 938


L44
4-hydroxyphenylpyruvate dioxygenase
 939


L45
5-13 amino acids from the N termini of human Ck and CH1 domains linker
 940


L46
5-13 amino acids from the N termini of human Ck and CH1 domains linker
ERK


L47
5-13 amino acids from the N termini of human Ck and CH1 domains linker
 941


L48
5-13 amino acids from the N termini of human Ck and CH1 domains linker
 942


L49
5-13 amino acids from the N termini of human Ck and CH1 domains linker
 943


L50
5-13 amino acids from the N termini of human Ck and CH1 domains linker
 944


L51
5′-exonuclease
 945


L52
5-methyltetrahydropteroyltriglutamate--homocysteinemethyltransferase
ARL


L53
5-methyltetrahydropteroyltriglutamate--homocysteinemethyltransferase
 946


L54
5-methyltetrahydropteroyltriglutamate--homocysteinemethyltransferase
 947


L55
5-methyltetrahydropteroyltriglutamate--homocysteinemethyltransferase
 948


L56
5-methyltetrahydropteroyltriglutamate--homocysteinemethyltransferase
 949


L57
5′-nucleotidase
 950


L58
5′-nucleotidase
 951


L59
5′-nucleotidase
 952


L60
5′-nucleotidase
 953


L61
704aa long hypothetical glycosyltransferase
 954


L62
704aa long hypothetical glycosyltransferase
 955


L63
80 kDa nuclear cap binding protein
 956


L64
80 kDa nuclear cap binding protein
 957


L65
80 kDa nuclear cap binding protein
 958


L66
80 kDa nuclear cap binding protein
 959


L67
Acetaldehyde dehydrogenase (acylating)
 960


L68
Acetaldehyde dehydrogenase (acylating)
 961


L69
Acetolactate synthase isozyme III small subunit
 962


L70
Acetylcholine receptor protein, alpha chain
 963


L71
Acetylcholine receptor protein, beta chain
 964


L72
Aconitate hydratase 2
 965


L73
Aconitate hydratase 2
 966


L74
Aconitate hydratase 2
 967


L75
Aconitate hydratase 2
 968


L76
Aconitate hydratase 2
 969


L77
Acriflavine resistance protein B
DWY


L78
Acriflavine resistance protein B
GGS


L79
Acriflavine resistance protein B
IDQ


L80
Acriflavine resistance protein B
NKV


L81
Acriflavine resistance protein B
SEA


L82
Acriflavine resistance protein B
 970


L83
Acriflavine resistance protein B
 971


L84
Acriflavine resistance protein B
 972


L85
Acriflavine resistance protein B
 973


L86
Acriflavine resistance protein B
 974


L87
Acriflavine resistance protein B
 975


L88
Acriflavine resistance protein B
 976


L89
Acriflavine resistance protein B
 977


L90
Acriflavine resistance protein B
 978


L91
Acriflavine resistance protein B
 979


L92
Acriflavine resistance protein B
 980


L93
Acriflavine resistance protein B
 981


L94
Acriflavine resistance protein B
 982


L95
Acriflavine resistance protein B
 983


L96
Acriflavine resistance protein B
 984


L97
Acriflavine resistance protein B
 985


L98
Acriflavine resistance protein B
 986


L99
Acriflavine resistance protein B
 987


L100
Acriflavine resistance protein B
 988


L101
Acriflavine resistance protein B
 989


L102
Acriflavine resistance protein B
 990


L103
Acriflavine resistance protein B
 991


L104
Acriflavine resistance protein B
 992


L105
Acriflavine resistance protein B
 993


L106
Acyl-CoA thioesterase II
 994


L107
Acyl-CoA thioesterase II
 995


L108
Acyl-CoA thioesterase II
 996


L109
Acyl-CoA thioesterase II
 997


L110
Acyl-CoA thioesterase II
 998


L111
Acyl-coenzyme A thioesterase 4
 999


L112
Acyl-coenzyme A thioesterase 4
1000


L113
Acyl-coenzyme A thioesterase 4
1001


L114
Acyl-coenzyme A thioesterase 4
1002


L115
Acyl-coenzyme A thioesterase 4
1003


L116
Adenine glycosylase
1004


L117
Adenylate cyclase
1005


L118
Aerolysin
1006


L119
Aerolysin
1007


L120
Agglutinin
DWK


L121
Agglutinin isolectin 1
1008


L122
Agglutinin isolectin 1
1009


L123
Aldehyde ferredoxin oxidoreductase
1010


L124
Aldehyde oxidoreductase
1011


L125
Aldehyde oxidoreductase
1012


L126
Aldehyde oxidoreductase
1013


L127
Aldehyde oxidoreductase
1014


L128
Aldehyde oxidoreductase
1015


L129
Alkyl hydroperoxide reductase subunit F
1016


L130
Alkyl hydroperoxide reductase subunit F
1017


L131
Alkyl hydroperoxide reductase subunit F
1018


L132
Alkyl hydroperoxide reductase subunit F
1019


L133
Alkyl hydroperoxide reductase subunit F
1020


L134
Alkyl hydroperoxide reductase subunit F
1021


L135
Alkyl hydroperoxide reductase subunit F
1022


L136
Alkyl hydroperoxide reductase subunit F
1023


L137
Alkyl hydroperoxide reductase subunit F
1024


L138
Alkyl hydroperoxide reductase subunit F
1025


L139
Allantoicase
1026


L140
Allantoicase
1027


L141
Alliin lyase 1
SAV


L142
Alliin lyase 1
1028


L143
Alliin lyase 1
1029


L144
Alliin lyase 1
1030


L145
Alliin lyase 1
1031


L146
Alpha amylase
1032


L147
Alpha amylase
1033


L148
Alpha-actinin 1
1034


L149
Alpha-actinin 1
1035


L150
Alpha-adaptin C
1036


L151
Alpha-amylase
1037


L152
Alpha-glucuronidase
LSD


L153
Alpha-glucuronidase
1038


L154
Alpha-glucuronidase
1039


L155
Alpha-glucuronidase
1040


L156
Alpha-glucuronidase
1041


L157
Alpha-glucuronidase
1042


L158
Alpha-glucuronidase
1043


L159
Alpha-glucuronidase
1044


L160
Alpha-glucuronidase
1045


L161
Alpha-glucuronidase
1046


L162
Alpha-glucuronidase
1047


L163
Alpha-glucuronidase
1048


L164
Alpha-glucuronidase
1049


L165
Alpha-glucuronidase
1050


L166
Alpha-glucuronidase
1051


L167
Alpha-glucuronidase
1052


L168
Alpha-glucuronidase
1053


L169
Alpha-glucuronidase
1054


L170
Alpha-glucuronidase
1055


L171
Alpha-glucuronidase
1056


L172
Alpha-glucuronidase
1057


L173
Alpha-glucuronidase
1058


L174
Alpha-L-arabinofuranosidase B
1059


L175
Alpha-mannosidase
1060


L176
Alr2269 protein
1061


L177
AMP nucleosidase
1062


L178
AMP nucleosidase
1063


L179
AMP nucleosidase
1064


L180
Angiopoietin-1 receptor
DAG


L181
Angiopoietin-1 receptor
NSG


L182
Angiopoietin-1 receptor
TSA


L183
Angiopoietin-1 receptor
VPR


L184
Angiopoietin-1 receptor
1065


L185
Angiopoietin-1 receptor
1066


L186
Angiopoietin-1 receptor
1067


L187
Angiopoietin-1 receptor
1068


L188
Angiopoietin-1 receptor
1069


L189
Angiopoietin-1 receptor
1070


L190
Angiopoietin-1 receptor
1071


L191
Angiopoietin-1 receptor
1072


L192
Angiopoietin-1 receptor
1073


L193
Angiopoietin-1 receptor
1074


L194
Angiopoietin-1 receptor
1075


L195
Angiopoietin-1 receptor
1076


L196
Angiopoietin-1 receptor
1077


L197
Angiopoietin-1 receptor
1078


L198
Angiopoietin-1 receptor
1079


L199
Angiopoietin-1 receptor
1080


L200
Angiopoietin-1 receptor
1081


L201
Angiopoietin-1 receptor
1082


L202
Angiopoietin-1 receptor
1083


L203
Angiopoietin-1 receptor
1084


L204
Angiopoietin-1 receptor
1085


L205
Annexin A2
QNK


L206
Annexin A2
1086


L207
Annexin A2
1087


L208
Anthranilate phosphoribosyltransferase
1088


L209
AP-2 complex subunit beta-2
1089


L210
Archaeosine tRNA-guanine transglycosylase
LGI


L211
Archaeosine tRNA-guanine transglycosylase
1090


L212
Archaeosine tRNA-guanine transglycosylase
1091


L213
Archaeosine tRNA-guanine transglycosylase
1092


L214
Archaeosine tRNA-guanine transglycosylase
1093


L215
Archaeosine tRNA-guanine transglycosylase
1094


L216
Archaeosine tRNA-guanine transglycosylase
1095


L217
Archaeosine tRNA-guanine transglycosylase
1096


L218
Archeal exosome RNA binding protein rrp4
1097


L219
Archeal exosome RNA binding protein rrp4
1098


L220
Archeal exosome RNA binding protein rrp4
1099


L221
Arginyl-tRNA synthetase
IDY


L222
Arginyl-tRNA synthetase
1100


L223
Arginyl-tRNA synthetase
1101


L224
Arginyl-tRNA synthetase
1102


L225
Arrestin
1103


L226
Arrestin
1104


L227
Arsenite oxidase
1105


L228
Artificial linker
PGS


L229
Artificial linker
ATK


L230
Artificial linker
ASK


L231
Artificial linker
1106


L232
Artificial tinker
1107


L233
Artificial linker
1108


L234
Artificial linker
1109


L235
Artificial tinker
1110


L236
Artificial linker
1111


L237
ATP phosphoribosyltransferase
ANR


L238
ATP-dependent DNA helicase
YDP


L239
ATP-dependent DNA helicase
1112


L240
ATP-dependent DNA helicase
1113


L241
ATP-dependent DNA helicase
1114


L242
ATP-dependent DNA helicase
1115


L243
ATP-dependent DNA helicase
1116


L244
ATP-dependent DNA helicase
1117


L245
ATP-dependent DNA helicase
1118


L246
ATP-dependent DNA helicase
1119


L247
AT-rich DNA-binding protein
1120


L248
AT-rich DNA-binding protein
1121


L249
Axonin-1
DEG


L250
Axonin-1
ECF


L251
Axonin-1
1122


L252
Axonin-1
1123


L253
Axonin-1
1124


L254
Axonin-1
1125


L255
Axonin-1
1126


L256
Axonin-1
1127


L257
Axonin-1
1128


L258
Bacilysin biosynthesis protein BacB
1129


L259
Bacilysin biosynthesis protein BacB
1130


L260
Bacilysin biosynthesis protein BacB
1131


L261
Bacilysin biosynthesis protein BacB
1132


L262
Bacilysin biosynthesis protein BacB
1133


L263
Bacteriophage Mu transposase
1134


L264
Bacteriophage Mu transposase
1135


L265
Benzoyl-CoA-dihydrodiol lyase
1136


L266
Benzoyl-CoA-dihydrodiol lyase
1137


L267
Benzoyl-CoA-dihydrodiol lyase
1138


L268
Benzoyl-CoA-dihydrodiol lyase
1139


L269
Benzoyl-CoA-dihydrodiol lyase
1140


L270
Benzoylformate decarboxylase
1141


L271
Benzoylformate decarboxylase
1142


L272
Benzoylformate decarboxylase
1143


L273
Beta-amylase
1144


L274
Beta-galactosidase
AIS


L275
Beta-galactosidase
1145


L276
Beta-galactosidase
1146


L277
Beta-galactosidase
1147


L278
Beta-galactosidase
1148


L279
Beta-galactosidase
1149


L280
Beta-galactosidase
1150


L281
Beta-galactosidase
1151


L282
Beta-galactosidase
1152


L283
Beta-galactosidase
1153


L284
Beta-galactosidase
1154


L285
Beta-galactosidase
1155


L286
Beta-galactosidase
1156


L287
Beta-galactosidase
1157


L288
Beta-galactosidase
1158


L289
Beta-galactosidase
1159


L290
Beta-galactosidase
1160


L291
Beta-galactosidase
1161


L292
Beta-galactosidase
1162


L293
Beta-galactosidase
1163


L294
Beta-galactosidase
1164


L295
Beta-galactosidase
1165


L296
Beta-galactosidase
1166


L297
Beta-N-acetylhexosaminidase
QRE


L298
Beta-N-acetylhexosaminidase
1167


L299
Beta-N-acetylhexosaminidase
1168


L300
Beta-N-acetylhexosaminidase
1169


L301
Bifunctional NMN adenylyltransferase/Nudix hydrolase
1170


L302
Bifunctional purine biosynthesis protein PURH
1171


L303
Biliverdin reductase A
EHV


L304
Biliverdin reductase A
LME


L305
Biliverdin reductase A
1172


L306
Biliverdin reductase A
1173


L307
Biodegradative arginine decarboxylase
TVQ


L308
Biodegradative arginine decarboxylase
1174


L309
Biodegradative arginine decarboxylase
1175


L310
Biodegradative arginine decarboxylase
1176


L311
Biodegradative arginine decarboxylase
1177


L312
Biodegradative arginine decarboxylase
1178


L313
Biodegradative arginine decarboxylase
1179


L314
Biodegradative arginine decarboxylase
1180


L315
Biodegradative arginine decarboxylase
1181


L316
Biodegradative arginine decarboxylase
1182


L317
Biodegradative arginine decarboxylase
1183


L318
Biodegradative arginine decarboxylase
1184


L319
Biodegradative arginine decarboxylase
1185


L320
Biotin carboxylase
1186


L321
Bowman-Birk trypsin inhibitor
1187


L322
Bpt4 gene 59 helicase assembly protein
KQI


L323
BRCA1-associated RING domain protein 1
1188


L324
BRCA1-associated RING domain protein 1
1189


L325
BRCA1-associated RING domain protein 1
1190


L326
Breast cancer 2
1191


L327
Breast cancer 2
1192


L328
Breast cancer 2
1193


L329
Breast cancer 2
1194


L330
Breast cancer 2
1195


L331
Breast cancer 2
1196


L332
Butyrate response factor 2
1197


L333
C4b-binding protein
YKR


L334
C4b-binding protein
1198


L335
C5a peptidase
1199


L336
C5a peptidase
1200


L337
C5a peptidase
1201


L338
C5a peptidase
1202


L339
C5a peptidase
1203


L340
C5a peptidase
1204


L341
C5a peptidase
1205


L342
C5a peptidase
1206


L343
C5a peptidase
1207


L344
C5a peptidase
1208


L345
C5a peptidase
1209


L346
C5a peptidase
1210


L347
C5a peptidase
1211


L348
Calcium-binding protein
1212


L349
CarA
1213


L350
CarA
1214


L351
Carbamoyl phosphate synthetase (small chain)
1215


L352
Carbamoyl phosphate synthetase (small chain)
1216


L353
Carbamoyl phosphate synthetase (small chain)
1217


L354
Carbamoyl phosphate synthetase (small chain)
1218


L355
Carbamoyl phosphate synthetase (small chain)
1219


L356
Carbon monoxide dehydrogenase/acetyl-CoA synthase subunitalpha
1220


L357
Carboxypeptidase Gp180 residues 503-882
HRG


L358
Catabolite activation-like protein
1221


L359
Catabolite activation-like protein
1222


L360
Catechol 2,3-dioxygenase
1223


L361
Cation-independent mannose 6-phosphate receptor
1224


L362
CD3 epsilon and gamma ectodomain fragment complex
1225


L363
CD3 epsilon and gamma ectodomain fragment complex
1226


L364
Cell filamentation protein
SNP


L365
Cell filamentation protein
1227


L366
Cell filamentation protein
1228


L367
Cellular coagulation factor XIII zymogen
DIT


L368
Cellular coagulation factor XIII zymogen
NSD


L369
Cellular coagulation factor XIII zymogen
TDT


L370
Cellular coagulation factor XIII zymogen
1229


L371
Cellular coagulation factor XIII zymogen
1230


L372
Cellular coagulation factor XIII zymogen
1231


L373
Cellular coagulation factor XIII zymogen
1232


L374
Cellular coagulation factor XIII zymogen
1233


L375
Cellular coagulation factor XIII zymogen
1234


L376
Cellular coagulation factor XIII zymogen
1235


L377
Cellular coagulation factor XIII zymogen
1236


L378
Cellular coagulation factor XIII zymogen
1237


L379
Cellular coagulation factor XIII zymogen
1238


L380
Cellular coagulation factor XIII zymogen
1239


L381
Cellular coagulation factor XIII zymogen
1240


L382
Cellular coagulation factor XIII zymogen
1241


L383
Cellular coagulation factor XIII zymogen
1242


L384
Cellular coagulation factor XIII zymogen
1243


L385
Cellular coagulation factor XIII zymogen
1244


L386
Cellular coagulation factor XIII zymogen
1245


L387
Cellular coagulation factor XIII zymogen
1246


L388
Cellular coagulation factor XIII zymogen
1247


L389
Cellulase
1248


L390
Cellulase
1249


L391
Cellulase
1250


L392
Cellulase
1251


L393
Cellulase
1252


L394
Cellulase
1253


L395
Cellulase
1254


L396
Cellulase
1255


L397
Cellulase
1256


L398
Cellulase linker
1257


L399
Cellulase linker
1258


L400
Cellulase linker
1259


L401
Cellulase linker
1260


L402
Chaperone protein FimC
KLR


L403
Chaperone protein FimC
QAA


L404
Chaperone protein FimC
1261


L405
Chaperone protein FimC
1262


L406
Chaperone protein HscB
RHP


L407
Chaperone protein HscB
1263


L408
CheB methylesterase
1264


L409
CheB methylesterase
1265


L410
CheB methylesterase
1266


L411
Chelatase, putative
1267


L412
Chemotaxis receptor methyltransferase cheR
1268


L413
Chemotaxis receptor methyltransferase cheR
1269


L414
Chemotaxis receptor methyltransferase cheR
1270


L415
Cholesterol oxidase
1271


L416
Cholesterol oxidase
1272


L417
Cholesterol oxidase
1273


L418
Cholesterol oxidase
1274


L419
Cholesterol oxidase
1275


L420
Cholesterol oxidase
1276


L421
Cholesterol oxidase
1277


L422
Cholesterol oxidase
1278


L423
Cholesterol oxidase
1279


L424
Cholesterol oxidase
1280


L425
Cholesterol oxidase
1281


L426
Cholesterol oxidase
1282


L427
Chromatin structure-remodeling complex protein RSC4
KNL


L428
Chromatin structure-remodeling complex protein RSC4
1283


L429
Chromatin structure-remodeling complex protein RSC4
1284


L430
Chromatin structure-remodeling complex protein RSC4
1285


L431
Chromodomain-helicase-DNA-binding protein 1
1286


L432
Chromodomain-helicase-DNA-binding protein 1
1287


L433
Cleavable disulfide
1288


L434
Cleavable disulfide
1289


L435
Cleavable disulfide
1290


L436
Cleavable disulfide
1291


L437
Cleavable disulfide
1292


L438
Cleavable disulfide
1293


L439
Cleavable disulfide
1294


L440
Cleavable disulfide
1295


L441
Cleavable disulfide
1296


L442
Cleavable disulfide
1297


L443
Cleavable disulfide
1298


L444
Colicin Ia
1299


L445
Collagen adhesin
1300


L446
Complement C3 beta chain
1301


L447
Complement C3 beta cliain
1302


L448
Complement C3 beta chain
1303


L449
Complement C3 beta cliain
1304


L450
Complement decay-accelerating factor
EIY


L451
Complement factor H
KRP


L452
Complement receptor type 2
1305


L453
Conserved hypothetical protein
1306


L454
Conserved hypothetical protein MTH1747
DIR


L455
Conserved hypothetical protein MTH1747
1307


L456
Conserved hypothetical protein MTH1747
1308


L457
Conserved hypothetical protein MTH1747
1309


L458
Conserved hypothetical protein MTH1747
1310


L459
Conserved hypothetical protein MTH1747
1311


L460
Conserved hypothetical protein MTH1747
1312


L461
Conserved hypothetical protein MTH1747
1313


L462
Conserved protein (MTH177)
1314


L463
Creatine amidinohydrolase
1315


L464
Cruciferin
1316


L465
Cruciferin
1317


L466
Cruciferin
1318


L467
Cruciferin
1319


L468
Cruciferin
1320


L469
Cruciferin
1321


L470
Cruciferin
1322


L471
CSL3
1323


L472
CSL3
1324


L473
CTP synthase
1325


L474
CTP synthase
1326


L475
Cullin homolog
HKN


L476
Cullin homolog
1327


L477
Cullin homolog
1328


L478
Cullin homolog
1329


L479
Cullin homolog
1330


L480
Cullin homolog
1331


L481
Cyclin A2
1332


L482
Cysteine-rich secretory protein
1333


L483
Cytidine deaminase
1334


L484
Cytidine deaminase
1335


L485
Cytidine deaminase
1336


L486
Cytochrome b-c1 complex subunit Rieske, mitochondrial
1337


L487
Cytochrome c oxidase subunit 2
QAV


L488
Cytochrome c oxidase subunit 2
1338


L489
Cytochrome c oxidase subunit 2
1339


L490
Cytochrome c oxidase subunit 2
1340


L491
Cytochrome c oxidase subunit 2
1341


L492
Cytochrome c4
GGK


L493
Cytochrome c4
QGM


L494
D-aminopeptidase
1342


L495
DDMC
1343


L496
DDMC
1344


L497
Deltex protein
1345


L498
Deoxyuridine 5′-triphosphate nucleotidohydrolase
1346


L499
Diaminopimelate epimerase
1347


L500
Diaminopimelate epimerase
1348


L501
Diaminopimelate epimerase
1349


L502
Di-heme peroxidase
SGC


L503
Di-heme peroxidase
1350


L504
Dihydropyrimidine dehydrogenase
1351


L505
Dihydropyrimidine dehydrogenase
1352


L506
Dihydropyrimidine dehydrogenase
1353


L507
Dihydropyrimidine dehydrogenase
1354


L508
Dihydropyrimidine dehydrogenase
1355


L509
Dihydropyrimidine dehydrogenase
1356


L510
Dihydropyrimidine dehydrogenase
1357


L511
Dihydropyrimidine dehydrogenase
1358


L512
Dihydropyrimidine dehydrogenase
1359


L513
Dihydropyrimidine dehydrogenase
1360


L514
Dihydropyrimidine dehydrogenase
1361


L515
Dihydropyrimidine dehydrogenase
1362


L516
Dihydropyrimidine dehydrogenase
1363


L517
Dihydropyrimidine dehydrogenase
1364


L518
Dihydropyrimidine dehydrogenase
1365


L519
Dihydropyrimidine dehydrogenase
1366


L520
Dihydropyrimidine dehydrogenase
1367


L521
Dihydropyrimidine dehydrogenase
1368


L522
Dihydropyrimidine dehydrogenase
1369


L523
Dihydropyrimidine dehydrogenase
1370


L524
Dihydropyrimidine dehydrogenase
1371


L525
Dihydropyrimidine dehydrogenase
1372


L526
Dihydropyrimidine dehydrogenase
1373


L527
Dihydropyrimidine dehydrogenase
1374


L528
Dihydropyrimidine dehydrogenase
1375


L529
Dihydropyrimidine dehydrogenase
1376


L530
Dihydropyrimidine dehydrogenase
1377


L531
Dihydropyrimidine dehydrogenase
1378


L532
Dihydropyrimidine dehydrogenase
1379


L533
Dihydropyrimidine dehydrogenase
1380


L534
Dihydropyrimidine dehydrogenase
1381


L535
Discoidin-1 subunit A
1382


L536
Discoidin-1 subunit A
1383


L537
Discoidin-1 subunit A
1384


L538
Dissimilatory copper-containing nitritereductase
1385


L539
D-lactate dehydrogenase
DTF


L540
D-lactate dehydrogenase
1386


L541
D-lactate dehydrogenase
1387


L542
D-lactate dehydrogenase
1388


L543
D-lactate dehydrogenase
1389


L544
D-lactate dehydrogenase
1390


L545
D-lactate dehydrogenase
1391


L546
DNA damage-binding protein 1
LCA


L547
DNA damage-binding protein 1
1392


L548
DNA damage-binding protein 1
1393


L549
DNA damage-binding protein 1
1394


L550
DNA damage-binding protein 1
1395


L551
DNA damage-binding protein 1
1396


L552
DNA damage-binding protein 1
1397


L553
DNA damage-binding protein 1
1398


L554
DNA damage-binding protein 1
1399


L555
DNA damage-binding protein 1
1400


L556
DNA damage-binding protein 1
1401


L557
DNA damage-binding protein 1
1402


L558
DNA damage-binding protein 1
1403


L559
DNA damage-binding protein 1
1404


L560
DNA damage-binding protein 1
1405


L561
DNA damage-binding protein 1
1406


L562
DNA damage-binding protein 1
1407


L563
DNA damage-binding protein 1
1408


L564
DNA damage-binding protein 1
1409


L565
DNA damage-binding protein 1
1410


L566
DNA damage-binding protein 1
1411


L567
DNA damage-binding protein 1
1412


L568
DNA damage-binding protein 1
1413


L569
DNA gyrase B
ALS


L570
DNA gyrase B
1414


L571
DNA gyrase B
1415


L572
DNA gyrase B
1416


L573
DNA gyrase B
1417


L574
DNA gyrase B
1418


L575
DNA gyrase B
1419


L576
DNA gyrase B
1420


L577
DNA gyrase B
1421


L578
DNA gyrase B
1422


L579
DNA gyrase B
1423


L580
DNA gyrase B
1424


L581
DNA ligase
1425


L582
DNA ligase
1426


L583
DNA ligase
1427


L584
DNA ligase
1428


L585
DNA ligase
1429


L586
DNA mismatch repair protein MutS
MDA


L587
DNA mismatch repair protein MutS
SII


L588
DNA mismatch repair protein MutS
1430


L589
DNA mismatch repair protein MutS
1431


L590
DNA mismatch repair protein MutS
1432


L591
DNA mismatch repair protein MutS
1433


L592
DNA mismatch repair protein MutS
1434


L593
DNA polymerase
FSP


L594
DNA polymerase
RQF


L595
DNA polymerase
1435


L596
DNA polymerase
1436


L597
DNA polymerase
1437


L598
DNA polymerase
1438


L599
DNA polymerase
1439


L600
DNA polymerase
1440


L601
DNA polymerase
1441


L602
DNA polymerase
1442


L603
DNA polymerase alpha subunit B
1443


L604
DNA polymerase alpha subunit B
1444


L605
DNA polymerase alpha subunit B
1445


L606
DNA polymerase alpha subunit B
1446


L607
DNA polymerase alpha subunit B
1447


L608
DNA polymerase alpha subunit B
1448


L609
DNA polymerase alpha subunit B
1449


L610
DNA polymerase alpha subunit B
1450


L611
DNA polymerase alpha subunit B
1451


L612
DNA polymerase alpha subunit B
1452


L613
DNA polymerase eta
ALS


L614
DNA polymerase eta
1453


L615
DNA polymerase eta
1454


L616
DNA polymerase eta
1455


L617
DNA polymerase eta
1456


L618
DNA polymerase eta
1457


L619
DNA polymerase I
AGV


L620
DNA polymerase I
ELE


L621
DNA polymerase I
1458


L622
DNA primase
DHK


L623
DNA primase
1459


L624
DNA primase
1460


L625
DNA primase
1461


L626
DNA primase
1462


L627
DNA primase
1463


L628
DNA primase
1464


L629
DNA primase
1465


L630
DNA primase/helicase
AGY


L631
DNA primase/helicase
1466


L632
DNA primase/helicase
1467


L633
DNA primase/helicase
1468


L634
DNA primase/helicase
1469


L635
DNA primase/helicase
1470


L630
DNA primase/helicase
1471


L637
DNA primase/helicase
1472


L638
DNA primase/helicase
1473


L639
DNA primase/helicase
1474


L640
DNA primase/helicase
1475


L641
DNA topoisomerase 2
EES


L642
DNA topoisomerase 2
IPI


L643
DNA topoisomerase 2
KEL


L644
DNA topoisomerase 2
1476


L645
DNA topoisomerase 2
1477


L646
DNA topoisomerase 2
1478


L647
DNA topoisomerase 2
1479


L648
DNA topoisomerase 2
1480


L649
DNA topoisomerase 2
1481


L650
DNA topoisomerase 2
1482


L651
DNA topoisomerase 2
1483


L652
DNA topoisomerase 2
1484


L653
DNA topoisomerase I
1485


L654
DNA topoisomerase I
1486


L655
DNA topoisomerase I
1487


L656
DNA topoisomerase II, alpha isozyme
PDL


L657
DNA topoisomerase II, alpha isozyme
1488


L658
DNA topoisomerase II, alpha isozyme
1489


L659
DNA topoisomerase II, alpha isozyme
1490


L660
DNA topoisomerase II, alpha isozyme
1491


L661
DNA topoisomerase II, alpha isozyme
1492


L662
DNA topoisomerase II, alpha isozyme
1493


L663
DNA topoisomerase II, alpha isozyme
1494


L664
DNA topoisomerase II, alpha isozyme
1495


L665
DNA topoisomerase VI A subunit
1496


L666
DNA topoisomerase VI A subunit
1497


L667
DNA topoisomerase VI A subunit
1498


L668
DNA topoisomerase VI A subunit
1499


L669
DNA topoisomerase VI A subunit
1500


L670
DNA topoisomerase VI A subunit
1501


L671
DNA-3-methyladenine glycosylase 2
1502


L672
DNA-binding response regulator MtrA
1503


L673
DNA-directed RNA polymerase beta chain
1504


L674
DNA-directed RNA polymerase beta chain
1505


L675
DNA-directed RNA polymerase beta chain
1506


L676
DNA-directed RNA polymerase beta chain
1507


L677
DNA-directed RNA polymerase beta chain
1508


L678
DNA-directed RNA polymerase beta chain
1509


L679
DNA-directed RNA polymerase beta chain
1510


L680
DNA-directed RNA polymerase beta chain
1511


L681
DNA-directed RNA polymerase II 14.2 kDa polypeptide
1512


L682
DNA-directed RNA polymerase II 14.2 kDa polypeptide
1513


L683
DNA-directed RNA polymerase, subunit E′ (rpoe1)
1514


L684
DNA-directed RNA polymerase, subunit E′ (rpoe1)
1515


L685
DNA-directed RNA polymerases I, II, and III 27 kDa polypeptide
IIP


L686
DNA-directed RNA polymerases I, II, and III 27 kDa polypeptide
1516


L687
DNA-directed RNA polymerases I, II, and III 27 kDa polypeptide
1517


L688
DNA-directed RNA polymerases I, II, and III 27 kDa polypeptide
1518


L689
DNA-directed RNA polymerases I, II, and III 27 kDa polypeptide
1519


L690

Drosophila neuroglian
1520


L691
Dystroglycan
1521


L692
Dystrophin
1522


L693
Dystrophin
1523


L694
Dystrophin
1524


L695
Dystrophin
1525


L696
Dystrophin
1526


L697
Dystrophin
1527


L698
Dystrophin
1528


L699
E2A DNA-binding protein
1529


L700
E2A DNA-binding protein
1530


L701
E3 sumo-protein ligase SIZ1
1531


L702
E3 sumo-protein ligase SIZ1
1532


L703
E3 sumo-protein ligase SIZ1
1533


L704
Early switch protein xol-l 2.2k splice form
1534


L705
EGF-like module containing mucin-like hormonereceptor-like 2 precursor
1535


L706
EGF-like module containing mucin-like hormonereceptor-like 2 precursor
1536


L707
Elongation factor 1-gamma 1
1537


L708
Elongation factor 1-gamma 1
1538


L709
Elongation factor g
1539


L710
Elongation factor G
1540


L711
Elongation factor G
1541


L712
Elongation factor G
1542


L713
Elongation factor G
1543


L714
Elongation factor G
1544


L715
Elongation factor G
1545


L716
Elongation factor G
1546


L717
Elongation factor G
1547


L718
Elongation factor G
1548


L719
Elongation factor P
1549


L720
Elongation factor Ts
1550


L721
Elongation factor Ts
1551


L722
Elongation factor Ts
1552


L723
Elongation factor Tu (ef-Tu)
1553


L724
Endoglucanase
1554


L725
Endonuclease PI-SceI
1555


L726
Endonuclease PI-SceI
1556


L727
Endonuclease PI-SceI
1557


L728
Endonuclease PI-SceI
1558


L729
Endonuclease PI-SceI
1559


L730
Endonuclease PI-SceI
1560


L731
Endonuclease PI-SceI
1561


L732
Endonuclease PI-SceI
1562


L733
Endonuclease PI-SceI
1563


L734
Enterobactin synthetase component F
1564


L735
Enterobactin synthetase component F
1565


L736
Enterobactin synthetase component F
1566


L737
Enterobactin synthetase component F
1567


L738
Enterobactin synthetase component F
1568


L739
Enterobactin synthetase component F
1569


L740
Enterobactin synthetase component F
1570


L741
Enterobactin synthetase component F
1571


L742
Enterobactin synthetase component F
1572


L743
Enterochelin esterase
1573


L744
Epo receptor
EVV


L745
Epo receptor
1574


L746
Erythrocyte binding antigen region II
1575


L747
Erythrocyte binding antigen region II
1576


L748
Erythrocyte binding antigen region II
1577


L749
Erythrocyte binding antigen region II
1578


L750
Erythrocyte binding antigen region II
1579


L751
E-selectin
1580


L752
Esterase EstA
SAP


L753
Esterase EstA
1581


L754
Esterase EstA
1582


L755
Eukaryotic peptide chain release factor GTP-binding subunit
1583


L756
Exonuclease I
RQP


L757
Exonuclease I
1584


L758
FascIclIn I
SDP


L759
FascIclIn I
1585


L760
Fibrillin-1
1586


L761
Fibrillin-1
1587


L762
Fibrillin-1
1588


L763
Fibrillin-1
1589


L764
Fibrillin-1
1590


L765
Fibronectin
1591


L766
Fibronectin
1592


L767
Fibronectin
1593


L768
Flagellar hook protein FlgE
1594


L769
Flagellar hook protein FlgE
1595


L770
Flagellar hook protein FlgE
1596


L771
Flagellar hook protein FlgE
1597


L772
Flagellar hook protein FlgE
1598


L773
Flagellar hook protein FlgE
1599


L774
Flagellar hook protein FlgE
1600


L775
Flavohemoprotein
1601


L776
Flexible G/S rich linker
G


L777
Flexible G/S rich linker
S


L778
Flexible G/S rich linker
GG


L779
Flexible G/S rich linker
GS


L780
Flexible G/S rich linker
GGS


L781
Flexible G/S rich linker
GGG


L782
Flexible G/S rich linker
1602


L783
Flexible G/S rich linker
1603


L784
Flexible G/S rich linker
1604


L785
Flexible G/S rich linker
1605


L786
Flexible G/S rich linker
1606


L787
Flexible G/S rich linker
1607


L788
Flexible G/S rich linker
1608


L789
Flexible G/S rich linker
1609


L790
Flexible G/S rich linker
1610


L791
Flexible G/S rich linker
1611


L792
Flexible G/S rich linker
1612


L793
Flexible G/S rich linker
1613


L794
Flexible G/S rich linker
1614


L795
Flexible G/S rich linker
1615


L796
Focal adhesion kinase 1
1616


L797
FolC bifunctional protein
1617


L798
FolC bifunctional protein
1618


L799
FolC bifunctional protein
1619


L800
FolC bifunctional protein
1620


L801
FolC bifunctional protein
1621


L802
FolC bifunctioiial protein
1622


L803
FolC bifunctional protein
1623


L804
FolC bifunctional protein
1624


L805
Follistatin
1625


L806
Formate dehydrogenase (large subunit)
YDK


L807
Formate dehydrogenase (large subunit)
1626


L808
Formate dehydrogenase (large subunit)
1627


L809
Formate dehydrogenase (large subunit)
1628


L810
Formate dehydrogenase (large subunit)
1629


L811
Formate dehydrogenase (large subunit)
1630


L812
Formate dehydrogenase (large subunit)
1631


L813
Formate dehydrogenase (large subunit)
1632


L814
Formate dehydrogenase (large subunit)
1633


L815
Formate dehydrogenase (large subunit)
1634


L816
Formate dehydrogenase (large subunit)
1635


L817
Formate dehydrogenase (large subunit)
1636


L818
Formate dehydrogenase(large subunit)
1637


L819
Formate dehydrogenase, nitrate-inducible major subunit
1638


L820
Formate dehydrogenase, nitrate-inducible, major subunit
1639


L821
Formate dehydrogenase, nitrate-inducible, major subunit
1640


L822
Formate dehydrogenase, nitrate-inducible, major subunit
1641


L823
Formate dehydrogenase, nitrate-inducible, major subunit
1642


L824
Formate dehydrogenase, nitrate-inducible, major subunit
1643


L825
Formate dehydrogenase, nitrate-inducible, major subunit
1644


L826
Formate dehydrogenase, nitrate-inducible, major subunit
1645


L827
Formate dehydrogenase, nitrate-inducible, major subunit
1646


L828
Formate dehydrogenase, nitrate-inducible, major subunit
1647


L829
Formate dehydrogenase, nitrate-inducible, major subunit
1648


L830
Formate dehydrogenase, nitrate-inducible, major subunit
1649


L831
Formate dehydrogenase, nitrate-inducible, major subunit
1650


L832
Formate dehydrogenase, nitrate-inducible, major subunit
1651


L833
Fumarylacetoacetate hydrolase
1652


L834
Galactose oxidase
GSV


L835
Galactose oxidase
GWK


L836
Galactose oxidase
IAE


L837
Galactose oxidase
KRQ


L838
Galactose oxidase
QDT


L839
Galactose oxidase
TPN


L840
Galactose oxidase
1653


L841
Galactose oxidase
1654


L842
Galactose oxidase
1655


L843
Galactose oxidase
1656


L844
Galactose oxidase
1657


L845
Galactose oxidase
1658


L846
Galactose oxidase
1659


L847
Galactose oxidase
1660


L848
Galactose oxidase
1661


L849
Galactose oxidase
1662


L850
Galactose oxidase
1663


L851
Galactose oxidase
1664


L852
Galactose oxidase
1665


L853
Galactose oxidase
1666


L854
Galactose oxidase
1667


L855
Galactose oxidase
1668


L856
Galactose oxidase
1669


L857
Galactose oxidase
1670


L858
Galactose oxidase
1671


L859
Galactose oxidase
1672


L860
Galactose oxidase
1673


L861
Galactose oxidase
1674


L862
Galactose oxidase
1675


L863
Galactose oxidase
1676


L864
Gamma B-crystallin
1677


L865
Gamma-delta T-cell receptor
1678


L866
Gelation factor
DSS


L867
Gelation factor
1679


L868
Gelation factor
1680


L869
Gelation factor
1681


L870
Gene activator alpha
1682


L871
Gingipain R
1683


L872
Glucodextranase
1684


L873
Glucodextranase
1685


L874
Glucodextranase
1686


L875
Glucosamine-fructose-6-phosphate aminotransferase
YEQ


L876
Glucosamine-fructose-6-phosphate aminotransferase
1687


L877
Glucosamine-fructose-6-phosphate aminotransferase
1688


L878
Glucosamine-fructose-6-phosphate aminotransferase
1689


L879
Glucosamine-fructose-6-phosphate aminotransferase
1690


L880
Glucosamine-fructose-6-phosphate aminotransferase
1691


L881
Glucosamine-fructose-6-phosphate aminotransferase
1692


L882
Glucosamine-fructose-6-phosphate aminotransferase
1693


L883
Glucosamine-fructose-6-phosphate aminotransferase
1694


L884
Glucosamine-fructose-6-phosphate aminotransferase
1695


L885
Glucosamine-fructose-6-phosphate aminotransferase
1696


L886
Glucose-1-phosphate adenylyltransferase small subunit
1697


L887
Glucose-1-phosphate adenylyltransferase small subunit
1698


L888
Glucose-6-phosphate isomerase
KNA


L889
Glucose-6-phosphate isomerase
VGF


L890
Glucose-6-phosphate isomerase
1699


L891
Glucose-6-phosphate isomerase
1700


L892
Glucose-6-phosphate isomerase, conjectural
1701


L893
Glutamate dehydrogenase
1702


L894
Glutamate dehydrogenase
1703


L895
Glutamate receptor interacting protein
1704


L896
Glutamate synthase [NADPH] large chain
1705


L897
Glutamate synthase [NADPH] large chain
1706


L898
Glutamate synthase [NADPH] large chain
1707


L899
Glutamate synthase [NADPH] large chain
1708


L900
Glutamate synthase [NADPH] large chain
1709


L901
Glutamate synthase [NADPH] large chain
1710


L902
Glutamate synthase [NADPH] large chain
1711


L903
Glutamine synthetase
1712


L904
Glutamine synthetase
1713


L905
Glutamyl-tRNA synthetase
1714


L906
Glutamyl-tRNA synthetase
1715


L907
Glutamyl-tRNA synthetase
1716


L908
Glutamyl-tRNA synthetase
1717


L909
Glutamyl-tRNA synthetase
1718


L910
Glutamyl-tRNA synthetase
1719


L911
Glutamyl-tRNA synthetase
1720


L912
Glutamyl-tRNA synthetase
1721


L913
Glutaredoxin 2
1722


L914
Glutathione S-transferase
1723


L915
Glutathione S-transferase
1724


L916
Glutathione S-transferase
1725


L917
Glutathione S-transferase 1-6
1726


L918
Glutathione S-transferase A1
1727


L919
Glutathione S-transferase I
NKP


L920
Glutathione S-transferase I
1728


L921
Glutathione synthetase
1729


L922
Glutathione transferase GST1-4
1730


L923
Glutathione transferase GST1-4
1731


L924
Glutathione transferase sigma class
1732


L925
Glvcerol-3-phosphate dehydrogenase [NAD(P)+]
1733


L926
Glycine cleavage system transcriptional repressor, putative
1734


L927
Glycolipid-anchored surface protein 2
1735


L928
Glycolipid-anchored surface protein 2
1736


L929
Glycyl-tRNA synthetase
KFA


L930
Glycyl-tRNA synthetase
1737


L931
Glycyl-tRNA synthetase
1738


L932
Glycyl-tRNA synthetase
1739


L933
Glycyl-tRNA synthetase
1740


L934
Glycyl-tRNA synthetase
1741


L935
Glycyl-tRNA synthetase
1742


L936
Glycyl-tRNA synthetase
1743


L937
Glycyl-tRNA synthetase
1744


L938
Glycyl-tRNA synthetase
1745


L939
Growth hormone receptor
1746


L940
Growth hormone receptor
1747


L941
Harmonin
1748


L942
HasR protein
1749


L943
HasR protein
1750


L944
Hemin transport protein HemS
1751


L945
Hemin transport protein HemS
1752


L946
Hemin transport protein HemS
1753


L947
Hemoglobin
1754


L948
Hemolytic lectin CEL-iii
1755


L949
Hepatocyte nuclear factor 6
1756


L950
Histidyl-tRNA synthetase
1757


L951
HNH homing endonuclease
1758


L952
HNH homing endonuclease
1759


L953
HNH homing endonuclease
1760


L954
Homoserine dehydrogenase
1761


L955
Homoserine kinase
1762


L956
Homoserine kinase
1763


L957
Homoserine kinase
1764


L958
Homoserine kinase
1765


L959
HTH-type transcriptional regulator MqsA (Ygit/B3021)
1766


L960
HTH-type transcriptional repressor
1767


L961
HTH-type transcriptional repressor YvoA
1768


L962
Human IgG1 middle hinge linker
1769


L963
Human IgG1 upper hinge linker
1770


L964
Human IgG3 middle hinge linker
1771


L965
Human IgG3m15 middle hinge linker
1772


L966
Human IgG4 lower hinge linker
1773


L967
Human IgG4 middle hinge linker
1774


L968
Human IgG4 upper hinge linker
1775


L969
Hybrid cluster protein
1776


L970
Hybrid cluster protein
1777


L971
Hybrid cluster protein
1778


L972
Hybrid cluster protein
1779


L973
Hybrid cluster protein
1780


L974
Hypothetical conserved protein, GK1056
1781


L975
Hypothetical membrane spanning protein
1782


L976
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1783


L977
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1784


L978
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1785


L979
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1786


L980
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1787


L981
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1788


L982
Hypothetical methylmalonyl-CoA decarboxylase alpha subunit
1789


L983
Hypothetical protein
AEP


L984
Hypothetical protein
1790


L985
Hypothetical protein APE0525
PTL


L986
Hypothetical protein APE0525
1791


L987
Hypothetical protein LOC449832
1792


L988
Hypothetical protein LOC449832
1793


L989
Hypothetical protein PA4388
1794


L990
Hypothetical protein PA5201
ASE


L991
Hypothetical protein PA5201
QDP


L992
Hypothetical protein PA5201
VKL


L993
Hypothetical protein PA5201
1795


L994
Hypothetical protein PA5201
1796


L995
Hypothetical protein PA5201
1797


L996
Hypothetical protein PA5201
1798


L997
Hypothetical protein PA5201
1799


L998
Hypothetical protein PA5201
1800


L999
Hypothetical protein PA5201
1801


L1000
Hypothetical protein PA5201
1802


L1001
Hypothetical protein PA5201
1803


L1002
Hypothetical protein PA5201
1804


L1003
Hypothetical protein PA5201
1805


L1004
Hypothetical protein PA5201
1806


L1005
Hypothetical protein PA5201
1807


L1006
Hypothetical protein PA5201
1808


L1007
Hypothetical protein PA5201
1809


L1008
Hypothetical protein PA5201
1810


L1009
Hypothetical protein PA5201
1811


L1010
Hypothetical protein PA5201
1812


L1011
Hypothetical protein PA5201
1813


L1012
Hypothetical protein PA5201
1814


L1013
Hypothetical protein PH0495
ASN


L1014
Hypothetical protein PH0495
1815


L1015
Hypothetical protein PH0495
1816


L1016
Hypothetical protein PH0495
1817


L1017
Hypothetical protein PH0495
1818


L1018
Hypothetical protein PH0510
1819


L1019
Hypothetical protein PH0510
1820


L1020
Hypothetical protein PH1313
1821


L1021
Hypothetical protein PH1313
1822


L1022
Hypothetical protein SLR0953
1823


L1023
Hypothetical protein SLR0953
1824


L1024
Hypothetical protein SLR0953
1825


L1025
Hypothetical protein SLR0953
1826


L1026
Hypothetical protein SLR0953
1827


L1027
Hypothetical protein YIGZ
1828


L1028
Hypothetical protein YIGZ
1829


L1029
Hypothetical protein YJIA
1830


L1030
Hypothetical protein YJIA
1831


L1031
Hypothetical protein YJIA
1832


L1032
Hypothetical protein YJIA
1833


L1033
Hypothetical protein YJIA
1834


L1034
Hypothetical tRNA/rRNA methyltransferase YJFH
1835


L1035
Hypothetical tRNA/rRNA methyltransferase YJFH
1836


L1036
IclR transcriptional regulator
1837


L1037
IclR transcriptional regulator
1838


L1038
IclR transcriptional regulator
1839


L1039
IclR transcriptional regulator
1840


L1040
Integrase
1841


L1041
Interferon, alpha-inducible protein (clone IFI-15k)
1842


L1042
Interleukin-1 receptor, type I
AIF


L1043
Interleukin-1 receptor, type I
1843


L1044
Interleukin-1 receptor, type I
1844


L1045
Interleukin-1 receptor, type I
1845


L1046
Interleukin-12 subunit p40
FFI


L1047
Interleukin-12 subunit p40
1846


L1048
Interleukin-12 subunit p40
1847


L1049
Interleukin-12 subunit p40
1848


L1050
Interleukin-12 subunit p40
1849


L1051
Interleukin-12 subunit p40
1850


L1052
Interleukin-12 subunit p40
1851


L1053
Interleukin-12 subunit p40
1852


L1054
Interletiktn-2 receptor alpha chain
1853


L1055
Interleukin-2 receptor alpha chain
1854


L1056
Internalin B
VTQ


L1057
Internalin B
1855


L1058
Internalin B
1856


L1059
Internalin B
1857


L1060
Internalin B
1858


L1061
Internalin B
1859


L1062
Internalin B
1860


L1063
Internalin B
1861


L1064
Internalin B
1862


L1065
Internalin B
1863


L1066
Internalin B
1864


L1067
Internalin B
1865


L1068
Internalin B
1866


L1069
Intimin
SLV


L1070
Intimin
1867


L1071
Intimin
1868


L1072
Intimin
1869


L1073
Intron-encoded DNA endonuclease I-anil
1870


L1074
Intron-encoded DNA endonuclease I-anil
1871


L1075
Invasin
KST


L1076
Invasin
1872


L1077
Invasin
1873


L1078
Invasin
1874


L1079
Invasin
1875


L1080
Invasin
1876


L1081
Invasin
1877


L1082
Invasin
1878


L1083
Invasin
1879


L1084
Invasin
1880


L1085
Invasin
1881


L1086
Invasin
1882


L1087
Invasin
1883


L1088
Iron hydrogenase 1
GAE


L1089
Iron hydrogenase 1
1884


L1090
Iron hydrogenase 1
1885


L1091
Iron hydrogenase 1
1886


L1092
Iron hydrogenase 1
1887


L1093
Iron hydrogenase 1
1888


L1094
Iron hydrogenase 1
1889


L1095
Iron hydrogenase 1
1890


L1096
Iron hydrogenase 1
1891


L1097
Iron hydrogenase 1
1892


L1098
Iron hydrogenase 1
1893


L1099
Iron hydrogenase 1
1894


L1100
Iron hydrogenase 1
1895


L1101
Iron hydrogenase 1
1896


L1102
Iron transport protein
1897


L1103
Isoflavanone 4′-O-methyltransferase
1898


L1104
Isoflavanone 4′-O-methyltransferase
1899


L1105
Junctional adhesion molecule 1
1900


L1106
Junctional adhesion molecule 1
1901


L1107
Junctional adhesion molecule 1
1902


L1108
Kanamycin nucleotidyltransferase
1903


L1109
Kanamycin nucleotidyltransferase
1904


L1110
Kanamycin nucleotidyltransferase
1905


L1111
Kanamycin nucleotidyltransferase
1906


L1112
Kelch-like protein 11
1907


L1113
Kexin
ISE


L1114
Kexin
1908


L1115
Kexin
1909


L1116
Kexin
1910


L1117
Kexin
1911


L1118
Kexin
1912


L1119
Kexin
1913


L1120
Kexin
1914


L1121
Ku70
1915


L1122
Ku70
1916


L1123
Ku70
1917


L1124
Ku70
1918


L1125
Ku80
1919


L1126
Laccase-1
1920


L1127
Laccase-1
1921


L1128
Laccase-1
1922


L1129
Laccase-1
1923


L1130
Laminin
DKC


L1131
L-aspartate dehydrogenase
SAS


L1132
L-aspartate dehydrogenase
1924


L1133
L-aspartate dehydrogenase
1925


L1134
Leucine dehydrogenase
1926


L1135
Leucine dehydrogenase
1927


L1136
Light chain of HyHel10 antibody fragment (fab)
1928


L1137
Lin2111 protein
1929


L1138
Lin2111 protein
1930


L1139
Lipopolysaccharide-responsive and beige-like anchor protein
1931


L1140
Lipopolysaccharide-responsive and beige-like anchor protein
1932


L1141
Lipovitellin (LV-1N, LV-1C)
1933


L1142
Lipovitellin (LV-1N, LV-1C)
1934


L1143
Lipovitellin (LV-1N, LV-1C)
1935


L1144
Lipovitellin (LV-1N, LV-1C)
1936


L1145
Lipovitellin (LV-1N, LV-1C)
1937


L1146
Lipoxygenase-1
1938


L1147
Lipoxygenase-1
1939


L1148
Low affinity immunoglobulin gamma Fc region receptor II-A
1940


L1149
Luciferase
1941


L1150
LysR-type regulatory protein
1942


L1151
Macrolide-specific efflux protein MacA
ATE


L1152
Macrolide-specific efflux protein MacA
1943


L1153
Macrolide-specific efflux protein MacA
1944


L1154
Magnesium transporter, putative
1945


L1155
Main hemagglutinin component
1946


L1156
Major centromere autoantigen B
1947


L1157
Major surface antigen p30
1948


L1158
Major surface antigen p30
1949


L1159
Major vault protein
1950


L1160
Major vault protein
1951


L1161
Maltose phosphorylase
1952


L1162
Maltose phosphorylase
1953


L1163
Maltose phosphorylase
1954


L1164
Maltose phosphorylase
1955


L1165
Maltose phosphorylase
1956


L1166
Manganese-dependent inorganic pyrophosphatase
1957


L1167
Manganese-dependent inorganic pyrophosphatase
1958


L1168
Mannan-binding lectin
1959


L1169
Mannan-binding lectin
1960


L1170
Mannan-binding lectin
1961


L1171
Mannitol dehydrogenase
HNA


L1172
Mannitol dehydrogenase
1962


L1173
Membrane cofactor protein
RET


L1174
Membrane cofactor protein
1963


L1175
Membrane-associated prostaglandin E synthase-2
1964


L1176
Membrane-associated prostaglandin E synthase-2
1965


L1177
Membrane-associated prostaglandin E synthase-2
1966


L1178
Membrane-associated prostaglandin E synthase-2
1967


L1179
Membrane-associated prostaglandin E synthase-2
1968


L1180
Membrane-bound lytic murein transglycosylase A
1969


L1181
Methionyl-tRNA synthetase
1970


L1182
Methyl-accepting chemotaxis protein
VRP


L1183
Methyl-accepting chemotaxis protein
1971


L1184
Methyl-accepting chemotaxis protein
1972


L1185
Methyl-accepting chemotaxis protein
1973


L1186
Methyl-coenzyme M reductase
1974


L1187
Methyl-coenzyme M reductase
1975


L1188
Methyl-coenzyme M reductase
1976


L1189
Methyl-coenzyme M reductase
1977


L1190
Methylene tetrahydromethanopterin dehydrogenase
1978


L1191
Methylene tetrahydromethanopterin dehydrogenase
1979


L1192
Mg2+ transporter MgtE
1980


L1193
Mg2+ transporter MgtE
1981


L1194
Mg2+ transporter MgtE
1982


L1195
Mitochondrial aconitase
1983


L1196
Mitochondrial aconitase
1984


L1197
Modification methylase TaqI
EGK


L1198
Modification methylase TaqI
PAT


L1199
Modification methylase TaqI
1985


L1200
Modification methylase TaqI
1986


L1201
Modification methylase TaqI
1987


L1202
Modification methylase TaqI
1988


L1203
Modification methylase TaqI
1989


L1204
Modification methylase TaqI
1990


L1205
Modification methylase TaqI
1991


L1206
Modification methylase TaqI
1992


L1207
Multidrag-efflux transporter 1 regulator
1993


L1208
Muramoyl-pentapeptide carboxypeptidase
1994


L1209
MutL
1995


L1210
MutL
1996


L1211
MutL
1997


L1212
MutL
1998


L1213
MutL
1999


L1214
MutL
2000


L1215
MutL
2001


L1216
MutL
2002


L1217
MutL
2003


L1218
MutM (Fpg) protein
2004


L1219
MutM (Fpg) protein
2005


L1220
MutM (Fpg) protein
2006


L1221
MutM (Fpg) protein
2007


L1222
Myotubularin-related protein 2
THW


L1223
Myotubularin-related protein 2
2008


L1224
Myotubularin-related protein 2
2009


L1225
Myotubularin-related protein 2
2010


L1226
Myotubularin-related protein 2
2011


L1227
Myotubularin-related protein 2
2012


L1228
N utilization substance protein A
EIP


L1229
N utilization substance protein A
2013


L1230
N utilization substance protein A
2014


L1231
N utilization substance protein A
2015


L1232
N-acetylglucosamine kinase
CAY


L1233
N-acetylglucosamine kinase
ISP


L1234
N-acetylglucosamine kinase
2016


L1235
N-acyl-D-glutamate deacylase
2017


L1236
N-acyl-D-glutamate deacylase
2018


L1237
N-acyl-D-glutamate deacylase
2019


L1238
N-acyl-D-glutamate deacylase
2020


L1239
N-acyl-D-glutamate deacylase
2021


L1240
N-acyl-D-glutamate deacylase
2022


L1241
N-acyl-D-glutamate deacylase
2023


L1242
NAD-dependent malic enzyme
2024


L1243
NAD-dependent malic enzyme
2025


L1244
NADH peroxidase
ADT


L1245
NADH peroxidase
AVG


L1246
NADH peroxidase
TLI


L1247
NADH peroxidase
2026


L1248
NADH peroxidase
2027


L1249
NADH peroxidase
2028


L1250
NADH peroxidase
2029


L1251
NADH peroxidase
2030


L1252
NADH peroxidase
2031


L1253
NADH pyrophosphatase
2032


L1254
Naphthalene 1,2-dioxygenase alpha subunit
2033


L1255
Naphthalene 1,2-dioxygenase alpha subunit
2034


L1256
NEDD8-activating enzyme E1 catalytic subunit
2035


L1257
NEDD8-activating enzyme E1 regulatory subunit
2036


L1258
NEDD8-activating enzyme E1 regulatory subunit
2037


L1259
NEDD8-activating enzyme E1 regulatory subunit
2038


L1260
Nei endonuclease VIII-Like 1
2039


L1261
Nei endonuclease VIII-Like 1
2040


L1262
Nei endonuclease VIII-Like 1
2041


L1263
Nei endonuclease VIII-Like 1
2042


L1264
Neural cell adhesion molecule 2
2043


L1265
Neural cell adhesion molecule 2
2044


L1266
Neural cell adhesion molecule 2
2045


L1267
Neural cell adhesion molecule 2
2046


L1268
Neural cell adhesion molecule 2
2047


L1269
Neuroplastin
2048


L1270
Neuroplastin
2049


L1271
Neuroplastin
2050


L1272
Neutrophil cytosol factor 1
2051


L1273
Nickel responsive regulator
2052


L1274
NifU-like protein 2, chloroplast
2053


L1275
Nitric oxide reductase
ILM


L1276
Nitric oxide reductase
2054


L1277
Nitric oxide reductase
2055


L1278
Nitric oxide reductase
2056


L1279
Nitric oxide reductase
2057


L1280
Nitric oxide reductase
2058


L1281
NK receptor
2059


L1282
Nuclear factor of activated t-cells, cytoplasmic2
2060


L1283
Nucleolin RED12
2061


L1284
O-GlcNAcase NagJ
2062


L1285
Orange carotenoid protein
EGV


L1286
Orange carotenoid protein
2063


L1287
Orange carotenoid protein
2064


L1288
Orn/Lys/Arg decarboxylase family protein
LEL


L1289
Orn/Lys/Arg decarboxylase family protein
2065


L1290
Orn/Lys/Arg decarboxylase family protein
2066


L1291
Orn/Lys/Arg decarboxylase family protein
2067


L1292
Orn/Lys/Arg decarboxylase family protein
2068


L1293
Orn/Lys/Arg decarboxylase family protein
2069


L1294
Orn/Lys/Arg decarboxylase family protein
2070


L1295
Orn/Lys/Arg decarboxylase family protein
2071


L1296
Osteoclast-stimulating factor 1
2072


L1297
Oxygen-independent coproporphyrinogen III oxidase
2073


L1298
Oxygen-independent coproporphyrinogen III oxidase
2074


L1299
Oxygen-independent coproporphyrinogen III oxidase
2075


L1300
Oxygen-independent coproporphyrinogen III oxidase
2076


L1301
Oxygen-independent coproporphyrinogen III oxidase
2077


L1302
Oxygen-independent coproporphyrinogen III oxidase
2078


L1303
Oxygen-independent coproporphyrinogen III oxidase
2079


L1304
Oxygen-independent coproporphyrinogen III oxidase
2080


L1305
Oxygen-independent coproporphyrinogen III oxidase
2081


L1306
Oxygen-independent coproporphyrinogen III oxidase
2082


L1307
Paraneoplastic encephalomyelitis antigen HuD
2083


L1308
Paraneoplastic encephalomyelitis antigen HuD
2084


L1309
Penicillin binding protein 4
2085


L1310
Penicillin binding protein 4
2086


L1311
Penicillin binding protein 4
2087


L1312
Penicillin binding protein 4
2088


L1313
Penicillin binding protein 4
2089


L1314
Penicillin binding protein 4
2090


L1315
Penicillin binding protein 4
2091


L1316
Peptide-N(4)-(N-acetyl-beta-D-glucosaminyl)asparagine amidase F
DGV


L1317
Peptide-N(4)-(N-acetyl-beta-D-glucosaminyl)asparagine amidase F
2092


L1318
Peptide-N(4)-(N-acetyl-beta-D-glucosaminyl)asparagine amidase F
2093


L1319
Peptide-N(4)-(N-acetyl-beta-D-glucosaminyl)asparagine amidase F
2094


L1320
Peroxisomal primary amine oxidase
2095


L1321
Peroxisomal primary amine oxidase
2096


L1322
Peroxisome biogenesis factor 1
2097


L1323
Pesticidial crystal protein Cry2Aa
2098


L1324
Pesticidial crystal protein Cry2Aa
2099


L1325
Pesticidial crystal protein Cry2Aa
2100


L1326
Phase 1 flagellin
DLT


L1327
Phase 1 flagellin
2101


L1328
Phase 1 flagellin
2102


L1329
Phase 1 flagellin
2103


L1330
Phase 1 flagellin
2104


L1331
Phase 1 flagellin
2105


L1332
Phase 1 flagellin
2106


L1333
Phase 1 flagellin
2107


L1334
Phase 1 flagellin
2108


L1335
Phase 1 flagellin
2109


L1336
Phase 1 flagellin
2110


L1337
Phase 1 flagellin
2111


L1338
Phase 1 flagellin
2112


L1339
Phenylalanyl-tRNA synthetase beta chain
LGL


L1340
Phenylalanyl-tRNA synthetase beta chain
2113


L1341
Phenylalanyl-tRNA synthetase beta chain
2114


L1342
Phenylalanyl-tRNA synthetase beta chain
2115


L1343
Phenylalanyl-tRNA synthetase beta chain
2116


L1344
Phenylalanyl-tRNA synthetase beta chain
2117


L1345
Phenylalanyl-tRNA synthetase beta chain
2118


L1346
Phenylalanyl-tRNA synthetase beta chain
2119


L1347
Phenylalanyl-tRNA synthetase beta chain
2120


L1348
Phenylalanyl-tRNA synthetase beta chain
2121


L1349
Phenylalanyl-tRNA synthetase beta chain
2122


L1350
Phenylalanyl-tRNA synthetase beta chain
2123


L1351
Phenylalanyl-tRNA synthetase beta chain
2124


L1352
Phenylalanyl-tRNA synthetase beta chain
2125


L1353
Phosphatase
2126


L1354
Phosphatase
2127


L1355
Phosphatase
2128


L1356
Phosphatidylinositol transfer protein Sec14p
YGT


L1357
Phosphatidylinositol transfer protein Sec14p
2129


L1358
Phosphatidylinositol transfer protein Sec14p
2130


L1359
Phosphatidylserine synthase
2131


L1360
Phosphatidylserine synthase
2132


L1361
Phosphatidylserine synthase
2133


L1362
Phosphoglycolate phosphatase
2134


L1363
Phosphoglycolate phosphatase
2135


L1364
Phosphoglycolate phosphatase
2136


L1365
Phosphoglycolate phosphatase
2137


L1366
Phospholipase D
2138


L1367
Phospholipase D
2139


L1368
Phospholipase D
2140


L1369
Phosphoribosylamine-glycine ligase
2141


L1370
Phosphoribosylamine-glycine ligase
2142


L1371
Phosphotransferase system, enzyme I
2143


L1372
Photosystem II d1 protease
2144


L1373
Photosystem II d1 protease
2145


L1374
Photosystem II d1 protease
2146


L1375
Photosystem II d1 protease
2147


L1376
Photosystem II d1 protease
2148


L1377
Phthalate dioxygenase reductase
2149


L1378
P-hydroxybenzoate hydroxylase
DGL


L1379
P-hydroxybenzoate hydroxylase
IDL


L1380
P-hydroxybenzoate hydroxylase
RLK


L1381
P-hydroxybenzoate hydroxylase
2150


L1382
P-hydroxybenzoate hydroxylase
2151


L1383
P-hydroxybenzoate hydroxylase
2152


L1384
P-hydroxybenzoate hydroxylase
2153


L1385
P-hydroxybenzoate hydroxylase
2154


L1386
P-hydroxybenzoate hydroxylase
2155


L1387
P-hydroxybenzoate hydroxylase
2156


L1388
P-hydroxybenzoate hydroxylase
2157


L1389
P-hydroxybenzoate hydroxylase
2158


L1390
P-hydroxybenzoate hydroxylase
2159


L1391
P-hydroxybenzoate hydroxylase
2160


L1392
P-hydroxybenzoate hydroxylase
2161


L1393
P-hydroxybenzoate hydroxylase
2162


L1394
P-hydroxybenzoate hydroxylase
2163


L1395
P-hydroxybenzoate hydroxylase
2164


L1396
P-hydroxybenzoate hydroxylase
2165


L1397
P-hydroxybenzoate hydroxylase
2166


L1398
Phytase
LNF


L1399
Phytase
QSN


L1400
Phytase
2167


L1401
Phytase
2168


L1402
Phytase
2169


L1403
Phytase
2170


L1404
Phytase
2171


L1405
Phytase
2172


L1406
Phytase
2173


L1407
Phytase
2174


L1408
Pirin
LKS


L1409
Pirin
SGE


L1410
Pirin
2175


L1411
Pirin
2176


L1412
Pirin
2177


L1413
Pirin
2178


L1414
Pirin
2179


L1415
Pirin
2180


L1416
Poly(A) polymerase
2181


L1417
Poly(A) polymerase
2182


L1418
Poly(A) polymerase
2183


L1419
Poly(A) polymerase
2184


L1420
Poly(A) polymerase
2185


L1421
Poly(A) polymerase
2186


L1422
Poly(A) polymerase
2187


L1423
Poly(A) polymerase
2188


L1424
Poly(A) polymerase
2189


L1425
Poly(A) polymerase
2190


L1426
Poly(A) polymerase
2191


L1427
Poly(A) polymerase
2192


L1428
Poly(rC)-binding protein 2
2193


L1429
Polymerase x
2194


L1430
Polymerase x
2195


L1431
Polypeptide N-acetylgalactosaminyltransferase 2
2196


L1432
Polypeptide N-acetylgalactosaminyltransferase 2
2197


L1433
Polyphosphate kinase
2198


L1434
Polyphosphate kinase
2199


L1435
Polyphosphate kinase
2200


L1436
Polypyrimidine tract-binding protein
2201


L1437
Porcine pancreatic spasmolytic polypeptide
2202


L1438
Possible 3-mercaptopyruvate sulfurtransferase
LFR


L1439
Possible 3-mercaptopyruvate sulfurtransferase
YGM


L1440
Possible 3-mercaptopyruvate sulfurtransferase
2203


L1441
Possible 3-mercaptopyruvate sulfurtransferase
2204


L1442
Possible 3-mercaptopyruvate sulfurtransferase
2205


L1443
Postsynaptic density protein 95
2206


L1444
Postsynaptic density protein 95
2207


L1445
Predicted sugar phosphatases of the HAD superfamily
IAI


L1446
Predicted sugar phosphatases of the HAD superfamily
2208


L1447
Predicted sugar phosphatases of the HAD superfamily
2209


L1448
Predicted sugar phosphatases of the HAD superfamily
2210


L1449
Predicted sugar phosphatases of the HAD superfamily
2211


L1450
Predicted sugar phosphatases of the HAD superfamily
2212


L1451
Predicted sugar phosphatases of the HAD superfamily
2213


L1452
Predicted sugar phosphatases of the HAD superfamily
2214


L1453
Predicted sugar phosphatases of the HAD superfamily
2215


L1454
Preprotein translocase SecA
ITF


L1455
Preprotein translocase SecA
LID


L1456
Preprotein translocase SecA
2216


L1457
Preprotein translocase SecA
2217


L1458
Preprotein translocase SecA
2218


L1459
Preprotein translocase SecA
2219


L1460
Preprotein translocase SecA
2220


L1461
Preprotein translocase SecA
2221


L1462
Preprotein translocase SecA
2222


L1463
Preprotein translocase SecA
2223


L1464
Preprotein translocase SecA
2224


L1465
Preprotein translocase SecA
2225


L1466
Preprotein translocase SecA
2226


L1467
Preprotein translocase SecA
2227


L1468
Preprotein translocase SecA
2228


L1469
Preprotein translocase SecA
2229


L1470
Preprotein translocase SecA
2230


L1471
Preprotein translocase SecA
2231


L1472
Preprotein translocase SecA
2232


L1473
PrfA
ING


L1474
Probable 16s rRNA-processing protein RimM
2233


L1475
Probable biphenyl-2,3-diol 1,2-dioxygenase BphC
2234


L1476
Probable chorismate mutase
LLA


L1477
Probable chorismate mutase
2235


L1478
Probable chorismate mutase
2236


L1479
Probable ferredoxin-dependent nitrite reductase NirA
VPL


L1480
Probable ferredoxin-dependent nitrite reductase NirA
WGI


L1481
Probable ferredoxin-dependent nitrite reductase NirA
2237


L1482
Probable ferredoxin-dependent nitrite reductase NirA
2238


L1483
Probable ferredoxin-dependent nitrite reductase NirA
2239


L1484
Probable ferredoxin-dependent nitrite reductase NirA
2240


L1485
Probable ferredoxin-dependent nitrite reductase NirA
2241


L1486
Probable ferredoxin-dependent nitrite reductase NirA
2242


L1487
Probable ferredoxin-dependent nitrite reductase NirA
2243


L1488
Probable ferredoxin-dependent nitrite reductase NirA
2244


L1489
Probable ferredoxin-dependent nitrite reductase NirA
2245


L1490
Probable ferredoxin-dependent nitrite reductase NirA
2246


L1491
Probable ferredoxin-dependent nitrite reductase NirA
2247


L1492
Probable ferredoxin-dependent nitrite reductase NirA
2248


L1493
Probable galactokinase
2249


L1494
Probable galactokinase
2250


L1495
Probable galactokinase
2251


L1496
Probable galactokinase
2252


L1497
Probable galactokinase
2253


L1498
Probable galactokinase
2254


L1499
Probable galactokinase
2255


L1500
Probable galactokinase
2256


L1501
Probable galactokinase
2257


L1502
Probable galactokinase
2258


L1503
Probable galactokinase
2259


L1504
Probable galactokinase
2260


L1505
Probable glutathione S-transferase
2261


L1506
Probable GST-related protein
2262


L1507
Probable HPr(Ser) kinase/phosphatase
2263


L1508
Probable thiosulfate sulfur transferase
2264


L1509
Probable thiosulfate sulfur transferase
2265


L1510
Probable thiosulfate sulfur transferase
2266


L1511
Probable thiosulfate sulfur transferase
2267


L1512
Probable thiosulfate sulfur transferase
2268


L1513
Probable thiosulfate sulfur transferase
2269


L1514
Probable thiosulfate sulfur transferase
2270


L1515
Probable thiosulfate sulfur transferase
2271


L1516
Probable tRNA pseudouridine synthase D
2272


L1517
Probable tRNA pseudouridine synthase D
2273


L1518
Probable tRNA pseudouridine synthase D
2274


L1519
Probable tRNA pseudouridine synthase D
2275


L1520
Probable tRNA pseudouridine synthase D
2276


L1521
Probable tRNA pseudouridine synthase D
2277


L1522
Programed cell death protein 8
SKE


L1523
Programed cell death protein 8
TLQ


L1524
Programed cell death protein 8
2278


L1525
Programed cell death protein 8
2279


L1526
Programed cell death protein 8
2280


L1527
Programed cell death protein 8
2281


L1528
Programed cell death protein 8
2282


L1529
Programed cell death protein 8
2283


L1530
Programed cell death protein 8
2284


L1531
Programed cell death protein 8
2285


L1532
Programed cell death protein 8
2286


L1533
Programed cell death protein 8
2287


L1534
Programed cell death protein 8
2288


L1535
Programed cell death protein 8
2289


L1536
Programed cell death protein 8
2290


L1537
Programed cell death protein 8
2291


L1538
Programed cell death protein 8
2292


L1539
Programed cell death protein 8
2293


L1540
Programed cell death protein 8
2294


L1541
Programed cell death protein 8
2295


L1542
Proline oxidase
2296


L1543
Prolyl-tRNA synthetase
2297


L1544
Prostaglandin G/H synthase 1
PEI


L1545
Prostaglandin G/H synthase 1
2298


L1546
Protease
2299


L1547
Protease
2300


L1548
Protease
2301


L1549
Protease DegS
2302


L1550
Protease DegS
2303


L1551
Protease DegS
2304


L1552
Protease DegS
2305


L1553
Protease III
NAR


L1554
Protease III
RNP


L1555
Protease III
2306


L1556
Protease III
2307


L1557
Protease III
2308


L1558
Protease III
2309


L1559
Protease III
2310


L1560
Protease III
2311


L1561
Protease III
2312


L1562
Protease III
2313


L1563
Protease III
2314


L1564
Protease III
2315


L1565
Protease III
2316


L1566
Protease III
2317


L1567
Protease III
2318


L1568
Protease III
2319


L1569
Protease III
2320


L1570
Protease III
2321


L1571
Protease III
2322


L1572
Protease III
2323


L1573
Protease III
2324


L1574
Protease III
2325


L1575
Protection of telomeres 1
2326


L1576
Protection of telomeres 1
2327


L1577
Protein (CD58)
2328


L1578
Protein (CRP1)
2329


L1579
Protein (DNA polymerase)
2330


L1580
Protein (DNA polymerase)
2331


L1581
Protein (DNA polymerase)
2332


L1582
Protein (electron transfer flavoprotein)
2333


L1583
Protein (electron transfer flavoprotein)
2334


L1584
Protein (Ffh)
2335


L1585
Protein (Ffh)
2336


L1586
Protein (Ffh)
2337


L1587
Protein (Ffh)
2338


L1588
Protein (Ffh)
2339


L1589
Protein (FokI restriction endonuclease)
2340


L1590
Protein (FokI restriction endonuclease)
2341


L1591
Protein (FokI restriction endonuclease)
2342


L1592
Protein (FokI restriction endonuclease)
2343


L1593
Protein (FokI restriction endonuclease)
2344


L1594
Protein (FokI restriction endonuclease)
2345


L1595
Protein (FokI restriction endonuclease)
2346


L1596
Protein (FokI restriction endonuclease)
2347


L1597
Protein (FokI restriction endonuclease)
2348


L1598
Protein (neural cell adhesion molecule)
2349


L1599
Protein (neural cell adhesion molecule)
2350


L1600
Protein (neural cell adhesion molecule)
2351


L1601
Protein (nine-haem cytochrome c)
FTH


L1602
Protein (nine-haem cytochrome c)
2352


L1603
Protein (nine-haem cytochrome c)
2353


L1604
Protein (nine-haem cytochrome c)
2354


L1605
Protein (nine-haem cytochrome c)
2355


L1606
Protein (nine-haem cytochrome c)
2356


L1607
Protein (nine-haem cytochrome c)
2357


L1608
Protein (nine-haem cytochrome c)
2358


L1609
Protein (nine-haem cytochrome c)
2359


L1610
Protein (protease/helicase NS3)
2360


L1611
Protein (protease/helicase NS3)
2361


L1612
Protein (protease/helicase NS3)
2362


L1613
Protein (protease/helicase NS3)
2363


L1614
Protein disulfide oxidoreductase
2364


L1615
Protein disulfide oxidoreductase
2365


L1616
Protein disulfide-isomerase A4
2366


L1617
Protein kinase PKR
2367


L1618
Protein kinase PKR
2368


L1619
Protein TolB
VNK


L1620
Protein TolB
2369


L1621
Protein TolB
2370


L1622
Protein TolB
2371


L1623
Protein TolB
2372


L1624
Protein TolB
2373


L1625
Protein TolB
2374


L1626
Protein translation elongation factor 1A
2375


L1627
Protein transport protein Sec24
DRN


L1628
Protein transport protein Sec24
2376


L1629
Protein transport protein Sec24
2377


L1630
Protein transport protein Sec24
2378


L1631
Protein transport protein Sec24
2379


L1632
Protein transport protein Sec24
2380


L1633
Protein transport protein Sec24
2381


L1634
Protein transport protein Sec24
2382


L1635
Protein transport protein Sec24
2383


L1636
Pseudouridine synthase CBF5
AIQ


L1637
Pseudouridine synthase CBF5
2384


L1638
Pseudouridine synthase CBF5
2385


L1639
Putative acetylglutamate synthase
2386


L1640
Putative acetylglutamate synthase
2387


L1641
Putative acetylglutamate synthase
2388


L1642
Putative family 31 glucosidase Yicl
2389


L1643
Putative family 31 glucosidase Yicl
2390


L1644
Putative family 31 glucosidase Yicl
2391


L1645
Putative glutathione transferase
2392


L1646
Putative glutathione transferase
2393


L1647
Putative glutathione transferase
2394


L1648
Putative GNTR-family transcriptional regulator
2395


L1649
Putative GNTR-family transcriptional regulator
2396


L1650
Putative GNTR-family transcriptional regulator
2397


L1651
Putative HTH-type transcriptional regulator PH0061
2398


L1652
Putative HTH-type transcriptional regulator PH1519
2399


L1653
Putative HTH-type transcriptional regulator PH1519
2400


L1654
Putative metallopeptidase
2401


L1655
Putative N-acetylmannosamine kinase
2402


L1656
Putative N-acetylmannosamine kinase
2403


L1657
Putative N-acetylmannosamine kinase
2404


L1658
Putative NADP oxidoreductase BF3122
2405


L1659
Putative NADP oxidoreductase BF3122
2406


L1660
Putative NADP oxidoreductase BF3122
2407


L1661
Putative NADP oxidoreductase BF3122
2408


L1662
Putative oxidoreductase
2409


L1663
Putative secreted alpha-galactosidase
PLP


L1664
Putative secreted alpha-galactosidase
TNG


L1665
Putative secreted alpha-galactosidase
2410


L1666
Putative secreted alpha-galactosidase
2411


L1667
Putative secreted alpha-galactosidase
2412


L1668
Putative tagatose-6-phosphate ketose/aldose isomerase
DKA


L1669
Putative tagatose-6-phosphate ketose/aldose isomerase
2413


L1670
Putative tagatose-6-phosphate ketose/aldose isomerase
2414


L1671
Putative tagatose-6-phosphate ketose/aldose isomerase
2415


L1672
Putative transcriptional regulator GntR
2416


L1673
Putative transcriptional repressor (TetR/AcrR family)
KFR


L1674
Putative transcriptional repressor (TetR/AcrR family)
2417


L1675
Putative uncharacterized protein
2418


L1676
Putative uncharacterized protein
2419


L1677
Putative uncharacterized protein
2420


L1678
Putative uncharacterized protein
2421


L1679
Putative uncharacterized protein
2422


L1680
Putative uncharacterized protein
2423


L1681
Putative uncharacterized protein
2424


L1682
Putative uncharacterized protein
2425


L1683
Putative uncharacterized protein
2426


L1684
Pyruvate decarboxylase
CAA


L1685
Pyruvate decarboxylase
2427


L1686
Pyruvate decarboxylase
2428


L1687
Pyruvate decarboxylase
2429


L1688
Pyruvate decarboxylase
2430


L1689
Pyruvate decarboxylase
2431


L1690
Pyruvate dehydrogenase [lipoamide] kinase isozyme 2, mitochondrial
YVP


L1691
Pyruvate dehydrogenase [lipoamide] kinase isozyme 2, mitochondrial
2432


L1692
Pyruvate dehydrogenase [lipoamide] kinase isozyme 2, mitochondrial
2433


L1693
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
2434


L1694
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
2435


L1695
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
2436


L1696
Pyruvate phosphate dikinase
FNP


L1697
Pyruvate phosphate dikinase
SAL


L1698
Pyruvate phosphate dikinase
2437


L1699
Pyruvate phosphate dikinase
2438


L1700
Pyruvate phosphate dikinase
2439


L1701
Pyruvate phosphate dikinase
2440


L1702
Pyruvate phosphate dikinase
2441


L1703
Pyruvate phosphate dikinase
2442


L1704
Pyruvate phosphate dikinase
2443


L1705
Pyruvate phosphate dikinase
2444


L1706
Pyruvate phosphate dikinase
2445


L1707
Pyruvate phosphate dikinase
2446


L1708
Pyruvate-ferredoxin oxidoreductase
VRL


L1709
Pyruvate-ferredoxin oxidoreductase
2447


L1710
Pyruvate-ferredoxin oxidoreductase
2448


L1711
Pyruvate-ferredoxin oxidoreductase
2449


L1712
Pyruvate-ferredoxin oxidoreductase
2450


L1713
Pyruvate-ferredoxin oxidoreductase
2451


L1714
Pyruvate-ferredoxin oxidoreductase
2452


L1715
Pyruvate-ferredoxin oxidoreductase
2453


L1716
Pyruvate-ferredoxin oxidoreductase
2454


L1717
Pyruvate-ferredoxin oxidoreductase
2455


L1718
Pyruvate-ferredoxin oxidoreductase
2456


L1719
Pyruvate-ferredoxin oxidoreductase
2457


L1720
Pyruvate-ferredoxin oxidoreductase
2458


L1721
Pyruvate-ferredoxin oxidoreductase
2459


L1722
Pyruvate-ferredoxin oxidoreductase
2460


L1723
Pyruvate-ferredoxin oxidoreductase
2461


L1724
Pyruvate-ferredoxin oxidoreductase
2462


L1725
Pyruvate-ferredoxin oxidoreductase
2463


L1726
Pyruvate-ferredoxin oxidoreductase
2464


L1727
Pyruvate-ferredoxin oxidoreductase
2465


L1728
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2466


L1729
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2467


L1730
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2468


L1731
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2469


L1732
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2470


L1733
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2471


L1734
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2472


L1735
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2473


L1736
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2474


L1737
Quinohemoprotein amine dehydrogenase 60 kDa subunit
2475


L1738
Rag1
2476


L1739
Rag1
2477


L1740
Receptor-type tyrosine-protein phosphatase Mu
2478


L1741
Receptor-type tyrosine-protein phosphatase Mu
2479


L1742
RecG
2480


L1743
RecG
2481


L1744
RecG
2482


L1745
RecG
2483


L1746
RecG
2484


L1747
RecG
2485


L1748
RecG
2486


L1749
RecG
2487


L1750
RecG
2488


L1751
RecG
2489


L1752
RecG
2490


L1753
RecG
2491


L1754
Recombination endonuclease VII
2492


L1755
Recombining binding protein suppressor of hairless
2493


L1756
Restriction endonuclease
ERV


L1757
Restriction endonuclease
2494


L1758
Restriction endonuclease
2495


L1759
Restriction endonuclease
2496


L1760
Retinaldehyde-binding protein 1
QYP


L1761
Retinaldehyde-binding protein 1
2497


L1762
Retinaldehyde-binding protein 1
2498


L1763
Retinoblastoma pocket
2499


L1764
RfcS
ITD


L1765
RfcS
LTE


L1766
RfcS
2500


L1767
RfcS
2501


L1768
RfcS
2502


L1769
RfcS
2503


L1770
RfcS
2504


L1771
Rhamnogalacturonase B
2505


L1772
Rhamnogalacturonase B
2506


L1773
Rhamnogalacturonase B
2507


L1774
Rhamnogalacturonase B
2508


L1775
Rhamnogalacturonase B
2509


L1776
Rhodniin
2510


L1777
Rhodniin
2511


L1778
Riboflavin synthase
2512


L1779
Ribonuclease D
2513


L1780
Ribonuclease D
2514


L1781
Ribonuclease D
2515


L1782
Ribonuclease TTHA0252
2516


L1783
Ribonuclease TTHA0252
2517


L1784
Ribonuclease TTHA0252
2518


L1785
Ribonuclease THHA0252
2519


L1786
Ribonuclease TTHA0252
2520


L1787
Ribonuclease TTHA0252
2521


L1788
Ribonucleotide reductase r1 protein
2522


L1789
Ribonucleotide reductase r1 protein
2523


L1790
Ribonucleotide reductase r1 protein
2524


L1791
Ribonucleotide reductase r1 protein
2525


L1792
Ribonucleotide reductase r1 protein
2526


L1793
Ribonucleotide reductase r1 protein
2527


L1794
Ribosome maturation factor RimM
2528


L1795
Ribulose-1,5 bisphosphate carboxylase/oxygenase
RHA



large subunit N-methyltransferase


L1796
Ribulose-1,5 bisphosphate carboxylase/oxygenase
2529



large subunit N-methyltransferase


L1797
Rigid extended P-rich
2530


L1798
Rigid extended P-rich
2531


L1799
Rigid extended P-rich
2532


L1800
Rigid extended P-rich
2533


L1801
Rigid extended P-rich
2534


L1802
Rigid extended P-rich
2535


L1803
Rigid extended P-rich
2536


L1804
Rigid extended P-rich
2537


L1805
Rigid extended P-rich
2538


L1806
Rigid extended P-rich
2539


L1807
Rigid extended P-rich
2540


L1808
Rigid extended P-rich
2541


L1809
Rigid extended P-rich
2542


L1810
Rigid extended P-rich
2543


L1811
Rigid extended P-rich
2544


L1812
Rigid helical
2545


L1813
Rigid helical
2546


L1814
Rigid helical
2547


L1815
Rigid helical
2548


L1816
Rigid helical
2549


L1817
Rigid helical
2550


L1818
Rigid helical
2551


L1819
Rigid helical
2552


L1820
RNA binding domain of rho transcription termination factor
2553


L1821
RNA binding protein ZFa
2554


L1822
Rob transcription factor
2555


L1823
Rob transcription factor
2556


L1824
RP2 lipase
2557


L1825
Rubreiythrin
2558


L1826
S-adenosylmethionine synthetase
2559


L1827
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
QFD


L1828
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2560


L1829
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2561


L1830
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2562


L1831
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2563


L1832
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2564


L1833
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2565


L1834
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2566


L1835
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2567


L1836
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2568


L1837
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2569


L1838
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2570


L1839
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2571


L1840
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2572


L1841
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2573


L1842
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2574


L1843
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2575


L1844
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2576


L1845
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2577


L1846
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2578


L1847
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2579


L1848
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2580


L1849
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2581


L1850
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2582


L1851
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2583


L1852
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
2584


L1853
Scavenger mRNA-decapping enzyme DcpS
ETC


L1854
Scavenger mRNA-decapping enzyme DcpS
NIT


L1855
Scavenger mRNA-decapping enzyme DcpS
2585


L1856
Scavenger mRNA-decapping enzyme DcpS
2586


L1857
Sec18p (residues 22-210)
2587


L1858
Sec18p (residues 22-210)
2588


L1859
Sensor protein
2589


L1860
Sensor protein
2590


L1861
Septum site-determining protein MinC
2591


L1862
Serine acetyltransferase
2592


L1863
Serine protease/NTPase/helicase NS3
2593


L1864
Serine protease/NTPase/helicase NS3
2594


L1865
Serine protease/NTPase/helicase NS3
2595


L1866
Serine rich linker
2596


L1867
Serine rich linker
2597


L1868
Serine rich linker
2598


L1869
Serine rich linker
2599


L1870
Serine rich linker
2600


L1871
Serine rich linker
2601


L1872
Serine rich linker
2602


L1873
Seryl-tRNA synthetase
2603


L1874
Sialidase
2604


L1875
Sialidase B
SLT


L1876
Sialidase B
VRE


L1877
Sialidase B
2605


L1878
Sialidase B
2606


L1879
Sialidase B
2607


L1880
Sialidase B
2608


L1881
Sialidase B
2609


L1882
Sialidase B
2610


L1883
SIgnal peptIdase I
SRR


L1884
SIgnal peptIdase I
2611


L1885
SIgnal peptIdase I
2612


L1886
SIgnal peptIdase I
2613


L1887
SIgnal peptIdase I
2614


L1888
SIgnal peptIdase I
2615


L1889
SIgnal peptIdase I
2616


L1890
SIgnal peptIdase I
2617


L1891
SIgnal peptIdase I
2618


L1892
SIgnal peptIdase I
2619


L1893
SIgnal peptIdase I
2620


L1894
Signal recognition particle protein
2621


L1895
Signal transducer and activator of transcription1-alpha/beta
NDE


L1896
Signal transducer and activator of transcription1-alpha/beta
SSF


L1897
Signal transducer and activator of transcription1-alpha/beta
2622


L1898
Signal transducer and activator of transcription1-alpha/beta
2623


L1899
Signal transducer and activator of transcription1-alpha/beta
2624


L1900
Signal transducer and activator of transcription1-alpha/beta
2625


L1901
Signal transduction protein CBL
2626


L1902
Signal transduction protein CBL
2627


L1903
Similar to RAD54-like
AKP


L1904
Similar to RAD54-like
EYF


L1905
Similar to RAD54-like
RFE


L1906
Similar to RAD54-like
2628


L1907
Similar to RAD54-like
2629


L1908
Similar to RAD54-like
2630


L1909
Similar to RAD54-like
2631


L1910
Similar to RAD54-like
2632


L1911
Similar to RAD54-like
2633


L1912
Similar to RAD54-like
2634


L1913
Similar to RAD54-like
2635


L1914
Similar to RAD54-like
2636


L1915
Similar to RAD54-like
2637


L1916
SKD1 protein
LMQ


L1917
SKD1 protein
2638


L1918
SKD1 protein
2639


L1919
SKD1 protein
2640


L1920
SKD1 protein
2641


L1921
SKD1 protein
2642


L1922
Sll1358 protein
2643


L1923
Sll1358 protein
2644


L1924
Sll1358 protein
2645


L1925
Sll1358 protein
2646


L1926
Soluble IFN alpba/beta receptor
2647


L1927
Soluble IFN alpha/beta receptor
2648


L1928
Sporozoite-specific SAG protein
2649


L1929
Staphylococcal accessory regulator a homologue
2650


L1930
Staphylococcal nuclease domain-containing protein 1
2651


L1931
Staphylococcal nuclease domain-containing protein 1
2652


L1932
Staphylococcal nuclease domain-containing protein 1
2653


L1933
Staphylococcal nuclease domain-containing protein 1
2654


L1934
Staphylococcal nuclease domain-containing protein 1
2655


L1935
Staphylococcal nuclease domain-containing protein 1
2656


L1936
Stat protein
2657


L1937
Stat protein
2658


L1938
Stat protein
2659


L1939
Stat protein
2660


L1940
Stat protein
2661


L1941
Stat protein
2662


L1942
Stat protein
2663


L1943
Stat protein
2664


L1944
Stat protein
2665


L1945
Stat protein
2666


L1946
Stat protein
2667


L1947
Stat protein
2668


L1948
Stat protein
2669


L1949
Stat protein
2670


L1950
Stat protein
2671


L1951
Subtilisin-like protease
2672


L1952
Succinyl-CoA ligase [GDP-forming] alpha-chain, mitochondrial
2673


L1953
Succinyl-CoA ligase [GDP-forming] alpha-chain, mitochondrial
2674


L1954
Succinyl-CoA ligase [GDP-forming] alpha-chain, mitochondrial
2675


L1955
Succinyl-CoA ligase [GDP-forming] alpha-chain, mitochondrial
2676


L1956
Succinyl-CoA ligase [GDP-forming] alpha-chain, mitochondrial
2677


L1957
Succinyl-CoA ligase [GDP-forming] alpha-chain, mitochondrial
2678


L1958
Succinyl-CoA synthetase beta chain
ADG


L1959
Succinyl-CoA synthetase beta chain
RQP


L1960
Succinyl-CoA synthetase beta chain
2679


L1961
Succinyl-CoA synthetase beta chain
2680


L1962
Succinyl-CoA synthetase beta chain
2681


L1963
Succinyl-CoA synthetase beta chain
2682


L1964
Succinyl-CoA synthetase beta chain
2683


L1965
Succinyl-CoA synthetase beta chain
2684


L1966
Succinyl-CoA: 3-ketoacid-coenzyme A transferase
2685


L1967
Sulfurtransferase
2686


L1968
Superantigen SMEZ-2
2687


L1969
Superoxide dismutase 1 copper chaperone
2688


L1970
Surface layer protein
2689


L1971
Surface layer protein
2690


L1972
Surface layer protein
2691


L1973
Surface layer protein
2692


L1974
Surface layer protein
2693


L1975
Surface layer protein
2694


L1976
Surface layer protein
2695


L1977
Surface layer protein
2696


L1978
T lymphocyte activation antigen
2697


L1979
T lymphocyte activation antigen
2698


L1980
T-cell receptor alpha chain C region
2699


L1981
Terminal oxygenase component of carbazole
2700


L1982
Tetanus neurotoxin
2701


L1983
Tetracycline repressor protein class D
2702


L1984
The GTP-binding protein Obg
2703


L1985
The GTP-binding protein Obg
2704


L1986
The GTP-binding protein Obg
2705


L1987
The GTP-binding protein Obg
2706


L1988
Thioredoxin domain-containing protein 4
2707


L1989
Thioredoxin domain-containing protein 4
2708


L1990
Thiosulfate sulfurtransferase
IDP


L1991
Thiosulfate sulfurtransferase
2709


L1992
Thiosulfate sulfurtransferase
2710


L1993
Thiosulfate sulfurtransferase
2711


L1994
Thiosulfate sulfurtransferase
2712


L1995
Threonyl-tRNA synthetase
2713


L1996
Threonyl-tRNA synthetase
2714


L1997
Threonyl-tRNA synthetase
2715


L1998
Threonyl-tRNA synthetase
2716


L1999
Threonyl-tRNA synthetase
2717


L2000
Threonyl-tRNA synthetase
2718


L2001
Threonyl-tRNA synthetase
2719


L2002
Threonyl-tRNA synthetase
2720


L2003
Threonyl-tRNA synthetase
2721


L2004
Threonyl-tRNA synthetase 1
2722


L2005
Threonyl-tRNA synthetase 1
2723


L2006
Threonyl-tRNA synthetase 1
2724


L2007
Threonyl-tRNA synthetase 1
2725


L2008
Threonyl-tRNA synthetase 1
2726


L2009
Threonyl-tRNA synthetase 1
2727


L2010
Threonyl-tRNA synthetase 1
2728


L2011
Threonyl-tRNA synthetase 1
2729


L2012
Thrombospondin 1
2730


L2013
Tick-borne encephalitis virus glycoprotein
2731


L2014
Titin
2732


L2015
Titin
2733


L2016
TLR1789 protein
2734


L2017
TLR1789 protein
2735


L2018
Topoisomerase I
2736


L2019
Topoisomerase I
2737


L2020
Toxic shock syndrome toxin-1
2738


L2021
Toxic shock syndrome toxin-1
2739


L2022
Toxic shock syndrome toxin-1
2740


L2023
Toxic shock syndrome toxin-1
2741


L2024
T-plasminogen activator F1-G
VPV


L2025
T-plasminogen activator F1-G
2742


L2026
TpsB transporter FhaC
2743


L2027
TpsB transporter FhaC
2744


L2028
TpsB transporter FhaC
2745


L2029
Transcarbamylase
2746


L2030
Transcarbamylase
2747


L2031
Transcription antiterminator LicT
2748


L2032
Transcription elongation factor GreB
2749


L2033
Transcription initiation factor IIa gamma chain
2750


L2034
Transcription initiation factor IIb
2751


L2035
Transcription initiation factor IIb
2752


L2036
Transcriptional regulator (NtrC family)
2753


L2037
Transcriptional regulator AefR
2754


L2038
Transcriptional regulator AefR
2755


L2039
Transcriptional regulator AefR
2756


L2040
Transcriptional regulator AefR
2757


L2041
Transcriptional regulator AefR
2758


L2042
Transcriptional regulator, AsnC family
2759


L2043
Transcriptional regulator, AsnC family
2760


L2044
Transcriptional regulator, AsnC family
2761


L2045
Transcriptional regulator, biotin repressor family
2762


L2046
Transcriptional regulator, Crp/Fnr family
2763


L2047
Transcriptional regulator, GntR family
2764


L2048
Transcriptional regulator, HTH_3 family
2765


L2049
Transcriptional regulator, HTH_3 family
2766


L2050
Transcriptional regulator, HTH_3 family
2767


L2051
Transcriptional regulator, HTH_3 family
2768


L2052
Transcriptional regulator, HTH_3 family
2769


L2053
Transcriptional regulator, laci family
2770


L2054
Transcriptional regulatory protein ZraR
2771


L2055
Transcriptional regulatory protein ZraR
2772


L2056
Transcriptional regulatory protein ZraR
2773


L2057
Transcriptional regulatory protein ZraR
2774


L2058
Transcriptional regulatory protein ZraR
2775


L2059
Transcriptional regulatory protein ZraR
2776


L2060
Transcriptional regulatory protein ZraR
2777


L2061
Transferrin receptor protein
VSN


L2062
Transferrin receptor protein
2778


L2063
Transferrin receptor protein
2779


L2064
Transferrin receptor protein
2780


L2065
Transferrin receptor protein
2781


L2066
Translation initiation factor 5A
2782


L2067
Translation initiation factor 5A
2783


L2068
Translation initiation factor 5A
2784


L2069
Translation initiation factor IF2/eIF5b
2785


L2070
Translation initiation factor IF2/eIF5b
2786


L2071
Transposable element mariner, complete CDS
2787


L2072
Tricorn protease
2788


L2073
Tricorn protease
2789


L2074
Tricorn protease
2790


L2075
Trigger factor
2791


L2076
Trigger factor
2792


L2077
Trigger factor
2793


L2078
TRNA CCA-adding enzyme
RRI


L2079
TRNA CCA-adding enzyme
2794


L2080
TRNA CCA-adding enzyme
2795


L2081
TRNA CCA-adding enzyme
2796


L2082
TRNA CCA-adding enzyme
2797


L2083
TRNA nucleotidyltransferase
2798


L2084
TRNA-splicing endonuclease
2799


L2085
Tt1467 protein
LEA


L2086
Tt1467 protein
2800


L2087
Tumor suppressor p53-binding protein 1
2801


L2088
Tumor suppressor p53-binding protein 1
2802


L2089
Tumor suppressor p53-binding protein 1
2803


L2090
Tumor suppressor p53-binding protein 1
2804


L2091
Type A flavoprotein FprA
2805


L2092
Type A flavoprotein FprA
2806


L2093
Type A flavoprotein FprA
2807


L2094
Type A flavoprotein FprA
2808


L2095
Type A flavoprotein FprA
2809


L2096
Type I restriction enzyme specificity protein MG438
QMH


L2097
Type I restriction enzyme specificity protein MG438
2810


L2098
Type I restriction enzyme specificity protein MG438
2811


L2099
Type I restriction-modification enzyme, S subunit
2812


L2100
Type I restriction-modification enzyme, S subunit
2813


L2101
Type I site-specific restriction-modification system, R (restriction) subunit
2814


L2102
Type I site-specific restriction-modification system, R (restriction) subunit
2815


L2103
Type I site-specific restriction-modification system, R (restriction) subunit
2816


L2104
Type II DNA topoisomerase VI subunit B
2817


L2105
Type II DNA topoisomerase VI subunit B
2818


L2106
Type II DNA topoisomerase VI subunit B
2819


L2107
Type II DNA topoisomerase VI subunit B
2820


L2108
Type II DNA topoisomerase VI subunit B
2821


L2109
Type II DNA topoisomerase VI subunit B
2822


L2110
Type II DNA topoisomerase VI subunit B
2823


L2111
Type II DNA topoisomerase VI subunit B
2824


L2112
Type II DNA topoisomerase VI subunit B
2825


L2113
Type II DNA topoisomerase VI subunit B
2826


L2114
Type II DNA topoisomerase VI subunit B
2827


L2115
Type VI secretion system component
2828


L2116
Type VI secretion system component
2829


L2117
Type VI secretion system component
2830


L2118
Tyrosine-protein kinase receptor UFO
2831


L2119
Tyrosine-protein kinase receptor UFO
2832


L2120
Tyrosine-protein kinase ZAP-70
2833


L2121
Tyrosine-protein kinase ZAP-70
2834


L2122
Tyrosyl-DNA phosphodiesterase
2835


L2123
Tyrosyl-DNA phosphodiesterase
2836


L2124
Ubiquitin carboxyl-terminal hydrolase 7
2837


L2125
UDP-galactopyranose mutase
2838


L2126
UDP-galactopyranose mutase
2839


L2127
UDP-galactopyranose mutase
2840


L2128
UDP-galactopyranose mutase
2841


L2129
UDP-galactopyranose mutase
2842


L2130
UDP-glucose dehydrogenase
2843


L2131
UDP-N-acetylmuramate-L-alanine ligase
2844


L2132
UDP-N-acetylmuramate-L-alanine ligase
2845


L2133
UDP-N-acetylmuramoylalanine--D-glutamate ligase
2846


L2134
UDP-N-acetylmuramoylalanine--D-glutamate ligase
2847


L2135
UDP-N-acetylmuramoylalanine-D-glutamyl-lysine-D-alanyl-D-alanine
2848



ligase, MurF protein


L2136
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2849


L2137
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2850


L2138
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2851


L2139
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2852


L2140
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2853


L2141
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2854


L2142
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase
2855


L2143
Uncharacterized conserved protein
2856


L2144
Uncharacterized conserved protein
2857


L2145
Uncharacterized GST-like protein yfcF
2858


L2146
Uncharacterized GST-like proteinprotein
2859


L2147
Uncharacterized GST-like proteinprotein
2860


L2148
Uncharacterized GST-like proteinprotein
2861


L2149
Uncharacterized protein
2862


L2150
Uncharacterized protein
2863


L2151
Uncharacterized protein BT_1490
2864


L2152
Uncharacterized protein ypfl
TLR


L2153
Uncharacterized protein ypfl
VHP


L2154
Uncharacterized protein ypfl
2865


L2155
Uncharacterized protein ypfl
2866


L2156
Uncharacterized protein ypfl
2867


L2157
Uncharacterized protein ypfl
2868


L2158
Uncharacterized protein ypfl
2869


L2159
Uncharacterized protein ypfl
2870


L2160
Uncharacterized protein ypfl
2871


L2161
Uncharacterized protein ypfl
2872


L2162
Uncharacterized protein ypfl
2873


L2163
Uncharacterized protein ypfl
2874


L2164
Uncharacterized protein ypfl
2875


L2165
Uncharacterized protein ypfl
2876


L2166
Uncharacterized protein ypfl
2877


L2167
Uncharacterized protein ypfl
2878


L2168
Uncharacterized protein ypfl
2879


L2169
Unknown protein
2880


L2170
Unknown protein
2881


L2171
UPF0131 protein ykqA
2882


L2172
UPF0131 protein ykqA
2883


L2173
UPF0131 protein ykqA
2884


L2174
UPF0348 protein MJ0951
2885


L2175
UPF0348 protein MJ0951
2886


L2176
UPF0348 protein MJ0951
2887


L2177
UPF0348 protein MJ0951
2888


L2178
UPF0348 protein MJ0951
2889


L2179
UPF0348 protein MJ0951
2890


L2180
UPF0348 protein MJ0951
2891


L2181
UPF0348 protein MJ0951
2892


L2182
URE2 protein
2893


L2183
Uridine diphospho-N-acetylenolpyruvylglucosaminereductase
TAK


L2184
Uridine diphospho-N-acetylenolpyruvylglucosaminereductase
2894


L2185
Uridine diphospho-N-acetylenolpyruvylglucosaminereductase
2895


L2186
Uridine diphospho-N-acetylenolpyruvylglucosaminereductase
2896


L2187
Uridine diphospho-N-acetylenolpyruvylglucosaminereductase
2897


L2188
Urokinase plasminogen activator surface receptor
2898


L2189
Urokinase plasminogen activator surface receptor
2899


L2190
Vascular cell adhesion molecule-1
2900


L2191
VCP-like ATPase
2901


L2192
VCP-like ATPase
2902


L2193
Viral CASP8 and FADD-like apoptosis regulator
2903


L2194
Vitamin K-dependent protein Z
2904


L2195
VP1 protein
2905


L2196
V-type ATP synthase alpha chain
2906


L2197
Xaa-Pro aminopeptidase
2907


L2198
Xaa-Pro aminopeptidase
2908


L2199
Xaa-Pro aminopeptidase
2909


L2200
Xaa-Pro aminopeptidase
2910


L2201
Xanthine dehydrogenase
2911


L2202
Xanthine dehydrogenase
2912


L2203
Xanthine dehydrogenase
2913


L2204
Xanthine dehydrogenase
2914


L2205
X-prolyl dipeptidyl aminopeptidase
KSY


L2206
X-prolyl dipeptidyl aminopeptidase
LDG


L2207
X-prolyl dipeptidyl aminopeptidase
LLE


L2208
X-prolyl dipeptidyl aminopeptidase
TVS


L2209
X-prolyl dipeptidyl aminopeptidase
2915


L2210
X-prolyl dipeptidyl aminopeptidase
2916


L2211
X-prolyl dipeptidyl aminopeptidase
2917


L2212
X-prolyl dipeptidyl aminopeptidase
2918


L2213
X-prolyl dipeptidyl aminopeptidase
2919


L2214
X-prolyl dipeptidyl aminopeptidase
2920


L2215
X-prolyl dipeptidyl aminopeptidase
2921


L2216
X-prolyl dipeptidyl aminopeptidase
2922


L2217
X-prolyl dipeptidyl aminopeptidase
2923


L2218
X-prolyl dipeptidyl aminopeptidase
2924


L2219
X-prolyl dipeptidyl aminopeptidase
2925


L2220
X-prolyl dipeptidyl aminopeptidase
2926


L2221
X-prolyl dipeptidyl aminopeptidase
2927


L2222
X-prolyl dipeptidyl aminopeptidase
2928


L2223
X-prolyl dipeptidyl aminopeptidase
2929


L2224
X-prolyl dipeptidyl aminopeptidase
2930


L2225
X-prolyl dipeptidyl aminopeptidase
2931


L2226
X-prolyl dipeptidyl aminopeptidase
2932


L2227
X-prolyl dipeptidyl aminopeptidase
2933


L2228
X-prolyl dipeptidyl aminopeptidase
2934


L2229
X-prolyl dipeptidyl aminopeptidase
2935


L2230
X-prolyl dipeptidyl aminopeptidase
2936


L2231
X-prolyl dipeptidyl aminopeptidase
2937


L2232
X-prolyl dipeptidyl aminopeptidase
2938


L2233
Xylosidase/arabinosidase
2939


L2234
Xylosidase/arabinosidase
2940


L2235
Xylosidase/arabinosidase
2941


L2236
Xylosidase/arabinosidase
2942


L2237
Xylosidase/arabinosidase
2943


L2238
Xylosidase/arabinosidase
2944


L2239
Xylosidase/arabinosidase
2945


L2240
YkoF
2946


L2241
YkuI protein
2947









Internal ribosomal entry site (IRES) is a nucleotide sequence (>500 nucleotides) that allows for initiation of translation in the middle of an mRNA sequence (Kim. J. H. et al., 2011 PLoS One (4): e18556; the contents of which are herein incorporated by reference in its entirety). Use of an IRES sequence ensures co-expression of genes before and after the IRES, though the sequence following the IRES may be transcribed and translated at lower levels than the sequence preceding the IRES sequence.


2A peptides are small “self-cleaving” peptides (18-22 amino acids) derived from viruses such as foot-and-mouth disease virus (F2A), porcine teschovirus-1 (P2A). Thoseaasigna virus (T2A), or equine rhinitis A virus (E2A). The 2A designation refers specifically to a region of picornavirus polyproteins that lead to a ribosomal skip at the glycyl-prolyl bond in the C-terminus of the 2A peptide (Kim. J. H. et al., 2011. PLoS One 6(4): e18556; the contents of which are herein incorporated by reference in its entirety). This skip results in a cleavage between the 2A peptide and its immediate downstream peptide. As opposed to IRES linkers, 2A peptides generate stoichiometric expression of proteins flanking the 2A peptide and their shorter length can be advantageous in generating viral expression vectors.


Some payload regions encode linkers comprising furin cleavage sites. Furin is a calcium dependent serine endoprotease that cleaves proteins just downstream of a basic amino acid target sequence (Arg-X-(Arg,Lys)-Arg) (Thomas. G., 2002. Nature Reviews Molecular Cell Biology 3(10); 753-66; the contents of which are herein incorporated by reference in its entirety). Furin is enriched in the trans-golgi network where it is involved in processing cellular precursor proteins. Furin also plays a role in activating a number of pathogens. This activity can be taken advantage of for expression of polypeptides of the invention.


In some embodiments, the payload region may encode one or more linkers comprising cathepsin, matrix metalloproteinases or legumain cleavage sites. Such linkers are described e.g. by Cizeau and Macdonald in International Publication No. WO2008052322, the contents of which are herein incorporated in their entirety. Cathepsins are a family of proteases with unique mechanisms to cleave specific proteins Cathepsin B is a cysteine protease and cathepsin D is an aspartyl protease. Matrix metalloproteinases are a family of calcium-dependent and zinc-containing endopeptidases. Legumain is an enzyme catalyzing the hydrolysis of (-Asn-Xaa-) bonds of proteins and small molecule substrates.


In some embodiments, payload regions may encode linkers that are not cleaved. Such linkers may include a simple amino acid sequence, such as a glycine rich sequence. In some cases, linkers may comprise flexible peptide linkers comprising glycine and serine residues. The linker may comprise flexible peptide linkers of different lengths, e.g. nxG4S, where n=1-10 (SEQ ID NO:9222) and the length of the encoded linker varies between 5 and 50 amino acids. In a non-limiting example, the linker may be 5xG4S (SEQ ID NO: 9221) encoded by SEQ ID NO: 903. These flexible linkers are small and without side chains so they tend not to influence secondary protein structure while providing a flexible linker between antibody segments (George. R. A., et al., 2002. Protein Engineering 15(11): 871-9; Huston, J. S. et al., 1988. PNAS 85:5879-83, and Shan. D. et al., 1999. Journal of Immunology, 162(11):6589-95; the contents of each of which are herein incorporated by reference in their entirety). Furthermore, the polarity of the serine residues improves solubility and prevents aggregation problems.


In some embodiments, payload regions of the invention may encode small and unbranched serine-rich peptide linkers, such as those described by Huston et al, in U.S. Pat. No. 5,525,491, the contents of which are herein incorporated in their entirety Polypeptides encoded by the payload region of the invention, linked by serine-rich linkers, have increased solubility.


In some embodiments, payload regions of the invention may encode artificial linkers, such as those described by Whitlow and Filpula in U.S. Pat. No. 5,856,456 and Ladner et al, in U.S. Pat. No. 4,946,778, the contents of each of which are herein incorporated by their entirety.


Viral Genome Component: Introns

In one embodiment, the payload region comprises at least one element to enhance the expression such as one or more introns or portions thereof. Non-limiting examples of introns include, MVM (67-97 bps), F.IX truncated intron 1 (300 bps), β-globin SD/immunoglobulin heavy chain splice acceptor (250 bps), adenovirus splice donor/immunoglobin splice acceptor (500 bps), SV40 late splice donor/splice acceptor (19S/16S) (180 bps) and hybrid adenovirus splice donor/IgG splice acceptor (230 bps).


In one embodiment, the intron or intron portion may be 100-500 nucleotides in length. The intron may have a length of 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490 or 500, The intron may have a length between 80-100, 80-120, 80-140, 80-160, 80-180, 80-200, 80-250, 80-300, 80-350, 80-400, 80-450, 80-500, 200-300, 200-400, 200-500, 300-400, 300-500, or 400-500.


Payloads of the Invention

The AAV particles of the present disclosure comprise at least one payload region. As used herein. “payload” or “payload region” refers to one or more polynucleotides or polynucleotide regions encoded by or within a viral genome or an expression product of such polynucleotide or polynucleotide region, e.g., a transgene, a polynucleotide encoding a polypeptide or multi-polypeptide or a modulatory nucleic acid or regulatory nucleic acid Payloads of the present invention typically encode polypeptides (e.g., antibodies or antibody-based compositions) or fragments or variants thereof.


The payload region may be constructed in such a way as to reflect a region similar to or mirroring the natural organization of an mRNA.


The payload region may comprise a combination of coding and non-coding nucleic acid sequences.


In some embodiments, the AAV payload region may encode a coding or non-coding RNA.


In one embodiment, the AAV particle comprises a viral genome with a payload region comprising nucleic acid sequences encoding more than one polypeptide of interest (e.g., an antibody). In such an embodiment, a viral genome encoding more than one polypeptide may be replicated and packaged into a viral particle. A target cell transduced with a viral particle comprising more than one polypeptide may express each of the polypeptides in a single cell.


In one embodiment, as shown in FIG. 1, an AAV particle comprises a viral genome with a payload region comprising a nucleic acid sequence encoding a heavy chain and a light chain of an antibody. The heavy chain and light chain are expressed and assembled to form the antibody which is secreted.


In one embodiment, the payload region may comprise the components as shown in FIG. 2. The payload region 110 is located within the viral genome 100. At the 5′ and/or the 3′ end of the payload region 110 there may be at least one inverted terminal repeat (ITR) 120. Within the payload region, there is a promoter region 130, an intron region 140 and a coding region 150. When the coding region 150 comprises a heavy chain region 151 and light chain region 152 of an antibody, the two chains may be separated by a linker region 155.


In one embodiment, the coding region may comprise a heavy and light chain sequence and a linker. As shown in FIG. 3, the payload region may comprise a heavy chain and light chain sequence separated by a linker and/or a cleavage site. In one embodiment, the heavy and light chain sequence is sequence separated by an IRES sequence (1 and 2) In one embodiment, the heavy and light chain sequence is separated by a foot and mouth virus sequence (3 and 4). In one embodiment, the heavy and light chain sequence is separated by a foot and mouth virus sequence and a furin cleavage site (5 and 6) In one embodiment, the heavy and light chain sequence is separated by a porcine teschovirus-1 virus sequence (7 and 8) In one embodiment, the heavy and light chain sequence is separated by a porcine teschovirus-1 virus and a furin cleavage site (9 and 10). In one embodiment, the heavy and light chain sequence is separated by a 5xG4S (SEQ ID NO: 9221) sequence (11).


Where the AAV particle payload region encodes a polypeptide, the polypeptide may be a peptide or protein. A protein encoded by the AAV particle payload region may comprise an antibody, an antibody related composition, a secreted protein, an intracellular protein, an extracellular protein, and/or a membrane protein. The encoded proteins may be structural or functional. In addition to the antibodies or antibody-based composition, proteins encoded by the payload region may include, in combination, certain mammalian proteins involved in immune system regulation. The AAV viral genomes encoding polypeptides described herein may be useful in the fields of human disease, viruses, infections veterinary applications and a variety of in vivo and in vitro settings.


In some embodiments, the AAV particles are useful in the field of medicine for the treatment, prophylaxis, palliation or amelioration of neurological diseases and/or disorders.


Antibodies and Antibody-Based Compositions

Payload regions of the AAV particles of the invention may encode polypeptides that form one or more functional antibodies or antibody-based compositions. As used herein, the term “antibody” is referred to in the broadest sense and specifically covers various embodiments including, but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g. bispecific antibodies formed from at least two intact antibodies), and antibody fragments (e.g., diabodies) so long as they exhibit a desired biological activity (e.g., “functional”). Antibodies are primarily amino-acid based molecules but may also comprise one or more modifications (including, but not limited to the addition of sugar moieties, fluorescent moieties, chemical tags, etc.)


As used herein, “antibody-based” or “antibody-derived” compositions are monomeric or multi-meric polypeptides which comprise at least one amino-acid region derived from a known or parental antibody sequence and at least one amino acid region derived from a non-antibody sequence, e.g., mammalian protein.


Payload regions may encode polypeptides that form or function as any antibody, including antibodies that are known in the art and/or antibodies that are commercially available. The encoded antibodies may be therapeutic, diagnostic, or for research purposes. Further, polypeptides of the invention may include fragments of such antibodies or antibodies that have been developed to comprise one or more of such fragments (e.g., variable domains or complementarity determining regions (CDRs)).


In one embodiment, the viral genome of the AAV particles may comprise nucleic acids which have been engineered to enable expression of antibodies, antibody fragments, or components of any of those described in U.S. Pat. No. 7,041,807 related to YYX epitope; US20090175884, US20110305630, US20130330275 related to misfolded proteins in cancer; US20040175775 related to PrP in eye fluid, US20030114360 related to copolymers and methods of treating prion-related diseases: WO2009121176 insulin-induced gene peptide compositions, US20030022243, WO2003000853 related to protein aggregation assays; WO200078344 related to prion protein peptides and uses thereof. Each of these publications are incorporated by reference in their entireties.


Antibody Generation

In some embodiments, viral genomes of the AAV particles of the invention may encode antibodies or antibody-based compositions produced using methods known in the art. Such methods may include, but are not limited to immunization and display technologies (e.g., phage display, yeast display, and ribosomal display). Antibodies may be developed, for example, using any naturally occurring or synthetic antigen. As used herein, an “antigen” is an entity which induces or evokes an immune response in an organism. An immune response is characterized by the reaction of the cells, tissues and/or organs of an organism to the presence of a foreign entity. Such an immune response typically leads to the production by the organism of one or more antibodies against the foreign entity, e.g., antigen or a portion of the antigen. As used herein. “antigens” also refer to binding partners for specific antibodies or binding agents in a display library.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be derived from antibodies produced using hybridoma technology. Host animals (e.g. mice, rabbits, goats, and llamas) may be immunized by an injection with an antigenic protein to elicit lymphocytes that specifically bind to the antigen. Lymphocytes may be collected and fused with immortalized cell lines to generate hybridomas which can be cultured in a suitable culture medium to promote growth. The antibodies produced by the cultured hybridomas may be subjected to analysis to determine binding specificity of the antibodies for the target antigen. Once antibodies with desirable characteristics are identified, corresponding hybridomas may be subcloned through limiting dilution procedures and grown by standard methods. The antibodies produced by these cells may be isolated and purified using standard immunoglobulin purification procedures.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be produced using heavy and light chain variable region cDNA sequences selected from hybridomas or from other sources. Sequences encoding antibody variable domains expressed by hybridomas may be determined by extracting RNA molecules from antibody-producing hybridoma cells and producing cDNA by reverse transcriptase polymerase chain reaction (PCR). PCR may be used to amplify cDNA using primers specific for heavy and light chain sequences. PCR products may then be subcloned into plasmids for sequence analysis. Antibodies may be produced by insertion of resulting variable domain sequences into expression vectors.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be generated using display technologies. Display technologies used to generate polypeptides of the invention may include any of the display techniques (e.g display library screening techniques) disclosed in International Patent Application No. WO2014074532, the contents of which are herein incorporated by reference in their entirety. In some embodiments, synthetic antibodies may be designed, selected or optimized by screening target antigens using display technologies (e.g. phage display technologies). Phage display libraries may comprise millions to billions of phage particles, each expressing unique antibody fragments on their viral coats. Such libraries may provide richly diverse resources that may be used to select potentially hundreds of antibody fragments with diverse levels of affinity for one or more antigens of interest (McCafferty, et al., 1990. Nature, 348:552-4; Edwards. B. M. et al., 2003. JMB, 334: 103-18; Schofield, D. et al., 2007. Genome Biol. 8. R254 and Pershad, K. et al., 2010 Protein Engineering Design and Selection, 23.279-88; the contents of each of which are herein incorporated by reference in their entirety). Often, the antibody fragments present in such libraries comprise scFv antibody fragments, comprising a fusion protein of VH and VL antibody domains joined by a flexible linker. In some cases, scFvs may contain the same sequence with the exception of unique sequences encoding variable loops of the CDRs. In some cases, scFvs are expressed as fusion proteins, linked to viral coat proteins (e.g. the N-terminus of the viral pIII coat protein) VL chains may be expressed separately for assembly with VH chains in the periplasm prior to complex incorporation into viral coats. Precipitated library members may be sequenced from the bound phage to obtain cDNA encoding desired scFvs. Antibody variable domains or CDRs from such sequences may be directly incorporated into antibody sequences for recombinant antibody production, or mutated and utilized for further optimization through in vitro affinity maturation.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be produced using yeast surface display technology, wherein antibody variable domain sequences may be expressed on the cell surface of Saccharomyces cerevisiae. Recombinant antibodies may be developed by displaying the antibody fragment of interest as a fusion to e.g. Aga2p protein on the surface of the yeast, where the protein interacts with proteins and small molecules in a solution, scFvs with affinity towards desired receptors may be isolated from the yeast surface using magnetic separation and flow cytometry. Several cycles of yeast surface display and isolation may be done to attain scFvs with desired properties through directed evolution.


In one embodiment, the sequence of the polypeptides to be encoded in the viral genomes of the invention (e.g., antibodies) may be designed by VERSITOPE™ Antibody Generation and other methods used by BIOATLA® and described in United States Patent Publication No. US20130281303, the contents of which are herein incorporated by reference in their entirety. In brief, recombinant monoclonal antibodies are derived from B-cells of a host immuno-challenged with one or more target antigens. These methods of antibody generation do not rely on immortalized cell lines, such as hybridoma, thereby avoiding some of the associated challenges i.e., genetic instability and low production capacity, producing high affinity and high diversity recombinant monoclonal antibodies. In one embodiment, the method is a natural diversity approach. In another embodiment, the method is a high diversity approach.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be generated using BIOATLA® natural diversity approach. In the natural diversity approach of generating recombinant monoclonal antibodies described in United States Patent Publication No. US20130281303, the original pairings of variable heavy (VH) and variable light (VL) domains are retained from the host, yielding recombinant monoclonal antibodies that are naturally paired. These may be advantageous due to a higher likelihood of functionality as compared to non-natural pairings of VH and VL. To produce the recombinant monoclonal antibodies, first a non-human host (i.e., rabbit, mouse, hamster, guinea pig, camel or goat) is immuno-challenged with an antigen of interest. In some embodiments, the host may be a previously challenged human patient. In other embodiments, the host may not have been immuno-challenged. B-cells are harvested from the host and screened by fluorescence activated cell sorting (FACS), or other method, to create a library of B-cells enriched in B-cells capable of binding the target antigen. The cDNA obtained from the mRNA of a single B-cell is then amplified to generate an immunoglobulin library of VH and VL domains. This library of immunoglobulins is then cloned into expression vectors capable of expressing the VH and VL domains, wherein the VH and VL domains remain naturally paired. The library of expression vectors is then used in an expression system to express the VH and VL domains in order to create an antibody library. Screening of the antibody library yields antibodies able to bind the target antigen, and these antibodies can be further characterized. Characterization may include one or more of the following: isoelectric point, thermal stability, sedimentation rate, folding rate, neutralization or antigen activity, antagonist or agonistic activity, expression level, specific and non-specific binding, inhibition of enzymatic activity, rigidity/flexibility, shape, charge, stability across pH, in solvents, under UV radiation, in mechanical stress conditions, or in sonic conditions, half-life and glycosylation.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be generated using BIOATLA® high diversity approach. In the high diversity approach of generating recombinant monoclonal antibodies described in United States Patent Publication No. US20130281303, additional pairings of variable heavy (VH) and variable light (VL) domains are attained. To produce the recombinant monoclonal antibodies, B-cells harvested from the host are screened by fluorescence activated cell sorting (FACS), panning, or other method, to create a library of B-cells enriched in B-cells capable of binding the target antigen. The cDNA obtained from the mRNA of the pooled B-cells is then amplified to generate an immunoglobulihn library of VH and VL domains. This library of immunoglobulins is then used in a biological display system (mammalian, yeast or bacterial cell surface display systems) to generate a population of cells displaying antibodies, fragments or derivatives comprising the VH and VL domains wherein, the antibodies, fragments or derivatives comprise VH and VL domain combinations that were not present in the B-cells in vivo. Screening of the cell population by FACS, with the target antigen, yields a subset of cells capable of binding the target antigen and the antibodies displayed on these cells can be further characterized. In an alternate embodiment of the high diversity approach, the immunoglobulin library comprises only VH domains obtained from the B-cells of the immuno-challenged host, while the VL domain(s) are obtained from another source.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be evolved using BIOATLA® comprehensive approaches. The methods of generating recombinant monoclonal antibodies as described in United States Patent Publication No. US20130281303, further comprises evolving the recombinant antibody by comprehensive positional evolution (CPE™), CPE™ followed by comprehensive protein synthesis (CPS™), PCR shuffling, or other method.


In one embodiment, the sequence of the polypeptides to be encoded in the viral genomes of the invention (e.g., antibodies) may be derived from any of the BIOATLA® protein evolution methods described in International Publication WO2012009026, the contents of which are herein incorporated by reference in their entirety. In this method, mutations are systematically performed throughout the polypeptide or molecule of interest, a map is created providing useful informatics to guide the subsequent evolutionary steps. Not wishing to be bound by theory, these evolutionary methods typically start with a template polypeptide and a mutant is derived therefrom, which has desirable properties or characteristics. Non-limiting examples of evolutionary techniques include polymerase chain reaction (PCR), error prone PCR, oligonucleotide-directed mutagenesis, cassette mutagenesis, shuffling, assembly PCR, sexual PCR mutagenesis, in vivo mutagenesis, site-specific mutagenesis, gene reassembly, gene site saturated mutagenesis, in vitro mutagenesis, ligase chain reaction, oligonucleotide synthesis or any combination thereof.


In one embodiment, the BIOATLA® evolution method is Comprehensive Positional Evolution (CPE™). In CPE, naturally occurring amino acid variants are generated for each of the codons of the template polypeptide, wherein 63 different codon options exist for each amino acid variant. A set of polypeptides with single amino acid mutations are generated and the mutations are then confirmed by sequencing or other method known in the art and each amino acid change screened for improved function, neutral mutations, inhibitory mutations, expression and compatibility with the host system. An EvoMap™ is created that describes in detail the effects of each amino acid mutation on the properties and characteristics of that polypeptide. The data from the EvoMap™ may be utilized to produce polypeptides with more than one amino acid mutation, wherein the resultant multi-site mutant polypeptides can be screened for desirable characteristics.


In one embodiment, the BIOATLA® evolution method is Synergy Evolution, wherein an EvoMap™ is used to identify amino acid positions to introduce 2-20 mutations simultaneously to produce a combinatorial effect. The resulting multi-site mutant polypeptides may be screened on one or more pre-determined characteristics to identify “upmutants” wherein the function of the mutant is improved as compared to the parent polypeptide. In one embodiment, Synergy Evolution is used to enhance binding affinity of an antibody.


In one embodiment, the BIOATLA® evolution method is Flex Evolution, wherein an EvoMap™ is used to identify fully mutable sites within a polypeptide that may then be targeted for alteration, such as introduction of glycosylation sites or chemical conjugation.


In one embodiment, the BIOATLA® evolution method is Comprehensive Positional Insertion Evolution (CPI™), wherein an amino acid is inserted after each amino acid of a template polypeptide to generate a set of lengthened poly peptides. CPI may be used to insert 1, 2, 3, 4, or 5 amino acids at each new position. The resultant lengthened polypeptides are sequenced and assayed for one or more pre-determined properties and evaluated in comparison to its template or parent molecule. In one embodiment, the binding affinity and immunogenicity of the resultant poly peptides are assayed. In one embodiment, the lengthened poly peptides are further mutated and mapped to identify polypeptides with desirable characteristics.


In one embodiment, the BIOATLA® evolution approach is Comprehensive Positional Deletion Evolution (CPD™), wherein each amino acid of the template polypeptide is individually and systematically deleted one at a time. The resultant shortened polypeptides are then sequenced and evaluated by assay for at least one pre-determined feature. In one embodiment, the shortened polypeptides are further mutated and mapped to identify polypeptides with desirable characteristics.


In one embodiment, the BIOATLA® evolution approach is Combinatorial Protein Synthesis (CPS™), wherein mutants identified in CPE, CPI, CPD or other evolutionary technique are combined for polypeptide synthesis. These combined mutant polypeptides are then screened for enhanced properties and characteristics. In one embodiment CPS is combined with any of the aforementioned evolutionary or polypeptide synthesis methods.


In one embodiment, the sequence of the polypeptides to be encoded in the viral genomes of the invention (e.g., antibodies) may be derived from the BIOATLA® Comprehensive Integrated Antibody Optimization (CIAO!™) described in U.S. Pat. No. 8,859,467, the contents of which are herein incorporated by reference in their entirety. The CIAO!™ method allows for simultaneous evolution of polypeptide performance and expression optimization, within a eukaryotic cell host (i.e., mammalian or yeast cell host). First, an antibody library is generated in a mammalian cell production host by antibody cell surface display, wherein the generated antibody library targets a particular antigen of interest. The antibody library is then screened by any method known in the art, for one or more properties or characteristics. One or more antibodies of the library, with desirable properties or characteristics are chosen for further poly peptide evolution by any of the methods known in the art, to produce a library of mutant antibodies by antibody cell surface display in a mammalian cell production host. The generated mutant antibodies are screened for one or more predetermined properties or characteristics, whereby an upmutant is selected, wherein the upmutant has enhanced or improved characteristics as compared to the parent template poly peptide.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be humanized by the methods of BIOATLA® as described in United States Patent Publication US20130303399, the contents of which are herein incorporated by reference in their entirety. In this method, for generating enhanced full length humanized antibodies in mammalian cells, no back-mutations are required to retain affinity to the antigen and no CDR grafting or phage-display is necessary. The generated humanized antibody has reduced immunogenicity and equal or greater affinity for the target antigen as compared to the parent antibody. The variable regions or CDRs of the generated humanized antibody are derived from the parent or template, whereas the framework and constant regions are derived from one or more human antibodies. To start, the parent, or template antibody is selected, cloned and each CDR sequence identified and synthesized into a CDR fragment library. Double stranded DNA fragment libraries for VH and VL are synthesized from the CDR fragment encoding libraries, wherein at least one CDR fragment library is derived from the template antibody and framework (FW) fragment encoding libraries, wherein the FW fragment library is derived from a pool of human frameworks obtained from natively expressed and functional human antibodies. Stepwise liquid phase ligation of FW and CDR encoding fragments is then used to generate both VH and VL fragment libraries. The VH and VL fragment libraries are then cloned into expression vectors to create a humanization library, which is further transfected into cells for expression of full length humanized antibodies, and used to create a humanized antibody library. The humanized antibody library is then screened to determine expression level of the humanized antibodies, affinity or binding ability for the antigen, and additional improved or enhanced characteristics, as compared to the template or parent antibody. Non-limiting examples of characteristics that may be screened include equilibrium dissociation constant (KD), stability, melting temperature (Tm), pI, solubility, expression level, reduced immunogenicity and improved effector function.


In one embodiment, the sequences of the polypeptides to be encoded in the viral genomes of the invention may be generated by the BIOATLA® method for preparing conditionally active antibodies as described in International Publications WO02016033331 and WO2016036916, the contents of which are herein incorporated by reference in their entirety. As used herein, the term “conditionally active” refers to a molecule that is active at an aberrant condition. Further, the conditionally active molecule may be virtually inactive at normal physiological conditions. Aberrant conditions may result from changes in pH, temperature, osmotic pressure, osmolality, oxidative stress, electrolyte concentration, and/or chemical or proteolytic resistance, as non-limiting examples.


The method of preparing a conditionally active antibody is described in International Publications WO2016033331 and WO2016036916 and summarized herewithin. Briefly, a wild-type polypeptide is selected and the DNA is evolved to create mutant DNAs. Non-limiting examples of evolutionary techniques that may be used to evolve the DNA include polymerase chain reaction (PCR), error prone PCR, shuffling, oligonucleotide-directed mutagenesis, assembly PCR sexual PCR mutagenesis, in vivo mutagenesis, site-specific mutagenesis, gene reassembly, gene site saturated mutagenesis, in vitro mutagenesis, ligase chain reaction, oligonucleotide synthesis or any combination thereof. Once mutant DNAs are created, they are expressed in a eukaryotic cell production host (i.e., fungal, insect, mammalian, adenoviral, plant), wherein a mutant polypeptide is produced. The mutant poly peptide and the corresponding wild-type polypeptide are then subjected to assays under both normal physiological conditions and aberrant conditions in order to identify mutants that exhibit a decrease in activity in the assay at normal physiological conditions as compared to the wild-type polypeptide and/or an increase in activity in the assay under aberrant conditions, as compared to the corresponding wild-type polypeptide. The desired conditionally active mutant may then be produced in the aforementioned eukaryotic cell production host.


In one embodiment, the conditionally active antibody is a “mirac protein” as described by BIOATLA® in U.S. Pat. No. 8,709,755, the contents of which are herein incorporated by reference in their entirety. As used herein “mirac protein” refers to a conditionally active antibody that is virtually inactive at body temperature but active at lower temperatures.


In one embodiment, the sequence of the polypeptides to be encoded in the viral genomes of the invention (e.g., antibodies) may be derived based on any of the BIOATLA™ methods including, but not limited to, VERSITOPE™ Antibody Generation, natural diversity approaches and high diversity approaches for generating monoclonal antibodies, methods for generation of conditionally active polypeptides, humanized antibodies, mirac proteins, multi-specific antibodies or cross-species active mutant polypeptides. Comprehensive Integrated Antibody Optimization (CIAO!®), Comprehensive Positional Evolution (CPE™). Synergy Evolution, Flex Evolution, Comprehensive Positional Insertion Evolution (CPI™). Comprehensive Positional Deletion Evolution (CPD™), Combinatorial Protein Synthesis (CPS®), or any combination thereof. These methods are described in U.S. Pat. Nos. 8,859,467 and 8,709,755 and United States Publication Nos US20130281303, US20130303399, US20150065690, US20150252119, US20150086562 and US20100138945, and International Publication Nos. WO201505888, WO2012009026, WO2011109726, WO2016036916, and WO2016033331, the contents of each of which are herein incorporated by reference in their entirety.


Antibody Fragments and Variants

In some embodiments, antibody fragments encoded by payloads of the invention comprise antigen binding regions from intact antibodies. Examples of antibody fragments may include, but are not limited to Fab, Fab′, F(ab′)2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site. Also produced is a residual “Fc” fragment, whose name reflects its ability to crystallize readily. Pepsin treatment yields an F(ab′)2 fragment that has two antigen-binding sites and is still capable of cross-linking antigen. Compounds and/or compositions of the present invention may comprise one or more of these fragments. For the purposes herein, an “antibody” may comprise a heavy and light variable domain as well as an Fc region.


In one embodiment, the Fc region may be a modified Fc region, as described in US Patent Publication US20150065690, wherein the Fc region may have a single amino acid substitution as compared to the corresponding sequence for the wild-type Fc region, wherein the single amino acid substitution yields an Fc region with preferred properties to those of the wild-type Fc region. Non-limiting examples of Fc properties that may be altered by the single amino acid substitution include bind properties or response to pH conditions


As used herein, the term “native antibody” refers to a usually heterotetrameric glycoprotein of about 150,000 Daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Genes encoding antibody heavy and light chains are known and segments making up each have been well characterized and described (Matsuda, F. et al., 1998. The Journal of Experimental Medicine, 188(11); 2151-62 and Li. A. et al., 2004. Blood, 103(12, 4602-9, the content of each of which are herein incorporated by reference in their entirety). Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain.


As used herein, the term “variable domain” refers to specific antibody domains found on both the antibody heavy and light chains that differ extensively in sequence among antibodies and are used in the binding and specificity of each particular antibody for its particular antigen. Variable domains comprise hypervariable regions. As used herein, the term “hypervariable region” refers to a region within a variable domain comprising amino acid residues responsible for antigen binding. The amino acids present within the hypervariable regions determine the structure of the complementarity determining regions (CDRs) that become part of the antigen-binding site of the antibody. As used herein, the term “CDR” refers to a region of an antibody comprising a structure that is complimentary to its target antigen or epitope Other portions of the variable domain, not interacting with the antigen, are referred to as framework (FW) regions. The antigen-binding site (also known as the antigen combining site or paratope) comprises the amino acid residues necessary to interact with a particular antigen. The exact residues making up the antigen-binding site are typically elucidated by co-crystallography with bound antigen, however computational assessments can also be used based on comparisons with other antibodies (Strohl, W. R. Therapeutic Antibody Engineering. Woodhead Publishing, Philadelphia Pa. 2012 Ch. 3, p 47-54, the contents of which are herein incorporated by reference in their entirety). Determining residues making up CDRs may include the use of numbering schemes including, but not limited to, those taught by Kabat [Wu. T. T. et al., 1970, JEM, 132(2):211-50 and Johnson, G. et al., 2000, Nucleic Acids Res. 28(1): 214-8, the contents of each of which are herein incorporated by reference in their entirety], Chothia [Chothia and Lesk. J. Mol Biol 196, 901 (1987), Chothia et al., Nature 342, 877 (1989) and Al-Lazikani, B. et al., 1997, J. Mol. Biol. 273(4):927-48, the contents of each of which are herein incorporated by reference in their entirety], Lefranc (Lefranc, M. P. et al., 2005, Immunome Res 1:3) and Honegger (Honegger, A. and Pluckthun, A. 2001. J. Mol. Biol. 309(3):657-70, the contents of which are herein incorporated by reference in their entirety).


VH and VL domains have three CDRs each. VL CDRs are referred to herein as CDR-L1, CDR-L2 and CDR-L3, in order of occurrence when moving from N- to C-terminus along the variable domain polypeptide. VH CDRs are referred to herein as CDR-H1, CDR-H2 and CDR-H3, in order of occurrence when moving from N- to C-terminus along the variable domain polypeptide. Each of CDRs have favored canonical structures with the exception of the CDR-H3, which comprises amino acid sequences that may be highly variable in sequence and length between antibodies resulting in a variety of three-dimensional structures in antigen-binding domains (Nikoloudis, D. et al., 2014 Peer J 2:e456; the contents of which are herein incorporated by reference in their entirety). In some cases. CDR-H3s may be analyzed among a panel of related antibodies to assess anti body, diversity. Various methods of determining CDR sequences are known in the art and may be applied to known antibody sequences (Strohl. W. R. Therapeutic Antibody Engineering. Woodhead Publishing, Philadelphia Pa. 2012. Ch. 3, p 47-54, the contents of which are herein incorporated by reference in their entirety).


As used herein, the term “Fv” refers to an antibody fragment comprising the minimum fragment on an antibody needed to form a complete antigen-binding site. These regions consist of a dimer of one heavy chain and one light chain variable domain in tight, non-covalent association. Fv fragments can be generated by proteolytic cleavage, but are largely unstable. Recombinant methods are known in the art for generating stable Fv fragments, typically through insertion of a flexible linker between the light chain variable domain and the heavy chain variable domain [to form a single chain F, (scFv)] or through the introduction of a disulfide bridge between heavy and light chain variable domains (Strohl, W. R. Therapeutic Antibody Engineering Woodhead Publishing. Philadelphia Pa. 2012 Ch. 3, p 46-47, the contents of which are herein incorporated by reference in their entirety).


As used herein, the term “light chain” refers to a component of an antibody from any vertebrate species assigned to one of two clearly distinct types, called kappa and lambda based on amino acid sequences of constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains, antibodies can be assigned to different classes. There are five major classes of intact antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA, and IgA2.


As used herein, the term “single chain Fv” or “scFv” refers to a fusion protein of VH and VL antibody domains, wherein these domains are linked together into a single polypeptide chain by a flexible peptide linker. In some embodiments, the Fv polypeptide linker enables the scFv to form the desired structure for antigen binding. In some embodiments, scFvs are utilized in conjunction with phage display, yeast display or other display methods where they may be expressed in association with a surface member (e.g. phage coat protein) and used in the identification of high affinity peptides for a given antigen.


As used herein, the term “bispecific antibody” refers to an antibody capable of binding two different antigens. Such antibodies typically comprise regions from at least two different antibodies. Bispecific antibodies may include any of those described in Riethmuller, G, 2012. Cancer Immunity, 12:12-18, Marvin, J. S. et al., 2005. Acta Pharmacologica Sinuca, 26(6).649-58 and Schaefer, W. et al., 2011. PNAS. 108(27) 11187-92, the contents of each of which are herein incorporated by reference in their entirety.


As used herein, the term “diabody” refers to a small antibody fragment with two antigen-binding sites. Diabodies comprise a heavy chain variable domain VH connected to a light chain variable domain VL in the same polypeptide chain. By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example EP 404,097; WO 93/11161; and Hollinger et al. (Hollinger, P. et al., “Diabodies” Small bivalent and bispecific antibody fragments. PNAS. 1993, 90:6444-8) the contents of each of which are incorporated herein by reference in their entirety.


The term “intrabody” refers to a form of antibody that is not secreted from a cell in which it is produced, but instead targets one or more intracellular proteins. Intrabodies may be used to affect a multitude of cellular processes including, but not limited to intracellular trafficking, transcription, translation, metabolic processes, proliferative signaling and cell division. In some embodiments, methods of the present invention may include intrabody-based therapies. In some such embodiments, variable domain sequences and/or CDR sequences disclosed herein may be incorporated into one or more constructs for intrabody-based therapy.


As used herein, the term “monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous cells (or clones), i.e., the individual antibodies comprising the population are identical and/or bind the same epitope, except for possible variants that may arise during production of the monoclonal antibodies, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen


The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. The monoclonal antibodies herein include “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies.


As used herein, the term “humanized antibody” refers to a chimeric antibody comprising a minimal portion from one or more non-human (e.g., murine) antibody source(s) with the remainder derived from one or more human immunoglobulin sources. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from the hypervariable region from an antibody of the recipient are replaced by residues from the hypervariable region from an antibody of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and/or capacity.


In some embodiments, viral genomes of the present invention may encode antibody, mimetics. As used herein, the term “antibody mimetic” refers to any molecule which mimics the function or effect of an antibody and which binds specifically and with high affinity to their molecular targets. In some embodiments, antibody mimetics may be monobodies, designed to incorporate the fibronectin type III domain (Fn3) as a protein scaffold (U.S. Pat. Nos. 6,673,901; 6,348,584). In some embodiments, antibody mimetics may be those known in the art including, but are not limited to affibody molecules, affilins, affitins, anticalins, avimers, Centyrins, DARPINS™, Fynomers and Kunitz and domain peptides. In other embodiments, antibody mimetics may include one or more non-peptide regions.


As used herein, the term “antibody variant” refers to a modified antibody (in relation to a native or starting antibody) or a biomolecule resembling a native or starting antibody in structure and/or function (e.g., an antibody mimetic). Antibody variants may be altered in their amino acid sequence, composition or structure as compared to a native antibody. Antibody variants may include, but are not limited to, antibodies with altered isotypes (e.g., IgA, IgD, IgE, IgG1, IgG2, IgG3, IgG4, or IgM), humanized variants, optimized variants, multispecific antibody variants (e.g., bispecific variants), and antibody fragments.


The preparation of antibodies, whether monoclonal or polyclonal, is known in the art. Techniques for the production of antibodies are well known in the art and described, e.g. in Harlow and Lane “Antibodies. A Laboratory Manual”, Cold Spring Harbor Laboratory Press, 1988, Harlow and Lane “Using Antibodies: A Laboratory Manual” Cold Spring Harbor Laboratory Press, 1999 and “Therapeutic Antibody Engineering: Current and Future Advances Driving the Strongest Growth Area in the Pharmaceutical Industry” Woodhead Publishing, 2012.


Multispecific Antibodies

In some embodiments, payloads of the invention may encode antibodies that bind more than one epitope. As used herein, the terms “multibody” or “multispecific antibody” refer to an antibody wherein two or more variable regions bind to different epitopes. The epitopes may be on the same or different targets. In certain embodiments, a multi-specific antibody is a “bispecific antibody,” which recognizes two different epitopes on the same or different antigens.


In one embodiment, multi-specific antibodies may be prepared by the methods used by BIOATLA® and described in International Patent publication WO201109726, the contents of which are herein incorporated by reference in their entirety. First a library of homologous, naturally occurring antibodies is generated by any method known in the art (i.e., mammalian cell surface display), then screened by FACSAria or other screening method, for multi-specific antibodies that specifically bind to two or more target antigens. In one embodiment, the identified multi-specific antibodies are further evolved by any method known in the art, to produce a set of modified multi-specific antibodies. These modified multi-specific antibodies are screened for binding to the target antigens. In one embodiment, the multi-specific antibody may be further optimized by screening the evolved modified multi-specific antibodies for optimized or desired characteristics.


In one embodiment, multi-specific antibodies may be prepared by the methods used by BIOATLA® and described in Unites States Publication No. US20150252119, the contents of which are herein incorporated by reference in their entirety. In one approach, the variable domains of two parent antibodies, wherein the parent antibodies are monoclonal antibodies are evolved using any method known in the art in a manner that allows a single light chain to functionally complement heavy chains of two different parent antibodies. Another approach requires evolving the heavy chain of a single parent antibody to recognize a second target antigen. A third approach involves evolving the light chain of a parent antibody so as to recognize a second target antigen. Methods for polypeptide evolution are described in International Publication WO2012009026, the contents of which are herein incorporated by reference in their entirety, and include as non-limiting examples. Comprehensive Positional Evolution (CPE), Combinatorial Protein Synthesis (CPS). Comprehensive Positional Insertion (CPI), Comprehensive Positional Deletion (CPD), or any combination thereof. The Fc region of the multi-specific antibodies described in United States Publication No. US20150252119 may be created using a knob-in-hole approach, or any other method that allows the Fc domain to form heterodimers. The resultant multi-specific antibodies may be further evolved for improved characteristics or properties such as binding affinity for the target antigen.


Bispecific Antibodies

In some embodiments, payloads of the invention may encode bispecific antibodies. Bispecific antibodies are capable of binding two different antigens. Such antibodies typically comprise antigen-binding regions from at least two different antibodies. For example, a bispecific monoclonal antibody (BsMAb, BsAb) is an artificial protein composed of fragments of two different monoclonal antibodies, thus allowing the BsAb to bind to two different types of antigen.


In some cases, payloads encode bispecific antibodies comprising antigen-binding regions from two different anti-tau antibodies. For example, such bispecific antibodies may comprise binding regions from two different antibodies selected from Tables 3-42. Bispecific antibody frameworks may include any of those described in Riethmuller, G., 2012. Cancer Immunity, 12:12-18; Marvin, J. S. et al., 2005. Acta Pharmacologica Sinica, 26(6):649-58, and Schaefer, W. et al., 2011. PNAS. 108(27); 11187-92, the contents of each of which are herein incorporated by reference in their entirety.


New generations of BsMAb, called “trifunctional bispecific” antibodies, have been developed. These consist of two heavy and two light chains, one each from two different antibodies, where the two Fab regions (the arms) are directed against two antigens, and the Fc region (the foot) comprises the two heavy chains and forms the third binding site.


Of the two paratopes that form the tops of the variable domains of a bispecific antibody, one can be directed against a target antigen and the other against a T-lymphocytes antigen like CD3. In the case of trifunctional antibodies, the Fc region may additionally bind to a cell that expresses Fc receptors, like a macrophage, a natural killer (NK) cell or a dendritic cell. In sum, the targeted cell is connected to one or two cells of the immune system, which subsequently destroy it.


Other types of bispecific antibodies have been designed to overcome certain problems, such as short half-life, immunogenicity and side-effects caused by cytokine liberation. They include chemically linked Fabs, consisting only of the Fab regions, and various types of bivalent and trivalent single-chain variable fragments (scFvs), fusion proteins mimicking the variable domains of two antibodies. The furthest developed of these newer formats are the bi-specific T-cell engagers (BuTEs) and mAb2's, antibodies engineered to contain an Fcab antigen-binding fragment instead of the Fe constant region.


Using molecular genetics, two scFvs can be engineered in tandem into a single polypeptide, separated by a linker domain, called a “tandem scFv” (tascFv). TascFvs have been found to be poorly soluble and require refolding when produced in bacteria, or they may be manufactured in mammalian cell culture systems, which avoids refolding requirements but may result in poor yields. Construction of a tascFv with genes for two different scFvs yields a “bispecific single-chain variable fragments” (bis-scFvs). Only two tascFvs have been developed clinically by commercial firms, both are bispecific agents in active early phase development by Micromet for oncologic indications, and are described as “Bispecific T-cell Engagers (BiTE).” Blinatumomab is an anti-CD19/anti-CD3 bispecific tascFv that potentiates T-cell responses to B-cell non-Hodgkin lymphoma in Phase 2. MT110 is an anti-EP-CAM/anti-CD3 bispecific tascFv that potentiates T-cell responses to solid tumors in Phase 1. Bispecific, tetravalent “TandAbs” are also being researched by Affimed (Nelson, A. L., MAbs. 2010. January-February, 2(1):77-83).


In some embodiments, payloads may encode antibodies comprising a single antigen-binding domain. These molecules are extremely small, with molecular weights approximately one-tenth of those observed for full-sized mAbs. Further antibodies may include “nanobodies” derived from the antigen-binding variable heavy chain regions (VHHS) of heavy chain antibodies found in camels and llamas, which lack light chains (Nelson. A. L., MAbs. 2010 January-February; 2(1):77-83).


Disclosed and claimed in PCT Publication WO02014144573 to Memorial Sloan-Kettering Cancer Center are multimerization technologies for making dimeric multispecific binding agents (e.g., fusion proteins comprising antibody components) with improved properties over multispecific binding agents without the capability of dimerization.


In some cases, payloads of the invention may encode tetravalent bispecific antibodies (TetBiAbs as disclosed and claimed in PCT Publication WO2014144357) TetBiAbs feature a second pair of Fab fragments with a second antigen specificity attached to the C-terminus of an antibody, thus providing a molecule that is bivalent for each of the two antigen specificities. The tetravalent antibody is produced by genetic engineering methods, by linking an antibody heavy chain covalently to a Fab light chain, which associates with its cognate, co-expressed Fab heavy chain.


In some aspects, payloads of the invention may encode biosynthetic antibodies as described in U.S. Pat. No. 5,091,513, the contents of which are herein incorporated by reference in their entirety. Such antibody may include one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic VH and VL dimers, 2) VH-VL or VL-VH single chains wherein the VH and VL are attached by a polypeptide linker, or 3) individuals VH or VL domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The biosynthetic antibodies may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the biosynthetic antibodies, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.


In some embodiments, payloads may encode antibodies with antibody acceptor frameworks taught in U.S. Pat. No. 8,399,625. Such antibody acceptor frameworks may be particularly well suited accepting CDRs from an antibody of interest. In some cases. CDRs from anti-tau antibodies known in the art or developed according to the methods presented herein may be used.


Miniaturized Antibody

In one embodiment, the antibody encoded by the payloads of the invention may be a “miniaturized” antibody. Among the best examples of mAb miniaturization are the small modular immunopharmaceuticals (SMIPs) from Trubion Pharmaceuticals. These molecules, which can be monovalent or bivalent, are recombinant single-chain molecules containing one VL, one VH antigen-binding domain, and one or two constant “effector” domains, all connected by linker domains. Presumably, such a molecule might offer the advantages of increased tissue or tumor penetration claimed by fragments while retaining the immune effector functions conferred by constant domains. At least three “miniaturized” SMIPs have entered clinical development. TRU-015, an anti-CD20 SMIP developed in collaboration with Wyeth, is the most advanced project, having progressed to Phase 2 for rheumatoid arthritis (RA). Earlier attempts in systemic lupus erythrematosus (SLE) and B cell lymphomas were ultimately discontinued. Trubion and Facet Biotechnology are collaborating in the development of TRU-016, an anti-CD37 SMIP, for the treatment of CLL and other lymphoid neoplasias, a project that has reached Phase 2. Wyeth has licensed the anti-CD20 SMIP SBI-087 for the treatment of autoimmune diseases, including RA, SLE and possibly multiple sclerosis, although these projects remain in the earliest stages of clinical testing. (Nelson, A. L., MAbs. 2010. January-February; 2(1):77-83).


Diabodies

In some embodiments, payloads of the invention may encode diabodies. Diabodies are functional bispecific single-chain antibodies (bscAb). These bivalent antigen-binding molecules are composed of non-covalent dimers of scFvs, and can be produced in mammalian cells using recombinant methods. (See, e.g., Mack et al. Proc. Natl. Acad. Sci., 92, 7021-7025, 1995). Few diabodies have entered clinical development. An iodine-123-labeled diabody version of the anti-CEA chimeric antibody cT84.66 has been evaluated for pre-surgical immunoscintigraphic detection of colorectal cancer in a study sponsored by the Beckman Research Institute of the City of Hope (Clinicaltrials.gov NCT00647153) (Nelson, A. L., MAbs 2010. January-February; 2(1):77-83)


Unibody

In some embodiments, payloads may encode a “unibody,” in which the hinge region has been removed from IgG4 molecules. While IgG4 molecules are unstable and can exchange light-heavy chain heterodimers with one another, deletion of the hinge region prevents heavy chain-heavy chain pairing entirely, leaving highly specific monovalent light-heavy heterodimers, while retaining the Fc region to ensure stability and half-life in vivo. This configuration may minimize the risk of immune activation or oncogenic growth, as IgG4 interacts poorly with FcRs and monovalent unibodies fail to promote intracellular signaling complex formation. These contentions are, however, largely supported by laboratory, rather than clinical, evidence. Other antibodies may be “miniaturized” antibodies, which are compacted 100 kDa antibodies (see, e.g., Nelson, A. L., MAbs. 2010. January-February; 2(1):77-83).


Intrabodies

In some embodiments, payloads of the invention may encode intrabodies. Intrabodies are a form of antibody that is not secreted from a cell in which it is produced, but instead targets one or more intracellular proteins. Intrabodies are expressed and function intracellularly, and may be used to affect a multitude of cellular processes including, but not limited to intracellular trafficking, transcription, translation, metabolic processes, proliferative signaling and cell division. In some embodiments, methods described herein include intrabody-based therapies. In some such embodiments, variable domain sequences and/or CDR sequences disclosed herein are incorporated into one or more constructs for intrabody-based therapy. For example, intrabodies may target one or more glycated intracellular proteins or may modulate the interaction between one or more glycated intracellular proteins and an alternative protein.


More than two decades ago, intracellular antibodies against intracellular targets were first described (Biocca, Neuberger and Cattaneo EMBO J. 9: 101-108, 1990). The intracellular expression of intrabodies in different compartments of mammalian cells allows blocking or modulation of the function of endogenous molecules (Biocca, et al., EMBO J 9: 101-108, 1990; Colby et al., Proc. Natl. Acad. Sci. U.S.A. 101: 17616-21, 2004) Intrabodies can alter protein folding, protein-protein, protein-DNA, protein-RNA interactions and protein modification. They can induce a phenotypic knockout and work as neutralizing agents by direct binding to the target antigen, by diverting its intracellular trafficking or by inhibiting its association with binding partners. They have been largely employed as research tools and are emerging as therapeutic molecules for the treatment of human diseases such as viral pathologies, cancer and misfolding diseases. The fast growing bio-market of recombinant antibodies provides intrabodies with enhanced binding specificity, stability and solubility, together with lower immunogenicity, for their use in therapy (Biocca, abstract in Antibody Expression and Production Cell Engineering Volume 7, 2011, pp. 179-195).


In some embodiments, intrabodies have advantages over interfering RNA (iRNA); for example, iRNA has been shown to exert multiple non-specific effects, whereas intrabodies have been shown to have high specificity and affinity to target antigens. Furthermore, as proteins, intrabodies possess a much longer active half-life than iRNA. Thus, when the active half-life of the intracellular target molecule is long, gene silencing through iRNA may be slow to yield an effect, whereas the effects of intrabody expression can be almost instantaneous. Lastly, it is possible to design intrabodies to block certain binding interactions of a particular target molecule, while sparing others.


Intrabodies are often single chain variable fragments (scFvs) expressed from a recombinant nucleic acid molecule and engineered to be retained intracellularly (e.g., retained in the cytoplasm, endoplasmic reticulum, or periplasm). Intrabodies may be used, for example, to ablate the function of a protein to which the intrabody binds. The expression of intrabodies may also be regulated through the use of inducible promoters in the nucleic acid expression vector comprising the intrabody. Intrabodies may be produced for use in the viral genomes of the invention using methods known in the art, such as those disclosed and reviewed in. (Marasco et al., 1993 Proc. Natl. Acal. Sci. USA, 90; 7889-7893; Chen et al., 1994, Hum. Gene Ther. 5:595-601; Chen et al., 1994, Proc. Natl. Acad. Sci. USA, 91: 5932-5936; Macieiewski et al, 1995, Nature Med., 1: 667-673; Marasco, 1995, Immunotech, 1: 1-19; Mhashilkar, et al., 1995, EMBO J. 14: 1542-51; Chen et al., 1996, Hum. Gene Therap., 7: 1515-1525, Marasco, Gene Ther. 4:11-15, 1997, Rondon and Marasco, 1997, Annu. Rev. Microbiol. 51: 257-283; Cohen, et al., 1998, Oncogene 17:2445-56; Proba et al., 1998, J. Mol. Biol. 275:245-253; Cohen et al., 1998, Oncogene 17:2445-2456; Hassanzadeh, et al., 1998, FEBS Lett. 437:81-6; Richardson et al., 1998, Gene Ther 5:635-44; Ohage and Steipe, 1999, J. Mol. Biol 291:1119-1128; Ohage et al., 1999, J. Mol. Biol. 291:1129-1134; Wirtz and Steipe, 1999, Protein Sci. 8:2245-2250; Zhu et al., 1999, J. Immunol Methods 231:207-222; Arafat et al., 2000, Cancer Gene Ther. 7:1250-6; der Maur et al., 2002, J. Biol. Chem. 277:45075-85, Mhashilkar et al., 2002, Gene Ther. 9:307-19; and Wheeler et al., 2003, FASEB J. 17: 1733-5, and references cited therein). In particular, a CCR5 intrabody has been produced by Steinberger et al., 2000), Proc. Natl. Acad. Sci. USA 97:805-810). See generally Marasco. W A. 1998, “Intrabodies: Basic Research and Clinical Gene Therapy Applications” Springer: New York, and for a review of scFvs, see Pluckthun in “The Pharmacology of Monoclonal Antibodies,” 1994, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315.


Sequences from donor antibodies may be used to develop intrabodies. Intrabodies are often recombinantly expressed as single domain fragments such as isolated VH and VL domains or as a single chain variable fragment (scFv) antibody within the cell. For example, intrabodies are often expressed as a single polypeptide to form a single chain antibody comprising the variable domains of the heavy and light chains joined by a flexible linker polypeptide. Intrabodies typically lack disulfide bonds and are capable of modulating the expression or activity of target genes through their specific binding activity. Single chain antibodies can also be expressed as a single chain variable region fragment joined to the light chain constant region.


As is known in the art, an intrabody can be engineered into recombinant polynucleotide vectors to encode sub-cellular trafficking signals at its N or C terminus to allow expression at high concentrations in the sub-cellular compartments where a target protein is located. For example, intrabodies targeted to the endoplasmic reticulum (ER) are engineered to incorporate a leader peptide and, optionally, a C-terminal ER retention signal, such as the KDEL amino acid motif (SEQ ID NO: 9223). Intrabodies intended to exert activity in the nucleus are engineered to include a nuclear localization signal. Lipid moieties are joined to intrabodies in order to tether the intrabody to the cytosolic side of the plasma membrane. Intrabodies can also be targeted to exert function in the cytosol. For example, cytosolic intrabodies are used to sequester factors within the cytosol, thereby preventing them from being transported to their natural cellular destination.


There are certain technical challenges with intrabody expression. In particular, protein conformational folding and structural stability of the newly-synthesized intrabody within the cell is affected by reducing conditions of the intracellular environment.


Intrabodies of the invention may be promising therapeutic agents for the treatment of misfolding diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, because of their virtually infinite ability to specifically recognize the different conformations of a protein, including pathological isoforms, and because they can be targeted to the potential sites of aggregation (both intra- and extracellular sites). These molecules can work as neutralizing agents against anmyloidogenic proteins by preventing their aggregation, and/or as molecular shunters of intracellular traffic by rerouting the protein from its potential aggregation site (Cardinale, and Biocca, Curr Mol. Med 2008, 8:2-11)


Maxibodies

In one embodiment, the payloads of the invention encode a maxibody (bivalent scFV fused to the amino terminus of the Fc (CH2-CH3 domains) of IgG,


Chimeric Antigen Receptors

In some embodiments, the polypeptides encoded by the viral genomes of the invention (e.g., antibodies) may be used to generate chimeric antigen receptors (CARs) as described by BIOATLA® in International Publications WO2016033331 and WO2016036916, the contents of which are herein incorporated by reference in their entirety. As used herein, a “chimeric antigen receptor (CAR)” refers to an artificial chimeric protein comprising at least one antigen specific targeting region (ASTR), wherein the antigen specific targeting region comprises a full-length antibody or a fragment thereof that specifically binds to a target antigen. The ASTR may comprise any of the following; a full length heavy or light chain, an Fab fragment, a single chain Fv fragment, a divalent single chain antibody, or a diabody. As a non-limiting example the ASTR of a CAR may be any of the antibodies listed in Tables 3-42, antibody-based compositions or fragments thereof. Any molecule that is capable of binding a target antigen with high affinity can be used in the ASTR of a CAR. In one embodiment, the CAR may have more than one ASTR. These ASTRs may target two or more antigens or two or more epitopes of the same antigen. In one embodiment, the CAR is conditionally active. In one embodiment, the CAR is used to produce a genetically engineered cytotoxic cell carrying the CAR and capable of targeting the antigen bound by the ASTR.


Chimeric antigen receptors (CARs) are particularly useful in the treatment of cancers, though also therapeutically effective in treatment of a wide variety of other diseases and disorders. Non-limiting examples of disease categories that may be treated with CARs or CAR-based therapeutics include autoimmune disorders, B-cell mediated diseases, inflammatory diseases, neuronal disorders, cardiovascular disease and circulatory disorders, or infectious diseases. Not wishing to be bound by theory, CARs traditionally work by targeting antigens presented on the surface of or on the inside of cells to be destroyed e.g., cancer tumor cells, by the cytotoxic cell of the CAR.


Senescent Cell Surface Protein Antibodies

In some embodiments, the AAV particles may comprise nucleic acids which have been engineered to express of antibodies that selectively bind to surface marker proteins of senescent cells. For example, the antibodies may selectively bind to proteins that are in misfolded conformation. The binding antibodies may reduce the number of senescent cells and be used to treat age-related conditions, such as, but not limited to. Alzheimer's disease, cardiovascular disease, emphysema, sarcopenia, and tumorigenesis as well as conditions more cosmetic in nature such as signs of skin aging including wrinkling, sagging, discoloration, age-related tissue dysfunction, tumor formation, and other age-related conditions.


In one embodiment, the expressed antibodies binding to epitopes of senescent cell surface proteins may be, but are not limited to, such as prion epitopes presented by SEQ ID NOs: 1-14 of International Publication No. WO2014186878, CD44 epitopes presented by SEQ ID NOs: 47-51 of International Publication No. WO2014186878; TNFR epitopes presented by SEQ ID NOs: 52-56 of International Publication No. WO2014186878; NOTCH1 epitope presented by SEQ ID NOs: 57-61 of International Publication No. WO2014186878; FasR epitopes presented by SEQ ID NOs: 62-66 of International Publication No. WO2014186878; epidermal growth factor epitopes presented by SEQ ID NOs: 67-81 of International Publication No. WO2014186878; CD38 epitopes presented by SEQ ID NOs: 82-86 of International Publication No. WO2014186878, the contents of each of which are herein incorporated by reference in their entirety.


In one embodiment, the expressed antibodies may comprise peptides binding to senescent cell surface prion proteins, such as, but not limited to, those presented by SEQ ID NOs: 15-36 of International Publication No. WO2014186878, the contents of which are herein incorporated by reference in their entirety.


In one embodiment, the expressed antibody may be AMF-3a-118 or AMF 3d-19 (SEQ ID NO: 89-92 and 103-106 of International publication WO2014186878, respectively, the contents of which are herein incorporated by reference in their entirety) targeting senescent cell surface protein FasR, In one embodiment, the expressed antibody may be Ab c-120 (SEQ ID NO: 37-40 of International publication WO2014186878, the contents of which are herein incorporated by reference in their entirety) targeting senescent cell surface protein PrP.


Payload Antibodies of the Invention

In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences listed in Tables 3-42.


In some embodiments, the payload region of the AAV particle comprises a nucleic acid sequence encoding a payload antibody with at least 50% identity to one or more payload antibody polypeptides listed in Tables 3-42. The encoded antibody polypeptide may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more of the payload antibody polypeptides listed in Tables 3-42.


In one embodiment, the full sequence of the encoded antibody polypeptide may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more of the payload antibody polypeptides listed in Tables 3-42.


In one embodiment, the variable region sequence(s) of the encoded antibody polypeptide may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 064%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more of the pay load antibody polypeptides listed in Tables 3-42.


In one embodiment, the heavy chain of the encoded antibody polypeptide may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65% 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more of the payload heavy chain antibody polypeptides listed in Tables 3-42.


In one embodiment, the light chain of the encoded antibody polypeptide may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more of the payload light chain antibody polypeptides listed in Tables 3-42.


In one embodiment, the CDR region of the encoded antibody polypeptide may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the CDRs of one or more of the payload antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 90% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 91% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 92% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 93% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 94% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 95% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 96% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 97% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 98% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 99% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In one embodiment, the payload antibody has 100% identity to one or more of the antibody polypeptides listed in Tables 3-42.


In some embodiments, the payload region of the AAV particle comprises a nucleic acid sequence with at least 50% identity to one or more nucleic acid sequences listed in Tables 3-42. The payload nucleic acid sequence may have 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 90% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 91% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 92% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 93% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 94% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 95% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 96% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 97% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 98% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 99% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload nucleic acid sequence has 100% identity to one or more of the nucleic acid sequences listed in Tables 3-42.


In one embodiment, the payload region of the AAV particle comprises a nucleic acid sequence encoding a polypeptide which is an antibody, an antibody-based composition, or a fragment thereof. As a non-limiting example, the antibody may be one or more of the polypeptides listed in Tables 3-42. As another non-limiting example, the antibody may be one or more of the heavy chain sequences listed in Tables 3-42. As a non-limiting example, the antibody may be one or more of the light chain sequences listed in Tables 3-42.


In one embodiment, the payload region of the AAV particle comprises a nucleic acid sequence encoding a polypeptide comprising a heavy chain and a light chain sequence listed in Tables 3-42. The payload region may also comprise a linker between the heavy and light chain sequences. The linker may be a sequence known in the art or described in Table 2.


In one embodiment, the payload region of the AAV particle comprises a nucleic acid sequence encoding a polypeptide comprising a heavy chain and a light chain sequence listed in Tables 3-42, where the heavy chain sequence is from a different antibody than the light chain sequence. The payload region may also comprise a linker between the heavy and light chain sequences. The linker may be a sequence known in the art or described in Table 2.


In one embodiment, the payload region comprises, in the 5′ to 3′ direction, an antibody light chain sequence, a linker and a heavy chain sequence.


In one embodiment, the payload region comprises a nucleic acid sequence encoding, in the 5′ to 3′ direction, an antibody light chain sequence from Tables 3-42, a linker from Table 2 and a heavy chain sequence from Tables 3-42.


In one embodiment, the payload region comprises, in the 5′ to 3′ direction, an antibody heavy chain sequence, a linker and a light chain sequence.


In one embodiment, the payload region comprises a nucleic acid sequence encoding, in the 5′ to 3′ direction, an antibody heavy chain sequence from Tables 3-42, a linker from Table 2 and a light chain sequence from Tables 3-42.


In one embodiment, the payload region comprises a nucleic acid sequence encoding a single heavy chain. As a non-limiting example, the heavy chain is an amino acid sequence or fragment thereof described in Tables 3-42.


Shown in Tables 3-42 are a listing of antibodies and their polynucleotides and/or polypeptides sequences. These sequences may be encoded by or included in the AAV particles of the present invention. Variants or fragments of the antibody sequences described in Tables 3-42 may be utilized in the AAV particles of the present invention.


In some embodiments, the AAV particles may comprise codon-optimized versions of the nucleic acids encoding the polypeptides listed in Tables 3-42. In some cases, the payload region of the AAV particles of the invention may encode one or more isoforms or variants of these heavy and light chain antibody domains. Such variants may be humanized or optimized antibody domains comprising one or more complementarity determining regions (CDRs) from the heavy and light chains listed in Tables 3-42. Methods of determining CDRs are well known in the art and are described herein Payload regions may encode antibody variants with one or more heavy chain variable domain (VH) or light chain variable domain (VL) derived from the antibody sequences in Tables 3-42. In some cases, such variants may include bispecific antibodies. Bispecific antibodies encoded by payload regions of the invention may comprise variable domain pairs from two different antibodies.


In one embodiment, the AAV particles may comprise a heavy and a light chain of an antibody described herein and two promoters. As a non-limiting example, the AAV particles may comprise a nucleic acid sequence of a genome as described in FIG. 1 or FIG. 2 of US Patent Publication No. US20030219733, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the AAV particles may be a dual-promoter AAV for antibody expression as described by Lewis et al. (J. of Virology, September 2002, Vol. 76(17), p 8769-8775; the contents of which are herein incorporated by reference in its entirety).


Foodborne Illness and Gastroenteritis Related Antibodies

In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the gastrointestinal and food illness related payload antibody polypeptides listed in Tables 3-9.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 3 against Clostridium difficile toxins









TABLE 3







Antibodies against Clostridium Difficile toxins















SEQ


Antibody

Antibody
Reference
ID


No.
Description
Name
Information
NO





CD1
Camelid heavy chain only,

WO2015100409
2948



Toxin A and B,

SEQ ID NO: 164



CD2
Camelid heavy chain only,

WO2015100409
2949



Toxin A and B,

SEQ ID NO: 165



CD3
Camelid heavy chain only,

WO2015100409
2950



Toxin A and B,

SEQ ID NO: 166



CD4
Camelid heavy chain only,

WO2015100409
2951



Toxin A and B,

SEQ ID NO: 167



CD5
Heavy chain variable region,
PA-39
U.S. Pat. No.
2952



toxin A

8,986,697






SEQ ID NO: 1



CD6
Heavy chain variable region,
PA-39
U.S. Pat. No.
2953



toxin A

8,986,697






SEQ ID NO: 2



CD7
Heavy chain variable region,
PA-50
U.S. Pat. No.
2954



toxin A

8,986,697






SEQ ID NO: 5



CD8
Heavy chain variable region,
PA-50
U.S. Pat. No.
2955



toxin A

8,986,697






SEQ ID NO: 6



CD9
Heavy chain variable region,

US20130202618
2956



toxin A

SEQ ID NO: 1



CD10
Heavy chain variable region,

US20130202618
2957



toxin A

SEQ ID NO: 2



CD11
Heavy chain variable region,

US20130202618
2958



toxin A

SEQ ID NO: 5



CD12
Heavy chain variable region,

US20130202618
2959



toxin A

SEQ ID NO: 6



CD13
Heavy chain variable region,
H1H3067N
US20130230531
2960



toxin A and/or toxin B

SEQ ID NO: 34



CD14
Heavy chain variable region,
H1H3134N
US20130230531
2961



toxin A and/or toxin B

SEQ ID NO: 18



CD15
Heavy chain variable region,
H1H3117N
US20130230531
2962



toxin A and/or toxin B

SEQ ID NO: 2



CD16
Heavy chain variable region,
H1H3123N
US20130230531
2963



toxin A and/or toxin B

SEQ ID NO: 66



CD17
Heavy chain variable region,
H1H3121N
US20130230531
2964



toxin A and/or toxin B

SEQ ID NO: 50



CD18
Heavy chain variable region,
H1H3124N
US20130230531
2965



toxin A and/or toxin B

SEQ ID NO: 82



CD19
Heavy chain variable region,
H1H3328P
US20130230531
2966



toxin A and/or toxin B

SEQ ID NO: 130



CD20
Heavy chain variable region,
H1H3324P
US20130230531
2967



toxin A and/or toxin B

SEQ ID NO: 98



CD21
Heavy chain variable region,
H1H3325P
US20130230531
2968



toxin A and/or toxin B

SEQ ID NO: 114



CD22
Heavy chain variable region,
H1H3330P
US20130230531
2969



toxin A and/or toxin B

SEQ ID NO: 146



CD23
Heavy chain variable region,
H1H3350P
US20130230531
2970



toxin A and/or toxin B

SEQ ID NO: 162



CD24
Heavy chain variable region,
H1H3347P
US20130230531
2971



toxin A and/or toxin B

SEQ ID NO: 274



CD25
Heavy chain variable region,
H1H3335P
US20130230531
2972



toxin A and/or toxin B

SEQ ID NO: 194



CD26
Heavy chain variable region,
H1H3344P
US20130230531
2973



toxin A and/or toxin B

SEQ ID NO: 258



CD27
Heavy chain variable region,
H1H3339P
US20130230531
2974



toxin A and/or toxin B

SEQ ID NO: 226



CD28
Heavy chain variable region,
H1H3337P
US20130230531
2975



toxin A and/or toxin B

SEQ ID NO: 210



CD29
Heavy chain variable region,
H1H3343P
US20130230531
2976



toxin A and/or toxin B

SEQ ID NO: 242



CD30
Heavy chain variable region,
H1H3411P
US20130230531
2977



toxin A and/or toxin B

SEQ ID NO: 354



CD31
Heavy chain variable region,
H1H3354P
US20130230531
2978



toxin A and/or toxin B

SEQ ID NO: 290



CD32
Heavy chain variable region,
H1H3317P
US20130230531
2979



toxin A and/or toxin B

SEQ ID NO: 178



CD33
Heavy chain variable region,
H1H3355P
US20130230531
2980



toxin A and/or toxin B

SEQ ID NO: 306



CD34
Heavy chain variable region,
H1H3394P
US20130230531
2981



toxin A and/or toxin B

SEQ ID NO. 322



CD35
Heavy chain variable region,
H1H3401P
US20130230531
2982



toxin A and/or toxin B

SEQ ID NO: 338



CD36
Heavy chain variable region,
PA-41
U.S. Pat. No.
2983



toxin B

8,986,697






SEQ ID NO: 8



CD37
Heavy chain variable region,
PA-41
U.S. Pat. No.
2984



toxin B

8,986,697






SEQ ID NO: 9



CD38
Heavy chain variable region,

US20130202618
2985



toxin B

SEQ ID NO: 8



CD39
Heavy chain variable region,

US20130202618
2986



toxin B

SEQ ID NO: 9



CD40
Heavy chain, toxin A
3D8
U.S. Pat. No.
2987





8,609,111






SEQ ID NO: 1



CD41
Heavy chain, toxin A
1B11
U.S. Pat. No.
2988





8,609,111






SEQ ID NO: 2



CD42
Heavy chain, toxin A
33.3H2
U.S. Pat. No.
2989





8,609,111






SEQ ID NO: 3



CD43
Heavy chain, toxin A

US20140004118
2990





SEQ ID NO: 89



CD44
Heavy chain, toxin A

US20140004118
2991





SEQ ID NO: 93



CD45
Heavy chain, toxin B

US20130058962
2992





SEQ ID NO: 65



CD46
Heavy chain, toxin B
Bezlotoxumab

2993


CD47
Heavy-chain-only, toxin A

US20130058962
2994





SEQ ID NO: 59



CD48
Heavy-chain-only, toxin A

US20130058962
2995





SEQ ID NO: 60



CD49
Heavy-chain-only, toxin A

US20130058962
2996





SEQ ID NO: 61



CD50
Heavy-chain-only, toxin A

US20130058962
2997





SEQ ID NO: 62



CD51
Heavy-chain-only, toxin A

US20130058962
2998





SEQ ID NO: 63



CD52
Heavy-chain-only, toxin A

US20130058962
2999





SEQ ID NO: 64



CD53
Heavy-chain-only, toxin A

US20130058962
3000





SEQ ID NO: 87



CD54
Heavy-chain-only, toxin A

US20130058962
3001





SEQ ID NO: 95



CD55
Heavy-chain-only, toxin B
124-152
U.S. Pat. No.
3002





8,609,111






SEQ ID NO: 54



CD56
Heavy-chain-only, toxin B

US20130058962
3003





SEQ ID NO: 66



CD57
Heavy-chain-only, toxin B

US20130058962
3004





SEQ ID NO: 67



CD58
Heavy-chain-only, toxin B

US20130058962
3005





SEQ ID NO: 68



CD59
Heavy-chain-only, toxin B

US20130058962
3006





SEQ ID NO: 69



CD60
Heavy-chain-only, toxin B

US20130058962
3007





SEQ ID NO: 70



CD61
Heavy-chain-only, toxin B

US20130058962
3008





SEQ ID NO: 71



CD62
Heavy-chain-only, toxin B

US20130058962
3009





SEQ ID NO: 72



CD63
Heavy-chain-only, toxin B

US20130058962
3010





SEQ ID NO: 73



CD64
Heavy-chain-only, toxin B

US20130058962
3011





SEQ ID NO: 74



CD65
Heavy-chain-only, toxin B

US20130058962
3012





SEQ ID NO: 75



CD66
Heavy-chain-only, toxin B

US20130058962
3013





SEQ ID NO: 76;






SEQ ID NO: 87;






SEQ ID NO: 95



CD67
Light chain variable region, toxin
PA-39
U.S. Pat. No.
3014



A

8,986,697






SEQ ID NO: 3



CD68
Light chain variable region, toxin
PA-39
U.S. Pat. No.
3015



A

8,986,697






SEQ ID NO: 4



CD69
Light chain variable region, toxin
PA-50
U.S. Pat. No.
3016



A

8,986,697






SEQ ID NO: 7



CD70
Light chain variable region, toxin

US20130202618
3017



A

SEQ ID NO: 3



CD71
Light chain variable region, toxin

US20130202618
3018



A

SEQ ID NO: 4



CD72
Light chain variable region, toxin

US20130202618
3019



A

SEQ ID NO: 7



CD73
Light chain variable region, toxin
H1H3067N
US20130230531
3020



A and/or toxin B

SEQ ID NO: 42



CD74
Light chain variable region, toxin
H1H3134N
US20130230531
3021



A and/or toxin B

SEQ ID NO: 26



CD75
Light chain variable region, toxin
H1H3117N
US20130230531
3022



A and/or toxin B

SEQ ID NO: 10



CD76
Light chain variable region, toxin
H1H3123N
US20130230531
3023



A and/or toxin B

SEQ ID NO: 74



CD77
Light chain variable region, toxin
H1H3121N
US20130230531
3024



A and/or toxin B

SEQ ID NO: 58



CD78
Light chain variable region, toxin
H1H3124N
US20130230531
3025



A and/or toxin B

SEQ ID NO: 90



CD79
Light chain variable region, toxin
H1H3328P
US20130230531
3026



A and/or toxin B

SEQ ID NO: 138



CD80
Light chain variable region, toxin
H1H3324P
US20130230531
3027



A and/or toxin B

SEQ ID NO: 106



CD81
Light chain variable region, toxin
H1H3325P
US20130230531
3028



A and/or toxin B

SEQ ID NO: 122



CD82
Light chain variable region, toxin
H1H3330P
US20130230531
3029



A and/or toxin B

SEQ ID NO: 154



CD83
Light chain variable region, toxin
H1H3350P
US20130230531
3030



A and/or toxin B

SEQ ID NO: 170



CD84
Light chain variable region, toxin
H1H3347P
US20130230531
3031



A and/or toxin B

SEQ ID NO: 282



CD85
Light chain variable region, toxin
H1H3335P
US20130230531
3032



A and/or toxin B

SEQ ID NO: 202



CD86
Light chain variable region, toxin
H1H3344P
US20130230531
3033



A and/or toxin B

SEQ ID NO: 266



CD87
Light chain variable region, toxin
H1H3339P
US20130230531
3034



A and/or toxin B

SEQ ID NO: 234



CD88
Light chain variable region, toxin
H1H3337P
US20130230531
3035



A and/or toxin B

SEQ ID NO: 218



CD89
Light chain variable region, toxin
H1H3343P
US20130230531
3036



A and/or toxin B

SEQ ID NO: 250



CD90
Light chain variable region, toxin
H1H3411P
US20130230531
3037



A and/or toxin B

SEQ ID NO: 362



CD91
Light chain variable region, toxin
H1H3354P
US20130230531
3038



A and/or toxin B

SEQ ID NO: 298



CD92
Light chain variable region, toxin
H1H3317P
US20130230531
3039



A and/or toxin B

SEQ ID NO: 186



CD93
Light chain variable region, toxin
H1H3355P
US20130230531
3040



A and/or toxin B

SEQ ID NO: 314



CD94
Light chain variable region, toxin
H1H3394P
US20130230531
3041



A and/or toxin B

SEQ ID NO: 330



CD95
Light chain variable region, toxin
H1H3401P
US20130230531
3042



A and/or toxin B

SEQ ID NO: 346



CD96
Light chain variable region, toxin
PA-41
U.S. Pat. No.
3043



B

8,986,697






SEQ ID NO: 10



CD97
Light chain variable region, toxin

US20130202618
3044



B

SEQ ID NO: 10



CD98
Light chain, toxin A
3D8
U.S. Pat. No.
3045





8,609,111






SEQ ID NO: 4



CD99
Light chain, toxin A
1B11
U.S. Pat. No.
3046





8,609,111






SEQ ID NO: 5



CD100
Light chain, toxin A
33.3H2
U.S. Pat. No.
3047





8,609,111






SEQ ID NO: 6



CD101
Light chain, toxin A

US20140004118
3048





SEQ ID NO: 91



CD102
Light chain, toxin A

US20140004118
3049





SEQ ID NO: 95



CD103
Light chain, toxin B
124-152
U.S. Pat. No.
3050





8,609,111






SEQ ID NO: 58



CD104
Light chain, toxin B
Bezlotoxumab

3051


CD105
Recombinant camelid heavy

WO2015100409
3052



chain only, Toxin A and B

SEQ ID NO: 87



CD106
Recombinant camelid heavy

WO2015100409
3053



chain only, Toxin A and B

SEQ ID NO: 95



CD107
Recombinant camelid heavy-

WO2015100409
3054



chain-only, toxin A

SEQ ID NO: 59



CD108
Recombinant camelid heavy-

WO2015100409
3055



chain-only, toxin A

SEQ ID NO: 60



CD109
Recombinant camelid heavy-

WO2015100409
3056



chain-only, toxin A

SEQ ID NO: 61



CD110
Recombinant camelid heavy-

WO2015100409
3057



chain-only, toxin A

SEQ ID NO: 62



CD111
Recombinant camelid heavy-

WO2015100409
3058



chain-only, toxin A

SEQ ID NO: 63



CD112
Recombinant camelid heavy-

WO2015100409
3059



chain-only, toxin A

SEQ ID NO: 64



CD113
Recombinant camelid heavy-

WO2015100409
3060



chain-only, toxin B

SEQ ID NO: 65



CD114
Recombinant camelid heavy-

WO2015100409
3061



chain-only, toxin B

SEQ ID NO: 66



CD115
Recombinant camelid heavy-

WO2015100409
3062



chain-only, toxin B

SEQ ID NO: 67



CD116
Recombinant camelid heavy-

WO2015100409
3063



chain-only, toxin B

SEQ ID NO: 68



CD117
Recombinant camelid heavy-

WO2015100409
3064



chain-only, toxin B

SEQ ID NO: 69



CD118
Recombinant camelid heavy-

WO2015100409
3065



chain-only, toxin B

SEQ ID NO: 70



CD119
Recombinant camelid heavy-

WO2015100409
3066



chain-only, toxin B

SEQ ID NO: 71



CD120
Recombinant camelid heavy-

WO2015100409
3067



chain-only, toxin B

SEQ ID NO: 72



CD121
Recombinant camelid heavy-

WO2015100409
3068



chain-only, toxin B

SEQ ID NO: 73



CD122
Recombinant camelid heavy-

WO2015100409
3069



chain-only, toxin B

SEQ ID NO: 74



CD123
Recombinant camelid heavy-

WO2015100409
3070



chain-only, toxin B

SEQ ID NO: 75



CD124
Recombinant camelid heavy-

WO2015100409
3071



chain-only, toxin B

SEQ ID NO: 76



CD125
Toxin A
Actoxumab

3072


CD126
Toxin A
Actoxumab

3073


CD127
Toxin A
MK3415A
U.S. Pat. No.
3074




(Actoxumab +
7,625,559





bezlotoxumab)
SEQ ID NO: 1



CD128
Toxin A
MK3415A
U.S. Pat. No.
3075




(Actoxumab +
7,625,559





bezlotoxumab)
SEQ ID NO: 4



CD129
Toxin A
MK3415A
U.S. Pat. No.
3076




(Actoxumab +
7,625,559





bezlotoxumab)
SEQ ID NO: 54



CD130
Toxin A
MK3415A
U.S. Pat. No.
3077




(Actoxumab +
7,625,559





bezlotoxumab)
SEQ ID NO: 58



CD131
Toxin A
A4.2
US20130230537
3078





SEQ ID NO: 34



CD132
Toxin A
A5.1
US20130230537
3079





SEQ ID NO: 35



CD133
Toxin A
A19.2
US20130230537
3080





SEQ ID NO: 36



CD134
Toxin A
A20.1
US20130230537
3081





SEQ ID NO: 37



CD135
Toxin A
A24.1
US20130230537
3082





SEQ ID NO: 38



CD136
Toxin A
A26.8
US20130230537
3083





SEQ ID NO: 39



CD137
Toxin B
B5.2
US20130230537
3084





SEQ ID NO: 40



CD138
Toxin B
B7.3
US20130230537
3085





SEQ ID NO: 41



CD139
Toxin B
B13.6
US20130230537
3086





SEQ ID NO: 42



CD140
Toxin B
B15.3
US20130230537
3087





SEQ ID NO: 43



CD141
Toxin B
B15.5
US20130230537
3088





SEQ ID NO: 44









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 4 against Campylobacter jejuni









TABLE 4







Antibodies against Campylobacter jejuni















SEQ


Antibody


Reference
ID


No.
Description
Antibody Name
Information
NO














CAMP1
Consensus
FlagV1
WO2014063253
3089





SEQ ID NO: 7



CAMP2
—
FlagV1M
WO2014063253
3090





SEQ ID NO: 8



CAMP3
—
F1agV1F23M
WO2014063253
3091





SEQ ID NO: 9



CAMP4
—
FlagV1MDSB
WO2014063253
3092





SEQ ID NO: 10



CAMP5
—
FlagV1MDSB
WO2014063253
3093





SEQ ID NO: 11



CAMP6
Consensus
FlagV6
WO2014063253
3094





SEQ ID NO: 12



CAMP7
—
FlagV6M
WO2014063253
3095





SEQ ID NO: 13



CAMP8
—
F1agV6F23M
WO2014063253
3096





SEQ ID NO: 14



CAMP9
—
FlagV6MDSB
WO2014063253
3097





SEQ ID NO: 15



CAMP10
—
FlagV6F23MDSB
WO2014063253
3098





SEQ ID NO: 16









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 5 against bacterial infections of the intestine.









TABLE 5







Antibodies against bacterial infections of the intestine















SEQ


Antibody

Antibody
Reference
ID


No.
Description
Name
Information
NO





BACG1
Antibody against Listeria monocytogenes
Antibody
CN103497252
3099




from
SEQ ID NO: 1





CN103497252




BACG2
Bivalent monovalent antibody against Pseudomonas,
anti-
U.S. Pat. No.
3100




Clostridium, Staphylococcus, Pasteurella, Yersinia,
LYS3-
7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,
long
SEQ ID NO: 22





Salmonella, Shigella, and Listeria, Clostridium,
hinge/Cys-






Staphylococcus, Pseudomonas, Pasteurella, Yersinia,
Tag






Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria





BACG3
Heavy chain only, Antibody against Pseudomonas,
LYS2
U.S. Pat. No.
3101




Clostridium, Staphylococcus, Pasteurella, Yersinia,
VHH
7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,

SEQ ID NO: 18





Salmonella, Shigella, and Listeria, Clostridium,







Staphylococcus, Pseudomonas, Pasteurella, Yersinia,







Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria





BACG4
Heavy chain only, Antibody against Pseudomonas,
LYS3
U.S. Pat. No.
3102




Clostridium, Staphylococcus, Pasteurella, Yersinia,
VHH
7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,

SEQ ID NO: 24





Salmonella, Shigella, and Listeria, Clostridium,







Staphylococcus, Pseudomonas, Pasteurella, Yersinia,







Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria





BACG5
Heavy chain segment including variable region,
F10
U.S. Pat. No.
3103




Starhylococcus enterotoxin B

8,895,704






SEQ ID NO: 30



BACG6
Heavy chain variable region. Antibody against, P.
mAb 741
U.S. Pat. No.
3104



aeruginosa, Proteus Vulgaris, non-pathogenic E. coli,

8,263,078





Citrobacter freundii, Serratia marcenscens, Enterobacter

SEQ ID NO: 1





cloacae, Campylobacterjejuni, Helicobacter pylori,







Salmonella
typhimurium, Salmonellamuenchen, Proteus







mirabilis and Enteropathogenic E. coli,





BACG7
Heavy chain variable region, Antibody against, P.
mAb 763
U.S. Pat. No.
3105



aeruginosa, ProteusVulgaris, non-pathogenic E.Coli,

8,263,078





Citrobacter freundii, Serratia marcenscens, Enterobacter

SEQ ID NO: 2





cloacae, Campylobacterjejuni, Helicobacter pylori,







Salmonella
typhimurium, Salmonella muenchen, Proteus







mirabilis and Enteropathogenic E. coli.,





BACG8
Heavy chain variable region, antibody against flagellin

U.S. Pat. No.
3106



from Salmonella or Pseudomonas

8,173,130






SEQ ID NO: 1



BACG9
Heavy chain variable region, Antibody against Gram
INO 743
US20100239583
3107



negative (E. coli, Salmonella, Serratia, Proteus,

SEQ ID NO: 1





Enterobacter, Citrobacter, Campylobacter






and Pseudomonas)





BACG10
Heavy chain variable region, Antibody against
Abba3
U.S. Pat. No.
3108




Helicobacter
pyroli


8,025,880






SEQ ID NO: 18



BACG11
Heavy chain variable region, Antibody against
IgHV3-48*3
U.S. Pat. No.
3109




Helicobacter
pyroli


8,025,880






SEQ ID NO: 20



BACG12
Heavy chain variable region, Antibody against
clone 5
U.S. Pat. No.
3110




Helicobacter
pyroli


8,025,880






SEQ. ID NO: 21



BACG13
Heavy chain variable region, Antibody against
C4
U.S. Pat. No.
3111




Helicobacter
pyroli


8,025,880






SEQ ID NO: 22



BACG14
Heavy chain variable region, Antibody against
IgHV1-18*01
U.S. Pat. No.
3112




Helicobacter
pyroli


8,025,880






SEQ ID NO: 23



BACG15
Heavy chain variable region, Antibody against
C5
U.S. Pat. No.
3113




Helicobacter
pyroli


8,025,880






SEQ ID NO: 24



BACG16
Heavy chain variable region, antibody against many
SWLA3
WO2003007989
3114



pathogens,

SEQ ID NO: 4



BACG17
Heavy chain variable region, antibody against
SWLA3
US20040052814
3115




Streptococcus mutans, Escherichia coli, Shigella

SEQ ID NO: 4





dysenteriae, Salmonellatyphimurium, Streptococcus







pneumoniae, Staphylococcusaureus, and Pseudomonas






aeruginosa





BACG18
Heavy chain variable region, antibody against
SWLA3
US20040052814
3116




Streptococcus mutans, Escherichia coli, Shigella

SEQ ID NO: 8





dysenteriae, Salmonellatyphimurium, Streptococcus







pneumoniae, Staphylococcusaureus, and Pseudomonas






aeruginosa





BACG19
Heavy chain, antibody against E coli, Shigella,
Ab1
WO2012162253
3117



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 4





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG20
Heavy chain, antibody against E coli, Shigella,
Ab2
WO2012162253
3118



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ. ID NO: 14





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG21
Heavy chain, antibody against E coli, Shigella,
Ab3
WO2012162253
3119



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 24





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG22
Heavy chain, antibody against E coli, Shigella,
Ab4
WO2012162253
3120



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 34





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG23
Heavy chain, antibody against E coli, Shigella,
Ab5
WO2012162253
3121



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 44





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG24
Heavy chain, antibody against E coli, Shigella,
Ab6
WO2012162253
3122



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 54





Clostridium
difficile, iotavirus, RSV, HIV, nomoyirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG25
Heavy chain, antibody against E coli, Shigella,
Ab7
WO2012162253
3123



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 64





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG26
Heavy chain, antibody against E coli, Shigella,
Ab8
WO2012162253
3124



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 74





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG27
Heavy chain, antibody against E coli, Shigella,
Ab9
WO2012162253
3125



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 84





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG28
Heavy chain, antibody against E coli, Shigella,
Ab10
WO2012162253
3126



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 94





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG29
Heavy chain, antibody against E coli, Shigella,
Ab11
WO2012162253
3127



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 104





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG30
Heavy chain, antibody against E coli, Shigella,
Ab12
WO2012162253
3128



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID NO: 114





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG31
Heavy chain, antibody against E coli, Shigella,
Ab13
WO2012162253
3129



Entaamoeba histolytica, Salmonella. Campylobacter, or

SEQ ID NO: 124





Clostridium
difficile, iotavirus, RSV, HIV, nomoyirus,






adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG32
Heavy chain, antibody against E coli,Shigella,
Ab14
WO2012162253
3130



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 134




adenovirus, and astrovirus, other diseases causing






diarrhea,





BACG33
Heavy chain, Antibody against Escherichia coli

WO2014070117
3131



infection, Staphylococcus infection

SEQ ID NO: 3



BACG34
Heavy chain, Antibody against Listeria
6H8
U.S. Pat. No.
3132



monocytogenes or WR-tubercle bacillus

8,445,643






SEQ ID NO: 5



BACG35
Heavy chain, Antibody against Pseudomonas,

U.S. Pat. No.
3133




Clostridium, Staphylococcus, Pasteurella, Yersinia,

7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli.

SEQ ID NO: 25





Salmonella, Shigella, and Listeria, Clostridium,







Staphylococcus, Pseudomonas, Pasteurella, Yersinia,







Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria





BACG36
Heavy chain, Antibody against Pseudomonas,

U.S. Pat. No.
3134




Clostridium, Staphylococcus, Pasteurella, Yersinia,

7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,

SEQ ID NO: 26





Salmonella, Shigella, and Listeria, Clostridium,







Staphylococcus, Pseudomonas, Pasteurella, Yersinia,







Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria





BACG37
Heavy chain, Starhylococcus enterotoxin B
100C9
U.S. Pat. No.
3135





8,895,704






SEQ ID NO: 34



BACG38
Heavy chain, Starhylococcus enterotoxin B
79G9+
U.S. Pat. No.
3136





8,895,704






SEQ ID NO: 38



BACG39
Heavy chain, Starhylococcus enterotoxin B
79G9
U.S. Pat. No.
3137





8,895,704






SEQ ID NO: 126



BACG40
Heavy chain, Starhylococcus enterotoxin B
154G12
U.S. Pat. No.
3138





8,895,704






SEQ ID NO: 142



BACG41
Light chain variable region, Antibody against, P.
mAb 741
U.S. Pat. No.
3139



aeruginosa, ProteusVulgaris, non-pathogenic E. coli,

8,263,078





Citrobacter freundii, Serratia marcenscens, Enterobacter

SEQ ID NO: 3





cloacae, Campylobacterjejuni, Helicobacter pylori,







Salmonella
typhimurium, Salmonella muenchen, Proteus







mirabilis and Enteropathogenic E. coli





BACG42
Light chain variable region, Antibody against, P.
mAb 763
U.S. Pat. No.
3140



aeruginosa, ProteusVulgaris, non-pathogenic E. coli,

8,263,078





Citrobacter
freundii, Serratia marcenscens, Enterobacter

SEQ ID NO: 4





cloacae, Campylobacterjejuni, Helicobacter pylori,







Salmonella
typhimurium, Salmonella muenchen, Proteus







mirabilis and Enteropathogenic E. coli





BACG43
Light chain variable region, Antibody against E coli,
Ab1
WO2012162253
3141




Shigella, Entaamoeba histolytica, Salmonella,

SEQ ID NO: 1





Campylobacter, or Clostridiumdifficile, rotavirus, RSV,






HIV, norvovirus, adenovirus, and astrovirus, other






diseases causing diarrhea





BACG44
Light chain variable region, antibody against flagellin

U.S. Pat. No.
3142



from Salmonella or Pseudomonas

8,173,130






SEQ ID NO: 3



BACG45
Light chain variable region, Antibody against Gram
INO 743
US20100239583
3143



negative (E. coli, Salmonella, Serratia, Proteus,

SEQ ID NO: 2





Enterobacter, Citrobacter, Campylobacter






and Pseudomonas)





BACG46
Light chain variable region, Antibody against
Abba3
U.S. Pat. No.
3144




Helicobacter
pyroli


8,025,880






SEQ ID NO: 19



BACG47
Light chain variable region, Antibody against many
SWLA3
WO2003007989
3145



pathogens

SEQ ID NO: 7



BACG48
Light chain, Antibody against E. coli, Shigaella,
Ab 1
US201200294822
3146



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID NO: 2




or Clostridiumdifficile or a virus selected from rotavirus,






RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG49
Light chain, Antibody against E. coli, Shigaella,
Ab 1
US201200294822
3147



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID NO: 4




or Clostridiumdifficile or a virus selected from rotavirus,






RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG50
Light chain, Antibody against E. coli, Shigaella,
Ab 2
US201200294822
3148



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 12




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG51
Light chain, Antibody against E. coli, Shigaella,
Ab 2
US201200294822
3149



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 14




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG52
Light chain, Antibody against E. coli, Shigaella,
Ab 3
US201200294822
3150



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 22




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG53
Light chain, Antibody against E. coli, Shigaella,
Ab 3
US201200294822
3151



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 24




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG54
Light chain, Antibody against E. coli, Shigaella,
Ab 4
US201200294822
3152



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 32




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG55
Light chain, Antibody against E. coli, Shigaella,
Ab 4
US201200294822
3153



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 34




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG56
Light chain, Antibody against E. coli, Shigaella,
Ab 5
US201200294822
3154



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 42




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG57
Light chain, Antibody against E. coli, Shigaella,
Ab 5
US201200294822
3155



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 44




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG58
Light chain, Antibody against E. coli, Shigaella,
Ab 6
US201200294822
3156



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 52




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG59
Light chain, Antibody against E. coli, Shigaella,
Ab 6
US201200294822
3157



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 54




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG60
Light chain, Antibody against E. coli, Shigaella,
Ab 7
US201200294822
3158



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 62




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG61
Light chain, Antibody against E. coli, Shigaella,
Ab 7
US201200294822
3159



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 64




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG62
Light chain, Antibody against E. coli, Shigaella,
Ab 8
US201200294822
3160



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 72




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG63
Light chain, Antibody against E. coli, Shigaella,
Ab 8
US201200294822
3161



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 74




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG64
Light chain, Antibody against E. coli, Shigaella,
Ab 9
US201200294822
3162



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected front rotavirus,

NO: 82




RSV, HIV, norvovirus, adenovirus, and astrovirus





BAC065
Light chain, Antibody against Ecoli, Shigaella,
Ab 9
US201200294822
3163



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 84




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG66
Light chain, Antibody against E. coli, Shigaella,
Ab 10
US201200294822
3164



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 92




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG67
Light chain, Antibody against E. coli, Shigaella,
Ab 10
US201200294822
3165



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 94




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG68
Light chain, Antibody against E. coli, Shigaella,
Ab 11
US201200294822
3166



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 102




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG69
Light chain, Antibody against E. coli, Shigaella,
Ab 11
US201200294822
3167



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 104




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG70
Light chain, Antibody against E. coli, Shigaella,
Ab 12
US201200294822
3168



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 112




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG71
Light chain, Antibody against E. coli, Shigaella,
Ab 12
US201200294822
3169



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 114




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG72
Light chain, Antibody against E. coli, Shigaella,
Ab 13
US201200294822
3170



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 122




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG73
Light chain, Antibody against E. coli, Shigaella,
Ab 13
US201200294822
3171



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 124




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG74
Light chain, Antibody against E. coli, Shigaella,
Ab 14
US201200294822
3172



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 132




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG75
Light chain, Antibody against E.coli, Shigaella,
Ab 14
US201200294822
3173



Entaamoeba histolvtica, Salmonella, Campylobacter,

SEQ ID




or Clostridiumdifficile or a virus selected from rotavirus,

NO: 134




RSV, HIV, norvovirus, adenovirus, and astrovirus





BACG76
Light chain, Antibody against E coli, Shigella,
Ab2
WO2012162253
3174



Entaamoeba histolvtica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 11




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG77
Light chain, Antibody against E coli, Shigella,
Ab3
WO2012162253
3175



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 22




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG78
Light chain, Antibody against E coli, Shigella,
Ab4
WO2012162253
3176



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 31




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG79
Light chain, Antibody against E coli, Shigella,
Ab5
WO2012162253
3177



Entaamoeba histolytica, Salmonella. Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 42




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG80
Light chain, Antibody against E coli, Shigella,
Ab6
WO2012162253
3178



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostidium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 52




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG81
Light chain, Antibody against E coli, Shigella,
Ab7
WO2012162253
3179



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 61




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG82
Light chain, Antibody against E coli, Shigella,
Ab8
WO2012162253
3180



Entaamoeba histolytica, Salmonella. Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 71




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG83
Light chain, Antibody against E coli, Shigella,
Ab9
WO2012162253
3181



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 82




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG84
Light chain, Antibody against E coli, Shigella,
Ab10
WO2012162253
3182



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 91




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG85
Light chain, Antibody against E coli, Shigella,
Ab11
WO2012162253
3183



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 102




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG86
Light chain, Antibody against E coli, Shigella,
Ab12
WO2012162253
3184



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 112




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG87
Light chain, Antibody against E coli, Shigella,
Ab13
WO2012162253
3185



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, notvovirus,

NO: 122




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG88
Light chain, Antibody against E coli, Shigella,
Ab14
WO2012162253
3186



Entaamoeba histolytica, Salmonella, Campylobacter, or

SEQ ID





Clostridium
difficile, rotavirus, RSV, HIV, norvovirus,

NO: 132




adenovirus, and astrovirus, other diseases causing






diarrhea





BACG89
Light chain, Antibody against Escherichia coli infection,

WO2014070117
3187




Staphylococcus infection

SEQ ID NO: 4



BACG90
Light chain, Antibody against Listeriamonocytogenes or
6H8
U.S. Pat. No.
3188



WR-tubercle bacillus

8,445,643






SEQ ID NO: 6



BACG91
Light chain, Staphylococcus enterotoxin B
F10
U.S. Pat. No.
3189





8,895,704






SEQ ID NO: 28



BACG92
Light chain, Staphylococcus enterotoxin B
100C9
U.S. Pat. No.
3190





8,895,704






SEQ ID NO: 32



BACG93
Light chain, Staphylococcus enterotoxin B
79G9
U.S. Pat. No.
3191





8,895,704






SEQ ID NO: 36



BACG94
Light chain, Staphylococcus enterotoxin B
154G12
U.S. Pat. No.
3192





8,895,704






SEQ ID NO: 134



BACG95
ScFv, Antibody against Clostridiumperfringens, anti-
ScFv-1A8
Zhao, B. and
3193



alpha toxin 1A8

Xu, C.






“Cloning and






sequencing of






the ScFv-2E3






gene anti-






alpha toxin of







clostridium








perfringens







type A”, Chin.






J. Vet. Sci. 20,






246-248






(2000), CNBI






Accession #






AAU11282



BACG96
ScFv, Antibody against Clostridiumperfringens, anti-
ScFv-2E3
Zhao, B. and
3194



alpha toxin 2E3

Xu, C.






“Cloning and






sequencing of






the ScFv-2E3






gene anti-






alpha toxin of







clostridium








perfringens







type A”, Chin.






J. Vet. Sci. 20,






246-248






(2000), NCBI






Accession #






AAU11283



BACG97
Variable fragment, Antibody against Pseudomonas,
αTT2
U.S. Pat. No.
3195




Clostridium, Staphylococcus, Pasteurella, Yersinia,

7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,

SEQ ID NO: 8





Salmonella, Shigella, and Listeria, Clostridium,







Staphylococcus, Pseudomonas, Pasteurella, Yersinia,







Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria





BACG98
Variable fragment, antibody against Pseudomonas,
αTT1
U.S. Pat. No.
3196




Clostridium, Staphylococcus, Pasteurella, Yersinia,

7,655,759





Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,

SEQ ID NO: 7





Salmonella, Shigella, and Listeria, Clostridium,







Staphylococcus, Pseudomonas, Pasteurella, Yersinia,







Bacillus anthracis, Neisseria, Vibrio, enterotoxic E. coli,







Salmonella, Shigella, and Listeria bacteria,









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 6 against Hepatitis A and/or Hepatitis E.









TABLE 6







Antibodies against Hepatitis A and Hepatitis E











Antibody



SEQ


No.
Description
Antibody Name
Reference Information
ID NO





HEPAE1
Heavy chain variable region,
HEV-Fab-216
CN1486990A; CN100497391C
3197



HEV Ab, a humanized






neutralizing genetically






engineered antibody





HEPAE2
Heavy chain variable region,
HEV-Fab-315
CN1486990A; CN100497391C
3198



HEV Ab, a humanized






neutralizing genetically






engineered antibody





HEPAE3
Heavy chain variable region,
HEV-Fab-319
CN1486990A; CN100497391C
3199



HEV Ab, a humanized






neutralizing genetically






engineered antibody





HEPAE4
Heavy chain variable region,
HEV-Fab-328
CN1486990A; CN100497391C
3200



HEV Ab, a humanized






neutralizing genetically






engineered antibody





HEPAE5
Heavy chain variable region,
HEV-Fab-404
CN1486990A; CN100497391C
3201



HEV Ab, a humanized






neutralizing genetically






engineered antibody





HEPAE6
Heavy chain variable region,
13D8
US7786264 SEQ ID NO. 8;
3202



HEV monoclonal antibody

US20060233822;






US20100003281; EP1452541;






EP2322625



HEPAE7
Heavy chain variable region,
16D7
US7786264 SEQ ID NO. 20;
3203



HEV monoclonal antibody

US20060233822;






US20100003281; EP1452541;






EP2322625



HEPAE8
Heavy chain variable region,
8C11
US7786264 SEQ ID NO. 12;
3204



HEV monoclonal antibody

US20060233822;






US20100003281; EP1452541;






EP2322625



HEPAE9
Heavy chain variable region,
8H3
US7786264 SEQ ID NO. 16;
3205



HEV monoclonal antibody

US20060233822;






US20100003281; EP1452541;






EP2322625



HEPAE10
Heavy chain variable region,
HEV # 31
US7148323 SEQ ID NO: 3;
3206



HEV neutralizing antibody

US20050233316; US6930176;






WO2001040270



HEPAE11
Heavy chain variable region,
HEV # 4
US7786264 SEQ ID NO: 1;
3207



HEV neutralizing antibody

US20050233316; US6930176;






WO2001040270



HEPAE12
Heavy chain variable region,
anti-HAV
Kim S. J., et al., Neutralizing
3208



partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCBI Accession






# AAO86899.1(124aa)



HEPAE13
Heavy chain variable region,
anti-HAV
Kim S. J., et al., Neutralizing
3209



partial. HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCBI Accession






# AAO86898.1(129aa)



HEPAE14
Heavy chain variable region,
anti-HAV
Kim S. J., et al., Neutralizing
3210



partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCBI Accession






# AAO86897.1(129aa)



HEPAE15
Heavy chain variable region,
anti-HA V
Kim S. J., et al., Neutralizing
3211



partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCBI Accession






# AAO86896.1(129aa)



HEPAE16
Heavy chain, HEV antibody
8g12
Gu Y., et al., Structural basis for
3212



(mouse monoclonal antibody),

tire neutralization of hepatitis E




E2 glycoprotein

virus by a cross-genotype






antibody; Cell Res. 25 (5),






604-620 (2015); NCBI Accession






# 4PLJ_H (229aa)



HEPAE17
Heavy chain, HEV antibody

Tang X., et al., Proc. Natl. Acad.
3213



(mouse monoclonal antibody), E2

Sci. U.S.A. 108 (25), 10266-




glycoprotein

10271 (2011); NCBI Accession #






3RKD_H(230aa)



HEPAE18
Light chain variable region,
HAV # 14
US7635476 SEQ ID NO: 4;
3214



gamma1, HAV,

US7282205; US20040260067;






US20070287667; WO2003040341



HEPAE19
Light chain variable region,
HAV # 4
US7635476 SEQ ID NO: 1;
3215



gamma1, HAV,

US7282205; US20040260067;






US20070287667; WO2003040341



HEPAE20
Light chain variable region,
HAV # 5
US7635476 SEQ ID NO: 2;
3216



gamma1, HAV,

US7282205; US20040260067;






US20070287667; WO2003040341



HEPAE21
Light chain variable region,
HAV # 6
US7635476 SEQ ID NO: 3;
3217



gamma1, HAV,

US7282205; US20040260067;






US20070287667; WO2003040341



HEPAE22
Light chain variable region, HEV
HEV-Fab-216
CN1486990A; CN100497391C
3218



Ab, a humanized neutralizing






genetically engineered antibody





HEPAE23
Light chain variable region, HEV
HEV-Fab-315
CN1486990A; CN100497391C
3219



Ab, a humanized neutralizing






genetically engineered antibody





HEPAE24
Light chain variable region, HEV
HEV-Fab-319
CN1486990A; CN100497391C
3220



Ab, a humanized neutralizing






genetically engineered antibody





HEPAE25
Light chain variable region, HEV
HEV-Fab-328
CN1486990A; CN100497391C
3221



Ab, a humanized neutralizing






genetically engineered antibody





HEPAE26
Light chain variable region, HEV
HEV-Fab-404
CN1486990A; CN100497391C
3222



Ab, a humanized neutralizing






genetically engineered antibody





HEPAE27
Light chain variable region,

WO2011114353 SEQ ID NO: 25
3223



monovalent, HAV





HEPAE28
Light chain variable region,
anti-HAV
Kim S. J., et al., Neutralizing
3224



partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCB1 Accession






# AAO86903.1(107aa)



HEPAE29
Light chain variable region,
anti-HAV
Kim S. J., el al., Neutralizing
3225



partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCBI Accession






# AAO86902.1(107aa)



HEPAE30
Light cliain variable region,
anti-HAV
Kim S. J., el al., Neutralizing




partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004), NCBI Accession






# AAO86901.1(107aa)



HEPAE31
Light chain variable region,
anti-HAV
Kim S. J., et al., Neutralizing




partial, HAV
capsid
human monoclonal antibodies to






hepatitis A virus recovered by






phage display; Virology 318 (2),






598-607 (2004). NCB I Accession






# AAO86900.1(107aa)



HEPAE32
Light chain variable, HEV
13D8
US7786264 SEQ ID NO. 6;
3228



monoclonal antibody

US20060233822; US20100003281;






EP1452541; EP2322625



HEPAE33
Light chain variable, HEV
16D7
US7786264 SEQ ID NO. 18;
3229



monoclonal antibody

US20060233822; US20100003281;






EP1452541; EP2322625



HEPAE34
Light chain variable, HEV
8C11
US7786264 SEQ ID NO: 10;
3230



monoclonal antibody

US20060233822; US20100003281;






EP1452541; EP2322625



HEPAE35
Light chain variable, HEV
8H3
US7786264 SEQ ID NO. 14;
3231



monoclonal antibody

US20060233822; US20100003281;






EP1452541; EP2322625



HEPAE36
Light chain variable, HEV
HEV # 31
US7148323 SEQ ID NO: 4;
3232



monoclonal antibody

US20050233316; US6930176;






WO2001040270



HEPAE37
Light chain variable, HEV
HEV # 4
US7148323 SEQ ID NO: 2;
3233



monoclonal antibody

US20050233316; US6930176;






WO2001040270



HEPAE38
Light chain, E2 glycoprotein,
8g12
Gu Y., et al., Structural basis for
3234



HEV antibody (mouse

the neutralization of hepatitis E




monoclonal antibody)

virus by a cross-genotype






antibody; Cell Res. 25 (5), 604-






620 (2015); NCBI Accession #






4PLJ_L (212aa)



HEPAE39
Light chain, E2 glycoprotein,

Tang X., et al., Proc. Natl. Acad.
3235



HEV antibody (mouse

Sci. U.S.A. 108(25), 10266-




monoclonal antibody)

10271 (2011), NCBI Accession #






3RKD_C (214aa)



HEPAE40
Monovalent Heavy chain variable

WO2011114353 SEQ ID NO: 24
3236



region, HAV





HEPAE41
ScFv, HAV, Monovalent human

WO2011114353 SEQ ID NO: 27
3237



antibody









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in Chinese Pub. No. CN103923881, CN103923882, CN1605628, CN1318565, CN1163512, the contents of each of which are herein incorporated by reference in their entirety, against HAV.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 7 against Norwalk virus.









TABLE 7







Antibodies against Norwalk virus











Antibody

Antibody

SEQ


No.
Description
Name
Reference Information
ID NO





NORV1
Heavy chain variable region,
B7
WO2014126921 SEQ ID NO: 8
3238



Norwalk virus





NORV2
Light chain variable region,
B7
WO2014126921 SEQ ID NO: 16
3239



Norwalk virus





NORV3
Heavy chain variable region,
B72
WO2014126921 SEQ ID NO: 120
3240



Norwalk virus





NORV4
Light chain variable region,
B72
WO2014126921 SEQ ID NO: 128
3241



Norwalk virus





NORV5
Heavy chain variable region,
C9
WO2014126921 SEQ ID NO: 88
3242



Norwalk virus





NORV6
Light chain variable region,
C9
WO2014126921 SEQ ID NO: 96
3243



Norwalk virus





NORV7
Heavy chain variable region,
D4
WO2014126921 SEQ ID NO: 136
3244



Norwalk virus





NORV8
Light chain variable region,
D4
WO2014126921 SEQ ID NO: 144
3245



Norwalk virus





NORV9
Heavy chain variable region,
D8
WO2014126921 SEQ ID NO: 24
3246



Norwalk virus





NORV10
Light chain variable region,
D8
WO2014126921 SEQ ID NO: 32
3247



Norwalk virus





NORV1
Heavy chain variable region,
E5
WO2014126921 SEQ ID NO: 40
3248



Norwalk virus





NORV12
Light chain variable region,
E5
WO2014126921 SEQ ID NO: 48
3249



Norwalk virus





NORV13
Heavy chain variable region,
FI1
WO2014126921 SEQ ID NO: 72
3250



Norwalk virus





NORV14
Light chain variable region,
FI1
WO2014126921 SEQ ID NO: 80
3251



Norwalk virus





NORV15
Heavy chain variable region,
G3
WO2014126921 SEQ ID NO: 104
3252



Norwalk virus





NORV16
Light chain variable region,
G3
WO2014126921 SEQ ID NO: 112
3253



Norwalk virus





NORV17
Heavy chain variable region,
G4
WO2014126921 SEQ ID NO: 56
3254



Norwalk virus





NORV18
Light chain variable region,
G4
WO2014126921 SEQ ID NO: 64
3255



Norwalk virus





NORV19
Heavy chain variable region,

WO2014183052 SEQ ID NO: 1
3256



Norwalk or MD2004 virus





NORV20
Heavy chain variable region,

WO2014183052 SEQ ID NO: 2
3257



Norwalk or MD2004 virus





NORV21
Heavy chain variable region,

WO2014183052 SEQ ID NO: 3
3258



Norwalk or MD2004 virus





NORV22
Heavy chain variable region,

WO2014183052 SEQ ID NO: 4
3259



Norwalk or MD2004 virus





NORV23
Heavy chain variable region,

WO2014183052 SEQ ID NO: 5
3260



Norwalk or MD2004 virus





NORV24
Heavy chain variable region,

WO2014183052 SEQ ID NO: 6
3261



Norwalk or MD2004 virus





NORV25
Heavy chain variable region,

WO2014183052 SEQ ID NO: 7
3262



Norwalk or MD2004 virus





NORV26
Heavy chain variable region,

WO2014183052 SEQ ID NO: 8
3263



Norwalk or MD2004 virus





NORV27
Heavy chain variable region,

WO2014183052 SEQ ID NO: 9
3264



Norwalk or MD2004 virus





NORV28
Heavy chain variable region,

WO2014183052 SEQ ID NO: 10
3265



Norwalk or MD2004 virus





NORV29
Heavy chain variable region,

WO2014183052 SEQ ID NO: 11
3266



Norwalk or MD2004 virus





NORV30
Heavy chain variable region,

WO2014183052 SEQ ID NO: 12
3267



Norwalk or MD2004 virus





NORV31
Heavy chain variable region,

WO2014183052 SEQ ID NO: 13
3268



Norwalk or MD2004 virus





NORV32
Heavy chain variable region,

WO2014183052 SEQ ID NO: 14
3269



Norwalk or MD2004 virus





NORV33
Heavy chain variable region,

WO2014183052 SEQ ID NO: 15
3270



Norwalk or MD2004 virus





NORV34
Heavy chain variable region,

WO2014183052 SEQ ID NO: 16
3271



Norwalk or MD2004 virus





NORV35
Heavy chain variable region,

WO2014183052 SEQ ID NO: 17
3272



Norwalk or MD2004 virus





NORV36
Heavy chain variable region,

WO2014183052 SEQ ID NO: 18
3273



Norwalk or MD2004 virus





NORV37
Heavy chain variable region,

WO2014183052 SEQ ID NO: 19
3274



Norwalk or MD2004 virus





NORV38
Heavy chain variable region,

WO2014183052 SEQ ID NO: 20
3275



Norwalk or MD2004 virus





NORV39
Heavy chain variable region,

WO2014183052 SEQ ID NO: 21
3276



Norwalk or MD2004 virus





NORV40
Heavy chain variable region,

WO2014183052 SEQ ID NO: 22
3277



Norwalk or MD2004 virus





NORV41
Heavy chain variable region,

WO2014183052 SEQ ID NO: 23
3278



Norwalk or MD2004 virus





NORV42
Heavy chain variable region,

WO2014183052 SEQ ID NO: 24
3279



Norwalk or MD2004 virus





NORV43
Heavy chain variable region,

WO2014183052 SEQ ID NO: 25
3280



Norwalk or MD2004 virus





NORV44
Heavy chain variable region,

WO2014183052 SEQ ID NO: 26
3281



Norwalk or MD2004 virus





NORV45
Heavy chain variable region,

WO2014183052 SEQ ID NO: 27
3282



Norwalk or MD2004 virus





NORV46
Heavy chain variable region,

WO2014183052 SEQ ID NO: 28
3283



Norwalk or MD2004 virus





NORV47
Heavy chain variable region,

WO2014183052 SEQ ID NO: 29
3284



Norwalk or MD2004 virus





NORV48
Heavy chain variable region,

WO2014183052 SEQ ID NO: 30
3285



Norwalk or MD2004 virus









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 8 against Rotavirus.









TABLE 8







Antibodies against rotavirus










Antibody


SEQ


No.
Description
Reference Information
ID NO





ROTV1
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 1
3286


ROTV2
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 2
3287


ROTV3
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 3
3288


R0TV4
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 4
3289


ROTV5
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 5
3290


ROTV6
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 6
3291


ROTV7
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 7
3292


ROTV8
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 8
3293


ROTV9
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 9
3294


ROTV10
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 10
3295


ROTV11
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 11
3296


ROTV12
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 12
3297


ROTV13
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 13
3298


ROTV14
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 14
3299


ROTV15
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 15
3300


ROTV16
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 16
3301


ROTV17
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 17
3302


ROTV18
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 18
3303


ROTV19
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 19
3304


ROTV20
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 20
3305


ROTV21
Heavy chain single domain
US8105592; US20090226418 SEQ ID NO: 21
3306


ROTV22
Human VP6 polypeptide
US20030166139 SEQ ID NO: 2
3307


ROTV23
Human VP6 polypeptide
US20030166139 SEQ ID NO: 4
3308


ROTV24

Aiyegbo, M. S., et al ″Human RotavirUSVp6-
3309




Specific Antibodies Mediate intracellular





Neutralization By Binding To A Quater





Structure in The Transcriptional Pore″, Plos One





8, 61101 (2013), NCBI Accession # 4HFW_B



ROTV25

Aiyegbo, M. S., et al ″Human RotavirUSVp6-
3310




Specific Antibodies Mediate intracellular





Neutralization By Binding To A Quater





Structure in The Transcriptional Pore″, Plos One





8, 61101 (2013), NCBI Accession # 4HFW_B









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 9 against Entamoeba histolytica.









TABLE 9







Antibodies against Entainoeba Histolytica










Antibody No.;


SEQ


Antibody Name
Description
Reference Information
ID NO





ENTH1
Heavy chain (partial sequence) gamma.,
Cheng, X. J. et al., Exp. Parasitol. 96
3311



Entamoeba histolytica antibody
(1), 52-56 (2000), NCBI Accession #





BAA97670.1 (220aa)



ENTH2
Heavy chain (partial sequence) gamma,
Tachibana, H. et al., Clin. Diagn. Lab.
3312



Entamoeba histolytica Antibody
Immunol. 6 (3), 383-387 (1999), NCBI





Accession # BAA82104.1 (222aa)



ENTH3
Heavy chain (partial sequence) gamma,
Tachibana, H. et al., Clin. Diagn. Lab.
3313



Entamoeba histolytica Antibody
Immunol. 6 (3), 383-387 (1999), NCBI





Accession # BAA82101.1 (226aa)



ENTH4
Heavy chain (partial sequence) IgG,
Tachibana, H., et al., Infect. Immun. 77
3314



Entamoeba histolytica Intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03695.1 (220aa)




Monoclonal Antibodies




ENTH5
Heavy chain (partial sequence) IgG,
Tachibana, H., el al., Infect. Immun. 77
3315



Entamoeba histolytica Intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03694.1 (226aa)




Monoclonal Antibodies




ENTH6
Heavy chain (partial sequence) IgG,
Tachibana, H., et al., Infect. Immun. 77
3316



Entamoeba histolytica Intermediate
(1), 549-556(2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03693.1 (221aa)




Monoclonal Antibodies




ENTH7
Heavy chain (partial sequence) IgG,
Tachibana. H., et al., Infect. Immun. 77
3317



Entamoeba histolytica Intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03692.1 (223aa)




Monoclonal Anybodies




ENTH8
Light chain (partial sequence) IgG,
Tachibana, H., et al., Infect. Immun. 77
3318



Entamoeba histolytica intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03699.1 (219aa)




Monoclonal Antibodies




ENTH9
Light chain (partial sequence) IgG,
Tachibana. H., et al., Infect. Immun. 77
3319



Entamoeba histolytica Intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03698.1 (220aa)




Monoclonal Antibodies




ENTH10
Light chain (partial sequence) IgG,
Tachibana, H., et al., Infect. Immun. 77
3320



Entamoeba histolytica Intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03697.1 (214aa)




Monoclonal Antibodies




ENTH11
Light chain (partial sequence) IgG,
Tachibana, H., et al., Infect. Immun. 77
3321



Entamoeba histolytica Intermediate
(1), 549-556 (2009), NCBI Accession #




Subunit Lectin-Specific Human
BAH03696.1 (214aa)




Monoclonal Antibodies




ENTH12
Light chain (partial sequence) kappa,
Cheng, X. J. et al., Exp. Parasitol. 96 (1),
3322



Entamoeba histolytica antibody
52-56 (2000), NCBI Accession #





BAA97671.1 (214aa)



ENTH13
Light chain (partial sequence) kappa,
Tachibana, H. et al., Clin. Diagn. Lab.
3323



Entamoeba histolytica antibody
Immunol. 6 (3), 383-387 (1999), NCBI





Accession # BAA821051 (215aa)



ENTH14
Light chain (partial sequence) kappa,
Tachibana, H. et al., Clin. Diagn. Lab.
3324



Entamoeba histolytica antibody
Immunol. 6 (3), 383-387 (1999), NCBI





Accession # BAA82100.1 (214aa)



ENTH15/
Single chain Fv Antibody 350-E2
NCBI Accession # AEY80059.1 (274aa)
3325


350-E2
against Entamoeba histolytica




ENTH16/
Single chain Fv Antibody JR4A11
NCBI Accession # AEY80058.1 (287aa)
3326


JR4A11
Entamoeba histolytica









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides, fragments or variants thereof described in International Pub. No. WO2001012646, the contents of which are herein incorporated by reference in their entirety, against listena monocytogenes, salmonella and/or leishmania.


Neglected Tropical Diseases

In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the neglected tropical disease related payload antibody polypeptides listed in Tables 10-13.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 10 against Dengue Fever Virus.









TABLE 10







Antibodies against Dengue Fever Virus











Antibody

Antibody

SEQ


No.
Description
Name
Reference Information
ID NO





DENG1
Bispecific, DENV serotype 1,
m366
US20150218255 SEQ ID NO: 96
3327



DENV serotype 2, DENV






serotype 3, and DENV serotype 4





DENG2
Fab Fragment
Fab 14c10
Teoh, E. P., el al., Sci Transl Med 4
3328





(139), 139RA83 (2012), NCBI






Accession # 4CAU_E(230 aa)



DENG3
Heavy chain
5j7 Fab
Fibriansah, G., el al., A highly
3329





potent human antibody neutralizes






dengue virus serotype 3 by binding






across three surface proteins; Nat






Commun 6, 6341 (2015), NCBI






Accession # 3J6U_H (135aa)



DENG4
Heavy Chain
Ede1 C8
Dejnirattisai, W., et al., A new
3330





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UTA_H (272 aa)



DENG5
Heavy Chain
Fab 2h12
Midgley, C.M., et al., J, Immunol.
3331





188 (1), 4971-4979 (2012), NCBI






Accession # 4AL8_H (217 aa)



DENG6
Heavy Chain Fab Fragment Of
1f4 Fab
Fibriansah. G., et al., A potent anti-
3332



Antibodv 1f4

dengue human antibody






preferentially recognizes the






conformation of E protein






monomers assembled on the virus






surface; EMBO Mol Med 6 (3),






358-371 (2014), NCBI Accession






# 4C2I_H (232 aa)



DENG7
Heavy chain variable region
9F12
WO2010093335 SEQ ID NO: 4
3333


DENG8
Heavy chain variable region,
9F12
US20150218255 SEQ ID NO: 83
3334



DENV serotype l, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG9
Heavy chain variable region,
m366
US20150218255 SEQ ID NO: 4
3335



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG10
Heavy chain variable region,
m366.6
US20150218255 SEQ ID NO: 24
3336



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG11
Heavy chain variable region,
m360.6
US20150218255 SEQ ID NO: 44
3337



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG12
Heavy chain variable region,
HMB-DV-1
US9073981 SEQ ID NO: 13
3338



DENV-I, DENV-2, DENV-3,






DENV-4





DENG13
Heavy chain variable region,
HMB-DV-2
US9073981 SEQ ID NO: 29
3339



DENV-I, DENV-2, DENV-3,






DENV-4





DENG14
Heavy chain variable region,
HMB-DV-3
US9073981 SEQ ID NO: 45
3340



DENV-I, DENV-2, DENV-3,






DENV-4





DENG15
Heavy chain variable region,
HMB-DV-4
US9073981 SEQ ID NO: 61
3341



DENV-I, DENV-2, DENV-3,






DENV-4





DENG16
Heavy chain variable region,
HMB-DV-4
US9073981 SEQ ID NO: 65
3342



DENV-I, DENV-2, DENV-3,






DENV-4





DENG17
Heavy chain variable region,
HMB-DV-5
US9073981 SEQ ID NO: 79
3343



DENV-I, DENV-2, DEN V-3,






DENV-4





DENG18
Heavy chain variable region,
HMB-DV-6,
US9073981 SEQ ID NO: 95
3344



DENV-I, DENV-2, DENV-3,
HMB-DV-7





DENV-4





DENG19
Heavy chain variable region,
HMB-DV-8
US9073981 SEQ ID NO: 117
3345



DENV-I, DENV-2, DENV-3,






DENV-4





DENG20
Heavy chain variable region,
HMB-DV-9
US9073981 SEQ ID NO: 131
3346



DENV-I, DENV-2, DENV-3,






DENV-4





DENG21
Heavy chain variable region,
HMB-DV-10
US9073981 SEQ ID NO: 145
3347



DENV-I, DENV-2, DENV-3,






DENV-4





DENG22
Heavy chain variable region,
HMB-DV-11
US9073981 SEQ ID NO: 151
3348



DENV-I, DENV-2, DENV-3,






DENV-4





DENG23
Heavy chain variable region,
HMB-DV-12
US9073981 SEQ ID NO: 165
3349



DENV-I, DENV-2, DENV-3,






DENV-4





DENG24
Heavy chain variable region,
HMB-DV-13
US9073981 SEQ ID NO: 181
3350



DENV-I, DENV-2, DENV-3,






DENV-4





DENG25
Heavy chain variable region,
HMB-DV-14
US9073981 SEQ ID NO: 195
3351



DENV-I, DENV-2, DENV-3,






DENV-4





DENG26
Heavy chain variable region, DV-
A68
US20150225474 SEQ ID NO: 19
3352



1, DV-2, DV-3, and DV-10





DENG27
Heavy chain variable region, DV-
A100
US20150225474 SEQ ID NO: 20
3353



1, DV-2, DV-3, and DV-11





DENG28
Heavy chain variable region, DV-
C58
US20150225474 SEQ ID NO: 21
3354



1, DV-2, DV-3, and DV-12





DENG29
Heavy chain variable region, DV-
C98
US20150225474 SEQ ID NO: 32
3355



1, DV-2, DV-3, and DV-13





DENG30
Heavy chain variable region, DV-
A11
US20150225474 SEQ ID NO: 33
3356



1, DV-2, DV-3, and DV-14





DENG31
Heavy chain variable region, DV-
B11
US20150225474 SEQ ID NO: 36
3357



1, DV-2, DV-3, and DV-15





DENG32
Heavy chain variable region, DV-
D88
US20150225474 SEQ ID NO: 1
3358



1, DV-2, DV-3, and PV-4





DENG33
Heavy chain variable region, DV-
mAb11
WO2014144061 SEQ ID NO: 1
3359



1, DV-2, PV-3, and DV-1





DENG34
Heavy chain variable region, DV-
F38
US20150225474 SEQ ID NO: 80
3360



1, DV-2, DV-3, and PV-5





DENG35
Heavy chain variable region, DV-
A48
US20150225474 SEQ ID NO: 16
3361



1, DV-2, PV-3. and DV-6





DENG36
Heavy drain variable region, DV-
C8S
US20150225474 SEQ ID NO: 17
3362



1, DV-2, PV-3, and DV-7





DENG37
Heavy chain variable region, DV-
F108
US20150225474 SEQ ID NO: 18
3363



1, DV-2, DV-3, and PV-8





DENG38
Heavy chain variable region, DV-
B48
US20150225474 SEQ ID NO: 18
3364



1, DV-2, PV-3, and PV-9





DENG39
Heavy chain, Antigen-binding
2d22
Fibriansah, G., et al., DENGUE
3365



Fragment Of Human Antibody

VIRUS. Cryo-EM structure of an




2d22

antibody that neutralizes dengue






virus type 2 by locking E protein






dimers; Science 349 (6243), 88-91






(2015), NCBI Accession #






5A1Z_K (128 aa)



DENG40
Heavy chain, Dengue virus NS-1

US7473424; US20040209244;
3366



protein

WO2004067567; EP1592712






SEQ ID NO: 3



DENG41
Heavy chain, Dengue virus
DB32-6
US8637035 SEQ ID NO: 1
3367



serotype 2





DENG42
Heavy chain, Dengue virus
DB2-3
US8637035 SEQ ID NO: 13
3368



serotype 2





DENG43
Heavy chain, Dengue virus
DB13-19
US8637035 SEQ ID NO: 14
3369



serotype 2





DENG44
Heavy chain, Dengue virus
DB23-3
US8637035 SEQ ID NO: 15
3370



serotype 2





DENG45
Heavy chain. Dengue virus
DB25-2
US8637035 SEQ ID NO: 16
3371



serotype 2





DENG46
Heavy chain, Dengue virus
DB42-3
US8637035 SEQ ID NO: 17
3372



serotype 2





DENG47
Heavy chain, Dengue virus type
1A5
US8337853 SEQ ID NO: 97
3373



10





DENG48
Heavy chain. Dengue virus type
2H7
US8337853 SEQ ID NO: 113
3374



11





DENG49
Heavy chain, Dengue virus type
2H5
US8337853 SEQ ID NO: 129
3375



12





DENG50
Heavy chain, Dengue virus type
3A2
US20130089543 SEQ ID NO: 145
3376



13





DENG51
Heavy chain, Dengue virus type
1B2
US20130089543 SEQ ID NO: 161
3377



14





DENG52
Heavy chain. Dengue virus type
1A10
US20130089543 SEQ ID NO: 177
3378



13





DENG53
Heavy chain, Dengue virus type 4
5H2
US7622113 SEQ ID NO: 1
3379


DENG54
Heavy chain, Dengue virus type 5
5H7
US7622113 SEQ ID NO: 17
3380


DENG55
Heavy chain, Dengue vires type 6
3Cl
US7622113 SEQ ID NO: 33
3381


DENG56
Heavy chain, Dengue virus type 7
3E4
US7622113 SEQ ID NO: 49
3382


DENG57
Heavy chain, Dengue virus type 8
7G4
US7622113 SEQ ID NO: 65
3383


DENG58
Heavy chain, Dengue virus type 9
5D9
US7622113 SEQ ID NO: 81
3384


DENG59
Heavy chain, DV 1
14c10 clone
US20130259871 Fig 4b
3385




8




DENG60
Heavy chain, DV-1, DV-2, DV-3,
Antibody
US20140056913 SEQ ID NO: 1
3386



and DV-4
4e11




DENG61
Heavy chain, DV-1, DV-2, DV-3,
Variant of
US20140056913 SEQ ID NO: 21
3387



and DV-4
4E11




DENG62
Heavy chain, DV-1, DV-2, DV-3,
4E5A
WO20155123362 SEQ ID NO: 29
3388



and DV-4





DENG63
Light Chain
5j7 Fab
Fibriansah, G., et al., A highly
3389





potent human antibody neutralizes






dengue virus serotype 3 by binding






across three surface proteins; Nat






Commun 6, 6341 (2015), NCBI






Accession # 3J6U_L (118aa)



DENG64
Light Chain
Ede1 C8
Dejnirattisai, W., et al., A new
3390





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UTA_L (217 aa)



DENG65
Light Chain
Fab 2h12
Midgley, C. M., et al., J, Immunol.
3391





188 (10), 4971-4979 (2012), NCBI






Accession # 4AL8_L (213 aa)



DENG66
Light Chain Fab Fragment Of
1f4 Fab
Fibriansah, G., et al., A potent anti-
3392



Antibody 1f4

dengue human antibody






preferentially recognizes the






conformation of E protein






monomers assembled on the virus






surface; EMBO Mol Med 6 (3),






358-371 (2014), NCBI Accession






# 4C2I_N (239 aa)



DENG67
Light chain variable region
9F12
WO2010093335 SEQ ID NO: 6



DENG68
Light chain variable region,
9F12
US20150218255 SEQ ID NO: 84
3393



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG69
Light chain variable region,
m366
US20150218255 SEQ ID NO: 6
3394



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG70
Light chain variable region,
m366.6
US20150218255 SEQ ID NO: 26
3395



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4





DENG71
Light chain variable region,
m360.6
US20150218255 SEQ ID NO: 46
3396



DENV serotype 1, DENV






serotype 2, DENV serotype 3, and






DENV serotype 4
HMB-DV-1
US9073981 SEQ ID NO: 14
3397


DENG72
Light chain variable region,






DENV-I, DENV-2, DENV-3,






DENV-4





DENG73
Light chain variable region,
HMB-DV-2
US9073981 SEQ ID NO: 30
3398



DENV-I, DENV-2, DENV-3,






DENV-4





DENG74
Light chain variable region,
HMB-DV-3
US9073981 SEQ ID NO: 46
3399



DENV-I, DENV-2, DENV-3,






DENV-4





DENG75
Light chain variable region,
HMB-DV-4
US9073981 SEQ ID NO: 62
3401



DENV-I, DENV-2, DENV-3,






DENV-4





DENG76
Light chain variable region,
HMB-DV-5
US9073981 SEQ ID NO: 80
3402



DENV-I, DENV-2, DENV-3,






DENV-4





DENG77
Light chain variable region,
HMB-DV-6
US9073981 SEQ ID NO: 96
3403



DENV-I, DENV-2, DENV-3,






DENV-4





DENG78
Light chain variable region,
HMB-DV-7
US9073981 SEQ ID NO: 103
3404



DENV-I, DENV-2, DENV-3,






DENV-4





DENG79
Light chain variable region,
HNfB-DV-8
US9073981 SEQ ID NO: 118
3405



DENV-I, DENV-2, DENV-3,






DENV-4





DENG80
Light chain variable region,
HMB-DV-9
US9073981 SEQ ID NO: 132
3406



DENV-I, DENV-2, DENV-3,






DENV-4





DENG81
Light chain variable region,
HMB-DV-10,
US9073981 SEQ ID NO: 146
3407



DENV-I, DENV-2, DENV-3,
HMB-DV-11





DENV-4





DENG82
Light chain variable region,
HMB-DV-12
US9073981 SEQ ID NO: 166
3408



DENV-I, DENV-2, DENV-3,






DENV-4





DENG83
Light chain variable region,
HMB-DV-13
US9073981 SEQ ID NO: 182
3409



DENV-I, DENV-2, DENV-3,






DENV-4





DENG84
Light chain variable region,
HMB-DV-14
US9073981 SEQ ID NO: 196
3410



DENV-I, DENV-2, DENV-3,






DENV-4





DENG85
Light chain variable region, DV-1,
D88, F38,
US20150225474 SEQ ID NO: 2
3411



DV-2, DV-3, and DV-4
A48, C88,






F108, B48,






A68, A100,






C58, C78,






C68, D98,






D188, C128,






C98




DENG86
Light chain variable region, DV-1,
C78
US20S50225474 SEQ ID NO: 23
3412



DV-2, DV-3, and DV-4





DENG87
Light chain variable region, DV-1,
C68
US20150225474 SEQ ID NO: 25
3413



DV-2, DV-3, and DV-4





DENG88
Light chain variable region, DV-1,
D98
US20150225474 SEQ ID NO: 27
3414



DV-2, DV-3, and DV-4





DENG89
Light chain variable region, DV-1,
D188
US20150225474 SEQ ID NO: 29
3415



DV-2, DV-3, and DV-4





DENG90
Light chain variable region, DV-1,
C128
US20150225474 SEQ ID NO: 31
3416



DV-2, DV-3, and DV-4





DENG91
Light chain variable region, DV-1,
A11, B11
US20150225474 SEQ ID NO: 34
3417



DV-2, DV-3, and DV-4





DENG92
Light chain variable region, DV-1,
mAb11
WO2014144061 SEQ ID NO: 3
3418



DV-2, DV-3, and DV-4





DENG93
Light chain, Antigen-binding
2d22
Fibriansah, G., el al., DENGUE
3419



Fragment Of Human Antibody

VIRUS. Cryo-EM structure of an




2d22

antibody that neutralizes dengue






virus type 2 by locking E protein






dimers; Science 349 (6243), 88-91






(2015), NCBI Accession #






5A1Z_L (115 aa)



DENG94
Light cliain, Dengue virus NS-1

US7473424; US20040209244;
3420



protein

WO2004067567; EP1592712






SEQ ID NO: 4



DENG95
Light chain, Dengue virus
DB32-6
US8637035 SEQ ID NO: 5
3421



serotype 2





DENG96
Light chain, Dengue virus
DB2-3,
US8637035 SEQ ID NO: 19
3422



serotype 2
DB-19




DENG97
Light chain, Dengue virus
DB23-3
US8637035 SEQ ID NO: 20
3423



serotype 2





DENG98
Light chain, Dengue virus
DB25-2
US8637035 SEQ ID NO: 21
3424



serotype 2





DENG99
Light chain, Dengue virus
DB42-3
US8637035 SEQ ID NO: 22
3425



serotype 2





DENG100
Light chain, Dengue virus
5H2
US7622113 SEQ ID NO: 9
3426



serotype 4





DENG101
Light chain, Dengue virus
5A7
US7622113 SEQ ID NO: 25
3427



serotype 4





DENG102
Light chain, Dengue virus
3C1
US7622113 SEQ ID NO: 41
3428



serotype 4





DENG103
Light chain, Dengue virus
3E4
US7622113 SEQ ID NO: 57
3429



serotype 4





DENG104
Light chain, Dengue virus
7G4
US7622113 SEQ ID NO: 73
3430



serotype 4





DENG105
Light chain, Dengue virus
5D9
US7622153 SEQ II) NO: 89
3431



serotype 4





DENG106
Light chain, Dengue virus
1A5
US8337853 SEQ ID NO: 105
3432



serotype 4





DENG107
Light chain, Dengue virus
2H7
US8337853 SEQ ID NO: 121
3433



serotype 4





DENG108
Light chain, Dengue virus
2H5
US8337853 SEQ ID NO: 137
3434



serotype 4





DENG109
Light chain, Dengue virus
3A2
US20130089543 SEQ ID NO: 153
3435



serotype 4





DENG110
Light chain, Dengue virus
1B2
US20130089543 SEQ ID NO: 169
3436



serotype 4





DENG111
Light chain, Dengue virus
1A10
US20130089543 SEQ ID NO: 185
3437



serotype 4





DENG112
Light chain, DV 1
14c10 clone
US20130259871 Fig 4b
3438




8




DENG113
Light chain, DV-l, DV-2, DV-3,
Antibody
US20140056913 SEQ ID NO: 2
3439



and DV-4
4e11




DENG114
Light chain, DV-l, DV-2, DV-3,
Variant of
US20140056913 SEQ ID NO: 22
3440



and DV-4
4E11




DENG115
Light chain, DV-l, DV-2, DV-3,
4E5A
WO20155123362 SEQ ID NO: 30
3441



and DV-4





DENG116
scFv
9F12
WO2010093335 SEQ ID NO: 8
3442


DENG117
Scfv Fragment
Ede211
Dejnirattisai, W., et al., A new
3443





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UT7_L(153 aa)



DENG118
Scfv Fragment
Ede2 A11
Dejnirattisai, W., et al, A new
3444





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UT7_H (150 aa)



DENG119

Ede2A11
Dejnirattisai, W., et al., A new
3445





class of lightly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UTB_L (218 aa)
3446


DENG120

Ede1 C10
Dejnirattisai, W., et al., A new






class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UT9_L (154aa)



DENG121

Ede1 C10
Dejnirattisai, W., et al., A new
3447





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol 16






(2), 170-177 (2015), NCBI






Accession # 4UT9_H (144 aa)



DENG122

Ede2 B7
Dejnirattisai. W. et al., A new
3448





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients infected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UT6_L (218 aa)



DENG123

Ede2 B7
Dejnirattisai, W., et al., A new
3449





class of highly potent, broadly






neutralizing antibodies isolated






from viremic patients injected with






dengue virus; Nat. Immunol. 16






(2), 170-177 (2015), NCBI






Accession # 4UT6_H (283 aa)









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides, fragments or variants thereof described in International Pub. No. WO2013089647 and WO2013035345, U.S. Pat. Nos. 8,637,035 and 887,187, US Publication No. US20050123900, and Chinese Patent Publication No. CN102757480, the contents of which are herein incorporated by reference in their entirety, against Listeria monocytogenes, salmonella and/or leishmania.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 11 against Rabies Virus









TABLE 11







Antibodies against Rabies Virus











Antibody



SEQ


No.
Description
Antibody Name
Reference Information
ID NO





RABV1
Fab Heavy Chain Fd region

CN101696242 SEQ ID NO: 9
3450


RABV2
Fab Light chain

CN101696242 SEQ ID NO: 10
3451


RABV3
Heavy chain

US6890532 SEQ ID NO: 3
3452


RABV4
Heavy chain
Mab JB.1
US7071319 SEQ ID NO: 10
3453


RABV5
Heavy chain
Mab 57
US7071319 SEQ ID NO: 14
3454


RABV6
Heavy chain
CR04-098
US9005624 SEQ ID NO: 335
3455


RABV7
Heavy chain
CR57,
US9005624 SEQ ID NO: 123
3456




Rafivirumab




RABV8
Heavy chain
CR57,






Rafivirumab




RABV9
Heavy chain
CRJB
US9005624 SEQ ID NO: 127
3458


RABV10
Heavy chain
Foravirumab

3459


RABV11
Heavy chain, Anti-rabies SOJB

Presniak, M. et al.
3460



immunoglobulin

″Development of a cocktail of






recombinant-expressed human






rabies virus-neutralizing






monoclonal antibodies for






postexposure prophylaxis of






rabies″, J. Infect. Dis. 188 (1),






53-56 (2003), NCBI






Accession # AA017822.1



RABV12
Heavy chain variable region

CN101696242 SEQ ID NO: 4
3461


RABV13
Heavy chain variable region
SC04-001
US9005624 SEQ ID NO: 26
3462


RABV14
Heavy chain variable region
SC04-004
US9005624 SEQ ID NO: 27
3463


RABV15
Heavy chain variable region
SC04-008
US9005624 SEQ ID NO: 28
3464


RABV16
Heavy chain variable region
SC04-010
US9003624 SEQ ID NO: 29
3465


RABV17
Heavy chain variable region
SC04-018
US9005624 SEQ ID NO: 30
3466


RABV18
Heavy chain variable region
SC04-021
US9005624 SEQ ID NO: 31
3467


RABV19
Heavy chain variable region
SC04-026
US9005624 SEQ ID NO: 32
3468


RABV20
Heavy chain variable region
SC04-031
US9005624 SEQ ID NO: 33
3469


RABV21
Heavy chain variable region
SC04-038
US9005624 SEQ ID NO: 44
3470


RABV22
Heavy chain variable region
SC04-040
US9005624 SEQ ID NO: 35
3471


RABV23
Heavy chain variable region
SC04-060
US9005624 SEQ ID NO: 36
3472


RABV24
Heavy chain variable region
SC04-073
US9005624 SEQ ID NO: 37
3473


RABV25
Heavy chain variable region
SC04-097
US9005624 SEQ ID NO: 38
3474


RABV26
Heavy chain variable region
SC04-098
US9005624 SEQ ID NO: 39
3475


RABV27
Heavy chain variable region
SC04-103
US9005624 SEQ ID NO: 40
3476


RABV28
Heavy chain variable region
SC04-104
US9005624 SEQ ID NO: 41
3477


RABV29
Heavy chain variable region
SC04-108
US9005624 SEQ ID NO: 42
3478


RABV30
Heavy chain variable region
SC04-120
US9005624 SEQ ID NO: 43
3479


RABV31
Heavy chain variable region
SC04-125
US9005624 SEQ ID NO: 44
3480


RABV32
Heavy chain variable region
SC04-126
US9005624 SEQ ID NO: 45
3481


RABV33
Heavy chain variable region
SC04-140
US9005624 SEQ ID NO: 46
3482


RABV34
Heavy chain variable region
SC04-144
US9005624 SEQ ID NO: 47
3483


RABV35
Heavy chain variable region
SC04-146
US9005624 SEQ ID NO: 48
3484


RABV36
Heavy chain variable region
SC04-164
US9005624 SEQ ID NO: 49
3485


RABV37
Heavy chain variable region
RVFab5
WO201113757 SEQ ID NO: 2
3486


RABV38
Heavy chain variable region
RVFab8
WO2011137570 SEQ ID NO: 2
3487


RABV39
Heavy chain variable region

CN101337990 SEQ ID NO: 2
3488


RABV40
Heavy chain variable region

CN101337990 SEQ ID NO: 8
3489


RABV41
Heavy chain variable region
R8 VH
CN104193823 SEQ ID NO: 1
3490


RABV42
Heavy chain variable region
R5 VH
CN104193823 SEQ ID NO: 2
3491


RABV43
Heavy chain variable region
R7 VH, R9 VH
CN104193823 SEQ ID NO: 3
3492


RABV44
Heavy chain variable region

CN101235086 SEQ ID NO: 38
3493


RABV45
Heavy chain, Anti-rabies

Prosniak, M. et al.
3494



SOJA immunoglobulin

″Development of a cocktail of






recombinant-expressed human






rabies virus-neutralizing






monoclonal antibodies for






postexposnre prophylaxis of






rabies″, J. Infect. Dis. 188 (1),






53-56 (2003), NCBI






Accession # AAO17823.1



RABV46
Light chain

US6890532 SEQ ID NO: 4
3495


RABV47
Light chain
Mab JB.1
US7071319 SEQ ID NO: 12
3496


RABV48
Light chain
Mab 57
US7071319 SEQ ID NO: 16
3497


RABV49
Light chain
CR04-098
US9005624 SEQ ID NO: 337
3498


RABV50
Light chain
CR57,
US9005624 SEQ ID NO: 125
3499




Rafivirumab




RABV51
Light chain
CR57,

3500




Rafivirumab




RABV52
Light chain
CRJB
US9005624 SEQ ID NO: 129
3501


RABV53
Light chain
Foravirumab

3502


RABV54
Light chain Kappa, Anti-rabies

Prosniak, M. et al.
3503



SOJA immunoglobulin

″Development of a cocktail of






recombinant-expressed human






rabies virus-neutralizing






monoclonal antibodies for






postexposnre prophylaxis of






rabies″, J. Infect. Dis. 188 (1),






53-56 (2003), NCBI






Accession # AAO17825.1



RABV55
Light chain kappa, Anti-rabies

Prosniak, M. et al.
3504



SOJA immunoglobulin [Homo

″Development of a cocktail of




sapiens]

recombinant-expressed human






rabies virus-neutralizing






monoclonal antibodies for






postexposnre prophylaxis of






rabies″, J. Infect. Dis. 188 (1),






53-56 (2003), NCBI






Accession # AAO17821.1



RABV56
Light chain Lambda, Anti-rabies

Prosniak, M. et al.
3505



S057 immunoglobulin

″Development of a cocktail of






recombinant-expressed human






rabies virus-neutralizing






monoclonal antibodies for






postexposnre prophylaxis of






rabies″, J. Infect. Dis. 188 (1),






53-56 (2003), NCBI






Accession # AAO17824.1



RABV57
Light cliain lambda, Anti-rabies

Prosniak, M. et al.
3506



SOJB immunoglobulin

″Development of a cocktail of






recombinant-expressed human






rabies virus-neutralizing






monoclonal antibodies for






postexposnre prophylaxis of






rabies″, J. Infect. Dis. 188 (1),






53-56 (2003), NCBI






Accession # AAO17826.1



RABV58
Light chain variable region
SC04-001
US9005624 SEQ ID NO: 50
3507


RABV59
Light chain variable region
SC04-00-1
US9005624 SEQ ID NO: 51
3508


RABV60
Light chain variable region
SC04-008
US9005624 SEQ ID NO: 52
3509


RABV61
Light chain variable region
SC04-010
US9005624 SEQ ID NO: 55
3510


RABV62
Light chain variable region
SC04-018
US9005624 SEQ ID NO: 54
3511


RABV63
Light chain variable region
SC04-021
US9005624 SEQ ID NO: 55
3512


RABV64
Light chain variable region
SC04-026
US9005624 SEQ ID NO: 56
3513


RABV65
Light chain variable region
SC04-031
US9005624 SEQ ID NO: 57
3514


RABV66
Light chain variable region
SC04-038
US9005624 SEQ ID NO: 58
3515


RABV67
Light chain variable region
SC04-040
US9005624 SEQ ID NO: 59
3516


RABV68
Light chain variable region
SC04-060
US9005624 SEQ ID NO: 60
3517


RABV69
Light chain variable region
SC04-073
US9005624 SEQ ID NO: 61
3518


RABV70
Light chain variable region
SC04-097
US9005624 SEQ ID NO: 62
3519


RABV71
Light chain variable region
SC04-098
US9005624 SEQ ID NO: 63
3520


RABV72
Light chain variable region
SC04-103
US9005624 SEQ ID NO: 64
3521


RABV73
Light chain variable region
SC04-104
US9005624 SEQ ID NO: 65
3522


RABV74
Light chain variable region
SC04-108
US9005624 SEQ ID NO: 66
3523


RABV75
Light chain variable region
SC04-120
US9005624 SEQ ID NO: 67
3524


RABV76
Light chain variable region
SC04-125
US9005624 SEQ ID NO: 68
3525


RABV77
Light chain variable region
SC04-126
US9005624 SEQ ID NO: 69
3526


RABV78
Light chain variable region
SC04-140
US9005624 SEQ ID NO: 70
3527


RABV79
Light chain variable region
SC04-144
US9005624 SEQ ID NO: 71
3528


RABV80
Light chain variable region
SC04-146
US9005624 SEQ ID NO: 72
3529


RABV81
Light chain variable region
SC04-164
US9005624 SEQ ID NO: 73
3530


RABV82
Light chain variable region
RVFab5
WO201113757 SEQ ID NO: 1
3531


RABV83
Light chain variable region
RVFab8
WO2011137570 SEQ ID NO: 1
3432


RABV84
Light chain variable region

CN101337990 SEQ ID NO: 4
3433


RABV85
Light chain variable region

CN101337990 SEQ ID NO: 10
3434


RABV86
Light chain variable region
R8 VL
CN104193823 SEQ ID NO: 4
3435


RABV87
Light chain variable region
R5 VL
CN104193823 SEQ ID NO: 5
3436


RABV88
Light chain variable region
R7 VL
CN104193823 SEQ ID NO: 6
3437


RABV89
Light chain variable region
R9 VL
CN104193823 SEQ ID NO: 7
3438


RABV90
Light chain variable region

CN101696242 SEQ ID NO: 8
3439


RABV91
Light chain variable region

CN101235086 SEQ ID NO: 39
3440









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 12 against Chagas Virus.









TABLE 12







Antibodies against Chagas Virus










Antibody


SEQ


No.
Description
Reference Information
ID NO





CHAG1
Heavy Chain Of The Fab Fragment,
Buschiazzo et al., PLoS Pathol. 8 (1), E1002474
3541



Trypanosoma cruzi trans-sialidase
(2012), NCBI Accession # 3OPZ_J (222aa)



CHAG2
Light chain of Fab fragment,
Buschiazzo et al., PLoS Pathog. 8 (1), E1002474
3542



Trypanosoma cmzi trans-sialidase
(2012), NCBI Accession # 3OPZ_N (213aa)










In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 13 against Chikungunya Virus.









TABLE 13







Antibodies against Chikungunya Virus











Antibody

Antibody

SEQ


No.
Description
Name
Reference Information
ID NO





CHIK1
Heavy chain Fab
9.8b
Sun, S. et al., Structural analyses at pseudo
3543



fragment

atomic resolution of Chikungunya virus and






antibodies show mechanisms of






neutralization, Elife 2, E00435 (2013), NCBI






Accession # 4GO9_H (218 aa)



CHIK2
Heavy chain
5F101717E2
US20130189279 SEQ ID NO: 6
3544



variable





CHIK3
Heavy chain
8B10F8
US20130189279 SEQ ID NO: 26
3545



variable





CHIK4
Light chain Fab
9.8b
Sun, S. et al., Structural analyses at pseudo
3546



fragment

atomic resolution of Chikungunya virus and






antibodies show mechanisms of






neutralization, Elife 2, E00435 (2013), NCBI






Accession # 4GO9_L (212 aa)



CHIK5
Light chain
5F10F175E2
US20130189279 SEQ ID NO: 8
3547



variable





CHIK6
Light chain
8B10F8
US20130189279 SEQ ID NO
3548



variable









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof encoding antibodies described International Pub No. WO1983001785 and U.S. Pat. No. 5,827,671, the contents of each of which are herein incorporated by reference in their entirety, against the protozoan parasite Leishmania.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof encoding antibodies against the Buruli ulcer (Mycobacterium ulcerans), Leprosy/Hansen's disease (Mycobacterium leprae), Leishmaniasis, Cysticercosis, Dracunculiasis (Guinea Worm Disease), Echinococcosis, Fascioliasis, Human African Trypanosomiasis (African Sleeping Sickness), Lymphatic filariasis, Onchocerciasis, Schistosomiasis, Soil-transmitted Helminths (STH).


Toxins

In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the toxin related payload antibody polypeptides listed in Tables 14-17.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 14 against Ricin Toxin.









TABLE 14







Antibodies against Ricin Toxin











Antibody

Antibody

SEQ


No.
Description
Name
Reference Information
ID NO





RICN1
Candid heavy-chain only
RTA:JIV-F5
WO2015100409 SEQ ID NO: 124
3549


RICN2
Candid heavy-chain only
JIV-F6
WO2015100409 SEQ ID NO: 126
3550


RICN3
Candid heavy-chain only
JIV-G 12
WO2015100409 SEQ ID NO: 128
3551


RICN4
Candid heavy-chain only
JIY-A7
WO2015100409 SEQ ID NO: 130
3552


RICN5
Candid heavy-chain only
JIY-D9
WO2015100409 SEQ ID NO: 132
3553


RICN6
Candid heavy-chain only
JIY-D10
WO2015100409 SEQ ID NO: 134
3554


RICN7
Candid heavy-chain only
JIY-E1
WO2015100409 SEQ ID NO: 136
3555


RICN8
Candid heavy-chain only
JIY-E3
WO2015100409 SEQ ID NO: 138
3556


RICN9
Candid heavy-chain only
JIY-E5
WO2015100409 SEQ ID NO: 140
3557


RICN10
Candid heavy-chain only
JIY-F10
WO2015100409 SEQ ID NO: 142
3558


RICN11
Candid heavy-chain only
JIY-G11
WO2015100409 SEQ ID NO: 144
3559


RICN12
Candid heavy-chain only
RTB:JIW-B1
WO2015100409 SEQ ID NO: 146
3560


RICN13
Candid heavy-chain only
JIW-C12
WO2015100409 SEQ ID NO: 148
3561


RICN14
Candid heavy-chain only
JIW-D12
WO2015100409 SEQ ID NO: 150
3562


RICN15
Candid heavy-chain only
JIW-G5
WO2015100409 SEQ ID NO: 152
3563


RICN16
Candid heavy-chain only
JIW-G 10
WO2015100409 SEQ ID NO: 154
3564


RICN17
Candid heavy-chain only
JIZ-B7
WO2015100409 SEQ ID NO: 156
3565


RICN18
Candid heavy-chain only
JIZ-B9
WO2015100409 SEQ ID NO: 158
3566


RICN19
Candid heavy-chain only
JIZ-D8
WO2015100409 SEQ ID NO: 160
3567


RICN20
Candid heavy-chain only
JIZ-G4
WO2015100409 SEQ ID NO: 162
3568









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 15 against Anthrax.









TABLE 15







Antibodies against Anthrax











Antibody

Antibody

SEQ


No.
Description
Name
Reference Information
ID NO





ANTH1
Camelid heavy-chain only
JHD-B6
WO2015100409 SEQ ID NO: 100
3569


ANTH2
Camelid heavy-chain only
JHE-D9
WO2015100409 SEQ ID NO: 102
3570


ANTH3
Camelid heavy-chain only
JIJ-A12
WO2015100409 SEQ ID NO: 104
3571


ANTH4
Camelid heavy-chain only
JIJ-B8
WO2015100409 SEQ ID NO: 106
3572


ANTH5
Camelid heavy-chain only
JIJ-C11
WO2015100409 SEQ ID NO: 108
3573


ANTH6
Camelid heavy-chain only
JIJ-D3
WO2015100409 SEQ ID NO: 110
3574


ANTH7
Camelid heavy-chain only
JIJ-E9
WO2015100409 SEQ ID NO: 112
3575


ANTH8
Camelid heavy-chain only
JIJ-F11
WO2015100409 SEQ ID NO: 114
3576


ANTH9
Camelid heavy-chain only
JIK-B8
WO2015100409 SEQ ID NO: 116
3577


ANTH10
Camelid heavy-chain only
JI-B 10
WO2015100409 SEQ ID NO: 118
3578


ANTH11
Camelid heavy-chain only
JIK-B 12
WO2015100409 SEQ ID NO: 120
3579


ANTH12
Camelid heavy-chain only
JIK-F4
WO2015100409 SEQ ID NO: 122
3580


ANTH13
CDR

WO2003063768 SEQ ID NO: 1
3581


ANTH14
CDR

WO2003063768 SEQ ID NO: 2
3582


ANTH15
CDR

WO2003063768 SEQ ID NO: 3
3583


ANTH16
Heavy chain

US8617548 SEC ID NO: 2
3584


ANTH17
Heavy chain
IQNPA Lambda
US7658925 SEQ ID NO: 2
3585


ANTH18
Heavy chain
IQNLF Lambda
US7658925 SEQ ID NO: 6
3586


ANTH19
Heavy chain
1A5
US20090022736 SEQ ID NO: 1
3587


ANTH20
Heavy chain
4A12
US20090022736 SEQ ID NO: 3
3588


ANTH21
Heavy chain
24B1
US20090022736 SEQ ID NO: 5
3589


ANTH22
Heavy chain
24G4
US20090022736 SEQ ID NO: 7
3590


ANTH23
Heavy chain
32E12
US20090022736 SEQ ID NO: 9
3591


ANTH24
Heavy chain
33F4
US20090022736 SEQ ID NO: 11
3592


ANTH25
Heavy chain
scfv 2LF
EP2778173 SEQ ID NO: 9
3593


ANTH26
Heavy chain

US20040258699 SEQ ID NO: 78
3594


ANTH27
Heavy chain

US20040258699 SEQ ID NO: 79
3595


ANTH28
Heavy chain

US20040258699 SEQ ID NO: 80
3596


ANTH29
Heavy chain

US20040258699 SEQ ID NO: 81
3597


ANTH30
Heavy chain

US20040258699 SEQ ID NO: 82
3598


ANTH31
Heavy chain

US20040258699 SEQ ID NO: 83
3599


ANTH32
Heavy chain

US20040258699 SEQ ID NO: 84
3600


ANTH33
Heavy chain

US20040258699 SEQ ID NO: 85
3601


ANTH34
Heavy chain

US20040258699 SEQ ID NO: 86
3602


ANTH35
Heavy chain

US20040258699 SEQ ID NO: 87
3603


ANTH36
Heavy chain

US20040258699 SEQ ID NO: 88
3604


ANTH37
Heavy chain

US20040258699 SEQ ID NO: 89
3605


ANTH38
Heavy chain

US20040258699 SEQ ID NO: 90
3606


ANTH39
Heavy chain

US20040258699 SEQ ID NO: 91
3607


ANTH40
Heavy chain

US20040258699 SEQ ID NO: 92
3608


ANTH41
Heavy chain

US20040258699 SEQ ID NO: 93
3609


ANTH42
Heavy chain

US20040258699 SEQ ID NO: 94
3610


ANTH43
Heavy chain

US20040258699 SEQ ID NO: 95
3611


ANTH44
Heavy chain

US20040258699 SEQ ID NO: 96
3612


ANTH45
Heavy chain

US20040258699 SEQ ID NO: 97
3613


ANTH46
Heavy chain

US20040258699 SEQ ID NO: 98
3614


ANTH47
Heavy chain

US20040258699 SEQ ID NO: 99
3615


ANTH48
Heavy chain

US20040258699 SEQ ID NO: 100
3616


ANTH49
Heavy chain

US20040258699 SEQ ID NO: 101
3617


ANTH50
Heavy chain

US20040258699 SEQ ID NO: 102
3618


ANTH51
Heavy chain

US20040258699 SEQ ID NO: 103
3619


ANTH52
Heavy chain

US20040258699 SEQ ID NO: 104
3620


ANTH53
Heavy chain

US20040258699 SEQ ID NO: 105
3621


ANTH54
Heavy chain

US20040258699 SEQ ID NO: 106
3622


ANTH55
Heavy chain

US20040258699 SEQ ID NO: 107
3623


ANTH56
Heavy chain

US20040258699 SEQ ID NO: 108
3624


ANTH57
Heavy chain

US20040258699 SEQ ID NO: 109
3625


ANTH58
Heavy chain

US20040258699 SEQ ID NO: 110
3626


ANTH59
Heavy chain

US20040258699 SEQ ID NO: 111
3627


ANTH60
Heavy chain

US20040258699 SEQ ID NO: 112
3628


ANTH61
Heavy chain

US20040258699 SEQ ID NO: 113
3629


ANTH62
Heavy chain

US20040258699 SEQ ID NO: 114
3630


ANTH63
Heavy chain

US20040258699 SEQ ID NO: 115
3631


ANTH64
Heavy chain

US20040258699 SEQ ID NO: 116
3632


ANTH65
Heavy chain

US20040258699 SEQ ID NO: 117
3633


ANTH66
Heavy chain

US20040258699 SEQ ID NO: 118
3634


ANTH67
Heavy chain and light chain
14B7 scFV
US7902344; US6916474 SEQ ID
3635



variable region

NO: 21



ANTH68
Heavy chain fd region
W1
US8685396 SEQ ID NO: 1
3636


ANTH69
Heavy chain fd region
W2
US8685396 SEQ ID NO: 17
3637


ANTH70
Heavy chain
W5
US8685396 SEQ ID NO: 33
3638


ANTH71
Heavy chain
A63-6
US8685396 SEQ ID NO: 34
3639


ANTH72
Heavy chain
F3-6
US8685396 SEQ ID NO: 35
3640


ANTH73
Heavy chain
F5-1
US8685396 SEQ ID NO: 36
3641


ANTH74
Heavy chain variable region
ETI-204
US2010156196 SEQ ID NO: 1
3642


ANTH75
Heavy chain variable region
6.20
WO2015107307 SEQ ID NO: 1
3643


ANTH76
Heavy chain variable region
33PA83
WO2009071860 SEQ ID NO: 1
3644


ANTH77
Heavy chain variable region
anti-γDPGA
US8501182 SEQ ID NO: 1
3645




antibody




ANTH78
Heavy chain variable region
4C
US8501182 SEQ ID NO: 3
3646


ANTH79
Heavy chain variable region
11D
US8501182 SEQ ID NO: 5
3647


ANTH80
Heavy chain variable region
F20G75
WO2007131363 SEQ ID NO: 16
3648


ANTH81
Heavy chain variable region
F20G76
WO2007131363 SEQ ID NO: 18
3649


ANTH82
Heavy chain variable region
F20G77
WO2007131363 SEQ ID NO: 20
3650


ANTH83
Heavy chain variable region
V2 variant
US8507655 SEQ ID NO: 7
3651


ANTH84
Heavy chain variable region
6.20 variant
US8507655 SEQ ID NO: 9
3652


ANTH85
Heavy chain variable region
J24.15 variant
US8507653 SEQ ID NO: 11
3653


ANTH86
Heavy chain variable region
J24.7 variant
US8507655 SEQ ID NO: 13
3654


ANTH87
Heavy chain variable region
V2 variant human
US85076S5 SEQ ID NO: 15
3655


ANTH88
Heavy chain variable region
6.20 variant
US8S07655 SEQ ID NO: 17
3656




human




ANTH89
Heavy chain variable region
J24.15 variant
US8507655 SEQ ID NO: 19
3657




human




ANTH90
Heavy chain variable region
J24.7 variant
US8507655 SEQ ID NO: 21
3658




human




ANTH91
Heavy chain variable region
HuMab 5E8
US8404820 SEQ ID NO: 2
3659


ANTH92
Heavy chain variable region
HnMab 2D5
US8404820 SEQ ID NO: 8
3660


ANTH93
Heavy chain variable region
HuMab 2H4
US8404820 SEQ ID NO: 12
3661


ANTH94
Heavy chain variable region
HuMab 5D5-
US8404820 SEQ ID NO: 16
3662




2E10




ANTH95
Heavy chain variable region
13E3
US8309P9P SEQ ID NO: 2
3663


ANTH96
Heavy chain variable region
3E1
US8309090 SEQ ID NO: 6
3667


ANTH97
Heavy chain variable region
KCTC 10756BP
US8268316 SEQ ID NO: 2
3665


ANTH98
Heavy chain variable region
M18 scFv
US7902344; US69I6474 SEQ ID
3666





NO: 23



ANTH99
Heavy chain variable region
21D9 MAb
US7442373 SEQ ID NO: 2
3667


ANTH100
Heavy chain variable region
1C6 Mab
US7442373 SEQ ID NO: 6
3668


ANTH101
Heavy chain variable region
4H7 Mab
US7442373 SEQ ID NO: 10
3669


ANTH102
Heavy chain variable region
22G12 Mab
US7442373 SEQ ID NO: 14
3670


ANTH103
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 20
3671




antibody 9-1




ANTH104
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 21
3672




antibody 7-1




ANTH105
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 22
3673




antibody 24-2




ANTH106
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 23
3674




antibody 21-4




ANTH107
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 24
3675




antibody 10-2




ANTH108
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 25
3676




antibody 22-1




ANTH109
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 26
3677




antibody 13-3




ANTH110
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 27
3678




antibody 8-3




ANTH111
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO 29
3679




antibody 6-1




ANTH112
Heavy chain variable region
monoclonal
WO1999055842 SEQ ID NO: 30
3680




antibody 3-1




ANTH113
Heavy chain variable region,
EF12A
US8961975 SEQ ID NO: 51
3681



Edema factor binding





ANTH114
Heavy chain variable region,
EF13D
US8961975 SEQ ID NO: 33
3682



Edema factor binding





ANTH115
Heavy chain variable region,
EF14H
US8961975 SEQ ID NO: 52
3683



Edema factor binding





ANTH116
Heavy chain variable region,
EF15A
US8961975 SEQ ID NO: 53
3684



Edema factor binding





ANTH117
Heavy chain variable region,
LF9D
US8961975 SEQ ID NO: 49
3685



Lethal factor





ANTH118
Heavy chain variable region,
LF10E
US8961975 SEQ ID NO: 1
3686



Lethal factor





ANTH119
Heavy chain, Antibody
Obiltoxaximab

3687



against inhalational anthrax





ANTH120
Kappa light chain

US20040258699 SEQ ID NO: 19
3688


ANTH121
Kappa light chain

US20040258699 SEQ ID NO: 20
3689


ANTH122
Kappa light chain

US20040258699 SEQ ID NO: 21
3690


ANTH123
Kappa tight chain

US20040258699 SEQ ID NO: 22
3691


ANTH124
Kappa light chain

US20040258699 SEQ ID NO: 23
3692


ANTH125
Kappa light chain

US20040258699 SEQ ID NO: 24
3693


ANTH126
Kappa light chain

US20040258699 SEQ ID NO: 25
3694


ANTH127
Kappa light chain

US20040258699 SEQ ID NO: 26
3695


ANTH128
Kappa tight chain

US20040258699 SEQ ID NO: 39
3696


ANTH129
Kappa light chain

US20040258699 SEQ ID NO: 40
3697


ANTH130
Kappa light chain

US20040258699 SEQ ID NO: 41
3698


ANTH131
Kappa light chain

US20040258699 SEQ ID NO: 42
3699


ANTH132
Kappa light chain

US20040258699 SEQ ID NO: 43
3700


ANTH133
Kappa light chain

US20040258699 SEQ ID NO: 44
3701


ANTH134
Kappa light chain

US20040258699 SEQ ID NO: 45
3702


ANTH135
Kappa light chain

US20040258699 SEQ ID NO: 46
3703


ANTH136
Kappa light chain

US20040258699 SEQ ID NO: 47
3704


ANTH137
Kappa light chain

US20040258699 SEQ ID NO: 48
3705


ANTH138
Kappa light chain

US20040258699 SEQ ID NO: 49
3706


ANTH139
Kappa light chain

US20040258699 SEQ ID NO: 50
3707


ANTH140
Kappa light chain

US20040258699 SEQ ID NO: 51
3708


ANTH141
Kappa light chain

US20040258699 SEQ ID NO: 52
3709


ANTH142
Kappa light chain

US20040258699 SEQ ID NO: 53
3710


ANTH143
Kappa light chain

US20040258699 SEQ ID NO: 54
3711


ANTH144
Kappa light chain

US20040258699 SEQ ID NO: 55
3712


ANTH145
Kappa light chain

US20040258699 SEQ ID NO: 56
3713


ANTH146
Kappa light chain

US20040258699 SEQ ID NO: 57
3714


ANTH147
Kappa light chain

US20040258699 SEQ ID NO: 58
3715


ANTH148
Kappa light chain

US20040258699 SEQ ID NO: 59
3716


ANTH149
Kappa light chain

US20040258699 SEQ ID NO: 60
3717


ANTH150
Kappa light chain

US20040258699 SEQ ID NO: 61
3718


ANTH151
Lambda light chain

US20040258699 SEQ ID NO: 27
3719


ANTH152
Lambda light chain

US20040258699 SEQ ID NO: 28
3720


ANTH153
Lambda light chain

US20040258699 SEQ ID NO: 29
3721


ANTH154
Lambda light chain

US20040258699 SEQ ID NO: 30
3722


ANTH155
Lambda light chain

US20040258699 SEQ ID NO: 31
3723


ANTH156
Lambda light chain

US20040258699 SEQ ID NO: 32
3724


ANTH157
Lambda light chain

US20040258699 SEQ ID NO: 33
3725


ANTH158
Lambda light chain

US20040258699 SEQ ID NO: 34
3726


ANTH159
Lambda light chain

US20040258699 SEQ ID NO: 35
3727


ANTH160
Lambda tight chain

US20040258699 SEQ ID NO: 36
3728


ANTH161
Lambda light chain

US20040258699 SEQ ID NO: 37
3729


ANTH162
Lambda light chain

US20040258699 SEQ ID NO: 38
3730


ANTH163
Lambda light chain

US20040258699 SEQ ID NO: 62
3731


ANTH164
Lambda light chain

US20040258699 SEQ ID NO: 63
3732


ANTH165
Lambda light chain

US20040258699 SEQ ID NO: 64
3733


ANTH166
Lambda light chain

US20040258699 SEQ ID NO: 65
3734


ANTH167
Lambda light chain

US20040258699 SEQ ID NO: 66
3735


ANTH168
Lambda light chain

US20040258699 SEQ ID NO: 67
3736


ANTH169
Lambda light chain

US20040258699 SEQ ID NO: 68
3737


ANTH170
Lambda light chain

US20040258699 SEQ ID NO: 69
3738


ANTH171
Lambda light chain

US20040258699 SEQ ID NO: 70
3739


ANTH172
Lambda light chain

US20040258699 SEQ ID NO: 71
3740


ANTH173
Lambda light chain

US20040258699 SEQ ID NO: 72
3741


ANTH174
Lambda light chain

US20040258699 SEQ ID NO: 73
3742


ANTH175
Lambda light chain

US20040258699 SEQ ID NO: 74
3743


ANTH178
Lambda light chain

US20040258699 SEQ ID NO: 75
3744


ANTH177
Lambda light chain

US20040258699 SEQ ID NO: 76
3745


ANTH178
Lambda light chain

US20040258699 SEQ ID NO: 77
3746


ANTH179
Light chain

US8617548 SEQ ID NO: 1
3747


ANTH180
Light chain
IQNPA Lkappa
US7658925 SEQ ID NO: 4
3748


ANTH181
Light chain
IQNPA Lkappa
US7658925 SEQ ID NO: 8
3749


ANTH182
Light chain
1A5
US20090022736 SEQ ID NO: 2
3750


ANTH183
Light chain
4A12
US20090022736 SEQ ID NO: 4
3751


ANTH184
Light chain
24B1
US20090022736 SEQ ID NO: 6
3752


ANTH185
Light chain
24G4
US20090022736 SEQ ID NO: 8
3753


ANTH186
Light chain
′32E12
US20090022736 SEQ ID NO: 10
3754


ANTH187
Light chain
33F4
US20090022736 SEQ ID NO: 12
3755


ANTH188
Light chain
scFv 2LF
EP2778173 SEQ ID NO: 6
3756


ANTH189
Light chain
Obiltoxaximab

3757


ANTH190
Light chain region
W1
US8685396 SEQ ID NO: 9
3758


ANTH191
Light chain region
W2
US8685396 SEQ ID NO: 25
3759


ANTH192
Light chain region
W5
USX685396 SEQ ID NO: 37
3760


ANTH193
Light chain region
A63-6
US8685396 SEQ ID NO: 38
3761


ANTH194
Light chain region
F3-6
US8685396 SEQ ID NO: 39
3762


ANTH195
Light chain region
F5-1
US8685396 SEQ ID NO: 40
3763


ANTH196
Light chain variable region
LF11H
US8961975 SEQ ID NO: 25
3764


ANTH197
Light chain variable region
LF9D
US8961975 SEQ ID NO: 17
3765


ANTH198
Light chain variable region
LF10E
US8961975 SEQ ID NO: 9
3766


ANTH199
Light chain variable region
6.20
WO2015107307 SEQ ID NO: 2
3767


ANTH200
Light chain variable region
35PA83
WO200907186USEQ ID NO: 2
3768


ANTH201
Light chain variable region
anti-γDPGA
US8501182 SEQ ID NO: 2
3769




antibody




ANTH202
Light chain variable region
4C
US8501182 SEQ ID NO: 4
3770


ANTH203
Light chain variable region
11D
US8501182 SEQ ID NO: 6
3771


ANTH204
Light chain variable region
F20G75
WO2007131363 SEQ ID NO: 10
3772


ANTH205
Light chain variable region
F20G76
WO2007131363 SEQ ID NO: 12
3773


ANTH206
Light chain variable region
F20G77
WO2007131363 SEQ ID NO: 14
3774


ANTH207
Light chain variable region
V2 variant
US8507655 SEQ ID NO: 8
3775


ANTH208
Light chain variable region
6.20 variant
US8507655 SEQ ID NO: 10
3776


ANTH209
Light chain variable region
J24.15 variant
US8507655 SEQ ID NO: 12
3777


ANTH210
Light chain variable region
J24.7 variant
US8507655 SEQ ID NO: 14
3778


ANTH211
Light chain variable region
V2 variant human
US8507655 SEQ ID NO: 16
3779


ANTH212
Light chain variable region
6.20 vaiiant
US8507655 SEQ ID NO: 18
3780




human




ANTH213
Light chain variable region
J24.15 variant
US8507655 SEQ ID NO: 20
3781




human




ANTH214
Light chain variable region
J24.7 variant
US8507655 SEQ ID NO: 22
3782




human




ANTH215
Light chain variable region
HuMab 5E8
US8401820 SEQ ID NO: 4
3783




(Major)




ANTH216
Light chain variable region
HuMab 5E8
US8404820 SEQ ID NO: 6
3784




(Minor)




ANTH217
Light chain variable region
HuMab 2P5
US8404820 SEQ ID NO: 10
3785


ANTH218
Light chain variable region
HuMab 2H4
US8404820 SEQ ID NO: 14
3786


ANTH219
Light chain variable region
HuMab 5D5-
US8404820 SEQ ID NO: 18
3787




2E10




ANTH220
Light chain variable region
13E3
US8309090 SEQ ID NO: 4
3788


ANTH221
Light chain variable region
3E1
US8309090 SEQ ID NO: 8
3789


ANTH222
Light chain variable region
KCTC 10756BP
US8268316 SEQ ID NO: 7
3790


ANTH223
Light chain variable region
modified M18
US7902344; US6916474 SEQ ID
3791




sequence
NO: 25



ANTH224
Light chain variable region
21D9 MAb
US7442373 SEQ ID NO: 4
3792


ANTH225
Light chain variable region
1C6 Mab
US7442373 SEQ ID NO: 8
3793


ANTH226
Light chain variable region
4H7 Mab
US7442373 SEQ ID NO: 12
3794


ANTH227
Light chain variable region
22G12 Mab
US7442373 SEQ ID NO: 16
3795


ANTH228
Light chain variable region
ETI-204
US20120156196 SEQ ID NO: 2
3796



antibody against anthrax toxin,





ANTH229
Light chain variable region,
EF12A
US8961975 SEQ ID NO: 54
3797



Edema factor





ANTH230
Light chain variable region,
EF13D
US8961975 SEQ ID NO: 41
3798



Edema factor





ANTH231
Light chain variable region,
EF14H
US8961973 SEQ ID NO: 55
3799



Edema factor





ANTH232
Light chain variable region,
EP15A
US8961975 SEQ ID NO: 56
3800



Edema factor





ANTH233
Scfv
PWB2447 scFv
US7601351; US7906119;
3801





US20110189197 SEQ ID NO 48



ANTH234
Scfv
PWC2004 scFv
US7601351; US7906119;
3802





US20110189197 SEQ ID NO: 49



ANTH235
Scfv
PWD0283 scFv
US7601351; US7906119;
3803





US20110189197 SEQ ID NO 50



ANTH236
Scfv
PWP0323 scFv
US7601351; US7906119;
3804





US20110189197 SEQ ID NO: 51



ANTH237
Scfv
PWD0422 scFv
US7601351; US7906119;
3805





US20110189197 SEQ ID NO: 52



ANTH238
Scfv
PWD0587 scFv
US7601351; US7906119;
3806





US20110189197 SEQ ID NO: 53



ANTH239
Scfv
PWD0791 scFv
US7601351; US7906119;
3807





US20110189197 SEQ ID NO: 54



ANTH240
Scfv
PHP2222 scFv
US7601351; US7906119;
3808





US20110189197 SEQ ID NO: 55



ANTH241
Scfv
PHD2581 scFv
US7601351; US7906119;
3809





US20110189197 SEQ ID NO: 56



ANTH242

Abthrax
US20120136196 SEQ ID NO: 48
3810


ANTH243

Abthrax
US20120156196 SEQ ID NO: 49
3811


ANTH244


WO2003063768 SEQ ID NO: 4
3812


ANTH245


WO2003063768 SEQ ID NO: 5
3813









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 16 against Botulinum Toxin.









TABLE 16







Antibodies against Botulinum Toxin















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





BOTT1
Heavy-chain-only

US20130058962 SEQ ID NO: 56
3814


BOTT2
Heavy-chain-only

US20130058962 SEQ ID NO: 57
3815


BOTT3
Heavy-chain-only

US20130058962 SEQ ID NO: 58
3816


BOTT4
Heavy-chain only binding
JDA-D12
WO2015100409 SEQ ID NO: 20
3817



agents specific to BoNT/A



holotoxin


BOTT5
Heavy-chain only binding
JDQ-A5
WO2015100409 SEQ ID NO: 22
3818



agents specific to BoNT/A



holotoxin


BOTT6
Heavy-chain only binding
JDQ-B5
WO2015100409 SEQ ID NO: 24
3819



agents specific to BoNT/A



holotoxin


BOTT7
Heavy-chain only binding
JDQ-C2
WO2015100409 SEQ ID NO: 26
3820



agents specific to BoNT/A



holotoxin


BOTT8
Heavy-chain only binding
JDQ-F 12
WO2015100409 SEQ ID NO: 28
3821



agents specific to BoNT/A



holotoxin


BOTT9
Heavy-chain only binding
JDQ-G5
WO2015100409 SEQ ID NO: 30
3822



agents specific to BoNT/A



holotoxin


BOTT10
Heavy-chain only binding
JDQ-H7
WO2015100409 SEQ ID NO: 32
3823



agents specific to BoNT/A



holotoxin


BOTT11
Heavy-chain only binding
JEQ-A5
WO2015100409 SEQ ID NO: 34
3824



agents specific to BoNT/A



holotoxin


BOTT12
Heavy-chain only binding
JEQ-H11
WO2015100409 SEQ ID NO: 36
3825



agents specific to BoNT/A



holotoxin


BOTT13
Heavy-chain only binding agent
E-9
WO2015100409 SEQ ID NO: 38
3826


BOTT14
Heavy-chain only binding agent
B2
WO2015100409 SEQ ID NO: 40
3827


BOTT15
Heavy-chain only binding agent
C5
WO2015100409 SEQ ID NO: 42
3828


BOTT16
Heavy-chain only binding agent
F9
WO2015100409 SEQ ID NO: 44
3829


BOTT17
Heavy-chain only binding agent
heavy-chain only
WO2015100409 SEQ ID NO: 46
3830




binding agent


BOTT18
Heavy-chain only binding agent
heavy-chain only
WO2015100409 SEQ ID NO: 48
3831



with tag
binding agent




with tag


BOTT19
Heavy-chain only binding agent
heavy-chain only
WO2015100409 SEQ ID NO: 50
3832



with tag
binding agent




with tag


BOTT20
Heavy-chain only dimer
heavy-chain only
WO2015100409 SEQ ID NO: 52
3833



binding agent with two tags
dimer binding




agent with two




tags


BOTT21
Recombinant camelid heavy-
H7
WO2015100409 SEQ ID NO: 56
3834



chain-only antibody


BOTT22
Recombinant camelid heavy-
B5
WO2015100409 SEQ ID NO: 57
3835



chain-only antibody


BOTT23
Recombinant camelid heavy-

WO2015100409 SEQ ID NO: 58
3836



chain-only antibody


BOTT24
Scfv
scFv#2
WO2015100409 SEQ ID NO: 2
3837


BOTT25
Scfv
scFv#3
WO2015100409 SEQ ID NO: 4
3838


BOTT26
Scfv
scFv#7
WO2015100409 SEQ ID NO: 6
3839


BOTT27
Scfv
scFv#8
WO2015100409 SEQ ID NO: 8
3840


BOTT28
Scfv
scFv#21
WO2015100409 SEQ ID NO: 10
3841


BOTT29
Scfv
scFv#E
WO2015100409 SEQ ID NO: 12
3842


BOTT30
Scfv
scFv#7-2E
WO2015100409 SEQ ID NO: 14
3843









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 17 against Shiga Toxin.









TABLE 17







Antibodies against Shiga Toxin















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





SHIG1
Camelid heavy-chain only
JET-H12
WO2015100409 SEQ ID NO: 96
3844


SHIG2
Camelid heavy-chain only
JFG-H6
WO2015100409 SEQ ID NO: 98
3845


SHIG3
Heavy chain

US2014013548 SEQ ID NO: 44
3846


SHIG4
Heavy chain

US2014013548 SEQ ID NO: 21
3847


SHIG5
Heavy chain of cαstx1
Shigamab
US20120195891 SEQ ID NO: 1
3848


SHIG6
Heavy chain of cαstx1
Shigamab
US20120195891 SEQ ID NO: 2
3849


SHIG7
Heavy chain of cαstx2
Shigamab
US20120195891 SEQ ID NO: 3
3850


SHIG8
Heavy chain of cαstx2
Shigamab
US20120195891 SEQ ID NO: 4
3851


SHIG9
Heavy chain single domain

WO2014191904 SEQ ID NO: 7
3852


SHIG10
Heavy chain single domain

WO2014191904 SEQ ID NO: 8
3853


SHIG11
Heavy chain single domain

WO2014191904 SEQ ID NO: 9
3854


SHIG12
Heavy chain single domain

WO2014191904 SEQ ID NO: 10
3855


SHIG13
Heavy chain single domain

WO2014191904 SEQ ID NO: 11
3856


SHIG14
Heavy chain single domain

WO2014191904 SEQ ID NO: 12
3857


SHIG15
Heavy chain single domain

WO2014191904 SEQ ID NO: 13
3858


SHIG16
Heavy chain single domain

WO2014191904 SEQ ID NO: 14
3859


SHIG17
Heavy chain single domain

WO2014191904 SEQ ID NO: 15
3860


SHIG18
Heavy chain single domain

WO2014191904 SEQ ID NO: 16
3861


SHIG19
Heavy chain single domain

WO2014191904 SEQ ID NO: 17
3862


SHIG20
Heavy chain single domain

WO2014191904 SEQ ID NO: 18
3863


SHIG21
Heavy chain single domain

WO2014191904 SEQ ID NO: 19
3864


SHIG22
Heavy chain single domain

WO2014191904 SEQ ID NO: 20
3865


SHIG23
Heavy chain single domain

WO2014191904 SEQ ID NO: 21
3866


SHIG24
Heavy chain single domain

WO2014191904 SEQ ID NO: 22
3867


SHIG25
Heavy chain single domain

WO2014191904 SEQ ID NO: 23
3868


SHIG26
Heavy chain single domain

WO2014191904 SEQ ID NO: 24
3869


SHIG27
Heavy chain single domain

WO2014191904 SEQ ID NO: 25
3870


SHIG28
Heavy chain single domain

WO2014191904 SEQ ID NO: 26
3871


SHIG29
Heavy chain single domain

WO2014191904 SEQ ID NO: 27
3872


SHIG30
Heavy chain single domain

WO2014191904 SEQ ID NO: 28
3873


SHIG31
Heavy chain single domain

WO2014191904 SEQ ID NO: 29
3874


SHIG32
Heavy chain single domain

WO2014191904 SEQ ID NO: 30
3875


SHIG33
Heavy chain single domain

WO2014191904 SEQ ID NO: 31
3876


SHIG34
Heavy chain single domain

WO2014191904 SEQ ID NO: 32
3877


SHIG35
Heavy chain single domain

WO2014191904 SEQ ID NO: 33
3878


SHIG36
Heavy chain single domain

WO2014191904 SEQ ID NO: 34
3879


SHIG37
Heavy chain single domain

WO2014191904 SEQ ID NO: 35
3880


SHIG38
Heavy chain single domain

WO2014191904 SEQ ID NO: 36
3881


SHIG39
Heavy chain single domain

WO2014191904 SEQ ID NO: 37
3882


SHIG40
Heavy chain single domain

WO2014191904 SEQ ID NO: 38
3883


SHIG41
Heavy chain single domain

WO2014191904 SEQ ID NO: 39
3884


SHIG42
Heavy chain single domain

WO2014191904 SEQ ID NO: 40
3885


SHIG43
Heavy chain single domain

WO2014191904 SEQ ID NO: 41
3886


SHIG44
Heavy chain single domain

WO2014191904 SEQ ID NO: 42
3887


SHIG45
Heavy chain single domain

WO2014191904 SEQ ID NO: 43
3888


SHIG46
Heavy chain single domain

WO2014191904 SEQ ID NO: 44
3889


SHIG47
Heavy chain single domain

WO2014191904 SEQ ID NO: 45
3890


SHIG48
Heavy chain single domain

WO2014191904 SEQ ID NO: 46
3891


SHIG49
Heavy chain single domain

WO2014191904 SEQ ID NO: 47
3892


SHIG50
Heavy-chain-only

US20130058962 SEQ ID NO: 77
3893


SHIG51
Heavy-chain-only

US20130058962 SEQ ID NO: 78
3894


SHIG52
Heavy-chain-only

US20130058962 SEQ ID NO: 79
3895


SHIG53
Heavy-chain-only

US20130058962 SEQ ID NO: 80
3896


SHIG54
Heavy-chain-only

US20130058962 SEQ ID NO: 81
3897


SHIG55
Heavy-chain-only

US20130058962 SEQ ID NO: 82
3898


SHIG56
Heavy-chain-only

US20130058962 SEQ ID NO: 83
3899


SHIG57
Heavy-chain-only

US20130058962 SEQ ID NO: 84
3900


SHIG58
Heavy-chain-only

US20130058962 SEQ ID NO: 85
3901


SHIG59
Heavy-chain-only

US20130058962 SEQ ID NO: 86
3902


SHIG60
Light chain

US2014013548 SEQ ID NO: 42
3903


SHIG61
Light chain

US2014013548 SEQ ID NO: 19
3904


SHIG62
Recombinant camelid heavy-
JET-A9
WO2015100409 SEQ ID NO: 77
3905



chain-only antibody, STX1


SHIG63
Recombinant camelid heavy-
JGG-D4
WO2015100409 SEQ ID NO: 78
3906



chain-only antibody, STX1


SHIG64
Recombinant camelid heavy-
JFD-A4
WO2015100409 SEQ ID NO: 84
3907



chain-only antibody, STX1,



STX2


SHIG65
Recombinant camelid heavy-
JFD-A5
WO2015100409 SEQ ID NO: 85
3908



chain-only antibody, STX1,



STX2


SHIG66
Recombinant camelid heavy-
JGG-G6
WO2015100409 SEQ ID NO: 86
3909



chain-only antibody, STX1,



STX2


SHIG67
Recombinant camelid heavy-
JEN-D10
WO2015100409 SEQ ID NO: 79
3910



chain-only antibody, STX2


SHIG68
Recombinant camelid heavy-
JGH-G1
WO2015100409 SEQ ID NO: 80
3911



chain-only antibody, STX2


SHIG69
Recombinant camelid heavy-
JEU-A6
WO2015100409 SEQ ID NO: 81
3912



chain-only antibody, STX2


SHIG70
Recombinant camelid heavy-
JEU-D2
WO2015100409 SEQ ID NO: 82
3913



chain-only antibody, STX2


SHIG71
Recombinant camelid heavy-
JGH-G9
WO2015100409 SEQ ID NO: 83
3914



chain-only antibody, STX2









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in US Pub. No. US20090280104, the contents of each of which are herein incorporated by reference in their entirety, against Shiga toxin


Tropical Diseases

In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the tropical disease related payload antibody polypeptides listed in Tables 18-20.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 18 against Plasmodium falciparum causing Malaria.









TABLE 18







Antibodies against Plasmodium Falciparum causing Malaria















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





MALA1
Heavy chain
immunoglobulin
Wajanarogana, S. et al., Construction of a
3915




heavy chain
human functional single-chain variable fragment




variable region,
(scFv) antibody recognizing the malaria parasite




partial

Plasmodium falciparum, Biotechnol. Appl.





Biochem. 44 (PT 1), 55-61 (2006), NCBI





Accession # AAX76832.1 (129aa)


MALA2
Heavy chain
anti-MSP1
Sowa, K. M. et al., Isolation of a monoclonal
3916




MAD20 block2
antibody from a malaria patient-derived phage




ScFv Ig heavy
display library recognizing the Block 2 region




chain variable
of Plasmodium falciparum merozoite surface




region, partial
protein-1, Mol. Biochem. Parasitol. 112 (1),





143-147 (2001), NCBI Accession #AAK08696.1





(119aa)


MALA3
Heavy chain
immunoglobulin
Lundquist, R. et al., Human recombinant
3917




heavy chain
antibodies against Plasmodium falciparum




variable region,
merozoite surface protein 3 cloned from




partial
peripheral blood leukocytes of individuals with





immunity to malaria demonstrate antiparasitic





properties, Infect. Immun. 74 (6), 3222-3231,





(2006), NCBI Accession # AAT09786.1





(113aa)


MALA4
Heavy chain
2A10 anti-
NCBI Accession # BAK41504.1 (118aa)
3918



variable region
malaria




antibody


MALA5
Heavy chain

U.S. Pat. No. 7,811,569 to Dziegiel; SEQ ID NO: 1
3919


MALA6
Heavy chain,

U.S. Pat. No. 7,811,569 to Dziegiel; SEQ ID NO: 3
3920



Anti-ang-2



antibody


MALA7
Heavy chain

U.S. Pat. No. 7,811,569 to Dziegiel; SEQ ID NO: 5
3921


MALA8
Heavy chain

US20150197562 SEQ ID NO: 14
3922



variable region


MALA9
Heavy chain
mAh 5D5
US20150158941 SEQ ID NO: 16
3923



variable region


MALA10
Heavy chain

US20140112930 SEQ ID NO: 18
3924



variable region


MALA11
Heavy chain
M071Xi0199
WO2014087007; SEQ ID NO: 182
3925



variable region


MALA12
Heavy chain
M071Xi2204
WO2014087007; SEQ ID NO: 186
3926



variable region


MALA13
Heavy chain
M071Xi0237
WO2014087007; SEQ ID NO: 190
3927



variable region


MALA14
Heavy chain
M071Xi2127
WO2014087007; SEQ ID NO: 194
3928



variable region


MALA15
Heavy chain
M071Xi0092
WO2014087007; SEQ ID NO: 198
3929



variable region


MALA16
Heavy chain
M071Xi2057
WO2014087007; SEQ ID NO: 202
3930



variable region


MALA17
Heavy chain
M070Xi3010
WO2014087007; SEQ ID NO: 206
3931



variable region


MALA18
Heavy chain
M071Xi0227
WO2014087007; SEQ ID NO: 210
3932



variable region


MALA19
Heavy chain
M071Xi0081
WO2014087007; SEQ ID NO: 214
3933



variable region


MALA20
Heavy chain
M071Xi0124
WO2014087007; SEQ ID NO: 218
3934



variable region


MALA21
Heavy chain
M036Xi0326
WO2014087007; SEQ ID NO: 222
3935



variable region


MALA22
Heavy chain
M070Xi3195
WO2014087007; SEQ ID NO: 226
3936



variable region


MALA23
Heavy chain
M070Xi3062
WO2014087007; SEQ ID NO: 230
3937



variable region


MALA24
Heavy chain
M071Xi2217
WO2014087007; SEQ ID NO: 234
3938



variable region


MALA25
Heavy chain
M036Xi0003
WO2014087007; SEQ ID NO: 238
3939



variable region


MALA26
Heavy chain, Eba-
R217
Chen et al., PLoS Pathol. 9 (5), E1003390
3940



175

(2013), NCBI Accession # 4QEX_I (215aa)


MALA27
Heavy chain, Eba-
R218
Chen et al., PLoS Pathol. 9 (5), E1003390
3941



175

(2013), NCBI Accession # 4K2U_I (233aa)


MALA28
Light chain
anti-MSP1
Sowa, K. M. et al., Isolation of a monoclonal
3942




MAD20 block2
antibody from a malaria patient-derived phage




ScFv Ig heavy
display library recognizing the Block 2 region




chain variable
of Plasmodium falciparum merozoite surface




region, partial
protein-1, Mol. Biochem. Parasitol. 112 (1),





143-147 (2001), NCBI Accession





#AAK08697.1 (119aa)


MALA29
Light chain
anti-MSP1
Sowa, K. M. et al., Isolation of a monoclonal
3943




MAD20 block2
antibody from a malaria patient-derived phage




ScFv Ig light
display library recognizing the Block 2 region




chain variable
of Plasmodium falciparum merozoite surface




region, partial
protein-1, Mol. Biochem. Parasitol. 112 (1),





143-147 (2001), NCBI Accession





#AAK08698.1 (110aa)


MALA30
Light chain
immunoglobulin
Wajanarogana, S. et al., Construction of a
3944




light chain
human functional single-chain variable fragment




variable region,
(scFv) antibody recognizing the malaria parasite




partial

Plasmodium falciparum, Biotechnol. Appl.





Biochem. 44 (PT 1), 55-61 (2006) AAX76833.1





(107aa)


MALA31
Kappa light chain
immunoglobulin
Lundquist, R. et al., Human recombinant
3945




kappa light
antibodies against Plasmodium falciparum




chain variable
merozoite surface protein 3 cloned from




region, partial
peripheral blood leukocytes of individuals with





immunity to malaria demonstrate antiparasitic





properties, Infect. Immun. 74 (6), 3222-3231,





(2006), NCBI Accession # AAT09787.1





(113aa)


MALA32
Light chain
2A10 anti-
NCBI Accession # BAK41503.1 (108aa)
3946



variable region
malaria




antibody


MALA33
Light chain

U.S. Pat. No. 7,811,569 to Dziegiel; SEQ ID NO: 2
3947


MALA34
Light chain, Anti-

U.S. Pat. No. 7,811,569 to Dziegiel; SEQ ID NO: 4
3948



ang-2 antibody


MALA35
Light chain

U.S. Pat. No. 7,811,569 to Dziegiel; SEQ ID NO: 6
3949


MALA36
Light chain

US20150197562 SEQ ID NO: 15
3950



variable region


MALA37
Light chain

US20150197562 SEQ ID NO: 19
3951



variable region


MALA38
Light chain
mAb 5D5
US20150158941 SEQ ID NO: 14
3952



variable region


MALA39
Light chain

US20140112930 SEQ ID NO: 20
3953



variable region


MALA40
Light chain
M071Xi0199
WO2014087007; SEQ ID NO: 184
3954



variable region


MALA41
Light chain
M071Xi2204
WO2014087007; SEQ ID NO: 188
3955



variable region


MALA42
Light chain
M071Xi0237
WO2014087007; SEQ ID NO: 192
3956



variable region


MALA43
Light chain
M071Xi2127
WO2014087007; SEQ ID NO: 196
3957



variable region


MALA44
Light chain
M071Xi0092
WO2014087007; SEQ ID NO: 200
3958



variable region


MALA45
Light chain
M071Xi2057
WO2014087007; SEQ ID NO: 204
3959



variable region


MALA46
Light chain
M070Xi3010
WO2014087007; SEQ ID NO: 208
3960



variable region


MALA47
Light chain
M071Xi0227
WO2014087007; SEQ ID NO: 212
3961



variable region


MALA48
Light chain
M071Xi0081
WO2014087007; SEQ ID NO: 216
3962



variable region


MALA49
Light chain
M071Xi0124
WO2014087007; SEQ ID NO: 220
3963



variable region


MALA50
Light chain
M036Xi0326
WO2014087007; SEQ ID NO: 224
3964



variable region


MALA51
Light chain
M070Xi3195
WO2014087007; SEQ ID NO: 228
3965



variable region


MALA52
Light chain
M070Xi3062
WO2014087007; SEQ ID NO: 232
3966



variable region


MALA53
Light chain
M071Xi2217
WO2014087007; SEQ ID NO: 236
3967



variable region


MALA54
Light chain
M036Xi0003
WO2014087007; SEQ ID NO: 240
3968



variable region


MALA55
Light chain, Eba-
R217
Chen et al., PLoS Pathol. 9 (5), E1003390
3969



175

(2013), NCBI Accession # 4QEX_M (214aa)


MALA56
Light chain, Eba-
R218
Chen et al., PLoS Pathol. 9 (5), E1003390
3970



175

(2013), NCBI Accession # 4K2U_M (234aa)


MALA57
Vivax apical
F8.12.19
NCBI Accession # 2J4W_L (213aa)
3971



membrane antigen



1 monoclonal



antibody, seqres









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 19 against Ebola and/or Margburg Viruses.









TABLE 19







Antibodies against Ebola and Marburg viruses















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





EBOL1
Chain A, Sudan Ebolavirus
16f6
Bale et al., Structural basis for
3972



Glycoprotein (Strain Boniface)

differential neutralization of





ebolaviruses; Viruses 4 (4), 447-470





(2012), NCBI Accession # 3VE0_B





(212aa)


EBOL2
Chain B, Sudan Ebolavirus
16f6
Bale et al., Structural basis for
3973



Glycoprotein (Strain Boniface)

differential neutralization of





ebolaviruses; Viruses 4 (4), 447-470





(2012), NCBI Accession # 3VE0_A





(220aa)


EBOL3
Ebola Virus Glycoprotein
13f6-1-2
Lee J. E. et al., Complex of a protective
3974




Fab
antibody with its Ebola virus GP





peptide epitope: unusual features of a V





lambda x light chain; J. Mol. Biol. 375





(1), 202-216 (2008), NCBI Accession #





2QHR_L (218aa)


EBOL4
Ebola Virus Glycoprotein
13f6-1-2
Lee J. E. et al., Complex of a protective
3975




Fab
antibody with its Ebola virus GP





peptide epitope: unusual features of a V





lambda x light chain; J. Mol. Biol. 375





(1), 202-216 (2008), NCBI Accession #





2QHR_H (222aa)


EBOL5
Fab heavy chain Envelope
Mr78
Hashiguchi, T., et al., Cell 160 (5),
3976



Glycoprotein Gp1

904-912 (2015), NCBI Accession #





3X2D_P (226aa)


EBOL6
Fab light chain, Envelope
Mr78
Hashiguchi, T., et al., Cell 160 (5),
3977



Glycoprotein Gp1

904-912 (2015), NCBI Accession #





3X2D_O (213aa)


EBOL7
Fusion protein, Zaire Ebola virus,

US20140356354 SEQ ID NO: 2
3978



Mayinga strain glycoprotein


EBOL8
Heavy chain Ebolavirus-Protective

Olal, D., et al., Structure of an
3979



Antibody

Antibody in Complex with Its Mucin





Domain Linear Epitope That Is





Protective against Ebola Virus; J. Virol.





86 (5), 2809-2816 (2012), NCBI





Accession # 2Y6S_H (213aa)


EBOL9
Heavy chain Filovirus (Ebola or

US20140356354 SEQ ID NO: 6
3980



Marburg)


EBOL10
Heavy chain Filovirus (Ebola or

US20140356354 SEQ ID NO: 7
3981



Marburg)


EBOL11
Heavy chain Filovirus (Ebola or

US20140356354 SEQ ID NO: 8
3982



Marburg)


EBOL12
Heavy chain Filovirus (Ebola or

US20140356354 SEQ ID NO: 9
3983



Marburg)


EBOL13
Heavy chain Filovirus (Ebola or

US20140356354 SEQ ID NO: 10
3984



Marburg)


EBOL14
Heavy chain Filovirus (Ebola or

US20140356354 SEQ ID NO: 11
3985



Marburg)


EBOL15
Heavy chain variable region, Zaire

WO2015127136 SEQ ID NO: 71
3986



ebolavirus (ZEBOV) glycoprotein


EBOL16
Heavy chain variable region, Zaire

WO2015127136 SEQ ID NO: 47
3987



ebolavirus (ZEBOV) glycoprotein


EBOL17
Heavy chain variable region, Zaire

WO2015127136 SEQ ID NO: 23
3988



ebolavirus (ZEBOV) glycoprotein


EBOL18
Heavy chain variable region, Ebola
16H11
U.S. Pat. No. 9,097,713 SEQ ID NO: 2
3989



Sudan Boniface virus (ESB)



glycoprotein (GP)


EBOL19
Heavy chain variable region, Ebola
19B3
U.S. Pat. No. 9,097,713 SEQ ID NO: 4
3990



Sudan Boniface virus (ESB)



glycoprotein (GP)


EBOL20
Heavy chain variable region, Ebola
17F6
U.S. Pat. No. 9,097,713 SEQ ID NO: 6
3991



Sudan Boniface virus (ESB)



glycoprotein (GP)


EBOL21
Heavy chain variable region, Ebola
16F6
U.S. Pat. No. 9,097,713 SEQ ID NO: 8
3992



Sudan Boniface virus (ESB)



glycoprotein (GP)


EBOL22
Heavy chain variable region, Ebola
EGP 6D8
U.S. Pat. No. 7,335,356 SEQ ID NO: 22
3993



virus GP
1-2


EBOL23
Heavy chain variable region, Ebola
EGP13F6-1-2
U.S. Pat. No. 7,335,356 SEQ ID NO: 32
3994



virus GP


EBOL24
Heavy chain variable region, Ebola
EGP13C6-1-1
U.S. Pat. No. 7,335,356 SEQ ID NO: 12
3995



virus GP


EBOL25
Heavy chain variable region,

WO2015127140 SEQ ID NO: 14
3996



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL26
Heavy chain variable region,

WO2015127140 SEQ ID NO: 38
3997



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL27
Heavy chain variable region,

WO2015127140 SEQ ID NO: 62
3998



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL28
Heavy chain variable region,

WO2015127140 SEQ ID NO: 86
3999



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL29
Heavy chain variable region,

WO2015127140 SEQ ID NO: 110
4000



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL30
Heavy chain variable region,

WO2015127140 SEQ ID NO: 134
4001



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL31
Heavy chain variable region,

WO2015127140 SEQ ID NO: 158
4002



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL32
Heavy chain, Ebola virus
Fab Kz52
Lee J. E. et al., Structure of the Ebola
4003



glycoprotein,

virus glycoprotein bound to an





antibody from a human survivor;





Nature 454 (7201), 177-182 (2008),





NCBI Accession # 3CSY_G (226aa)


EBOL33
Light chain variable region, Ebola
16F6
U.S. Pat. No. 9,097,713 SEQ ID NO: 10
4004



Sudan Boniface virus (ESB)



glycoprotein (GP)


EBOL34
Light chain variable region, Ebola
EGP 6D8
U.S. Pat. No. 7,335,356 SEQ ID NO: 27
4005



virus GP
1-2


EBOL35
Light chain variable region, Ebola
EGP13F6-1-2
U.S. Pat. No. 7,335,356 SEQ ID NO: 37
4006



virus GP


EBOL36
Light chain variable region, Ebola
EGP13C6-1-1
U.S. Pat. No. 7,335,356 SEQ ID NO: 16
4007



virus GP


EBOL37
Light chain variable region,

WO2015127140 SEQ ID NO: 2
4008



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL38
Light chain variable region,

WO2015127140 SEQ ID NO: 26
4009



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL39
Light chain variable region,

WO2015127140 SEQ ID NO: 50
4010



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest vires or Reston virus



glycoprotein


EBOL40
Light chain variable region,

WO2015127140 SEQ ID NO: 74
4011



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL41
Light chain variable region,

WO2015127140 SEQ ID NO: 98
4012



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL42
Light chain variable region,

WO2015127140 SEQ ID NO: 122
4013



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL43
Light chain variable region,

WO2015127140 SEQ ID NO: 146
4014



Marburg virus, Ebola virus, Sudan



virus, Bundibugyo virus, Tai



Forest virus or Reston virus



glycoprotein


EBOL44
Light chain variable region, Zaire

WO2015127136 SEQ ID NO: 59
4015



ebolavirus (ZEBOV) glycoprotein


EBOL45
Light chain variable region, Zaire

WO2015127136 SEQ ID NO: 35
4016



ebolavirus (ZEBOV) glycoprotein


EBOL46
Light chain variable region, Zaire

WO2015127136 SEQ ID NO: 11
4017



ebolavirus (ZEBOV) glycoprotein


EBOL47
light chain, Ebola virus
Fab Kz52
Lee J. E. et al., Structure of the Ebola
4018



glycoprotein

virus glycoprotein bound to an





antibody from a human survivor;





Nature 454 (7201), 177-182 (2008),





NCBI Accession # 3CSY_H (217aa)


EBOL48
Light chain, Ebolavirus-Protective

Olal, D., et al., Structure of an
4019



Antibody

Antibody in Complex with Its Mucin





Domain Linear Epitope That Is





Protective against Ebola Virus; J. Virol.





86 (5), 2809-2816 (2012), NCBI





Accession # 2Y6S_L (217aa)


EBOL49
Light chain, Filovirus (Ebola or

US20140356354 SEQ ID NO: 12
4020



Marburg)


EBOL50
Light chain, Filovirus (Ebola or

US20140356354 SEQ ID NO: 13
4021



Marburg)


EBOL51
Light chain, Filovirus (Ebola or

US20140356354 SEQ ID NO: 14
4022



Marburg)


EBOL52
Light chain, Filovirus (Ebola or

US20140356354 SEQ ID NO: 15
4023



Marburg)


EBOL53
Light chain, Filovirus (Ebola or

US20140356354 SEQ ID NO: 16
4024



Marburg)









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in U.S. Pat. No. 7,335,356 and EP Pub. No. EP1539238, the contents of each of which are herein incorporated by reference in their entirety, against Ebola.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 20 against Mosquito-borne disease.









TABLE 20







Antibodies against Mosquito-borne diseases















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





MOSQ1
Gamma heavy chain,

Thibodeaux, B. A. “Development of a human-
4025



partial, anti-Saint Louis

murine chimeric immunoglobulin M antibody



encephalitis virus

for use in the serological detection of human



envelope glycoprotein

flavivirus antibodies”, Clin. Vaccine



immunoglobulin

Immunol. 16 (5), 679-685, 2009), NCBI





Accession # ACI62179


MOSQ2
Gamma heavy chain,

Thibodeaux, B. A. “Development of a human-
4026



partial, anti-Saint Louis

murine chimeric immunoglobulin M antibody



encephalitis virus

for use in the serological detection of human



envelope glycoprotein

flavivirus antibodies”, Clin. Vaccine



immunoglobulin

Immunol. 16 (5), 679-685, 2009), NCBI





Accession # ACI62180


MOSQ3
Heavy chain variable
anti-
US20080292644 SEQ ID NO: 69
4027



region, Japanese
DLVR1/CLEC5A



encephalitis virus


MOSQ4
Heavy chain variable
anti-
US20080292644 SEQ ID NO: 70
4028



region, Japanese
DLVR1/CLEC5A



encephalitis virus


MOSQ5
Heavy chain variable
anti-
US20080292644 SEQ ID NO: 71
4029



region, Japanese
DLVR1/CLEC5A



encephalitis virus


MOSQ6
Heavy chain variable

CN103864925 SEQ ID NO: 2
4030



region, Japanese



encephalitis virus


MOSQ7
Heavy chain variable

Throsby, M. “Isolation and characterization
4031



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20480.1


MOSQ8
Heavy chain variable

Throsby, M. “Isolation and characterization
4032



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20479.1


MOSQ9
Heavy chain variable

Throsby, M. “Isolation and characterization
4033



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20478.1


MOSQ10
Heavy chain variable

Throsby, M. “Isolation and characterization
4034



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20477.1


MOSQ11
Heavy chain variable

Throsby, M. “Isolation and characterization
4035



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20476.1


MOSQ12
Heavy chain variable

Throsby, M. “Isolation and characterization
4036



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20475.1


MOSQ13
Heavy chain variable

Throsby, M. “Isolation and characterization
4037



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20474.1


MOSQ14
Heavy chain variable

Throsby, M. “Isolation and characterization
4038



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20473.1


MOSQ15
Heavy chain variable

Throsby, M. “Isolation and characterization
4039



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20472.1


MOSQ16
Heavy chain variable

Throsby, M. “Isolation and characterization
4040



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006). NCBI





Accession # ABF20471.1


MOSQ17
Heavy chain variable
mAbl 1
WO2014144061 SEQ ID NO: 1
3359



region, WNV, Dengue,



St. Louis encephalitis,



yellow fever virus,



Japanese encephalitis



virus, Murray Valley



encephalitis virus


MOSQ18
Heavy chain, WNV
CR4348
U.S. Pat. No. 8,911,738 SEQ ID NO: 30
4041


MOSQ19
Heavy chain, WNV
CR4354
U.S. Pat. No. 8,911,738 SEQ ID NO: 32
4042


MOSQ20
Heavy chain, WNV
CR4261
U.S. Pat. No. 8,911,738 SEQ ID NO: 60
4043


MOSQ21
Heavy chain, WNV
CR4267
U.S. Pat. No. 8,911,738 SEQ ID NO: 62
4044


MOSQ22
Heavy chain, WNV
CR4328
U.S. Pat. No. 8,911,738 SEQ ID NO: 64
4045


MOSQ23
Heavy chain, WNV
CR4335
U.S. Pat. No. 8,911,738 SEQ ID NO: 66
4046


MOSQ24
Heavy chain, WNV
CR4383
U.S. Pat. No. 8,911,738 SEQ ID NO: 68
4047


MOSQ25
Heavy chain, WNV
CRM4354
U.S. Pat. No. 8,911,738 SEQ ID NO: 148
4048


MOSQ26
Heavy chain variable
Antibody from
U.S. Pat. No. 8,911,738 SEQ ID NO: 20
4049



region, WNV
U.S. Pat. No. 8,911,738


MOSQ27
Heavy chain variable
E16 heavy chain
U.S. Pat. No. 7,572,456 SEQ ID NO: 21
4050



region, WNV
version 1


MOSQ28
Heavy chain variable
E16 heavy chain
U.S. Pat. No. 7,572,456 SEQ ID NO: 22
4051



region, WNV
version 2


MOSQ29
Heavy chain variable
E16 heavy chain
U.S. Pat. No. 7,572,456 SEQ ID NO: 23
4052



region, WNV
version 3


MOSQ30
Heavy chain variable
Antibody from
U.S. Pat. No. 8,911,738 SEQ ID NO: 18
4053



region, WNV
U.S. Pat. No. 8,911,738


MOSQ31
Heavy chain variable
hu-E16/E16p
U.S. Pat. No. 8,663,950 SEQ ID NO: 2
4054



region, WNV


MOSQ32
Heavy chain variable
hu-E16/E16p
U.S. Pat. No. 8,663,950 SEQ ID NO: 3
4055



region, WNV


MOSQ33
Heavy chain variable
E16
U.S. Pat. No. 7,527,973 SEQ ID NO: 4
4056



region, WNV


MOSQ34
Heavy chain variable
E24
U.S. Pat. No. 7,527,973 SEQ ID NO: 8
4057



region, WNV


MOSQ35
Heavy chain variable
E34
U.S. Pat. No. 7,527,973 SEQ ID NO: 12
4058



region, WNV


MOSQ36
Heavy chain variable
11
US20090130123 SEQ ID NO: 23
4059



region, WNV


MOSQ37
Heavy chain variable
71
US20090130123 SEQ ID NO: 24
4060



region, WNV


MOSQ38
Heavy chain variable
73
US20090130123 SEQ ID NO: 25
4061



region, WNV


MOSQ39
Heavy chain variable
85
US20090130123 SEQ ID NO: 26
4062



region, WNV


MOSQ40
Heavy chain variable
15
US20090130123 SEQ ID NO: 27
4063



region, WNV


MOSQ41
Heavy chain variable
95
US20090130123 SEQ ID NO: 28
4064



region, WNV


MOSQ42
Heavy chain variable
84
US20090130123 SEQ ID NO: 29
4065



region, WNV


MOSQ43
Heavy chain variable
10
US20090130123 SEQ ID NO: 30
4066



region, WNV


MOSQ44
Heavy chain variable
69
US20090130123 SEQ ID NO: 31
4067



region, WNV


MOSQ45
Heavy chain variable
79
US20090130123 SEQ ID NO: 32
4068



region, WNV


MOSQ46
Heavy chain variable
94
US20090130123 SEQ ID NO: 33
4069



region, WNV


MOSQ47
Heavy chain variable
9FI2
WO2010093335 SEQ ID NO: 4
3333



region, WNV


MOSQ48
Heavy chain variable

Throsby, M. “Isolation and characterization
4070



region, partial sequence,

of human monoclonal antibodies from



WMV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20481.1


MOSQ49
Heavy chain translation,
hu-E16/E16p
U.S. Pat. No. 8,663,950 SEQ ID NO: 5
4071



WNV


MOSQ50
Heavy chain variable
anti-yellow fever
Thibodeaux, B. A. “A humanized IgG but not
4072



region, Yellow fever
virus vaccine
IgM antibody is effective in prophylaxis and



virus
strain 17D E
therapy of yellow fever infection in an




glycoprotein
AG129/17D-204 peripheral challenge mouse





model” Antiviral Res. 94 (1), 1-8 (2012),





NCBI Accession # ADO17683


MOSQ51
Light chain variable
anti-
US20080292644 SEQ ID NO: 66
4073



region, Japanese
DLVR1/CLEC5A



encephalitis virus


MOSQ52
Light chain variable
anti-
US20080292644 SEQ ID NO: 67
4074



region, Japanese
DLVR1/CLEC5A



encephalitis virus


MOSQ53
Light chain variable
anti-
US20080292644 SEQ ID NO: 68
4075



region, Japanese
DLVR1/CLEC5A



encephalitis virus


MOSQ54
Light chain variable

CN103864925 SEQ ID NO: 1
4076



region, Japanese



encephalitis virus


MOSQ55
Light chain variable
mAbl 1
WO2014144061 SEQ ID NO: 3
3418



region, WNV, Dengue,



St. Louis encephalitis,



yellow fever virus,



Japanese encephalitis



virus, Murray Valley



encephalitis virus


MOSQ56
Light chain, WNV
CR4348
U.S. Pat. No. 8,911,738 SEQ ID NO: 34
4077


MOSQ57
Light chain, WNV
CR4354
U.S. Pat. No. 8,911,738 SEQ ID NO: 36
4078


MOSQ58
Light chain, WNV
CR4261
U.S. Pat. No. 8,911,738 SEQ ID NO: 70
4079


MOSQ59
Light chain, WNV
CR4267
U.S. Pat. No. 8,911,738 SEQ ID NO: 72
4080


MOSQ60
Light chain, WNV
CR4328
U.S. Pat. No. 8,911,738 SEQ ID NO: 74
4081


MOSQ61
Light chain, WNV
CR4335
U.S. Pat. No. 8,911,738 SEQ ID NO: 76
4082


MOSQ62
Light chain, WNV
CR4383
U.S. Pat. No. 8,911,738 SEQ ID NO: 78
4083


MOSQ63
Light chain variable
Antibody from
U.S. Pat. No. 8,911,738 SEQ ID NO: 22
4084



region, WNV
U.S. Pat. No. 8,911,738


MOSQ64
Light chain variable
Antibody from
U.S. Pat. No. 8,911,738 SEQ ID NO: 24
4085



region, WNV
U.S. Pat. No. 8,911,738


MOSQ65
Light chain variable
E16
U.S. Pat. No. 7,527,973 SEQ ID NO: 2
4086



region, WNV


MOSQ66
Light chain variable
E24
U.S. Pat. No. 7,527,973 SEQ ID NO: 6
4087



region, WNV


MOSQ67
Light chain variable
E34
U.S. Pat. No. 7,527,973 SEQ ID NO: 10
4088



region, WNV


MOSQ68
Light chain variable
E16 light chain
U.S. Pat. No. 7,572,456 SEQ ID NO: 25
4089



region, WNV
version 1


MOSQ69
Light chain variable
E16 light chain
U.S. Pat. No. 7,572,456 SEQ ID NO: 26
4090



region, WNV
version 2


MOSQ70
Light chain variable
11
US20090130123 SEQ ID NO: 34
4091



region, WNV


MOSQ71
Light chain variable
71
US20090130123 SEQ ID NO: 35
4092



region, WNV


MOSQ72
Light chain variable
73
US20090130123 SEQ ID NO: 36
4093



region, WNV


MOSQ73
Light chain variable
85
US20090130123 SEQ ID NO: 37
4094



region, WNV


MOSQ74
Light chain variable
15
US20090130123 SEQ ID NO: 38
4095



region, WNV


MOSQ75
Light chain variable
95
US20090130123 SEQ ID NO: 39
4096



region, WNV


MOSQ76
Light chain variable
84
US20090130123 SEQ ID NO: 40
4097



region, WNV


MOSQ77
Light chain variable
10
US20090130123 SEQ ID NO: 41
4098



region, WNV


MOSQ78
Light chain variable

US20090130123 SEQ ID NO: 42
4099



region, WNV


MOSQ79
Light chain variable
79
US20090130123 SEQ ID NO: 43
4100



region, WNV


MOSQ80
Light chain variable
94
US20090130123 SEQ ID NO: 44
4101



region, WNV


MOSQ81
Light chain variable
9FI2
WO2010093335 SEQ ID NO: 6
3393



region, WNV


MOSQ82
Light chain variable

Throsby, M. “Isolation and characterization
4102



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20470.1


MOSQ83
Light chain variable

Throsby, M. “Isolation and characterization
4103



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20469.1


MOSQ84
Light chain variable

Throsby, M. “Isolation and characterization
4104



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20468.1


MOSQ85
Light chain variable

Throsby, M. “Isolation and characterization
4105



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20467.1


MOSQ86
Light chain variable

Throsby, M. “Isolation and characterization
4106



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20466.1


MOSQ87
Light chain variable

Throsby, M. “Isolation and characterization
4107



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20465.1


MOSQ88
Light chain variable

Throsby, M. “Isolation and characterization
4108



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20464.1


MOSQ89
Light chain variable

Throsby, M. “Isolation and characterization
4109



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20463.1


MOSQ90
Light chain variable

Throsby, M. “Isolation and characterization
4110



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20462.1


MOSQ91
Light chain variable

Throsby, M. “Isolation and characterization
4111



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J,





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20461.1


MOSQ92
Light chain variable

Throsby, M. “Isolation and characterization
4112



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20460.1


MOSQ93
Light chain variable

Throsby, M. “Isolation and characterization
4113



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20459.1


MOSQ94
Light chain variable

Throsby, M. “Isolation and characterization
4114



region, partial sequence,

of human monoclonal antibodies from



WNV

individuals infected with west nile virus” J.





Virol. 80 (14), 6982-6992 (2006), NCBI





Accession # ABF20458.1


MOSQ95
Light chain translation,
hu-E16/E16p
U.S. Pat. No. 8,663,950 SEQ ID NO: 7
4115



WNV


MOSQ96
Light chain variable
anti-yellow fever
Thibodeaux, B. A. “A humanized IgG but not
4116



region, Yellow fever
virus vaccine
IgM antibody is effective in prophylaxis and



virus
strain 17D E
therapy of yellow fever infection in an




glycoprotein
AG129/17D-204 peripheral challenge mouse





model” Antiviral Res. 94 (1), 1-8 (2012),





NCBI Accession # ADO17684


MOSQ97
ScFv, WNV
9FI2
WO2010093335 SEQ ID NO: 8
3442


MOSQ98
Fc region, WNV,
mAb-11
WO2014144061 SEQ ID NO: 5
4117



Dengue, St. Louis



encephalitis, yellow



fever virus, Japanese



encephalitis virus,



Murray Valley



encephalitis virus


MOSQ99
Fc region, WNV,
mAb-11-LALA
WO2014144061 SEQ ID NO: 6
4118



Dengue, St. Louis



encephalitis, yellow



fever virus, Japanese



encephalitis virus,



Murray Valley



encephalitis virus


MOSQ100
ScFv, WNV
11
US20090130123 SEQ ID NO: 12
4119


MOSQ101
ScFv, WNV
71
US20090130123 SEQ ID NO: 13
4120


MOSQ102
ScFv, WNV
73
US20090130123 SEQ ID NO: 14
4121


MOSQ103
ScFv, WNV
85
US20090130123 SEQ ID NO: 15
4122


MOSQ104
ScFv, WNV
15
US20090130123 SEQ ID NO: 16
4123


MOSQ105
ScFv, WNV
95
US20090130123 SEQ ID NO: 17
4124


MOSQ106
ScFv, WNV
84
US20090130123 SEQ ID NO: 18
4125


MOSQ107
ScFv, WNV
10
US20090130123 SEQ ID NO: 19
4126


MOSQ108
ScFv, WNV
69
US20090130123 SEQ ID NO: 20
4127


MOSQ109
ScFv, WNV
79
US20090130123 SEQ ID NO: 21
4128


MOSQ110
ScFv, WNV
94
US20090130123 SEQ ID NO: 22
4129


MOSQ111
ScFvs, WNV
SC04-348
U.S. Pat. No. 8,911,738 SEQ ID NO: 26
4130


MOSQ112
ScFvs, WNV
SC04-354
U.S. Pat. No. 8,911,738 SEQ ID NO: 28
4131


MOSQ113
ScFv, Yellow
anti-yellow
Daffis, S. et al. “Antibody responses against
4132



fever virus
fever virus E
wild-type yellow fever virus and the 17D




protein scFv 7A
vaccine strain: characterization with human





monoclonal antibody fragments and





neutralization escape variants” Virology 337





(2), 262-272 (2005), NCBI Accession #





AAT76799


MOSQ114
ScFv, Yellow
anti-yellow
Daffis, S. et al. “Antibody responses against
4133



fever virus
fever virus E
wild-type yellow fever virus and the 17D




protein scFv
vaccine strain: characterization with human




R3(27)
monoclonal antibody fragments and





neutralization escape variants” Virology 337





(2), 262-272 (2005), NCBI Accession #





AAT76800


MOSQ115
ScFv, Yellow
anti-yellow
Daffis, S. et al. “Antibody responses against
4134



fever virus
fever virus E
wild-type yellow fever virus and the 17D




protein scFv 5A
vaccine strain: characterization with human





monoclonal antibody fragments and





neutralization escape variants” Virology 337





(2), 262-272 (2005), NCBI Accession #





AAT76801


MOSQ116
ScFv, Yellow
anti-yellow
Daffis, S. et al. “Antibody responses against
4135



fever virus
fever virus E
wild-type yellow fever virus and the 17D




protein scFv 1A
vaccine strain: characterization with human





monoclonal antibody fragments and





neutralization escape variants” Virology 337





(2), 262-272 (2005), NCBI Accession #





AAT76802


MOSQ117
ScFv, Yellow
anti-yellow
Daffis, S. et al. “Antibody responses against
4136



fever virus
fever virus E
wild-type yellow fever virus and the 17D




protein scFv 2A
vaccine strain: characterization with human





monoclonal antibody fragments and





neutralization escape variants” Virology 337





(2), 262-272 (2005), NCBI Accession #





AAT76803


MOSQ118
ScFv, Yellow
anti-yellow
Daffis, S. et al. “Antibody responses against
4137



fever virus
fever virus E
wild-type yellow fever virus and the 17D




protein scFv
vaccine strain: characterization with human




R3(9)
monoclonal antibody fragments and





neutralization escape variants” Virology 337





(2), 262-272 (2005), NCBI Accession #





AAT76804









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in U.S. Pat. No. 6,399,062 and US Pub. No. US20110171225, the contents of each of which are herein incorporated by reference in their entirety, against Malaria.


Infectious Diseases

In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the infectious disease related payload anti body polypeptides listed in Tables 21-42.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 21 against Influenza virus









TABLE 21







Antibodies against Influenza virus















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





INFL1
Fab Fragment Heavy
ch65
Whittle, J. R. et al., Broadly neutralizing
4138



chain

human antibody that recognizes the





receptor-binding pocket of influenza





virus hemagglutinin; Proc. Natl. Acad.





Sci. U.S.A. 108 (34), 14216-14221





(2011), NCBI Accession #3SMS_H


INFL2
Fab Heavy Chain
Fab Cr6261
Lingwood, D., et al., Structural and
4139




(Somatic Heavy
genetic basis for development of broadly




Chain With
neutralizing influenza antibodies; Nature




Germline-
489 (7417), 566-570 (2012), NCBI




Reverted Light
Accession #4EVN_M (242aa)




Chain)


INFL3
Fab heavy chain
Del2d1
Krause, J. C. et al., M Bio 2 (1), E00345-
4140





E00310 (2011), NCBI Accession





#3QHF_H


INFL4
Fab heavy chain
Fld194 Fab
Xiong, X. et al., Structures of complexes
4141





formed by H5 influenza hemagglutinin





with a potent broadly neutralizing human





monoclonal antibody; Proc. Natl. Acad.





Sci. U.S.A. 112 (30), 9430-9435 (2015),





NCBI Accession #5A3I_C (230aa)


INFL5
Fab heavy chain
H5.3
Winarski, K. L., Thornburg, N. J. et al.,
4142





Vaccine-elicited antibody that neutralizes





H5N1 influenza and variants binds the





receptor site and polymorphic sites





“PNAS 2015 112 (30) 9346-9351”, NCBI





Accession #4XNM_H


INFL6
Fab Heavy chain
5j8
Hong, M. et al., Antibody Recognition of
4143





the Pandemic H1N1 Influenza Virus





Hemagglutinin Receptor Binding Site; J.





Virol. 87 (22), 12471-12480 (2013),





NCBI Accession #4M5Z_H


INFL7
Fab lambda heavy
CR6261
Ekiert, D. C. et al., Antibody recognition
4144



chain

of a highly conserved influenza virus





epitope; Science 324 (5924), 246-251





(2009), NCBI Accession #3GBN_H


INFL8
Fab lambda light
CR6261
Ekiert, D. C. et al., Antibody recognition
4145



chain

of a highly conserved influenza virus





epitope; Science 324 (5924), 246-251





(2009), NCBI Accession #3GBN_L


INFL9
Fab lambda light
Fab Cr6261
Lingwood, D., et al., Structural and
4146



chain
(Somatic Heavy
genetic basis for development of broadly




Chain With
neutralizing influenza antibodies; Nature




Germline-
489 (7417), 566-570 (2012), NCBI




Reverted Light
Accession #4EVN_N (217aa)




Chain)


INFL10
Fab light chain
Del2d1
Krause, J. C. et al., M Bio 2 (1), E00345-
4147





E00310 (2011), NCBI Accession





#3QHF_L


INFL11
Fab Light Chain
Fld194 Fab
Xiong, X. et al., Structures of complexes
4148





formed by H5 influenza hemagglutinin





with a potent broadly neutralizing human





monoclonal antibody; Proc. Natl. Acad,





Sci. U.S.A. 112 (30), 9430-9435 (2015),





NCBI Accession #5A3I_D (219aa)


INFL12
Fab, heavy chain
F045-092
Lee, P. S. et al., Receptor mimicry by
4149





antibody F045-092 facilitates universal





binding to the H3 subtype of influenza





virus; Nat Commun 5, 3614 (2014),





NCBI Accession #4O5I_W


INFL13
Fab, Light Chain
F045-092
Lee, P. S. et al., Receptor mimicry by
4150





antibody F045-092 facilitates universal





binding to the H3 subtype of influenza





virus; Nat Commun 5, 3614 (2014),





NCBI Accession #4O5I_V


INFL14
Fab, light chain
H5.3
Winarski, K. L., Thornburg, N. J. et al.,
4151





“Vaccine-elicited antibody that





neutralizes H5N1 influenza and variants





binds the receptor site and polymorphic





sites “PNAS 2015 112 (30) 9346-9351”,





NCBI Accession #4XNM_L


INFL15
Gamma heavy chain
8i10
U.S. Pat. No. 8,858,948 SEQ ID NO: 69
4152



variable


INFL16
Gamma heavy chain
23K12
U.S. Pat. No. 8,858,948 SEQ ID NO: 100
4153



variable


INFL17
Heavy chain
CR6261,
WO 2008028946
4154




Diridavumab, CR-




6261


INFL18
Heavy chain
Firivumab, CT-P22
US20130004505
4155


INFL19
Heavy chain
CT-P22
US20130004505 SEQ ID NO: 41; WO
4156





2011/111966


INFL20
Heavy chain
Navivumab,
WO2013048153, US20140234336 SEQ
4157




CT149
ID NO: 40


INFL21
Heavy chain
AT10-004
US20150010566, WO2013081463 SEQ
4158





ID NO: 31


INFL22
Heavy chain
AT10-003
US20150010566, WO2013081463 SEQ
4159





ID NO: 32


INFL23
Heavy chain
AT10-002
US20150010566, WO2013081463 SEQ
4160





ID NO: 33


INFL24
Heavy chain
AT10-001
US20150010566, WO2013081463 SEQ
4161





ID NO: 34


INFL25
Heavy chain
AT10-005
US20150010566, WO2013081463 SEQ
4162





ID NO: 35


INFL26
Heavy chain
CT104
WO2011111966, US20130004505 SEQ
4163





ID NO: 37


INFL27
Heavy chain
CT120
WO2011111966, US20130004505 SEQ
4164





ID NO: 41


INFL28
Heavy chain
CT123
WO2011111966, US20130004505 SEQ
4165





ID NO: 45


INFL29
Heavy chain
2A
US20140011982 SEQ ID NO: 2
4166


INFL30
Heavy chain
F005-126
WO2014049520, US20140086927 SEQ
4167





ID NO: 2


INFL31
Heavy chain
BF1-1
WO2008156763 SEQ ID NO: 7
4168


INFL32
Heavy chain
BF1-19
WO2008156763 SEQ ID NO: 11
4169


INFL33
Heavy chain
BF1-10
WO2008156763 SEQ ID NO: 9
4170


INFL34
Heavy chain

WO2010127252, U.S. Pat. No. 8,894,997 SEQ
4171





ID NO: 3


INFL35
Heavy chain
A18
WO13170139 SEQ ID NO: 94
4172


INFL36
Heavy chain
Ab A18
U.S. Pat. No. 7,788,200 SEQ ID NO: 15
4173


INFL37
Heavy chain
Ab 014, Ab 028
U.S. Pat. No. 7,788,200 SEQ ID NO: 16
4174


INFL38
Heavy chain
Ab 071
U.S. Pat. No. 7,788,200 SEQ ID NO: 162
4175


INFL39
Heavy chain
Ab 072
U.S. Pat. No. 7,788,200 SEQ ID NO: 163
4176


INFL40
Heavy chain
Ab 078, Ab 079,
U.S. Pat. No. 7,788,200 SEQ ID NO: 164
4177




Ab 080, Ab 081


INFL41
Heavy chain
Ab 001, Ab 009,
U.S. Pat. No. 7,788,200 SEQ ID NO: 17
4178




Ab 017, Ab 160,




Ab 186, Ab 187,




Ab 188, Ab 189,




Ab 190, Ab 191,




Ab 192, Ab 193,




Ab 202, Ab 211


INFL42
Heavy chain
Ab 002, Ab 010,
U.S. Pat. No. 7,788,200 SEQ ID NO: 18
4179




Ab 026, Ab 203,




Ab 212


INFL43
Heavy chain
Ab 003, Ab 011,
U.S. Pat. No. 7,788,200 SEQ ID NO: 19
4180




Ab 027, Ab 194,




Ab 195, Ab 196,




Ab 197, Ab 198,




Ab 199, Ab 200,




Ab 204, Ab 213


INFL44
Heavy chain
Ab 086
U.S. Pat. No. 7,788,200 SEQ ID NO: 20
4181


INFL45
Heavy chain
Ab 154, Ab 155,
U.S. Pat. No. 7,788,200 SEQ ID NO: 21
4182




Ab 157


INFL46
Heavy chain
Ab 157, Ab 159
U.S. Pat. No. 7,788,200 SEQ ID NO: 22
4183


INFL47
Heavy chain
Ab 210, Ab 219
U.S. Pat. No. 7,788,200 SEQ ID NO: 23
4184


INFL48
Heavy chain
Ab A001, Ab
U.S. Pat. No. 7,788,200 SEQ ID NO: 24
4185




A002, Ab A003,




Ab A010, Ab




A011, Ab 031, Ab




037


INFL49
Heavy chain
Ab 004, Ab 005,
U.S. Pat. No. 7,788,200 SEQ ID NO: 25
4186




Ab 006, Ab 012,




Ab 013, Ab 032,




Ab 038, Ab 043,




Ab 044, Ab 045,




Ab 046, Ab 047,




Ab 048, Ab 049,




Ab 050, Ab 051,




Ab 052, Ab 067,




Ab 068, Ab 069,




Ab 070, Ab 073,




Ab 074, Ab 075,




Ab 076, Ab 077


INFL50
Heavy chain
Ab 007, Ab 008,
U.S. Pat. No. 7,788,200 SEQ ID NO: 26
4187




Ab A009, Ab A14,




Ab 015, Ab 033,




Ab 039


INFL51
Heavy chain
Ab 016, Ab A017,
U.S. Pat. No. 7,788,200 SEQ ID NO: 27
4188




Ab C18, Ab A019,




Ab 034, Ab 040


INFL52
Heavy chain
F005-126
WO2014049520 SEQ ID 2
4189


INFL53
Heavy chain
8f24
WO2012045001 SEQ ID 1
4190


INFL54
Heavy chain
3E22
WO2012045001 SEQ ID 5
4191


INFL55
Heavy chain
5117
WO2012045001 SEQ ID 9
4192


INFL56
Heavy chain

WO2012045001 SEQ ID 13
4193


INFL57
Heavy chain

WO2012045001 SEQ ID 29
4194


INFL58
Heavy chain

WO2012045001 SEQ ID 33
4195


INFL59
Heavy chain

WO2012045001 SEQ ID 17
4196


INFL60
Heavy chain
10A14
WO2012045001 SEQ ID 21
4197


INFL61
Heavy chain
8D4
WO2012045001 SEQ ID 25
4198


INFL62
Heavy chain
2B9
U.S. Pat. No. 9,115,201 SEQ ID NO: 6
4199


INFL63
Heavy chain
mAB 7A7
US20150239960, US20140170163,
4200





U.S. Pat. No. 8,673,314, US20110027270,





WO2010138564 SEQ ID NO: 6


INFL64
Heavy chain
mAB 12D1
US20150239960, US20140170163,
4201





U.S. Pat. No. 8,673,314, US20110027270,





WO2010138564 SEQ ID NO: 12


INFL65
Heavy chain
mAB 66A6
US20150239960, US20140170163,
4202





U.S. Pat. No. 8,673,314, US20110027270,





WO2010138564 SEQ ID NO: 16


INFL66
Heavy chain
M1 D12
US20110033473, WO2009125395 SEQ
4203





ID NO: 17


INFL67
Heavy chain
mAB1.12
WO2013030165 SEQ ID NO: 1
4204


INFL68
Heavy chain
mAB3.1
WO2013030165 SEQ ID NO: 3
4205


INFL69
Heavy chain
5A7
WO2015120097 SEQ ID NO: 7
4206


INFL70
Heavy chain
TRL053
WO2015120097 SEQ ID NO: 17
4207


INFL71
Heavy chain
TRL579
WO2015120097 SEQ ID NO: 27
4208


INFL72
Heavy chain
TRL784
WO2015120097 SEQ ID NO: 37
4209


INFL73
Heavy chain
TRL794
WO2015120097 SEQ ID NO: 47
4210


INFL74
Heavy chain
TRL798
WO2015120097 SEQ ID NO: 57
4211


INFL75
Heavy chain
TRL799
WO2015120097 SEQ ID NO: 67
4212


INFL76
Heavy chain
TRL809
WO2015120097 SEQ ID NO: 77
4213


INFL77
Heavy chain
TRL811
WO2015120097 SEQ ID NO: 87
4214


INFL78
Heavy chain
TRL812
WO2015120097 SEQ ID NO: 97
4215


INFL79
Heavy chain
TRL813
WO2015120097 SEQ ID NO: 107
4216


INFL80
Heavy chain
TRL823
WO2015120097 SEQ ID NO: 117
4217


INFL81
Heavy chain
TRL832
WO2015120097 SEQ ID NO: 127
4218


INFL82
Heavy chain
TRL833
WO2015120097 SEQ ID NO: 137
4219


INFL83
Heavy chain
TRL834
WO2015120097 SEQ ID NO: 147
4220


INFL84
Heavy chain
TRL835
WO2015120097 SEQ ID NO: 157
4221


INFL85
Heavy chain
TRL835
WO2015120097 SEQ ID NO: 158
4222


INFL86
Heavy chain
TRL837
WO2015120097 SEQ ID NO: 168
4223


INFL87
Heavy chain
TRL839
WO2015120097 SEQ ID NO: 178
4224


INFL88
Heavy chain
TRL841
WO2015120097 SEQ ID NO: 188
4225


INFL89
Heavy chain
TRL842
WO2015120097 SEQ ID NO: 198
4226


INFL90
Heavy chain
TRL845
WO2015120097 SEQ ID NO: 208
4227


INFL91
Heavy chain
TRL846
WO2015120097 SEQ ID NO: 217
4228


INFL92
Heavy chain
TRL847
WO2015120097 SEQ ID NO: 227
4229


INFL93
Heavy chain
TRL848
WO2015120097 SEQ ID NO: 237
4230


INFL94
Heavy chain
TRL849
WO2015120097 SEQ ID NO: 247
4231


INFL95
Heavy chain
TRL851
WO2015120097 SEQ ID NO: 257
4232


INFL96
Heavy chain
TRL854
WO2015120097 SEQ ID NO: 267
4233


INFL97
Heavy chain
TRL856
WO2015120097 SEQ ID NO: 277
4234


INFL98
Heavy chain
TRL858
WO2015120097 SEQ ID NO: 287
4235


INFL99
Heavy chain
humM2e-hBiTE-1
WO2014140368 SEQ ID NO: 8
4236


INFL100
Heavy chain
humM2e-hBiTE-2
WO2014140368 SEQ ID NO: 16
4237


INFL101
Heavy chain
humM2e-hBiTE-3
WO2014140368 SEQ ID NO: 24
4238


INFL102
Heavy chain
humM2e-hBiTE-4
WO2014140368 SEQ ID NO: 32
4239


INFL103
Heavy chain
VH of humM2e-
WO2014140368 SEQ ID NO: 40
4240




hBiTE-5


INFL104
Heavy chain
humM2e-hBiTE-6
WO2014140368 SEQ ID NO: 48
4241


INFL105
Heavy chain
humM2e-hBiTE-7
WO2014140368 SEQ ID NO: 56
4242


INFL106
Heavy chain
humM2e-hBiTE-8
WO2014140368 SEQ ID NO: 64
4243


INFL107
Heavy chain
humM2e-hBiTE-9
WO2014140368 SEQ ID NO: 72
4244


INFL108
Heavy chain
murM2e-hBiTE
WO2014140368 SEQ ID NO: 80
4245


INFL109
Heavy chain
FLA5.10
U.S. Pat. No. 8,124,092 SEQ ID NO: 1
4246


INFL110
Heavy chain
FLD21.140
U.S. Pat. No. 8,124,092 SEQ ID NO: 5
4247


INFL111
Heavy chain
FLA3.14
U.S. Pat. No. 8,124,092 SEQ ID NO: 9
4248


INFL112
Heavy chain
FLD20.19
U.S. Pat. No. 8,124,092 SEQ ID NO: 13
4249


INFL113
Heavy chain
FLD84
U.S. Pat. No. 8,124,092 SEQ ID NO: 42
4250


INFL114
Heavy chain
FLD93
U.S. Pat. No. 8,124,092 SEQ ID NO: 52
4251


INFL115
Heavy chain
FLD122
U.S. Pat. No. 8,124,092 SEQ ID NO: 62
4252


INFL116
Heavy chain
FLD127
U.S. Pat. No. 8,124,092 SEQ ID NO: 72
4253


INFL117
Heavy chain
FLD129
U.S. Pat. No. 8,124,092 SEQ ID NO: 82
4254


INFL118
Heavy chain
FLD132
U.S. Pat. No. 8,124,092 SEQ ID NO: 92
4255


INFL119
Heavy chain
FLD194
U.S. Pat. No. 8,124,092 SEQ ID NO: 102
4256


INFL120
Heavy chain
mAb2
WO2015112994 SEQ ID NO: 80
4257


INFL121
Heavy chain
mAb3
WO2015112994 SEQ ID NO: 84
4258


INFL122
Heavy chain

Tsibane, T. et al., Influenza Human
4259





Monoclonal Antibody 1F1 Interacts with





Three Major Antigenic Sites and





Residues Mediating Human Receptor





Specificity in H1N1 Viruses; PLoS





Pathol. 8 (12), E1003067 (2012), NCBI





Accession #4GXU_S


INFL123
Heavy chain
C05
Ekiert, D. C., et al., Cross-neutralization
4260





of influenza A viruses mediated by a





single antibody loop; Nature 489 (7417),





526-532 (2012), NCBI Accession





#4FNL_H (247aa)


INFL124
Heavy chain
CR8020
Ekiert, D. C., et al., A. highly conserved
4261





neutralizing epitope on group 2 influenza





A viruses; Science 333 (6044), 843-850





(2011); WO2010130636, NCBI





Accession #3SDY_H


INFL125
Heavy chain
CR8043
Friesen, R. H. et al., A common solution
4262





to group 2 influenza virus neutralization;





Proc. Natl. Acad. Sci. U.S.A. 111 (1),





445-450 (2014), NCBI Accession





#4NM8_H


INFL126
Heavy chain
CR8059
Dreyfus, C. et al., Highly conserved
4263





protective epitopes on influenza B





viruses; Science 337 (6100), 1343-1348





(2012), NCBI Accession #4FQK_H


INFL127
Heavy chain
CR8071
Dreyfus, C. et al., Highly conserved
4264





protective epitopes on influenza B





viruses; Science 337 (6100), 1343-1348





(2012), NCBI Accession #4FQJ_H





(234aa)


INFL128
Heavy chain
CR9114
WO2013079473; WO2014191435;
4265





Dreyfus, C., Laursen, N. S. et al., Highly





conserved protective epitopes on





influenza B viruses; Science 337 (6100),





1343-1348 (2012), NCBI Accession





#4FQY_H (230aa)


INFL129
Heavy chain
Ch67
Schmidt, A. G., et al., Preconfiguration of
4266





the antigen-binding site during affinity





maturation of a broadly neutralizing





influenza virus antibody; Proc. Natl.





Acad. Set. U.S.A. 110 (1), 264-269





(2013), NCBI Accession #4HKX_A





(231aa)


INFL130
Heavy chain
Fab 26/9
Schulze-Gahmen, U. et al., J. Biol.
4267





Chem. 263 (32), 17100-17105 (1988);





Churchill, M. E., et al., J. Mol. Biol. 241





(4), 534-556 (1994), NCBI Accession





#1FRG_H


INFL131
Heavy chain
Fab 3.1
Wyrzucki, A. et al., Alternative
4268





Recognition of the Conserved Stem





Epitope in Influenza A Virus





Hemagglutinin by a VH3-30-Encoded





Heterosubtypic Antibody; J. Virol. 88





(12), 7083-7092 (2014), NCBI Accession





#4PY8_I


INFL132
Heavy chain
Fab 2g1
Xu, R. et al., A recurring motif for
4269





antibody recognition of the receptor-





binding site of influenza hemagglutinin;





Nat. Struct. Mol. Biol. 20 (3), 363-370





(2013), NCBI Accession #4HG4_N





(223aa)


INFL133
Heavy chain
Fab 8m2
Xu, R. et al., A recurring motif for
4270





antibody recognition of the receptor-





binding site of influenza hemagglutinin;





Nat. Struct. Mol. Biol. 20 (3), 363-370





(2013), NCBI Accession #4HFU_H





(226aa)


INFL134
Heavy chain
Fab 8f8
Xu, R. et al., A recurring motif for
4271





antibody recognition of the receptor-





binding site of influenza hemagglutinin;





Nat. Struct. Mol. Biol. 20 (3), 363-370





(2013), NCBI Accession #4HF5_H





(233aa)


INFL135
Heavy chain
Fab 2d1
Xu, R., et al., Structural basis of
4272





preexisting immunity to the 2009 H1N1





pandemic influenza virus; Science 328





(5976), 357-360 (2010), NCBI Accession





#3LZF_H (230aa)


INFL136
Heavy chain
Fi6v3
Corti, D. et al., A neutralizing antibody
4273





selected from plasma cells that binds to





group 1 and group 2 influenza A





hemagglutinins; Science 333 (6044),





850-856 (2011), NCBI Accession





#3ZTJ_G


INFL137
Heavy Chain
Heavy chain
Iba, Y., et al., Conserved Neutralizing
4274




3WHE_N
Epitope at Globular Head of





Hemagglutinin in H3N2 Influenza





Viruses; J. Virol. (2014), NCBI





Accession #3WHE_M (226aa)


INFL138
Heavy chain
7A13
Krause et al. “Human Monoclonal
4275





Antibodies to Pandemic 1957 H2N2 and





Pandemic 1968 H3N2 Influenza Viruses”





J. Virol. 86 (11), 6334-6340 (2012),





NCBI Accession #AFH78447


INFL139
Heavy chain
2D1
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4276





NO: 7


INFL140
Heavy chain
1F1
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4277





NO: 1


INFL141
Heavy chain

WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4278





NO: 4


INFL142
Heavy chain
1I20
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4279





NO: 5


INFL143
Heavy chain
4D20
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4280





NO: 9


INFL144
Heavy chain

WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4281





NO: 11


INFL145
Heavy chain

US20140205614, US20100316654 SEQ
4282





ID NO: 21


INFL146
Heavy chain

US20140205614, US20100316654 SEQ
4283





ID NO: 22


INFL147
Heavy chain

US20140205614, US20100316654 SEQ
4284





ID NO: 23


INFL148
Heavy chain

US20140205614, US20100316654 SEQ
4285





ID NO: 24


INFL149
Heavy chain

US20140205614, US20100316654 SEQ
4286





ID NO: 25


INFL150
Heavy chain

US20140205614, US20100316654 SEQ
4287





ID NO: 26


INFL151
Heavy chain

US20140205614, US20100316654 SEQ
4288





ID NO: 27


INFL152
Heavy chain

US20140205614, US20100316654 SEQ
4289





ID NO: 28


INFL153
Heavy chain

US20140205614, US20100316654 SEQ
4290





ID NO: 29


INFL154
Heavy chain

US20140205614, US20100316654 SEQ
4291





ID NO: 30


INFL155
Heavy chain

US20140205614, US20100316654 SEQ
4292





ID NO: 31


INFL156
Heavy chain

US20140205614, US20100316654 SEQ
4293





ID NO: 32


INFL157
Heavy chain

US20140205614, US20100316654 SEQ
4294





ID NO: 33


INFL158
Heavy chain

US20140205614, US20100316654 SEQ
4295





ID NO: 34


INFL159
Heavy chain

US20140205614, US20100316654 SEQ
4296





ID NO: 35


INFL160
Heavy chain

US20140205614, US20100316654 SEQ
4297





ID NO: 36


INFL161
Heavy chain

US20140205614, US20100316654 SEQ
4298





ID NO: 37


INFL162
Heavy chain

US20140205614, US20100316654 SEQ
4299





ID NO: 38


INFL163
Heavy chain

US20140205614, US20100316654 SEQ
4300





ID NO: 39


INFL164
Heavy chain

US20140205614, US20100316654 SEQ
4301





ID NO: 40


INFL165
Heavy chain

US20140205614, US20100316654 SEQ
4302





ID NO: 41


INFL166
Heavy chain

US20140205614, US20100316654 SEQ
4303





ID NO: 42


INFL167
Heavy chain

US20140205614, US20100316654 SEQ
4304





ID NO: 43


INFL168
Heavy chain

US20140205614, US20100316654 SEQ
4305





ID NO: 44


INFL169
Heavy chain

US20140205614, US20100316654 SEQ
4306





ID NO: 45


INFL170
Heavy chain
mAb1
WO2015112994 SEQ ID NO: 76
4307


INFL171
Heavy chain
CR8033
Dreyfus, C., Laursen, N. S. et al., Highly
4308





conserved protective epitopes on





influenza B viruses; Science 337 (6100),





1343-1348 (2012), NCBI Accession #





4FQL_H


INFL172
Heavy chain (Partial)
monoclonal
Burioni, R. et al., Monoclonal antibodies
4309




antibody PN-
isolated from human B cells neutralize a




SIA28
broad range of H1 subtype influenza A





viruses including swine-origin Influenza





virus(S-OIV); Virology (2010), NCBI





Accession #ACX30936.1 (122aa)


INFL173
Heavy chain (Partial)
monoclonal
Burioni, R, et al., Monoclonal antibodies
4310




antibody PN-
isolated from human B cells neutralize a




SIA49
broad range of H1 subtype influenza A





viruses including swine-origin Influenza





virus(S-OIV); Virology (2010), NCBI





Accession #ACX30937.1 (127aa)


INFL174
Heavy chain cdr1
Ab1A2
WO2015028478 SEQ ID 6
4311


INFL175
Heavy chain cdr2
Ab1A2
WO2015028478 SEQ ID 7
4312


INFL176
Heavy chain cdr3
Ab1A2
WO2015028478 SEQ ID 8
4313


INFL177
Heavy chain constant

U.S. Pat. No. 8,992,929 SEQ ID NO. 22
4314



region, Human igg1


INFL178
Heavy chain Fab
CT147
WO2013048153, US20140234336 SEQ
4315





ID NO: 38


INFL179
Heavy chain Fab
CT164
WO2013048153, US20140234336 SEQ
4316





ID NO: 42


INFL180
Heavy chain Fab
CT166
WO2013048153, US20140234336 SEQ
4317





ID NO: 44


INFL181
Heavy chain G2
h2B9
U.S. Pat. No. 9,115,201 SEQ ID NO: 7
4318


INFL182
Heavy chain G5
h2B10
U.S. Pat. No. 9,115,201 SEQ ID NO: 8
4319


INFL183
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 1
4320



(exemplary)
US2013030234


INFL184
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 2
4321



(exemplary)
US2013030234


INFL185
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 3
4322



(exemplary)
US2013030234


INFL186
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 4
4323



(exemplary)
US2013030234


INFL187
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 5
4324



(exemplary)
US2013030234


INFL188
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 6
4325



(exemplary)
US2013030234


INFL189
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 7
4326



(exemplary)
US2013030234


INFL190
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 8
4327



(exemplary)
US2013030234


INFL191
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 9
4328



(exemplary)
US2013030234


INFL192
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 10
4329



(exemplary)
US2013030234


INFL193
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 11
4330



(exemplary)
US2013030234


INFL194
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 12
4331



(exemplary)
US2013030234


INFL195
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 13
4332



(exemplary)
US2013030234


INFL196
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 14
4333



(exemplary)
US2013030234


INFL197
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 15
4334



(exemplary)
US2013030234


INFL198
Heavy chain variable
HC-VD from
US2013030234 SEQ ID NO: 16
4335



(exemplary)
US2013030234


INFL199
Heavy chain variable
CR6141
US20150104459 SEQ ID NO: 199
4336



region


INFL200
Heavy chain variable
39.18 B11
US20140161822 SEQ ID NO: 154
4337



region


INFL201
Heavy chain variable
39.18 E12
US20140161822 SEQ ID NO: 158
4338



region


INFL202
Heavy chain variable
GG3
WO2014159960 SEQ ID NO: 17
4339



region


INFL203
Heavy chain variable
N547
U.S. Pat. No. 8,003,106 SEQ ID NO: 28
4340



region


INFL204
Heavy chain variable
L66
U.S. Pat. No. 8,003,106 SEQ ID NO: 30
4341



region


INFL205
Heavy chain variable
C40
U.S. Pat. No. 8,003,106 SEQ ID NO: 26
4342



region


INFL206
Heavy chain variable
14C2
U.S. Pat. No. 8,080,244 SEQ ID NO: 6
4343



region


INFL207
Heavy chain variable
h14C2
U.S. Pat. No. 8,080,244 SEQ ID NO: 2
4344



region


INFL208
Heavy chain variable
8G9
U.S. Pat. No. 8,603,467 SEQ ID NO: 2
4345



region


INFL209
Heavy chain variable
13D4
U.S. Pat. No. 8,603,467 SEQ ID NO: 6
4346



region


INFL210
Heavy chain variable
20A11
U.S. Pat. No. 8,603,467 SEQ ID NO: 10
4347



region


INFL211
Heavy chain variable
VN04-2-HuG1
US20100150941 SEQ ID NO: 5
4348



region


INFL212
Heavy chain variable
VN04-3-HuG1
US20100150941 SEQ ID NO: 7
4349



region


INFL213
Heavy chain variable
FI6 variant 1
U.S. Pat. No. 8,871,207 SEQ ID NO: 13
4350



region


INFL214
Heavy chain variable
FI6 variant 2
U.S. Pat. No. 8,871,207 SEQ ID NO: 33
4351



region


INFL215
Heavy chain variable
FI6 variant 3
U.S. Pat. No. 8,871,207 SEQ ID NO: 55
4352



region


INFL216
Heavy chain variable
FI6 variant 4, FI6
U.S. Pat. No. 8,871,207 SEQ ID NO: 59
4353



region
variant 5


INFL217
Heavy chain variable
FI28 variant 1
U.S. Pat. No. 8,871,207 SEQ ID NO: 29
4354



region


INFL218
Heavy chain variable
FI28 variant 2
U.S. Pat. No. 8,871,207 SEQ ID NO: 35
4355



region


INFL219
Heavy chain variable
21B15
U.S. Pat. No. 8,858,948 SEQ ID NO: 44
4356



region


INFL220
Heavy chain variable
3241_G23
U.S. Pat. No. 8,858,948 SEQ ID NO: 116
4357



region


INFL221
Heavy chain variable
3244_I10
U.S. Pat. No. 8,858,948 SEQ ID NO: 120
4358



region


INFL222
Heavy chain variable
3243_J07
U.S. Pat. No. 8,858,948 SEQ ID NO: 124
4359



region


INFL223
Heavy chain variable
3259_J21
U.S. Pat. No. 8,858,948 SEQ ID NO: 128
4360



region


INFL224
Heavy chain variable
3245_O19
U.S. Pat. No. 8,858,948 SEQ ID NO: 132
4361



region


INFL225
Heavy chain variable
3244_H04
U.S. Pat. No. 8,858,948 SEQ ID NO: 136
4362



region


INFL226
Heavy chain variable
3136_G05
U.S. Pat. No. 8,858,948 SEQ ID NO: 140
4363



region


INFL227
Heavy chain variable
3252_C13
U.S. Pat. No. 8,858,948 SEQ ID NO: 144
4364



region


INFL228
Heavy chain variable
3255_J06
U.S. Pat. No. 8,858,948 SEQ ID NO: 148
4365



region


INFL229
Heavy chain variable
3420_I23
U.S. Pat. No. 8,858,948 SEQ ID NO: 152
4366



region


INFL230
Heavy chain variable
3139_P23
U.S. Pat. No. 8,858,948 SEQ ID NO: 156
4367



region


INFL231
Heavy chain variable
3139_P23
U.S. Pat. No. 8,858,948 SEQ ID NO: 158
4368



region


INFL232
Heavy chain variable
3248_P18
U.S. Pat. No. 8,858,948 SEQ ID NO: 162
4369



region


INFL233
Heavy chain variable
3253_P10
U.S. Pat. No. 8,858,948 SEQ ID NO: 166
4370



region


INFL234
Heavy chain variable
3260_D19
U.S. Pat. No. 8,858,948 SEQ ID NO: 170
4371



region


INFL235
Heavy chain variable
3362_B11
U.S. Pat. No. 8,858,948 SEQ ID NO: 172
4372



region


INFL236
Heavy chain variable
3242_P05
U.S. Pat. No. 8,858,948 SEQ ID NO: 176
4373



region


INFL237
Heavy chain variable
2K11
Krause, J. C. et al. “Epitope-specific
4374



region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16793


INFL238
Heavy chain variable
2O10
Krause, J. C. et al. “Epitope-specific
4375



region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16795


INFL239
Heavy chain variable
4K8
Krause, J. C. et al. “Epitope-specific
4376



region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16799


INFL240
Heavy chain variable
6D9
Krause, J. C. et al. “Epitope-specific
4377



region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16801


INFL241
Heavy chain variable
4D20
Yu, X. et al “Neutralizing antibodies
4378



region

derived from the B cells of 1918





influenza pandemic survivors”, Nature





455 (7212), 532-536, NCBI Accession





#ACI04579


INFL242
Heavy chain variable
2B12
Yu, X. et al “Neutralizing antibodies
4379



region

derived from the B cells of 1918





influenza pandemic survivors”, Nature





455 (7212), 532-536, NCBI Accession





#ABY48866


INFL243
Heavy chain variable
8D4
NCBI Accession #AFI57036
4380



region


INFL244
Heavy chain variable
5B6
NCBI Accession #AFI57040
4381



region


INFL245
Heavy chain variable
A66
WO2009079259, US20110038935,
4382



region

US20140011982 SEQ ID NO: 32


INFL246
Heavy chain variable
D7
WO2009079259, US20110038935,
4383



region

US20140011982 SEQ ID NO: 6


INFL247
Heavy chain variable
D8, D80
WO2009079259, US20110038935,
4384



region

US20140011982 SEQ ID NO: 12


INFL248
Heavy chain variable
E88
WO2009079259, US20110038935,
4385



region

US20140011982 SEQ ID NO: 36


INFL249
Heavy chain variable
E90, F10
WO2009079259, US20110038935,
4386



region

US20140011982 SEQ ID NO: 18


INFL250
Heavy chain variable
F10
WO2009079259, US20110038935,
4387



region

US20140011982 SEQ ID NO: 112


INFL251
Heavy chain variable
G17
WO2009079259, US20110038935,
4388



region

US20140011982 SEQ ID NO: 24


INFL252
Heavy chain variable
H40
WO2009079259, US20110038935,
4389



region

US20140011982 SEQ ID NO: 28


INFL253
Heavy chain variable
CH65
WO2013020074, US20140302043 SEQ
4390



region

ID NO: 14


INFL254
Heavy chain variable
CH66
WO2013020074, US20140302043 SEQ
4391



region

ID NO: 15


INFL255
Heavy chain variable
CH67
WO2013020074, US20140302043 SEQ
4392



region

ID NO: 16


INFL256
Heavy chain variable
CL86OUCA
WO2013020074, US20140302043 SEQ
4393



region

ID NO: 13


INFL257
Heavy chain variable
Antibody 1
WO2015051010 SEQ ID NO: 2
4394



region


INFL258
Heavy chain variable
Antibody 2
WO2015051010 SEQ ID NO: 12
4395



region


INFL259
Heavy chain variable
Antibody 3
WO2015051010 SEQ ID NO: 22
4396



region


INFL260
Heavy chain variable
Antibody 4
WO2015051010 SEQ ID NO: 32
4397



region


INFL261
Heavy chain variable
Antibody 5
WO2015051010 SEQ ID NO: 42
4398



region


INFL262
Heavy chain variable
Antibody 6
WO2015051010 SEQ ID NO: 52
4399



region


INFL263
Heavy chain variable
Antibody 7
WO2015051010 SEQ ID NO: 62
4400



region


INFL264
Heavy chain variable
Antibody 8
WO2015051010 SEQ ID NO: 72
4401



region


INFL265
Heavy chain variable
Antibody 9
WO2015051010 SEQ ID NO: 82
4402



region


INFL266
Heavy chain variable
Antibody 10
WO2015051010 SEQ ID NO: 92
4403



region


INFL267
Heavy chain variable
Antibody 11
WO2015051010 SEQ ID NO: 102
4404



region


INFL268
Heavy chain variable
Antibody 12
WO2015051010 SEQ ID NO: 112
4405



region


INFL269
Heavy chain variable
Antibody 13
WO2015051010 SEQ ID NO: 122
4406



region


INFL270
Heavy chain variable
Antibody 14
WO2015051010 SEQ ID NO: 132
4407



region


INFL271
Heavy chain variable
Antibody 15
WO201505I010 SEQ ID NO: 142
4408



region


INFL272
Heavy chain variable
Antibody 3-GL
WO2015051010 SEQ ID NO: 152
4409



region


INFL273
Heavy chain variable
EM4C04
US20120282273 SEQ ID NO: 2
4410



region


INFL274
Heavy chain variable
005-2G02
WO2013059524, US20140348851 SEQ
4411



region

ID NO: 1


INFL275
Heavy chain variable
005-2G02
WO2013059524, US20140348851 SEQ
4412



region

ID NO: 9


INFL276
Heavy chain variable
09-2A06
WO2013059524, US20140348851 SEQ
4413



region

ID NO: 21


INFL277
Heavy chain variable
09-2A06
WO2013059524, US20140348851 SEQ
4414



region

ID NO: 29


INFL278
Heavy chain variable
09-3A01
WO2013059524, US20140348851 SEQ
4415



region

ID NO: 41


INFL279
Heavy chain variable
09-3A01
WO2013059524, US20140348851 SEQ
4416



region

ID NO: 49


INFL280
Heavy chain variable
70-IF02
WO2012096994, US20140046039 SEQ
4417



region

ID NO: 18


INFL281
Heavy chain variable

US20120058124 SEQ ID NO: 10
4418



region


INFL282
Heavy chain variable

US20120058124 SEQ ID NO: 11
4419



region


INFL283
Heavy chain variable

US20120058124 SEQ ID NO: 12
4420



region


INFL284
Heavy chain variable

US20120058124 SEQ ID NO: 13
4421



region


INFL285
Heavy chain variable

US20120058124 SEQ ID NO: 14
4422



region


INFL286
Heavy chain variable
81.39
US20140161822, US20140248286,
4423



region

WO2014078268 SEQ ID NO: 111


INFL287
Heavy chain variable
81.39
US20140161822, US20140248286,
4424



region

WO2014078268 SEQ ID NO: 115


INFL288
Heavy chain variable
39.29
US20140161822, US20140248286,
4425



region

WO2014078268 SEQ ID NO: 134


INFL289
Heavy chain variable
39.29
US20140161822, US20140248286,
4426



region

WO2014078268 SEQ ID NO: 138


INFL290
Heavy chain variable
39.29
US20140161822, US20140248286,
4427



region

WO2014078268 SEQ ID NO: 142


INFL291
Heavy chain variable
39.29
US20140161822, US20140248286,
4428



region

WO2014078268 SEQ ID NO: 148


INFL292
Heavy chain variable
36.89
US20140161822, US20140248286,
4429



region

WO2014078268 SEQ ID NO: 160


INFL293
Heavy chain variable
9.01F3
US20140161822, US20140248286,
4430



region

WO2014078268 SEQ ID NO: 164


INFL294
Heavy chain variable
23.06C2
US20140161822, US20140248286,
4431



region

WO2014078268 SEQ ID NO: 168


INFL295
Heavy chain variable
39.29
US20140161822, US20140248286,
4432



region

WO2014078268 SEQ ID NO: 234


INFL296
Heavy chain variable
F16 Variant 5
WO2013011347, US20140271655,
4433



region

US8871207 SEQ ID NO: 59


INFL297
Heavy chain variable
F16 Variant 3
WO2013011347, US20140271655,
4434



region

US8871207 SEQ ID NO: 55


INFL298
Heavy chain variable
F16 Variant 2
WO2010010466 SEQ ID NO: 33
4435



region


INFL299
Heavy chain variable
FC41
WO2010010467 SEQ ID NO 60
4436



region


INFL300
Heavy chain variable
FE43
WO2010010467 SEQ ID NO 74
4437



region


INFL301
Heavy chain variable
FB75, FB110,
WO2010010467 SEQ ID NO 121
4438



region
FB177


INFL302
Heavy chain variable
FE17
WO2010010467 SEQ ID NO 105
4439



region


INFL303
Heavy chain variable
FB79
WO2010010467 SEQ ID NO 131
4440



region


INFL304
Heavy chain variable
FC1C
WO2010010467 SEQ ID NO 139
4441



region


INFL305
Heavy chain variable
FC6
WO2010010467 SEQ ID NO 45
4442



region


INFL306
Heavy chain variable
FE53
WO2010010467 SEQ ID NO 89
4443



region


INFL307
Heavy chain variable
7A7
WO2010138564 SEQ ID NO: 6
4444



region


INFL308
Heavy chain variable
12DI
WO2010138564 SEQ ID NO: 12
4445



region


INFL309
Heavy chain variable
66A6
WO2010138564 SEQ ID NO: 16
4446



region


INFL310
Heavy chain variable
B-1
U.S. Pat. No. 8,975,378, US20110319600,
4447



region

WO2010073647 SEQ ID NO: 27


INFL311
Heavy chain variable
D1
U.S. Pat. No. 8,975,378, US20110319600,
4448



region

WO2010073647 SEQ ID NO: 29


INFL312
Heavy chain variable
E-2
U.S. Pat. No. 8,975,378, US20110319600,
4449



region

WO2010073647 SEQ ID NO: 31


INFL313
Heavy chain variable
B-3
U.S. Pat. No. 8,975,378, US20110319600,
4450



region

WO2010073647 SEQ ID NO: 33


INFL314
Heavy chain variable
5A7
WO2013114885, US20140377262 SEQ
4451



region

ID NO: 33


INFL315
Heavy chain variable
3A2
WO2013114885, US20140377262 SEQ
4452



region

ID NO: 37


INFL316
Heavy chain variable
10C4
WO2013114885, US20140377262 SEQ
4453



region

ID NO: 41


INFL317
Heavy chain variable
Fab49
WO2009144667, US20110076265 SEQ
4454



region

ID NO: 1


INFL318
Heavy chain variable
Fab28 IgG PN-
WO2009115972, WO2011117848,
4455



region
SIA28
US20110014187 SEQ ID NO: 1


INFL319
Heavy chain variable
TCN-522
US20120207760, U.S. Pat. No. 8,916,160 SEQ ID
4456



region

NO: 771; U.S. Pat. No. 8,900,590 SEQ ID NO: 32


INFL320
Heavy chain variable
CR8019
WO2010130636 SEQ ID NO: 26
4457



region


INFL321
Heavy chain variable
CR8020
WO2010130636 SEQ ID NO: 30
4458



region


INFL322
Heavy chain variable
CR8021
WO2010130636 SEQ ID NO: 34
4459



region


INFL323
Heavy chain variable
CR8038
WO2010130636 SEQ ID NO: 38
4460



region


INFL324
Heavy chain variable
CR8039
WO2010130636 SEQ ID NO: 42
4461



region


INFL325
Heavy chain variable
CR8040
WO2010130636 SEQ ID NO: 46
4462



region


INFL326
Heavy chain variable
CR8041
WO2010130636 SEQ ID NO: 50
4463



region


INFL327
Heavy chain variable
CR8043
WO2010130636 SEQ ID NO: 54
4464



region


INFL328
Heavy chain variable
CR8049
WO2010130636 SEQ ID NO: 58
4465



region


INFL329
Heavy chain variable
CR8050
WO2010130636 SEQ ID NO: 61
4466



region


INFL330
Heavy chain variable
CR8052
WO2010130636 SEQ ID NO: 65
4467



region


INFL331
Heavy chain variable
CR8055
WO2010130636 SEQ ID NO: 69
4468



region


INFL332
Heavy chain variable
CR8057
WO2010130636 SEQ ID NO: 73
4469



region


INFL333
Heavy chain variable
CR8069
WO2010130636 SEQ ID NO: 77
4470



region


INFL334
Heavy chain variable
CR6255
US20090311265, U.S. Pat. No. 8,691,223,
4471



region

U.S. Pat. No. 9,109,017, WO2008028946A SEQ ID





NO: 59


INFL335
Heavy chain variable
CR6257
US20090311265, U.S. Pat. No. 8,691,223,
4472



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 61


INFL336
Heavy chain variable
CR6260
US20090311265, U.S. Pat. No. 8,691,223,
4473



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 63


INFL337
Heavy chain variable
CR6261
US20090311265, U.S. Pat. No. 8,691,223,
4474



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 65


INFL338
Heavy chain variable
CR6262
US20090311265, U.S. Pat. No. 8,691,223,
4475



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 67


INFL339
Heavy chain variable
CR6268
US20090311265, U.S. Pat. No. 8,691,223,
4476



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 69


INFL340
Heavy chain variable
CR6307
US20090311265, U.S. Pat. No. 8,691,223,
4477



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 71


INFL341
Heavy chain variable
CR6310
US20090311265, U.S. Pat. No. 8,691,223,
4478



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 73


INFL342
Heavy chain variable
CR6314
US20090311265, U.S. Pat. No. 8,691,223,
4479



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 75


INFL343
Heavy chain variable
CR6323
US20090311265, U.S. Pat. No. 8,691,223,
4480



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 77


INFL344
Heavy chain variable
CR6325
US20090311265, U.S. Pat. No. 8,691,223,
4481



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 79


INFL345
Heavy chain variable
CR6331
US20090311265, U.S. Pat. No. 8,691,223,
4482



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 81


INFL346
Heavy chain variable
CR6344
US20090311265, U.S. Pat. No. 8,691,223,
4483



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 83


INFL347
Heavy chain variable
CR6141
US20090311265, U.S. Pat. No. 8,691,223,
4484



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 317


INFL348
Heavy chain variable
CR6272
US20090311265, U.S. Pat. No. 8,691,223,
4485



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 321


INFL349
Heavy chain variable
CR6296
US20090311265, U.S. Pat. No. 8,691,223,
4486



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 325


INFL350
Heavy chain variable
CR6301
US20090311265, U.S. Pat. No. 8,691,223,
4487



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 329


INFL351
Heavy chain variable
CR6327
US20090311265, U.S. Pat. No. 8,691,223,
4488



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 333


INFL352
Heavy chain variable
CR6328
US20090311265, U.S. Pat. No. 8,691,223,
4489



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 337


INFL353
Heavy chain variable
CR6329
US20090311265, U.S. Pat. No. 8,691,223,
4490



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 341


INFL354
Heavy chain variable
CR6332
US20090311265, U.S. Pat. No. 8,691,223,
4491



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 345


INFL355
Heavy chain variable
CR6334
US20090311265, U.S. Pat. No. 8,691,223,
4492



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 349


INFL356
Heavy chain variable
CR6336
US20090311265, U.S. Pat. No. 8,691,223,
4493



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 353


INFL357
Heavy chain variable
CR6339
US20090311265, U.S. Pat. No. 8,691,223,
4494



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 357


INFL358
Heavy chain variable
CR6342
US20090311265, U.S. Pat. No. 8,691,223,
4495



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 361


INFL359
Heavy chain variable
CR6343
US20090311265, U.S. Pat. No. 8,691,223,
4496



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 365


INFL360
Heavy chain variable
CR9003
US20140120113 SEQ ID NO: 2
4497



region


INFL361
Heavy chain variable
CR9004
US20140120113 SEQ ID NO: 6
4498



region


INFL362
Heavy chain variable
CR9005
US20140120113 SEQ ID NO: 10
4499



region


INFL363
Heavy chain variable
CR9006
US20140120113 SEQ ID NO: 14
4500



region


INFL364
Heavy chain variable
CR9007
US20140120113 SEQ ID NO: 18
4501



region


INFL365
Heavy chain variable
CR9008
US20140120113 SEQ ID NO: 22
4502



region


INFL366
Heavy chain variable
CR9009
US20140120113 SEQ ID NO: 26
4503



region


INFL367
Heavy chain variable
CR9010
US20140120113 SEQ ID NO: 30
4504



region


INFL368
Heavy chain variable
CR9011
US20140120113 SEQ ID NO: 34
4505



region


INFL369
Heavy chain variable
CR9012
US20140120113 SEQ ID NO: 38
4506



region


INFL370
Heavy chain variable
CR9029
US20140120113 SEQ ID NO: 42
4507



region


INFL371
Heavy chain variable
CR9030
US20140120113 SEQ ID NO: 46
4508



region


INFL372
Heavy chain variable
CR9031
US20140120113 SEQ ID NO: 50
4509



region


INFL373
Heavy chain variable
CR9112
US20140120113 SEQ ID NO: 54
4510



region


INFL374
Heavy chain variable
CR9113
US20140120113 SEQ ID NO: 58
4511



region


INFL375
Heavy chain variable
CR9114
US20140120113 SEQ ID NO: 62
4512



region


INFL376
Heavy chain variable
CR8033
U.S. Pat. No. 8,852,595 SEQ ID NO: 71
4513



region


INFL377
Heavy chain variable
CR8059
U.S. Pat. No. 8,852,595 SEQ ID NO: 75
4514



region


INFL378
Heavy chain variable
CR8071
U.S. Pat. No. 8,852,595 SEQ ID NO: 78
4515



region


INFL379
Heavy chain variable
CR10051
U.S. Pat. No. 8,852,595 SEQ ID NO: 81
4516



region


INFL380
Heavy chain variable
CR10049
U.S. Pat. No. 8,852,595 SEQ ID NO: 85
4517



region


INFL381
Heavy chain variable
CR10023
U.S. Pat. No. 8,852,595 SEQ ID NO: 89
4518



region


INFL382
Heavy chain variable
CR10032
U.S. Pat. No. 8,852,595 SEQ ID NO: 93
4519



region


INFL383
Heavy chain variable
CR11035
U.S. Pat. No. 8,852,595 SEQ ID NO: 101
4520



region


INFL384
Heavy chain variable
CR11036
U.S. Pat. No. 8,852,595 SEQ ID NO: 105
4521



region


INFL385
Heavy chain variable
CR11038
U.S. Pat. No. 8,852,595 SEQ ID NO: 109
4522



region


INFL386
Heavy chain variable
CR11039
U.S. Pat. No. 8,852,595 SEQ ID NO: 113
4523



region


INFL387
Heavy chain variable
CR8031
U.S. Pat. No. 8,852,595 SEQ ID NO: 119
4524



region


INFL388
Heavy chain variable
CR8032
U.S. Pat. No. 8,852,595 SEQ ID NO: 123
4525



region


INFL389
Heavy chain variable
CR8034
U.S. Pat. No. 8,852,595 SEQ ID NO: 127
4526



region


INFL390
Heavy chain variable
CR8035
U.S. Pat. No. 8,852,595 SEQ ID NO: 131
4527



region


INFL391
Heavy chain variable

U.S. Pat. No. 8,992,929 SEQ ID NO: 4
4528



region


INFL392
Heavy chain variable
M2e
U.S. Pat. No. 8,420,794 SEQ ID NO: 2
4529



region


INFL393
Heavy chain variable

U.S. Pat. No. 8,715,743, US20140275492 SEQ ID
4530



region

NO: 22


INFL394
Heavy chain variable

U.S. Pat. No. 8,715,743, US20140275492 SEQ ID
4531



region

NO: 25


INFL395
Heavy chain variable

U.S. Pat. No. 8,715,743, US20140275492 SEQ ID
4532



region

NO: 36


INFL396
Heavy chain variable
4A10
Krause, J. C. et al. “Epitope-specific
4533



region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16797


INFL397
Heavy chain variable
anti-1918 influenza
Yu, X., et al., Neutralizing antibodies
4534



region
HA Ig
derived front the B cells of 1918





influenza pandemic survivors; Nature





455 (7212), 532-536 (2008), NCBI





Accession #ACI04579.1 (129aa)


INFL398
Heavy chain variable
TCN-522
US20150086555 SEQ ID NO: 33
4535



region
(3212_I12)


INFL399
Heavy chain variable
TCN-521
US20150086555 SEQ ID NO: 21
4536



region
(3280_D18)


INFL400
Heavy chain variable
TCN-523
US20150086555 SEQ ID NO: 45
4537



region
(5248_A17)


INFL401
Heavy chain variable
TCN-563
US20150086555 SEQ ID NO: 57
4538



region
(5237_B21)


INFL402
Heavy chain variable
TCN-526
US20150086555 SEQ ID NO: 69
4539



region
(5084_C17)


INFL403
Heavy chain variable
TCN-527
US20150086555 SEQ ID NO: 81
4540



region
(5086_C06)


INFL404
Heavy chain variable
TCN-528
US20150086555 SEQ ID NO: 93
4541



region
(5087_P17)


INFL405
Heavy chain variable
TCN-529
US20150086555 SEQ ID NO: 105
4542



region
(5297_H01)


INFL406
Heavy chain variable
TCN-530
US20150086555 SEQ ID NO: 117
4543



region
(5248_H10)


INFL407
Heavy chain variable
TCN-531
US20150086555 SEQ ID NO: 129
4544



region
(5091_H13)


INFL408
Heavy chain variable
TCN-532
US20150086555 SEQ ID NO: 141
4545



region
(5262_H18)


INFL409
Heavy chain variable
TCN-533
US20150086555 SEQ ID NO: 153
4546



region
(5256_A17a),




TCN-564




(5256_A17b)


INFL410
Heavy chain variable
TCN-534
US20150086555 SEQ ID NO: 161
4547



region
(5249_B02)


INFL411
Heavy chain variable
TCN-535
US20150086555 SEQ ID NO: 173
4548



region
(5246_P19),




TCN-558




(5248_H10b)


INFL412
Heavy chain variable
TCN-536
US20150086555 SEQ ID NO: 184
4549



region
(5095_N01)


INFL413
Heavy chain variable
TCN-537
US20150086555 SEQ ID NO: 195
4550



region
(3194_D21)


INFL414
Heavy chain variable
TCN-538
US20150086555 SEQ ID NO: 207
4551



region
(3206_O17)


INFL415
Heavy chain variable
TCN-539
US20150086555 SEQ ID NO: 219
4552



region
(5056_A08)


INFL416
Heavy chain variable
TCN-540
US20150086555 SEQ ID NO: 231
4553



region
(5060_F05)


INFL417
Heavy chain variable
TCN-541
US20150086555 SEQ ID NO: 243
4554



region
(5062_M11)


INFL418
Heavy chain variable
TCN-542
US20150086555 SEQ ID NO: 255
4555



region
(5079_A16)


INFL419
Heavy chain variable
TCN-543
US20150086555 SEQ ID NO: 267
4556



region
(5081_G23)


INFL420
Heavy chain variable
TCN-544
US20150086555 SEQ ID NO: 279
4557



region
(5082_A19)


INFL421
Heavy chain variable
TCN-545
US20150086555 SEQ ID NO: 291
4558



region
(5082_I15)


INFL422
Heavy chain variable
TCN-546
US20150086555 SEQ ID NO: 302
4559



region
(5089_L08)


INFL423
Heavy chain variable
TCN-547
US20150086555 SEQ ID NO: 313
4560



region
(5092_F11)


INFL424
Heavy chain variable
TCN-548
US20150086555 SEQ ID NO: 325
4561



region
(5092_P01)


INFL425
Heavy chain variable
TCN-549
US20150086555 SEQ ID NO: 335
4562



region
(5092_P04)


INFL426
Heavy chain variable
TCN-550
US20150086555 SEQ ID NO: 346
4563



region
(5096_F06)


INFL427
Heavy chain variable
TCN-551
US20150086555 SEQ ID NO: 358
4564



region
(5243_D01)


INFL428
Heavy chain variable
TCN-552
US20150086555 SEQ ID NO: 370
4565



region
(5249_I23)


INFL429
Heavy chain variable
TCN-553
US20150086555 SEQ ID NO: 382
4566



region
(5261_C18)


INFL430
Heavy chain variable
TCN-554
US20150086555 SEQ ID NO: 392
4567



region
(5277_M05)


INFL431
Heavy chain variable
TCN-555
US20150086555 SEQ ID NO: 403
4568



region
(5246_L16)


INFL432
Heavy chain variable
TCN-556
US20150086555 SEQ ID NO: 408
4569



region
(5089_K12)


INFL433
Heavy chain variable
TCN-557
US20150086555 SEQ ID NO: 420
4570



region
(5081_A04)


INFL434
Heavy chain variable
TCN-559
US20150086555 SEQ ID NO: 434
4571



region
(5097_G08)


INFL435
Heavy chain variable
TCN-560
US20150086555 SEQ ID NO: 446
4572



region
(5084_P10)


INFL436
Heavy chain variable
TCN-504
US20150086555 SEQ ID NO: 510
4573



region
(3251_K17)


INFL437
Heavy chain variable
AB1
US20120093834, WO2009121004 SEQ
4574



region

ID NO: 4


INFL438
Heavy chain variable
AB2
US20120093834, WO2009121004 SEQ
4575



region

ID NO: 45


INFL439
Heavy chain variable
AB3
US20120093834, WO2009121004 SEQ
4576



region

ID NO: 9


INFL440
Heavy chain variable
AB4, AB5, AB6
US20120093834, WO2009121004 SEQ
4577



region

ID NO: 61


INFL441
Heavy chain variable
VN04-2
WO2008033105 SEQ ID NO: 5
4578



region


INFL442
Heavy chain variable
VN04-3
WO2008033105 SEQ ID NO: 7
4579



region


INFL443
Heavy chain variable
1286-C05
WO2010132604, US20120128671 SEQ
4580



region

ID NO: 1


INFL444
Heavy chain variable
1286-A11
WO2010132604, US20120128671 SEQ
4581



region

ID NO: 2


INFL445
Heavy chain variable
CR8001
WO2010130636 SEQ ID NO: 2
4582



region


INFL446
Heavy chain variable
CR8003
WO2010130636 SEQ ID NO: 6
4583



region


INFL447
Heavy chain variable
CR8015
WO2010130636 SEQ ID NO: 10
4584



region


INFL448
Heavy chain variable
CR8016
WO2010130636 SEQ ID NO: 14
4585



region


INFL449
Heavy chain variable
CR8017
WO2010130636 SEQ ID NO: 18
4586



region


INFL450
Heavy chain variable
CR8018
WO2010130636 SEQ ID NO: 22
4587



region


INFL451
Heavy chain variable
anti-1918 influenza
Yu, X., et al., Neutralizing antibodies
4588



region (Partial)
HA Ig
derived from the B cells of 1918





influenza pandemic survivors; Nature





455 (7212), 532-536 (2008), NCBI





Accession #ACI04581.1 (145aa)


INFL452
Heavy chain variable
1A2
WO2015028478 SEQ ID NO: 2
4589



region mouse IgG


INFL453
Heavy chain variable
7B8
WO2015028478 SEQ ID NO: 4
4590



region mouse IgG


INFL454
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4591



region, partial
antibody TCN-031
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23854.1





(120aa)


INFL455
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human, antibodies
4592



region, partial
antibody TCN-032
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23853.1





(120aa)


INFL456
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4593



region, partial
antibody 3362_B11
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23869.1





(123aa)


INFL457
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4594



region, partial
antibody
reveal a protective epitope that is highly




3260_D19
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23868.1





(118aa)


INFL458
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4595



region, partial
antibody 3253_P10
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23867.1





(121aa)


INFL459
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4596



region, partial
antibody 3248_P18
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23866.1





(120aa)


INFL460
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4597



region, partial
antibody 3139_P23
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23865.1





(119aa)


INFL461
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4598



region, partial
antibody 3420_I23
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23864.1





(121aa)


INFL462
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4599



region, partial
antibody 3255_J06
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23863.1





(119aa)


INFL463
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4600



region, partial
antibody 3252_C13
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession # ADK23862.1





(119aa)


INFL464
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4601



region, partial
antibody
reveal a protective epitope that is highly




3136_G05
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23861.1





(120aa)


INFL465
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4602



region, partial
antibody
reveal a protective epitope that is highly




3244_H04
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23860.1





(118aa)


INFL466
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4603



region, partial
antibody
reveal a protective epitope that is highly




3245_O19
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23859.1





(118aa)


INFL467
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4604



region, partial
antibody 3259_J21
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23858.1





(120aa)


INFL468
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4605



region, partial
antibody 3243_J07
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23857.1





(121aa)


INFL469
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4606



region, partial
antibody 3244_I10
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession # ADK23856.1





(121aa)


INFL470
Heavy chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
4607



region, partial
antibody
reveal a protective epitope that is highly




3241_G23
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23855.1





(122aa)


INFL471
Heavy chain variable
Monoclonal
Yasugi, M. et al., Emerging Antigenic
4608



region, partial
antibody clone 5E4
Variants at the Antigenic Site Sb in





Pandemic A(H1N1)2009 Influenza Virus





in Japan Detected by a Human





Monoclonal Antibody; PLoS ONE 8





(10), E77892 (2013), NCBI Accession





#BAM76754.1 (141aa)


INFL472
Heavy chain variable
100F4-HV
Hu, H., et al., A Human Antibody
4609



region, partial

Recognizing a Conserved Epitope of H5





Hemagglutinin Broadly Neutralizes





Highly Pathogenic Avian Influenza





H5N1 Viruses; J. Virol. 86 (6), 2978-





2989 (2012), NCBI Accession





#AEL30603.1 (121aa)


INFL473
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4610



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40460.1





(120aa)


INFL474
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4611



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40459.1





(127aa)


INFL475
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4612



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40458.1





(129aa)


INFL476
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4613



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40457.1





(132aa)


INFL477
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4614



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40456.1





(127aa)


INFL478
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4615



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40455.1





(121aa)


INFL479
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4616



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40454.1





(126aa)


INFL480
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4617



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40453.1





(120aa)


INFL481
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4618



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40452.1





(122aa)


INFL482
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4619



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40451.1





(125aa)


INFL483
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4620



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40450.1





(126aa)


INFL484
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4621



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40449.1





(129aa)


INFL485
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4622



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40448.1





(119aa)


INFL486
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4623



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40447.1





(120aa)


INFL487
Heavy chain variable
anti-stem HA
Pappas, L. et al., Rapid development of
4624



region, partial, Anti-
immunoglobulin
broadly influenza neutralizing antibodies



stem HA

through redundant mutations; Nature



immunoglobulin

(2014), NCBI Accession #AIN40446.1





(120aa)


INFL488
Heavy chain, Human
Fab 39.29
Nakamura, G. et al., An in vivo human-
4625



igg,

plasmablast enrichment technique allows





rapid identification of therapeutic





influenza a antibodies; Cell Host





Microbe 14 (1), 93-103 (2013), NCBI





Accession #4KVN_H (227aa)


INFL489
Heavy chain, Igg1
Fab H5m9
Zhu, X., et al., A Unique and Conserved
4626





Neutralization Epitope in H5N1





Influenza Viruses Identified by an





Antibody against the





A/Goose/Guangdong/1/96





Hemagglutinin; J. Virol. 87 (23), 12619-





12635 (2013), NCBI Accession





#4MHH_H (222aa)


INFL490
Immunoglobulin
T2-6A
Huang, K.-Y. A., et al., Focused antibody-
4627



heavy chain variable

response to influenza linked to antigenic



region, partial

drift; J. Clin. Invest. (2015), NCBI





Accession #AKF02484.1 (124aa)


INFL491
Kappa light chain

U.S. Pat. No. 8,992,929 SEQ ID NO. 24
4628



constant region,



human


INFL492
Kappa light chain
8D4
NCBI Accession #AFI57037
4629



variable


INFL493
Kappa light chain
5B6
NCBI Accession #AFI57041
4630



variable


INFL494
Kappa light chain
8i10
U.S. Pat. No. 8,858,948 SEQ ID NO: 56
4631



variable region


INFL495
Kappa light chain
23K12
U.S. Pat. No. 8,858,948 SEQ ID NO: 91
4632



variable region


INFL496
Kappa light chain
4K8
Krause, J. C. et al. “Epitope-specific
4633



variable region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16800


INFL497
Kappa light chain
6D9
Krause, J. C. et al. “Epitope-specific
4634



variable region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16802


INFL498
Kappa light chain
8G9
U.S. Pat. No. 8,603,467 SEQ ID NO: 4
4635



variable region


INFL499
Kappa light chain
13D4
U.S. Pat. No. 8,603,467 SEQ ID NO: 8
4636



variable region


INFL500
Kappa light chain
20A11
U.S. Pat. No. 8,603,467 SEQ ID NO: 12
4637



variable region


INFL501
Kappa light chain
EM4C04
US20120282273 SEQ ID NO: 1
4638



variable region


INFL502
Kappa, light chain
Fab H5m9
Zhu, X., et al., A Unique and Conserved
4639





Neutralization Epitope in H5N1





Influenza Viruses Identified by an





Antibody against the





A/Goose/Guangdong/1/96





Hemagglutinin; J. Virol. 87 (23), 12619-





12635 (2013), NCBI Accession #





4MHH_L(218aa)


INFL503
Lambda light chain
7A13
Krause et al. “Human Monoclonal
4640





Antibodies to Pandemic 1957 H2N2 and





Pandemic 1968 H3N2 Influenza Viruses”





J. Virol. 86 (11), 6334-6340 (2012),





NCBI Accession #AFH78448


INFL504
Lambda light chain
2K11
Krause, J. C. et al. “Epitope-specific
4641



variable

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16794


INFL505
Lambda light chain
2O10
Krause, J. C. et al. “Epitope-specific
4642



variable

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16796


INFL506
Lambda light chain
Monoclonal
Yasugi, M. et al., Emerging Antigenic
4643



variable region,
antibody clone 5E4
Variants at the Antigenic Site Sb in



partial

Pandemic A(H1N1)2009 Influenza Virus





in Japan Detected by a Human





Monoclonal Antibody; PLoS ONE 8





(10), E77892 (2013), NCBI Accession





#BAM76755.1 (126aa)


INFL507
Lambda light chain
T2-6A
Huang, K.-Y. A., et al., Focused antibody
4644



variable region,

response to influenza linked to antigenic



partial,

drift; J. Clin. Invest. (2015), NCBI



Immunoglobulin

Accession #AKF02488.1 (113aa)


INFL508
Light chain
CR6261,
WO2008028946
4645




Diridavumab, CR-




6261


INFL509
Light chain
Firivumab, CT-P22
US20130004505
4646


INFL510
Light chain
Navivumab,
WO2013048153, US20140234336 SEQ
4647




CT149
ID NO: 39


INFL511
Light chain
AT10-004
US20150010566, WO2013081463 SEQ
4648





ID NO: 36


INFL512
Light chain
AT10-003
US20150010566, WO2013081463 SEQ
4649





ID NO: 37


INFL513
Light chain
AT10-002
US20150010566, WO2013081463 SEQ
4650





ID NO: 38


INFL514
Light chain
AT10-001
US20150010566, WO2013081463 SEQ
4651





ID NO: 39


INFL515
Light chain
AT10-005
US20150010566, WO2013081463 SEQ
4652





ID NO: 40


INFL516
Light chain
CT104
WO2011111966, US20130004505 SEQ
4653





ID NO: 36


INFL517
Light chain
CT120
WO2011111966, US20130004505 SEQ
4654





ID NO: 40


INFL518
Light chain
CT123
WO2011111966, US20130004505 SEQ
4655





ID NO: 44


INFL519
Light chain
2A
US20140011982 SEQ ID NO: 4
4656


INFL520
Light chain
F005-126
WO2014049520, US20140086927 SEQ
4657





ID NO: 13


INFL521
Light chain
BF1-1
WO2008156763 SEQ ID NO: 8
4658


INFL522
Light chain
BF1-19
WO2008156763 SEQ ID NO: 12
4659


INFL523
Light chain
BF1-10
WO2008156763 SEQ ID NO: 10
4660


INFL524
Light chain
2D1
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4661





NO: 8


INFL525
Light chain
1F1
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4662





NO: 2


INFL526
Light chain
4D20
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
4663





NO: 10


INFL527
Light chain
A18
WO13170139 SEQ ID NO: 95
4664


INFL528
Light chain
Ab A18
U.S. Pat. No. 7,788,200 SEQ ID NO: 28
4665


INFL529
Light chain
Ab 067
U.S. Pat. No. 7,788,200 SEQ ID NO: 153
4666


INFL530
Light chain
Ab 068
U.S. Pat. No. 7,788,200 SEQ ID NO: 154
4667


INFL531
Light chain
Ab 069, Ab 079
U.S. Pat. No. 7,788,200 SEQ ID NO: 155
4668


INFL532
Light chain
Ab 070
U.S. Pat. No. 7,788,200 SEQ ID NO: 156
4669


INFL533
Light chain
Ab 073
U.S. Pat. No. 7,788,200 SEQ ID NO: 165
4670


INFL534
Light chain
Ab 074, Ab 080
U.S. Pat. No. 7,788,200 SEQ ID NO: 166
4671


INFL535
Light chain
Ab 075
U.S. Pat. No. 7,788,200 SEQ ID NO: 167
4672


INFL536
Light chain
Ab 076
U.S. Pat. No. 7,788,200 SEQ ID NO: 168
4673


INFL537
Light chain
Ab 077, Ab 081
U.S. Pat. No. 7,788,200 SEQ ID NO: 169
4674


INFL538
Light chain
Ab 014, Ab 154,
U.S. Pat. No. 7,788,200 SEQ ID NO: 29
4675




Ab 157


INFL539
Light chain
Ab 028, Ab 155
U.S. Pat. No. 7,788,200 SEQ ID NO: 30
4676


INFL540
Light chain
Ab 001, Ab 002,
U.S. Pat. No. 7,788,200 SEQ ID NO: 31
4677




Ab 003


INFL541
Light chain
Ab 009, Ab 010,
U.S. Pat. No. 7,788,200 SEQ ID NO: 32
4678




Ab 011


INFL542
Light chain
Ab 017, Ab B18,
U.S. Pat. No. 7,788,200 SEQ ID NO: 33
4679




Ab B18, Ab 019,




Ab 019


INFL543
Light chain
Ab 025, Ab 026,
U.S. Pat. No. 7,788,200 SEQ ID NO: 34
4680




Ab 027, Ab 028


INFL544
Light chain
Ab 159
U.S. Pat. No. 7,788,200 SEQ ID NO: 35
4681


INFL545
Light chain
Ab 160
U.S. Pat. No. 7,788,200 SEQ ID NO: 36
4682


INFL546
Light chain
Ab 186, Ab 194
U.S. Pat. No. 7,788,200 SEQ ID NO: 37
4683


INFL547
Light chain
Ab 187, Ab 195
U.S. Pat. No. 7,788,200 SEQ ID NO: 38
4684


INFL548
Light chain
Ab 188, Ab 196
U.S. Pat. No. 7,788,200 SEQ ID NO: 39
4685


INFL549
Light chain
Ab 189, Ab 197
U.S. Pat. No. 7,788,200 SEQ ID NO: 40
4686


INFL550
Light chain
Ab 190, Ab 198
U.S. Pat. No. 7,788,200 SEQ ID NO: 41
4687


INFL551
Light chain
Ab 191, Ab 199
U.S. Pat. No. 7,788,200 SEQ ID NO: 42
4688


INFL552
Light chain
Ab 192, Ab 200
U.S. Pat. No. 7,788,200 SEQ ID NO: 43
4689


INFL553
Light chain
Ab 193
U.S. Pat. No. 7,788,200 SEQ ID NO: 44
4690


INFL554
Light chain
Ab 202, Ab 203,
U.S. Pat. No. 7,788,200 SEQ ID NO: 45
4691




Ab 204, Ab 210,




Ab 031, Ab 032,




Ab 033, Ab 034


INFL555
Light chain
Ab 211, Ab 212,
U.S. Pat. No. 7,788,200 SEQ ID NO: 46
4692




Ab 213, Ab 219,




Ab 037, Ab 038,




Ab 039, Ab 040


INFL556
Light chain
Ab A001, Ab 004,
U.S. Pat. No. 7,788,200 SEQ ID NO: 47
4693




Ab 007, Ab 016


INFL557
Light chain
Ab A002, Ab 005,
U.S. Pat. No. 7,788,200 SEQ ID NO: 48
4694




Ab 008, Ab A017


INFL558
Light chain
Ab A003, Ab 006,
U.S. Pat. No. 7,788,200 SEQ ID NO: 49
4695




Ab A009, Ab C18


INFL559
Light chain
Ab A010, Ab 012,
U.S. Pat. No. 7,788,200 SEQ ID NO: 50
4696




Ab A14, Ab A019


INFL560
Light chain
Ab A011, Ab
U.S. Pat. No. 7,788,200 SEQ ID NO: 51
4697




013m Ab 0135


INFL561
Light chain
Ab 044, Ab 071,
U.S. Pat. No. 7,788,200 SEQ ID NO: 52
4698




Ab 072, Ab 078


INFL562
Light chain
Ab 051
U.S. Pat. No. 7,788,200 SEQ ID NO: 53
4699


INFL563
Light chain
Ab 049
U.S. Pat. No. 7,788,200 SEQ ID NO: 54
4700


INFL564
Light chain
Ab 047
U.S. Pat. No. 7,788,200 SEQ ID NO: 55
4701


INFL565
Light chain
Ab 050
U.S. Pat. No. 7,788,200 SEQ ID NO: 56
4702


INFL566
Light chain
Ab 045
U.S. Pat. No. 7,788,200 SEQ ID NO: 57
4703


INFL567
Light chain
Ab 048
U.S. Pat. No. 7,788,200 SEQ ID NO: 58
4704


INFL568
Light chain
Ab 046
U.S. Pat. No. 7,788,200 SEQ ID NO: 59
4705


INFL569
Light chain
Ab 043
U.S. Pat. No. 7,788,200 SEQ ID NO: 60
4706


INFL570
Light chain
Ab 052
U.S. Pat. No. 7,788,200 SEQ ID NO: 61
4707


INFL571
Light chain
F005-126
WO2014049520 SEQ ID 13
4708


INFL572
Light chain
8f24
WO2012045001 SEQ ID 3
4709


INFL573
Light chain
3E22
WO2012045001 SEQ ID 7
4710


INFL574
Light chain
5117
WO2012045001 SEQ ID 11
4711


INFL575
Light chain

WO2012045001 SEQ ID 15
4712


INFL576
Light chain

WO2012045001 SEQ ID 31
4713


INFL577
Light chain

WO2012045001 SEQ ID 35
4714


INFL578
Light chain

WO2012045001 SEQ ID 19
4715


INFL579
Light chain
10A14
WO2012045001 SEQ ID 23
4716


INFL580
Light chain
8D4
WO2012045001 SEQ ID 27
4717


INFL581
Light chain
2B9
U.S. Pat. No. 9,115,201 SEQ ID NO: 5
4718


INFL582
Light chain
mAB 7A7
US20150239960, US20140170163,
4719





U.S. Pat. No. 8,673,314, US20110027270,





WO2010138564 SEQ ID NO: 7


INFL583
Light chain
mAB 12D1
US20150239960, US20140170163,
4720





U.S. Pat. No. 8,673,314, US20110027270,





WO2010138564 SEQ ID NO: 13


INFL584
Light chain
mAB 66A6
US20150239960, US20140170163,
4721





U.S. Pat. No. 8,673,314, US20110027270,





WO2010138564 SEQ ID NO: 17


INFL585
Light chain
M1 D12
US20110033473, WO2009125395 SEQ
4722





ID NO: 15


INFL586
Light chain
mAB1.12
WO2013030165 SEQ ID NO: 2
4723


INFL587
Light chain
mAB3.1
WO2013030165 SEQ ID NO: 4
4724


INFL588
Light chain
5A7
WO2015120097 SEQ ID NO: 8
4725


INFL589
Light chain
TRL053
WO2015120097 SEQ ID NO: 18
4726


INFL590
Light chain
TRL579
WO2015120097 SEQ ID NO: 28
4727


INFL591
Light chain
TRL784
WO2015120097 SEQ ID NO: 38
4728


INFL592
Light chain
TRL794
WO2015120097 SEQ ID NO: 48
4729


INFL593
Light chain
TRL798
WO2015120097 SEQ ID NO: 58
4730


INFL594
Light chain
TRL799
WO2015120097 SEQ ID NO: 68
4731


INFL595
Light chain
TRL809
WO2015120097 SEQ ID NO: 78
4732


INFL596
Light chain
TRL811
WO2015120097 SEQ ID NO: 88
4733


INFL597
Light chain
TRL812
WO2015120097 SEQ ID NO: 98
4734


INFL598
Light chain
TRL813
WO2015120097 SEQ ID NO: 108
4735


INFL599
Light chain
TRL823
WO2015120097 SEQ ID NO: 118
4736


INFL600
Light chain
TRL832
WO2015120097 SEQ ID NO: 128
4737


INFL601
Light chain
TRL833
WO2015120097 SEQ ID NO: 138
4738


INFL602
Light chain
TRL834
WO2015120097 SEQ ID NO: 148
4739


INFL603
Light chain
TRL837
WO2015120097 SEQ ID NO: 167
4740


INFL604
Light chain
TRL839
WO2015120097 SEQ ID NO: 177
4741


INFL605
Light chain
TRL841
WO2015120097 SEQ ID NO: 187
4742


INFL606
Light chain
TRL842
WO2015120097 SEQ ID NO: 197
4743


INFL607
Light chain
TRL845
WO2015120097 SEQ ID NO: 207
4744


INFL608
Light chain
TRL846
WO2015120097 SEQ ID NO: 218
4745


INFL609
Light chain
TRL847
WO2015120097 SEQ ID NO: 228
4746


INFL610
Light chain
TRL848
WO2015120097 SEQ ID NO: 238
4747


INFL611
Light chain
TRL849
WO2015120097 SEQ ID NO: 248
4748


INFL612
Light chain
TRL851
WO2015120097 SEQ ID NO: 258
4749


INFL613
Light chain
TRL854
WO2015120097 SEQ ID NO: 268
4750


INFL614
Light chain
TRL856
WO2015120097 SEQ ID NO: 278
4751


INFL615
Light chain
TRL858
WO2015120097 SEQ ID NO: 288
4752


INFL616
Light chain
humM2e-hBiTE-1
WO2014140368 SEQ ID NO: 10
4753


INFL617
Light chain
humM2e-hBiTE-2
WO2014140368 SEQ ID NO: 18
4754


INFL618
Light chain
humM2e-hBiTE-3
WO2014140368 SEQ ID NO: 26
4755


INFL619
Light chain
humM2e-hBiTE-4
WO2014140368 SEQ ID NO: 34
4756


INFL620
Light chain
VH of humM2e-
WO2014140368 SEQ ID NO: 42
4757




hBiTE-5


INFL621
Light chain
humM2e-hBiTE-6
WO2014140368 SEQ ID NO: 50
4758


INFL622
Light chain
humM2e-hBiTE-7
WO2014140368 SEQ ID NO: 58
4759


INFL623
Light chain
humM2e-hBiTE-8
WO2014140368 SEQ ID NO: 66
4760


INFL624
Light chain
humM2e-hBiTE-9
WO2014140368 SEQ ID NO: 74
4761


INFL625
Light chain
murM2e-hBiTE
WO2014140368 SEQ ID NO: 82
4762


INFL626
Light chain
FLA5.10
U.S. Pat. No. 8,124,092 SEQ ID NO: 3
4763


INFL627
Light chain
FLD21.140
U.S. Pat. No. 8,124,092 SEQ ID NO: 7
4764


INFL628
Light chain
FLA3.14
U.S. Pat. No. 8,124,092 SEQ ID NO: 11
4765


INFL629
Light chain
FLD20.19
U.S. Pat. No. 8,124,092 SEQ ID NO: 15
4766


INFL630
Light chain
FLD84
U.S. Pat. No. 8,124,092 SEQ ID NO: 44
4767


INFL631
Light chain
FLD93
U.S. Pat. No. 8,124,092 SEQ ID NO: 54
4768


INFL632
Light chain
FLD122
U.S. Pat. No. 8,124,092 SEQ ID NO: 64
4769


INFL633
Light chain
FLD127
U.S. Pat. No. 8,124,092 SEQ ID NO: 74
4770


INFL634
Light chain
FLD129
U.S. Pat. No. 8,124,092 SEQ ID NO: 84
4771


INFL635
Light chain
FLD132
U.S. Pat. No. 8,124,092 SEQ ID NO: 94
4772


INFL636
Light chain
FLD194
U.S. Pat. No. 8,124,092 SEQ ID NO: 104
4773


INFL637
Light chain
mAb1
WO2015112994 SEQ ID NO: 77
4774


INFL638
Light chain
mAb2
WO2015112994 SEQ ID NO: 81
4775


INFL639
Light chain
mAb3
WO2015112994 SEQ ID NO: 85
4776


INFL640
Light chain
CT-P22
US20130004505 SEQ ID NO: 40;
4777





WO2011/111966


INFL641
Light chain
C05
Ekiert, D. C., et al., Cross-neutralization
4778





of influenza A viruses mediated by a





single antibody loop; Nature 489 (7417),





526-532 (2012), NCBI Accession





#4FNL_L (214aa)


INFL642
Light chain
CR8020
Ekiert, D. C., et al., A highly conserved
4779





neutralizing epitope on group 2 influenza





A viruses; Science 333 (6044), 843-850





(2011); WO2010130636, NCBI





Accession #3SDY_L


INFL643
Light chain
CR8033
Dreyfus, C., Laursen, N. S. et al., Highly
4780





conserved protective epitopes on





influenza B viruses; Science 337 (6100),





1343-1348 (2012), NCBI Accession #





4FQL_L


INFL644
Light chain
CR8043
Friesen, R. H. et al., A common solution
4781





to group 2 influenza virus neutralization;





Proc. Natl. Acad. Sci. U.S.A. 111 (1),





445-450 (2014), NCBI Accession





#4NM8_L


INFL645
Light chain
CR8059
Dreyfus, C. et al., Highly conserved
4782





protective epitopes on influenza B





viruses; Science 337 (6100), 1343-1348





(2012), NCBI Accession #4FQK_L


INFL646
Light chain
CR8071
Dreyfus, C. et al., Highly conserved
4783





protective epitopes on influenza B





viruses; Science 337 (6100), 1343-1348





(2012), NCBI Accession # 4FQJ_L





(216aa)


INFL647
Light chain
CR9114
WO2013079473; WO2014191435;
4784





Dreyfus, C., Laursen, N. S. et al., Highly





conserved protective epitopes on





influenza B viruses; Science 337 (6100),





1343-1348 (2012), NCBI Accession





#4FQY_L(216aa)


INFL648
Light chain
Ch67
Schmidt, A. G., et al., Preconfiguration of
4785





the antigen-binding site during affinity





maturation of a broadly neutralizing





influenza virus antibody; Proc. Natl.





Acad. Sci. U.S.A. 110 (1), 264-269





(2013), NCBI Accession #4HKX_B





(214aa)


INFL649
Light chain
Fab 26/9
Schulze-Gahmen, U. et al., J. Biol.
4786





Chem. 263 (32), 17100-17105 (1988);





Churchill, M. E., et al., J. Mol. Biol. 241





(4), 534-556 (1994), NCBI Accession





#LFRG_L


INFL650
Light chain
Fab 3.1
Wyrzucki, A. et al., Alternative
4787





Recognition of the Conserved Stem





Epitope in Influenza A Virus





Hemagglutinin by a VH3-30-Encoded





Heterosubtypic Antibody; J. Virol. 88





(12), 7083-7092 (2014), NCBI Accession





#4PY8_J


INFL651
Light chain
Fab 2g1
Xu, R. et al., A recurring motif for
4788





antibody recognition of the receptor-





binding site of influenza hemagglutinin;





Nat. Struct. Mol. Biol. 20 (3), 363-370





(2013), NCBI Accession #4HG4_M





(214aa)


INFL652
Light chain
Fab 8m2
Xu, R. et al., A recurring motif for
4789





antibody recognition of the receptor-





binding site of influenza hemagglutinin;





Nat. Struct. Mol. Biol. 20 (3), 363-370





(2013), NCBI Accession #4HFU_L





(215aa)


INFL653
Light chain
Fab 8f8
Xu, R. et al., A recurring motif for
4790





antibody recognition of the receptor-





binding site of influenza hemagglutinin;





Nat. Struct. Mol. Biol. 20 (3), 363-370





(2013), NCBI Accession # 4HF5_L





(218aa)


INFL654
Light chain
Fab 2d1
Xu, R., et al., Structural basis of
4791





preexisting immunity to the 2009 H1N1





pandemic influenza virus; Science 328





(5976), 357-360 (2010), NCBI Accession





#3LZF_L (217aa)


INFL655
Light chain
Fi6v3
Corti, D. et al., A neutralizing antibody
4792





selected from plasma cells that binds to





group 1 and group 2 influenza A





hemagglutinins; Science 333 (6044),





850-856 (2011), NCBI Accession





#3ZTN_L


INFL656
Light chain
Light chain from
Iba, Y., et al., Conserved Neutralizing
4793




3WHE_N
Epitope at Globular Head of





Hemagglutinin in H3N2 Influenza





Viruses; J. Virol. (2014), NCBI





Accession #3WHE_N (220aa)


INFL657
Light chain
monoclonal
Burioni, R. et al., Monoclonal antibodies
4794



(partial)
antibody PN-
isolated from human B cells neutralize a




SIA28
broad range of H1 subtype influenza A





viruses including swine-origin Influenza





virus(S-OIV); Virology (2010), NCBI





Accession #ACX30939.1 (105aa)


INFL658
Light chain
monoclonal
Burioni, R. et al., Monoclonal antibodies
4795



(partial)
antibody PN-
isolated from human B cells neutralize a




SIA49
broad range of H1 subtype influenza A





viruses including swine-origin Influenza





virus(S-OIV); Virology (2010), NCBI





Accession #ACX30938.1 (105aa)


INFL659
Light chain; Fab
5j8
Hong, M. et al., Antibody Recognition of
4796





the Pandemic H1N1 Influenza Virus





Hemagglutinin Receptor Binding Site; J.





Virol. 87 (22), 12471-12480 (2013),





NCBI Accession #4M5Z_L


INFL660
Light chain CDR 1
Ab1A2
WO2015028478 SEQ ID 9
4797


INFL661
Light chain CDR 2
Ab1A2
WO2015028478 SEQ ID 10
4798


INFL662
Light chain CDR 3
Ab1A2
WO2015028478 SEQ ID 11
4799


INFL663
Light chain Fab
CT147
WO2013048153, US20140234336 SEQ
4800





ID NO: 37


INFL664
Light chain Fab
CT164
WO2013048153, US20140234336 SEQ
4801





ID NO: 41


INFL665
Light chain Fab
CT166
WO2013048153, US20140234336 SEQ
4802





ID NO: 43


INFL666
Light chain Human
Fab 39.29
Nakamura, G. et al., An in vivo human-
4803



igg

plasmablast enrichment technique allows





rapid identification of therapeutic





influenza a antibodies; Cell Host





Microbe 14 (1), 93-103 (2013), NCBI





Accession #4KVN_L (215aa)


INFL667
Light chain K3
h2B11
U.S. Pat. No. 9,115,201 SEQ ID NO: 9
4804


INFL668
Light chain K3
h2B12
U.S. Pat. No. 9,115,201 SEQ ID NO: 10
4805


INFL669
Light chain partial
4A10
Krause, J. C. et al. “Epitope-specific
4806



region

human influenza antibody repertoires





diversify by B cell intraclonal sequence





divergence and interclonal convergence”





J. Immunol. 187 (7), 3704-3711 (2011),





NCBI Accession #AEO16798


INFL670
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 33
4807



(exemplary)
US2013030234


INFL671
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 34
4808



(exemplary)
US2013030234


INFL672
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 35
4809



(exemplary)
US2013030234


INFL673
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 36
4810



(exemplary)
US2013030234


INFL674
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 37
4811



(exemplary)
US2013030234


INFL675
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 38
4812



(exemplary)
US2013030234


INFL676
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 39
4813



(exemplary)
US2013030234


INFL677
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 40
4814



(exemplary)
US2013030234


INFL678
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 41
4815



(exemplary)
US2013030234


INFL679
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 42
4816



(exemplary)
US2013030234


INFL680
Light chain variable
LC-VD from
US2013030234 SEQ ID NO: 43
4817



(exemplary)
US2013030234


INFL681
Light chain variable
39.18 B11
US20140161822 SEQ ID NO: 156
4818



region


INFL682
Light chain variable
GG3
WO2014159960 SEQ ID NO: 25
4819



region


INFL683
Light chain variable
N547
U.S. Pat. No. 8,003,106 SEQ ID NO: 29
4820



region


INFL684
Light chain variable
L66
U.S. Pat. No. 8,003,106 SEQ ID NO: 31
4821



region


INFL685
Light chain variable
C40
U.S. Pat. No. 8,003,106 SEQ ID NO: 27
4822



region


INFL686
Light chain variable
14C2
U.S. Pat. No. 8,080,244 SEQ ID NO: 7
4823



region


INFL687
Light chain variable
h14C2
U.S. Pat. No. 8,080,244 SEQ ID NO: 1
4824



region


INFL688
Light chain variable
VN04-2-HuG1
US20100150941 SEQ ID NO: 6
4825



region


INFL689
Light chain variable
VN04-3-HuG1
US20100150941 SEQ ID NO: 8
4826



region


INFL690
Light chain variable
FI6 variant 1, FI6
U.S. Pat. No. 8,871,207 SEQ ID NO: 14
4827



region
variant 2


INFL691
Light chain variable
FI6 variant 3, FI6
U.S. Pat. No. 8,871,207 SEQ ID NO: 57
4828



region
variant 4


INFL692
Light chain variable
FI6 variant 5
U.S. Pat. No. 8,871,207 SEQ ID NO: 61
4829



region


INFL693
Light chain variable
FI28 vanant 1,
U.S. Pat. No. 8,871,207 SEQ ID NO: 30
4830



region
FI28 variant 2


INFL694
Light chain variable
21B15
U.S. Pat. No. 8,858,948 SEQ ID NO: 46
4831



region


INFL695
Light chain variable
3241_G23
U.S. Pat. No. 8,858,948 SEQ ID NO: 118
4832



region


INFL696
Light chain variable
3244_I10
U.S. Pat. No. 8,858,948 SEQ ID NO: 122
4833



region


INFL697
Light chain variable
3243_J07
U.S. Pat. No. 8,858,948 SEQ ID NO: 126
4834



region


INFL698
Light chain variable
3259_J21
U.S. Pat. No. 8,858,948 SEQ ID NO: 130
4835



region


INFL699
Light chain variable
3245_O19
U.S. Pat. No. 8,858,948 SEQ ID NO: 134
4836



region


INFL700
Light chain variable
3244_H04
U.S. Pat. No. 8,858,948 SEQ ID NO: 138
4837



region


INFL701
Light chain variable
3136_G05
U.S. Pat. No. 8,858,948 SEQ ID NO: 142
4838



region


INFL702
Light chain variable
3252_C13
U.S. Pat. No. 8,858,948 SEQ ID NO: 146
4839



region


INFL703
Light chain variable
3255_J06
U.S. Pat. No. 8,858,948 SEQ ID NO: 150
4840



region


INFL704
Light chain variable
3420_I23
U.S. Pat. No. 8,858,948 SEQ ID NO: 154
4841



region


INFL705
Light chain variable
3248_P18
U.S. Pat. No. 8,858,948 SEQ ID NO: 160
4842



region


INFL706
Light chain variable
3253_P10
U.S. Pat. No. 8,858,948 SEQ ID NO: 164
4843



region


INFL707
Light chain variable
3260_D19
U.S. Pat. No. 8,858,948 SEQ ID NO: 168
4844



region


INFL708
Light chain variable
3362_B11
U.S. Pat. No. 8,858,948 SEQ ID NO: 174
4845



region


INFL709
Light chain variable
3242_P05
U.S. Pat. No. 8,858,948 SEQ ID NO: 178
4846



region


INFL710
Light chain variable
A66
WO2009079259, US20110038935,
4847



region

US20140011982 SEQ ID NO: 34


INFL711
Light chain variable
D7, H98
WO2009079259, US20110038935,
4848



region

US20140011982 SEQ ID NO: 8


INFL712
Light chain variable
D8
WO2009079259, US20110038935,
4849



region

US20140011982 SEQ ID NO: 14


INFL713
Light chain variable
D80
WO2009079259, US20110038935,
4850



region

US20140011982 SEQ ID NO: 16


INFL714
Light chain variable
E88
WO2009079259, US20110038935,
4851



region

US20140011982 SEQ ID NO: 38


INFL715
Light chain variable
E90
WO2009079259, US20110038935,
4852



region

US20140011982 SEQ ID NO: 22


INFL716
Light chain variable
F10
WO2009079259, US20110038935,
4853



region

US20140011982 SEQ ID NO: 20


INFL717
Light chain variable
G17
WO2009079259, US20110038935,
4854



region

US20140011982 SEQ ID NO: 26


INFL718
Light chain variable
H40
WO2009079259, US20110038935,
4855



region

US20140011982 SEQ ID NO: 30


INFL719
Light chain variable
H98
WO2009079259, US20110038935,
4856



region

US20140011982 SEQ ID NO: 10


INFL720
Light chain variable
CH65
WO2013020074, US20140302043 SEQ
4857



region

ID NO: 10


INFL721
Light chain variable
CH66
WO2013020074, US20140302043 SEQ
4858



region

ID NO: 11


INFL722
Light chain variable
CH67
WO2013020074, US20140302043 SEQ
4859



region

ID NO: 12


INFL723
Light chain variable
CL86OUCA
WO2013020074, US20140302043 SEQ
4860



region

ID NO: 9


INFL724
Light chain variable
Antibody 1
WO2015051010 SEQ ID NO: 7
4861



region


INFL725
Light chain variable
Antibody 2
WO2015051010 SEQ ID NO: 17
4862



region


INFL726
Light chain variable
Antibody 3
WO2015051010 SEQ ID NO: 27
4863



region


INFL727
Light chain variable
Antibody 4
WO2015051010 SEQ ID NO: 37
4864



region


INFL728
Light chain variable
Antibody 5
WO2015051010 SEQ ID NO: 47
4865



region


INFL729
Light chain variable
Antibody 6
WO2015051010 SEQ ID NO: 57
4866



region


INFL730
Light chain variable
Antibody 7
WO2015051010 SEQ ID NO: 67
4867



region


INFL731
Light chain variable
Antibody 8
WO2015051010 SEQ ID NO: 77
4868



region


INFL732
Light chain variable
Antibody 9
WO2015051010 SEQ ID NO: 87
4869



region


INFL733
Light chain variable
Antibody 10
WO2015051010 SEQ ID NO: 97
4870



region


INFL734
Light chain variable
Antibody 11
WO2015051010 SEQ ID NO: 107
4871



region


INFL735
Light chain variable
Antibody 12
WO2015051010 SEQ ID NO: 117
4872



region


INFL736
Light chain variable
Antibody 13
WO2015051010 SEQ ID NO: 127
4873



region


INFL737
Light chain variable
Antibody 14
WO2015051010 SEQ ID NO: 137
4874



region


INFL738
Light chain variable
Antibody 15
WO2015051010 SEQ ID NO: 147
4875



region


INFL739
Light chain variable
Antibody 3-GL
WO2015051010 SEQ ID NO: 157
4876



region


INFL740
Light chain variable
005-2G02
WO2013059524, US20140348851 SEQ
4877



region

ID NO: 11


INFL741
Light chain variable
005-2G02
WO2013059524, US20140348851 SEQ
4878



region

ID NO: 19


INFL742
Light chain variable
09-2A06
WO2013059524, US20140348851 SEQ
4879



region

ID NO: 31


INFL743
Light chain variable
09-2A06
WO2013059524, US20140348851 SEQ
4880



region

ID NO: 39


INFL744
Light chain variable
09-3A01
WO2013059524, US20140348851 SEQ
4881



region

ID NO: 51


INFL745
Light chain variable
09-3A01
WO2013059524, US20140348851 SEQ
4882



region

ID NO: 59


INFL746
Light chain variable
70-IF02
WO2012096994, US20140046039 SEQ
4883



region

ID NO: 21


INFL747
Light chain variable

US20120058124 SEQ ID NO: 15
4884



region


INFL748
Light chain variable

US20120058124 SEQ ID NO: 16
4885



region


INFL749
Light chain variable

US20120058124 SEQ ID NO: 17
4886



region


INFL750
Light chain variable

US20120058124 SEQ ID NO: 18
4887



region


INFL751
Light chain variable

US20120058124 SEQ ID NO: 19
4888



region


INFL752
Light chain variable

US20120058124 SEQ ID NO: 20
4889



region


INFL753
Light chain variable

US20120058124 SEQ ID NO: 21
4890



region


INFL754
Light chain variable

US20120058124 SEQ ID NO: 22
4891



region


INFL755
Light chain variable

US20120058124 SEQ ID NO: 23
4892



region


INFL756
Light chain variable

US20120058124 SEQ ID NO: 24
4893



region


INFL757
Light chain variable

US20120058124 SEQ ID NO: 25
4894



region


INFL758
Light chain variable

US20120058124 SEQ ID NO: 26
4895



region


INFL759
Light chain variable

US20120058124 SEQ ID NO: 70
4896



region


INFL760
Light chain variable
81.39
US20140161822, US20140248286,
4897



region

WO2014078268 SEQ ID NO: 113


INFL761
Light chain variable
81.39
US20140161822, US20140248286,
4898



region

WO2014078268 SEQ ID NO: 117


INFL762
Light chain variable
81.39
US20140161822, US20140248286,
4899



region

WO2014078268 SEQ ID NO: 119


INFL763
Light chain variable
81.39
US20140161822, US20140248286,
4900



region

WO2014078268 SEQ ID NO: 122


INFL764
Light chain variable
81.39
US20140161822, US20140248286,
4901



region

WO2014078268 SEQ ID NO: 124


INFL765
Light chain variable
81.39
US20140161822, US20140248286,
4902



region

WO2014078268 SEQ ID NO: 126


INFL766
Light chain variable
81.39
US20140161822, US20140248286,
4903



region

WO2014078268 SEQ ID NO: 128


INFL767
Light chain variable
81.39
US20140161822, US20140248286,
4904



region

WO2014078268 SEQ ID NO: 130


INFL768
Light chain variable
81.39
US20140161822, US20140248286,
4905



region

WO2014078268 SEQ ID NO: 132


INFL769
Light chain variable
39.29
US20140161822, US20140248286,
4906



region

WO2014078268 SEQ ID NO: 136


INFL770
Light chain variable
39.29
US20140161822, US20140248286,
4907



region

WO2014078268 SEQ ID NO: 140


INFL771
Light chain variable
39.29
US20140161822, US20140248286,
4908



region

WO2014078268 SEQ ID NO: 144


INFL772
Light chain variable
39.29
US20140161822, US20140248286,
4909



region

WO2014078268 SEQ ID NO: 146


INFL773
Light chain variable
39.29
US20140161822, US20140248286,
4910



region

WO2014078268 SEQ ID NO: 150


INFL774
Light chain variable
39.29
US20140161822, US20140248286,
4911



region

WO2014078268 SEQ ID NO: 152


INFL775
Light chain variable
36.89
US20140161822, US20140248286,
4912



region

WO2014078268 SEQ ID NO: 162


INFL776
Light chain variable
9.01F3
US20140161822, US20140248286,
4913



region

WO2014078268 SEQ ID NO: 166


INFL777
Light chain variable
23.06C2
US20140161822, US20140248286,
4914



region

WO2014078268 SEQ ID NO: 170


INFL778
Light chain variable
39.29
US20140161822, US20140248286,
4915



region

WO2014078268 SEQ ID NO: 235


INFL779
Light chain variable
F16 Variant 3
WO2013011347, US20140271655,
4916



region

U.S. Pat. No. 8,871,207 SEQ ID NO: 57


INFL780
Light chain variable
F16 Variant 5
WO2013011347, US20140271655,
4917



region

U.S. Pat. No. 8,871,207 SEQ ID NO: 61


INFL781
Light chain variable
FC41
WO2010010467 SEQ ID NO 61
4918



region


INFL782
Light chain variable
FE43
WO2010010467 SEQ ID NO 75
4919



region


INFL783
Light chain variable
FB75, FB110,
WO2010010467 SEQ ID NO 122
4920



region
FB177


INFL784
Light chain variable
FB17
WO2010010467 SEQ ID NO 106
4921



region


INFL785
Light chain variable
FC6
WO2010010467 SEQ ID NO 46
4922



region


INFL786
Light chain variable
FE53
WO2010010467 SEQ ID NO 90
4923



region


INFL787
Light chain variable
7A7
WO2010138564 SEQ ID NO: 7
4924



region


INFL788
Light chain variable
12DI
WO2010138564 SEQ ID NO: 13
4925



region


INFL789
Light chain variable
66A6
WO2010138564 SEQ ID NO: 17
4926



region


INFL790
Light chain variable
B-1
U.S. Pat. No. 8,975,378, US20110319600,
4927



region

WO2010073647 SEQ ID NO: 28


INFL791
Light chain variable
D1
U.S. Pat. No. 8,975,378, US20110319600,
4928



region

WO2010073647 SEQ ID NO: 30


INFL792
Light chain variable
E-2
U.S. Pat. No. 8,975,378, US20110319600,
4929



region

WO2010073647 SEQ ID NO: 32


INFL793
Light chain variable
B-3
U.S. Pat. No. 8,975,378, US20110319600,
4930



region

WO2010073647 SEQ ID NO: 34


INFL794
Light chain variable
5A7
WO2013114885, US20140377262 SEQ
4931



region

ID NO: 35


INFL795
Light chain variable
3A2
WO2013114885, US20140377262 SEQ
4932



region

ID NO: 39


INFL796
Light chain variable
10C4
WO2013114885, US20140377262 SEQ
4933



region

ID NO: 43


INFL797
Light chain variable
Fab49
WO2009144667, US20110076265 SEQ
4934



region

ID NO: 2


INFL798
Light chain variable
Fab28, IgG PN-
WO2009115972, WO2011117848,
4935



region
SIA28
US20110014187 SEQ ID NO: 2


INFL799
Light chain variable
TCN-522
US20120207760, U.S. Pat. No. 8,916,160 SEQ ID
4936



region

NO: 778; U.S. Pat. No. 8,900,590 SEQ ID NO: 33


INFL800
Light chain variable
CR8018
WO2010130636 SEQ ID NO: 24
4937



region


INFL801
Light chain variable
CR8019
WO2010130636 SEQ ID NO: 28
4938



region


INFL802
Light chain variable
CR8020
WO2010130636 SEQ ID NO: 32
4939



region


INFL803
Light chain variable
CR8021
WO2010130636 SEQ ID NO: 36
4940



region


INFL804
Light chain variable
CR8038
WO2010130636 SEQ ID NO: 40
4941



region


INFL805
Light chain variable
CR8039
WO2010130636 SEQ ID NO: 44
4942



region


INFL806
Light chain variable
CR8040
WO2010130636 SEQ ID NO: 48
4943



region


INFL807
Light chain variable
CR8041
WO2010130636 SEQ ID NO: 52
4944



region


INFL808
Light chain variable
CR8043
WO2010130636 SEQ ID NO: 56
4945



region


INFL809
Light chain variable
CR8049
WO2010130636 SEQ ID NO: 59
4946



region


INFL810
Light chain variable
CR8050
WO2010130636 SEQ ID NO: 63
4947



region


INFL811
Light chain variable
CR8052
WO2010130636 SEQ ID NO: 67
4948



region


INFL812
Light chain variable
CR8055
WO2010130636 SEQ ID NO: 71
4949



region


INFL813
Light chain variable
CR8057
WO2010130636 SEQ ID NO: 75
4950



region


INFL814
Light chain variable
CR8069
WO2010130636 SEQ ID NO: 79
4951



region


INFL815
Light chain variable
CR6255
US20090311265, U.S. Pat. No. 8,691,223,
4952



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 85


INFL816
Light chain variable
CR6257
US20090311265, U.S. Pat. No. 8,691,223,
4953



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 87


INFL817
Light chain variable
CR6260
US20090311265, U.S. Pat. No. 8,691,223,
4954



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 89


INFL818
Light chain variable
CR6261
US20090311265, U.S. Pat. No. 8,691,223,
4955



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 91


INFL819
Light chain variable
CR6262
US20090311265, U.S. Pat. No. 8,691,223,
4956



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 93


INFL820
Light chain variable
CR6268
US20090311265, U.S. Pat. No. 8,691,223,
4957



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 95


INFL821
Light chain variable
CR6307
US20090311265, U.S. Pat. No. 8,691,223,
4958



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 97


INFL822
Light chain variable
CR6310
US20090311265, U.S. Pat. No. 8,691,223,
4959



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 99


INFL823
Light chain variable
CR6314
US20090311265, U.S. Pat. No. 8,691,223,
4960



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 101


INFL824
Light chain variable
CR6323
US20090311265, U.S. Pat. No. 8,691,223,
4961



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 103


INFL825
Light chain variable
CR6325
US20090311265, U.S. Pat. No. 8,691,223,
4962



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 105


INFL826
Light chain variable
CR6331
US20090311265, U.S. Pat. No. 8,691,223,
4963



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 107


INFL827
Light chain variable
CR6344
US20090311265, U.S. Pat. No. 8,691,223,
4964



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 109


INFL828
Light chain variable
CR6141
US20090311265, U.S. Pat. No. 8,691,223,
4965



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 319


INFL829
Light chain variable
CR6272
US20090311265, U.S. Pat. No. 8,691,223,
4966



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 323


INFL830
Light chain variable
CR6296
US20090311265, U.S. Pat. No. 8,691,223,
4967



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 327


INFL831
Light chain variable
CR6301
US20090311265, U.S. Pat. No. 8,691,223,
4968



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 331


INFL832
Light chain variable
CR6327
US20090311265, U.S. Pat. No. 8,691,223,
4969



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 335


INFL833
Light chain variable
CR6328
US20090311265, U.S. Pat. No. 8,691,223,
4970



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 339


INFL834
Light chain variable
CR6329
US20090311265, U.S. Pat. No. 8,691,223,
4971



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 343


INFL835
Light chain variable
CR6332
US20090311265, U.S. Pat. No. 8,691,223,
4972



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 347


INFL836
Light chain variable
CR6334
US20090311265, U.S. Pat. No. 8,691,223,
4973



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 351


INFL837
Light chain variable
CR6336
US20090311265, U.S. Pat. No. 8,691,223,
4974



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 355


INFL838
Light chain variable
CR6339
US20090311265, U.S. Pat. No. 8,691,223,
4975



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 359


INFL839
Light chain variable
CR6342
US20090311265, U.S. Pat. No. 8,691,223,
4976



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 363


INFL840
Light chain variable
CR6343
US20090311265, U.S. Pat. No. 8,691,223,
4977



region

U.S. Pat. No. 9,109,017, WO2008028946 SEQ ID





NO: 367


INFL841
Light chain variable
CR9003
US20140120113 SEQ ID NO: 4
4978



region


INFL842
Light chain variable
CR9004
US20140120113 SEQ ID NO: 8
4979



region


INFL843
Light chain variable
CR9005
US20140120113 SEQ ID NO: 12
4980



region


INFL844
Light chain variable
CR9006
US20140120113 SEQ ID NO: 16
4981



region


INFL845
Light chain variable
CR9007
US20140120113 SEQ ID NO: 20
4982



region


INFL846
Light chain variable
CR9008
US20140120113 SEQ ID NO: 24
4983



region


INFL847
Light chain variable
CR9009
US20140120113 SEQ ID NO: 28
4984



region


INFL848
Light chain variable
CR9010
US20140120113 SEQ ID NO: 32
4985



region


INFL849
Light chain variable
CR9011
US20140120113 SEQ ID NO: 36
4986



region


INFL850
Light chain variable
CR9012
US20140120113 SEQ ID NO: 40
4987



region


INFL851
Light chain variable
CR9029
US20140120113 SEQ ID NO: 44
4988



region


INFL852
Light chain variable
CR9030
US20140120113 SEQ ID NO: 48
4989



region


INFL853
Light chain variable
CR9031
US20140120113 SEQ ID NO: 52
4990



region


INFL854
Light chain variable
CR9112
US20140120113 SEQ ID NO: 56
4991



region


INFL855
Light chain variable
CR9113
US20140120113 SEQ ID NO: 60
4992



region


INFL856
Light chain variable
CR9114
US20140120113 SEQ ID NO: 64
4993



region


INFL857
Light chain variable
CR8033
U.S. Pat. No. 8,852,595 SEQ ID NO: 73
4994



region


INFL858
Light chain variable
CR8059
U.S. Pat. No. 8,852,595 SEQ ID NO: 77
4995



region


INFL859
Light chain variable
CR8071
U.S. Pat. No. 8,852,595 SEQ ID NO: 79
4996



region


INFL860
Light chain variable
CR10051
U.S. Pat. No. 8,852,595 SEQ ID NO: 83
4997



region


INFL861
Light chain variable
CR10049
U.S. Pat. No. 8,852,595 SEQ ID NO: 87
4998



region


INFL862
Light chain variable
CR10023
U.S. Pat. No. 8,852,595 SEQ ID NO: 91
4999



region


INFL863
Light chain variable
CR10032
U.S. Pat. No. 8,852,595 SEQ ID NO: 95
5000



region


INFL864
Light chain variable
CR11035
U.S. Pat. No. 8,852,595 SEQ ID NO: 103
5001



region


INFL865
Light chain variable
CR11036
U.S. Pat. No. 8,852,595 SEQ ID NO: 107
5002



region


INFL866
Light chain variable
CR11038
U.S. Pat. No. 8,852,595 SEQ ID NO: 111
5003



region


INFL867
Light chain variable
CR11039
U.S. Pat. No. 8,852,595 SEQ ID NO: 115
5004



region


INFL868
Light chain variable
CR8031
U.S. Pat. No. 8,852,595 SEQ ID NO: 121
5005



region


INFL869
Light chain variable
CR8032
U.S. Pat. No. 8,852,595 SEQ ID NO: 125
5006



region


INFL870
Light chain variable
CR8034
U.S. Pat. No. 8,852,595 SEQ ID NO: 129
5007



region


INFL871
Light chain variable

U.S. Pat. No. 8,992,929 SEQ ID NO: 2
5008



region


INFL872
Light chain variable
M2e
U.S. Pat. No. 8,420,794 SEQ ID NO: 1
5009



region


INFL873
Light chain variable

U.S. Pat. No. 8,715,743, US20140275492 SEQ ID
5010



region

NO: 16


INFL874
Light chain variable

U.S. Pat. No. 8,715,743, US20140275492 SEQ ID
5011



region

NO: 19


INFL875
Light chain variable

U.S. Pat. No. 8,715,743, US20140275492 SEQ ID
5012



region

NO: 32


INFL876
Light chain variable
anti-1918 influenza
Yu, X., et al., Neutralizing antibodies
5013



region
HA Ig
derived from the B cells of 1918





influenza pandemic survivors; Nature





455 (7212), 532-536 (2008), NCBI





Accession #ACI04582.1 (121aa)


INFL877
Light chain variable
anti-1918 influenza
Yu, X., et al., Neutralizing antibodies
5014



region
HA Ig
derived from the B cells of 1918





influenza pandemic survivors; Nature





455 (7212), 532-536 (2008), NCBI





Accession #ACI04580.1 (118aa)


INFL878
Light chain variable
4D20
Yu, X. et al “Neutralizing antibodies
5015



region

derived from the B cells of 1918





influenza pandemic survivors”, Nature





455 (7212), 532-536, NCBI Accession





#ACI04580


INFL879
Light chain variable
2B12
Yu, X. et al “Neutralizing antibodies
5016



region

derived from the B cells of 1918





influenza pandemic survivors”, Nature





455 (7212), 532-536, NCBI Accession





#ABY48869


INFL880
Light chain variable
TCN-535
US20150086555 SEQ ID NO: 180
5017



region
(5246_P19)


INFL881
Light chain variable
TCN-536
US20150086555 SEQ ID NO: 191
5018



region
(5095_N01)


INFL882
Light chain variable
TCN-537
US20150086555 SEQ ID NO: 202
5019



region
(3194_D21)


INFL883
Light chain variable
TCN-538
US20150086555 SEQ ID NO: 214
5020



region
(3206_O17)


INFL884
Light chain variable
TCN-539
US20150086555 SEQ ID NO: 226
5021



region
(5056_A08)


INFL885
Light chain variable
TCN-540
US20150086555 SEQ ID NO: 238
5022



region
(5060_F05)


INFL886
Light chain variable
TCN-541
US20150086555 SEQ ID NO: 250
5023



region
(5062_M11)


INFL887
Light chain variable
TCN-542
US20150086555 SEQ ID NO: 262
5024



region
(5079_A16)


INFL888
Light chain variable
TCN-543
US20150086555 SEQ ID NO: 274
5025



region
(5081_G23)


INFL889
Light chain variable
TCN-544
US20150086555 SEQ ID NO: 286
5026



region
(5082_A19)


INFL890
Light chain variable
TCN-545
US20150086555 SEQ ID NO: 298
5027



region
(5082_I15)


INFL891
Light chain variable
TCN-546
US20150086555 SEQ ID NO: 309
5028



region
(5089_L08)


INFL892
Light chain variable
TCN-547
US20150086555 SEQ ID NO: 320
5029



region
(5092_F11)


INFL893
Light chain variable
TCN-548
US20150086555 SEQ ID NO: 331
5030



region
(5092_P01)


INFL894
Light chain variable
TCN-549
US20150086555 SEQ ID NO: 342
5031



region
(5092_P04)


INFL895
Light chain variable
TCN-550
US20150086555 SEQ ID NO: 353
5032



region
(5096_F06)


INFL896
Light chain variable
TCN-551
US20150086555 SEQ ID NO: 365
5033



region
(5243_D01)


INFL897
Light chain variable
TCN-552
US20150086555 SEQ ID NO: 377
5034



region
(5249_I23)


INFL898
Light chain variable
TCN-553
US20150086555 SEQ ID NO: 389
5035



region
(5261_C18)


INFL899
Light chain variable
TCN-554
US20150086555 SEQ ID NO: 399
5036



region
(5277_M05)


INFL900
Light chain variable
TCN-555
US20150086555 SEQ ID NO: 405
5037



region
(5246_L16)


INFL901
Light chain variable
TCN-556
US20150086555 SEQ ID NO: 415
5038



region
(5089_K12)


INFL902
Light chain variable
TCN-557
US20150086555 SEQ ID NO: 427
5039



region
(5081_A04)


INFL903
Light chain variable
TCN-559
US20150086555 SEQ ID NO: 441
5040



region
(5097_G08)


INFL904
Light chain variable
TCN-560
US20150086555 SEQ ID NO: 453
5041



region
(5084_P10)


INFL905
Light chain variable
TCN-564
US20150086555 SEQ ID NO: 519
5042



region
(5256_A17b)


INFL906
Light chain variable
CR8001
WO2010130636 SEQ ID NO: 4
5043



region


INFL907
Light chain variable
CR8003
WO2010130636 SEQ ID NO: 8
5044



region


INFL908
Light chain variable
CR8015
WO2010130636 SEQ ID NO: 12
5045



region


INFL909
Light chain variable
CR8016
WO2010130636 SEQ ID NO: 16
5046



region


INFL910
Light chain variable
CR8017
WO2010130636 SEQ ID NO: 20
5047



region


INFL911
Light chain variable
TCN-522
US20150086555 SEQ ID NO: 40
5048



region
(3212_I12)


INFL912
Light chain variable
TCN-521
US20150086555 SEQ ID NO: 28
5049



region
(3280_D18)


INFL913
Light chain variable
TCN-523
US20150086555 SEQ ID NO: 52
5050



region
(5248_A17),




TCN-533




(5256_A17a),




TCN-534




(5249_B02)


INFL914
Light chain variable
TCN-563
US20150086555 SEQ ID NO: 64
5051



region
(5237_B21)


INFL915
Light chain variable
TCN-526
US20150086555 SEQ ID NO: 76
5052



region
(5084_C17)


INFL916
Light chain variable
TCN-527
US20150086555 SEQ ID NO: 88
5053



region
(5086_C06)


INFL917
Light chain variable
TCN-528
US20150086555 SEQ ID NO: 100
5054



region
(5087_P17)


INFL918
Light chain variable
TCN-529
US20150086555 SEQ ID NO: 112
5055



region
(5297_H01)


INFL919
Light chain variable
TCN-530
US20150086555 SEQ ID NO: 124
5056



region
(5248_H10),




TCN-558




(5248_H10b)


INFL920
Light chain variable
TCN-531
US20150086555 SEQ ID NO: 136
5057



region
(5091_H13)


INFL921
Light chain variable
TCN-532
US20150086555 SEQ ID NO: 148
5058



region
(5262_H18)


INFL922
Light chain variable
TCN-534
US20150086555 SEQ ID NO: 168
5059



region
(5249_B02)


INFL923
Light chain variable
TCN-504
US20150086555 SEQ ID NO: 524
5060



region
(3251_K17)


INFL924
Light chain variable
AB1
US20120093834, WO2009121004 SEQ
5061



region

ID NO: 71


INFL925
Light chain variable
AB2
US20120093834, WO2009121004 SEQ
5062



region

ID NO: 140


INFL926
Light chain variable
AB3
US20120093834, WO2009121004 SEQ
5063



region

ID NO: 81


INFL927
Light chain variable
AB4
US20120093834, WO2009121004 SEQ
5064



region

ID NO: 158


INFL928
Light chain variable
AB5
US20120093834, WO2009121004 SEQ
5065



region

ID NO: 159


INFL929
Light chain variable
AB6
US20120093834, WO2009121004 SEQ
5066



region

ID NO: 160


INFL930
Light chain variable
VN04-2
WO2008033105 SEQ ID NO: 6
5067



region


INFL931
Light chain variable
VN04-3
WO2008033105 SEQ ID NO: 8
5068



region


INFL932
Light chain variable
1286-C05
WO2010132604, US20120128671 SEQ
5069



region

ID NO: 3


INFL933
Light chain variable
1286-C05
WO2010132604, US20120128671 SEQ
5070



region

ID NO: 4


INFL934
Light chain variable
1286-C05
WO2010132604, US20120128671 SEQ
5071



region

ID NO: 5


INFL935
Light chain variable
1286-A11
WO2010132604, US20120128671 SEQ
5072



region

ID NO: 6


INFL936
Light chain variable
IA2
WO2015028478 SEQ ID NO: 3
5073



region mouse IgG


INFL937
Light chain variable
7B8
WO2015028478 SEQ ID NO: 5
5074



region mouse IgG


INFL938
Light chain variable
monoclonal
U.S. Pat. No. 8,900,590, US2012039899, Grandea,
5075



region, partial
antibody TCN-031
A. G. et al., Human antibodies reveal a





protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Set. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23871.1





(106aa)


INFL939
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5076



region, partial
antibody TCN-032
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23870.1





(107aa)


INFL940
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5077



region, partial
antibody 3362_B11
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession # ADK23886.1





(107aa)


INFL941
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5078



region, partial
antibody
reveal a protective epitope that is highly




3260_D19
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23885.1





(106aa)


INFL942
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5079



region, partial
antibody 3253_P10
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession





#ADK23884.1(107aa)


INFL943
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5080



region, partial
antibody 3248_P18
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23883.1





(106aa)


INFL944
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5081



region, partial
antibody 3139_P23
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession





#ADK23882.1(107aa)


INFL945
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5082



region, partial
antibody 3420_I23
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession





#ADK23881.1(108aa)


INFL946
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5083



region, partial
antibody 3255_J06
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession





#ADK23880.1(108aa)


INFL947
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5084



region, partial
antibody 3252_C13
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23879.1





(108aa)


INFL948
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5085



region, partial
antibody
reveal a protective epitope that is highly




3136_G05
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23878.1





(108aa)


INFL949
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5086



region, partial
antibody
reveal a protective epitope that is highly




3244_H04
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23877.1





(107aa)


INFL950
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5087



region, partial
antibody
reveal a protective epitope that is highly




3245_O19
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23876.1





(107aa)


INFL951
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5088



region, partial
antibody 3259_J21
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23875.1





(107aa)


INFL952
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5089



region, partial
antibody 3243_J07
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23874.1





(108aa)


INFL953
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5090



region, partial
antibody 3244_I10
reveal a protective epitope that is highly





conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23873.1





(108aa)


INFL954
Light chain variable
monoclonal
Grandea, A. G. et al., Human antibodies
5091



region, partial
antibody
reveal a protective epitope that is highly




3241_G23
conserved among human and nonhuman





influenza A viruses; Proc. Natl. Acad.





Sci. U.S.A. 107 (28), 12658-12663





(2010), NCBI Accession #ADK23872.1





(108aa)


INFL955
Light chain variable
100F4-LV
Hu, H., et al., A Human Antibody
5092



region, partial

Recognizing a Conserved Epitope of H5





Hemagglutinin Broadly Neutralizes





Highly Pathogenic Avian Influenza





H5N1 Viruses; J. Virol. 86 (6), 2978-





2989 (2012), NCBI Accession





#AEL30604.1 (112aa)


INFL956
Light Chain, Fab
ch65
Whittle, J. R. et al., Broadly neutralizing
5093



Fragment

human antibody that recognizes the





receptor-binding pocket of influenza





virus hemagglutinin; Proc. Natl. Acad.





Sci. U.S.A. 108 (34), 14216-14221





(2011), NCBI Accession #3SM5_L


INFL957
Light chain
1I20
WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
5094





NO: 6


INFL958
Light chain

WO2010127252, U.S. Pat. No. 8,894,997 SEQ ID
5095





NO: 12


INFL959
Monoclonal antibody
Neutralizing
Wu, Y. et al., A potent broad-spectrum
5096



heavy chain
Human
protective human monoclonal antibody




Monoclonal
crosslinking two hemagglutinin




Antibody With
monomers of influenza A virus; Nat




1968 H3 Ha
Commun 6, 7708 (2015), NCBI





Accession #4UBD_C


INFL960
Monoclonal antibody
Neutralizing
Wu, Y. et al., A potent broad-spectrum
5097



light chain
Human
protective human monoclonal antibody




Monoclonal
crosslinking two hemagglutinin




Antibody With
monomers of influenza A virus; Nat




1968 H3 Ha
Commun 6, 7708 (2015), NCBI





Accession #4UBD_D


INFL961
Mutated heavy chain
8G9 mutated
U.S. Pat. No. 8,603,467 SEQ ID NO: 42
5098



variable


INFL962
Mutated heavy chain
13D4 mutated
U.S. Pat. No. 8,603,467 SEQ ID NO: 46
5099



variable (VH-LV)


INFL963
Mutated heavy chain
13D4 mutated
U.S. Pat. No. 8,603,467 SEQ ID NO: 44
5100



variable (VH-SV)


INFL964
Nanobody
202-C8
US20110182897, WO2009147248 SEQ
5101





ID NO: 138


INFL965
Nanobody
203-B12
US20110182897, WO2009147248 SEQ
5102





ID NO: 2439


INFL966
Nanobody
203-H9
US20110182897, WO2009147248 SEQ
5103





ID NO: 2445


INFL967
Scfv
JM7_B-G7
WO2012072788 SEQ ID NO: 7
5104


INFL968
Scfv
JM7_S-F8
WO2012072788 SEQ ID NO: 15
5105


INFL969
Scfv
JM7JH-F1
WO2012072788 SEQ ID NO: 17
5106


INFL970
Scfv
JM7_S-A9
WO2012072788 SEQ ID NO: 19
5107


INFL971
Scfv
JM7_S-A10
WO2012072788 SEQ ID NO: 21
5108


INFL972
Scfv
JM7_B-H
WO2012072788 SEQ ID NO: 23
5109


INFL973
Scfv
JM6_SC-H1
WO2012072788 SEQ ID NO: 25
5110


INFL974
Scfv
jM6_SC_D3
WO2012072788 SEQ ID NO: 27
5111


INFL975
Scfv
H2526
Schmidt, A. G. et al., Viral receptor-
5112





binding site antibodies with diverse





germline origins; Cell 161 (5), 1026-





1034 (2015), NCBI Accession #4YJZ_L


INFL976
Scfv fragment
AVC4
WO2010040572A2 FIG. 6
5113


INFL977
Scfv fragment
AVD1
WO2010040572A2 FIG. 8
5114


INFL978
Scfv fragment
AVE2
WO2010040572A2 FIG. 10
5115


INFL979
Scfv fragment
AVA6
WO2010040572A2 FIG. 12
5116


INFL980
Scfv fragment
AVG4
WO2010040572A2 FIG. 14
5117


INFL981
Scfv heavy chain
SC06-141
US20150104459 SEQ ID NO: 309
5118



variable region


INFL982
Scfv heavy chain
SC06-255
US20150104459 SEQ ID NO: 313
5119



variable region


INFL983
Scfv heavy chain
SC06-257
US20150104459 SEQ ID NO: 317
5120



variable region


INFL984
Scfv heavy chain
SC6-260
US20150104459 SEQ ID NO: 321
5121



variable region


INFL985
Scfv heavy chain
SC06-261
US20150104459 SEQ ID NO: 325
5122



variable region


INFL986
Scfv heavy chain
SC06-262
US20150104459 SEQ ID NO: 329
5123



variable region


INFL987
Scfv heavy chain
SC06-268
US20150104459 SEQ ID NO: 333
5124



variable region


INFL988
Scfv heavy chain
SC06-272
US20150104459 SEQ ID NO: 337
5125



variable region


INFL989
Scfv heavy chain
SC06-296
US20150104459 SEQ ID NO: 341
5126



variable region


INFL990
Scfv heavy chain
SC06-301
US20150104459 SEQ ID NO: 345
5127



variable region


INFL991
Scfv heavy chain
SC06-307
US20150104459 SEQ ID NO: 349
5128



variable region


INFL992
Scfv heavy chain
SC06-310
US20150104459 SEQ ID NO: 353
5129



variable region


INFL993
Scfv heavy chain
SC06-314
US20150104459 SEQ ID NO: 357
5130



variable region


INFL994
Scfv heavy chain
SC06-323
US20150104459 SEQ ID NO: 361
5131



variable region


INFL995
Scfv heavy chain
SC06-325
US20150104459 SEQ ID NO: 365
5132



variable region


INFL996
Scfv heavy chain
SC06-327
US20150104459 SEQ ID NO: 369
5133



variable region


INFL997
Scfv heavy chain
SC06-328
US20150104459 SEQ ID NO: 373
5134



variable region


INFL998
Scfv heavy chain
SC06-329
US20150104459 SEQ ID NO: 377
5135



variable region


INFL999
Scfv heavy chain
SC06-331
US20150104459 SEQ ID NO: 381
5136



variable region


INFL1000
Scfv heavy chain
SC06-332
US20150104459 SEQ ID NO: 385
5137



variable region


INFL1001
Scfv heavy chain
SC06-334
US20150104459 SEQ ID NO: 389
5138



variable region


INFL1002
Scfv heavy chain
SC06-336
US20150104459 SEQ ID NO: 393
5139



variable region


INFL1003
Scfv heavy chain
SC06-339
US20150104459 SEQ ID NO: 397
5140



variable region


INFL1004
Scfv heavy chain
SC06-342
US20150104459 SEQ ID NO: 401
5141



variable region


INFL1005
Scfv heavy chain
SC06-343
US20150104459 SEQ ID NO: 405
5142



variable region


INFL1006
Scfv heavy chain
SC06-344
US20150104459 SEQ ID NO: 409
5143



variable region


INFL1007
Scfv heavy chain
CR6255
US20150104459 SEQ ID NO: 417
5144



variable region


INFL1008
Scfv heavy chain
CR6257
US20150104459 SEQ ID NO: 423
5145



variable region


INFL1009
Scfv heavy chain
CR6260
US20150104459 SEQ ID NO: 429
5146



variable region


INFL1010
Scfv heavy chain
CR6261
US20150104459 SEQ ID NO: 435
5147



variable region


INFL1011
Scfv heavy chain
CR6262
US20150104459 SEQ ID NO: 441
5148



variable region


INFL1012
Scfv heavy chain
CR6268
US20150104459 SEQ ID NO: 447
5149



variable region


INFL1013
Scfv heavy chain
CR6272
US20150104459 SEQ ID NO: 453
5150



variable region


INFL1014
Scfv heavy chain
CR696
US20150104459 SEQ ID NO: 459
5151



variable region


INFL1015
Scfv heavy chain
CR6301
US20150104459 SEQ ID NO: 465
5152



variable region


INFL1016
Scfv heavy chain
CR6307
US20150104459 SEQ ID NO: 471
5153



variable region


INFL1017
Scfv heavy chain
CR6310
US20150104459 SEQ ID NO: 477
5154



variable region


INFL1018
Scfv heavy chain
CR6314
US20150104459 SEQ ID NO: 483
5155



variable region


INFL1019
Scfv heavy chain
CR6323
US20150104459 SEQ ID NO: 489
5156



variable region


INFL1020
Scfv heavy chain
CR6325
US20150104459 SEQ ID NO: 495
5157



variable region


INFL1021
Scfv heavy chain
CR6327
US20150104459 SEQ ID NO: 501
5158



variable region


INFL1022
Scfv heavy chain
CR6328
US20150104459 SEQ ID NO: 507
5159



variable region


INFL1023
Scfv heavy chain
CR6329
US20150104459 SEQ ID NO: 513
5160



variable region


INFL1024
Scfv heavy chain
CR6331
US20150104459 SEQ ID NO: 519
5161



variable region


INFL1025
Scfv heavy chain
CR6332
US20150104459 SEQ ID NO: 525
5162



variable region


INFL1026
Scfv heavy chain
CR6334
US20150104459 SEQ ID NO: 531
5163



variable region


INFL1027
Scfv heavy chain
CR6336
US20150104459 SEQ ID NO: 537
5164



variable region


INFL1028
Scfv heavy chain
CR6339
US20150104459 SEQ ID NO: 543
5165



variable region


INFL1029
Scfv heavy chain
CR6342
US20150104459 SEQ ID NO: 550
5166



variable region


INFL1030
Scfv heavy chain
CR6343
US20150104459 SEQ ID NO: 556
5167



variable region


INFL1031
Scfv heavy chain
CR6344
US20150104459 SEQ ID NO: 562
5168



variable region


INFL1032
Scfv light chain
SC06-141
US20150104459 SEQ ID NO: 310
5169



variable region


INFL1033
Scfv light chain
SC06-255
US20150104459 SEQ ID NO: 314
5170



variable region


INFL1034
Scfv light chain
SC06-257
US20150104459 SEQ ID NO: 318
5171



variable region


INFL1035
Scfv light chain
SC6-260
US20150104459 SEQ ID NO: 322
5172



variable region


INFL1036
Scfv light chain
SC06-261
US20150104459 SEQ ID NO: 326
5173



variable region


INFL1037
Scfv light chain
SC06-262
US20150104459 SEQ ID NO: 330
5174



variable region


INFL1038
Scfv light chain
SC06-268
US20150104459 SEQ ID NO: 334
5175



variable region


INFL1039
Scfv light chain
SC06-272
US20150104459 SEQ ID NO: 338
5176



variable region


INFL1040
Scfv light chain
SC06-296
US20150104459 SEQ ID NO: 342
5177



variable region


INFL1041
Scfv light chain
SC06-301
US20150104459 SEQ ID NO: 346
5178



variable region


INFL1042
Scfv light chain
SC06-307
US20150104459 SEQ ID NO: 350
5179



variable region


INFL1043
Scfv light chain
SC06-310
US20150104459 SEQ ID NO: 354
5180



variable region


INFL1044
Scfv light chain
SC06-314
US20150104459 SEQ ID NO: 358
5181



variable region


INFL1045
Scfv light chain
SC06-323
US20150104459 SEQ ID NO: 362
5182



variable region


INFL1046
Scfv light chain
SC06-325
US20150104459 SEQ ID NO: 366
5183



variable region


INFL1047
Scfv light chain
SC06-327
US20150104459 SEQ ID NO: 370
5184



variable region


INFL1048
Scfv light chain
SC06-328
US20150104459 SEQ ID NO: 374
5185



variable region


INFL1049
Scfv light chain
SC06-329
US20150104459 SEQ ID NO: 378
5186



variable region


INFL1050
Scfv light chain
SC06-331
US20150104459 SEQ ID NO: 382
5187



variable region


INFL1051
Scfv light chain
SC06-332
US20150104459 SEQ ID NO: 386
5188



variable region


INFL1052
Scfv light chain
SC06-334
US20150104459 SEQ ID NO: 390
5189



variable region


INFL1053
Scfv light chain
SC06-336
US20150104459 SEQ ID NO: 394
5190



variable region


INFL1054
Scfv light chain
SC06-339
US20150104459 SEQ ID NO: 398
5191



variable region


INFL1055
Scfv light chain
SC06-342
US20150104459 SEQ ID NO: 402
5192



variable region


INFL1056
Scfv light chain
SC06-343
US20150104459 SEQ ID NO: 406
5193



variable region


INFL1057
Scfv light chain
SC06-344
US20150104459 SEQ ID NO: 410
5194



variable region


INFL1058
Scfv light chain
CR6141
US20150104459 SEQ ID NO: 414
5195



variable region


INFL1059
Scfv light chain
CR6255
US20150104459 SEQ ID NO: 420
5196



variable region


INFL1060
Scfv light chain
CR6257
US20150104459 SEQ ID NO: 426
5197



variable region


INFL1061
Scfv light chain
CR6260
US20150104459 SEQ ID NO: 432
5198



variable region


INFL1062
Scfv light chain
CR6261
US20150104459 SEQ ID NO: 438
5199



variable region


INFL1063
Scfv light chain
CR6262
US20150104459 SEQ ID NO: 444
5200



variable region


INFL1064
Scfv light chain
CR6268
US20150104459 SEQ ID NO: 450
5201



variable region


INFL1065
Scfv light chain
CR6272
US20150104459 SEQ ID NO: 456
5202



variable region


INFL1066
Scfv light chain
CR696
US20150104459 SEQ ID NO: 462
5203



variable region


INFL1067
Scfv light chain
CR6301
US20150104459 SEQ ID NO: 468
5204



variable region


INFL1068
Scfv light chain
CR6307
US20150104459 SEQ ID NO: 474
5205



variable region


INFL1069
Scfv light chain
CR6310
US20150104459 SEQ ID NO: 480
5206



variable region


INFL1070
Scfv light chain
CR6314
US20150104459 SEQ ID NO: 486
5207



variable region


INFL1071
Scfv light chain
CR6323
US20150104459 SEQ ID NO: 492
5208



variable region


INFL1072
Scfv light chain
CR6325
US20150104459 SEQ ID NO: 498
5209



variable region


INFL1073
Scfv light chain
CR6327
US20150104459 SEQ ID NO: 504
5210



variable region


INFL1074
Scfv light chain
CR6328
US20150104459 SEQ ID NO: 510
5211



variable region


INFL1075
Scfv light chain
CR6329
US20150104459 SEQ ID NO: 516
5212



variable region


INFL1076
Scfv light chain
CR6331
US20150104459 SEQ ID NO: 522
5213



variable region


INFL1077
Scfv light chain
CR6332
US20150104459 SEQ ID NO: 528
5214



variable region


INFL1078
Scfv light chain
CR6334
US20150104459 SEQ ID NO: 534
5215



variable region


INFL1079
Scfv light chain
CR6336
US20150104459 SEQ ID NO: 540
5216



variable region


INFL1080
Scfv light chain
CR6339
US20150104459 SEQ ID NO: 547
5217



variable region


INFL1081
Scfv light chain
CR6342
US20150104459 SEQ ID NO: 553
5218



variable region


INFL1082
Scfv light chain
CR6343
US20150104459 SEQ ID NO: 559
5219



variable region


INFL1083
Scfv light chain
CR6344
US20150104459 SEQ ID NO: 565
5220



variable region


INFL1084
Vhch antibody
641 I-9
Schmidt, A. G. et al., Viral receptor-
5221





binding site antibodies with diverse





germline origins; Cell 161 (5), 1026-





1034 (2015), NCBI Accession #4YK4_Z


INFL1085
Vlcl antibody
641 I-9
Schmidt, A. G. et al., Viral receptor-
5222





binding site antibodies with diverse





germline origins; Cell 161 (5), 1026-





1034 (2015), NCBI Accession #4YK4_Y









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in U.S. Pat. Nos. 8,003,106 and 8,540,995. International Patent Publication No. WO2015028478, WO02012045001. US Publication No. US20150239960 and US20130251715, the contents of each of which are herein incorporated by reference in their entirety, against influenza.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 22 against Respiratory Syncytial Virus.









TABLE 22







Antibodies against Respiratory Syncytial Virus











Antibody



SEQ ID


No.
Description
Antibody Name
Reference Information
NO





RSV1
Heavy chain variable, F and G
clone 888
US20110189171;
5223



Proteins

US7879329SEQ ID NO: 43



RSV2
Heavy chain variable, F and G
mAb 824
US20110189171; US7879329
5224



Proteins

SEQ ID NO: 178



RSV3
Heavy chain variable, F and G
clone 735
US20110189171; US7879329
5225



Proteins

SEQ ID NO: 1



RSV4
Heavy chain variable, F and G
clone 736
US20110189171; US7879329
5226



Proteins

SEQ ID NO: 2



RSV5
Heavy chain variable, F and G
clone 744
US20110189171; US7879329
5227



Proteins

SEQ ID NO: 3



RSV6
Heavy chain variable, F and G
clone 793
US20110189171; US7879329
5228



Proteins

SEQ ID NO: 4



RSV7
Heavy chain variable, F and G
clone 795
US20110189171; US7879329
5229



Proteins

SEQ ID NO: 5



RSV8
Heavy chain variable, F and G
clone 796
US2011018917; US7879329
5230



Proteins

SEQ ID NO: 6



RSV9
Heavy chain variable, F and G
clone 799
US20110189171; US7879329
5231



Proteins

SEQ ID NO: 7



RSV10
Heavy chain variable, F and G
clone 800
US20110189171; US7879329
5232



Proteins

SEQ ID NO: 8



RSV11
Heavy chain variable, F and G
clone 801
US20110189171; US7879329
5233



Proteins

SEQ ID NO: 9



RSV12
Heavy chain variable, F and G
clone 804
US20110189171; US7879329
5234



Proteins

SEQ ID NO: 10



RSV13
Heavy chain variable, F and G
clone 810
US20110189171; US7879329
5235



Proteins

SEQ ID NO: 11



RSV14
Heavy chain variable, F and G
clone 811
US20110189171; US7879329
5236



Proteins

SEQ ID NO: 12



RSV15
Heavy chain variable, F and G
clone 812
US20110189171; US7879329
5237



Proteins

SEQ ID NO: 13



RSV16
Heavy chain variable, F and G
clone 814
US20110189171; US7879329
5238



Proteins

SEQ ID NO: 14



RSV17
Heavy chain variable, F and G
clone 816
US20110189171; US7879329
5239



Proteins

SEQ ID NO: 15



RSV18
Heavy chain variable, F and G
clone 817
US20110189171; US7879329
5240



Proteins

SEQ ID NO: 16



RSV19
Heavy chain variable, F and G
clone 818
US20110189171; US7879329
5241



Proteins

SEQ ID NO: 17



RSV20
Heavy chain variable, F and G
clone 819
US20110189171; US7879329
5242



Proteins

SEQ ID NO: 18



RSV21
Heavy chain variable, F and G
clone 824
US20110189171; US7879329
5243



Proteins

SEQ ID NO: 19



RSV22
Heavy chain variable, F and G
clone 825
US20110189171; US7879329
5244



Proteins

SEQ ID NO: 20



RSV23
Heavy chain variable, F and G
clone 827
US20110189171; US7879329
5245



Proteins

SEQ ID NO: 21



RSV24
Heavy chain variable, F and G
clone 829
US20110189171; US7879329
5246



Proteins

SEQ ID NO: 22



RSV25
Heavy chain variable, F and G
clone 830
US20110189171; US7879329
5247



Proteins

SEQ ID NO: 23



RSV26
Heavy chain variable, F and G
clone 831
US20110189171; US7879329
5248



Proteins

SEQ ID NO: 24



RSV27
Heavy chain variable, F and G
clone 835
US20110189171; US7879329
5249



Proteins

SEQ ID NO: 25



RSV28
Heavy chain variable, F and G
clone 838
US20110189171; US7879329
5250



Proteins

SEQ ID NO: 26



RSV29
Heavy chain variable, F and G
clone 841
US20110189171; US7879329
5251



Proteins

SEQ ID NO: 27



RSV30
Heavy chain variable, F and G
clone 853
US20110189171; US7879329
5252



Proteins

SEQ ID NO: 28



RSV31
Heavy chain variable, F and G
clone 855
US20110189171; US7879329
5253



Proteins

SEQ ID NO: 29



RSV32
Heavy chain variable, F and G
clone 856
US20110189171; US7879329
5254



Proteins

SEQ ID NO: 30



RSV33
Heavy chain variable, F and G
clone 857
US20110189171; US7879329
5255



Proteins

SEQ ID NO: 31



RSV34
Heavy chain variable, F and G
clone 858
US20110189171; US7879329
5256



Proteins

SEQ ID NO: 32



RSV35
Heavy chain variable, F and G
clone 859
US20110189171; US7879329
5257



Proteins

SEQ ID NO: 33



RSV36
Heavy chain variable, F and G
clone 861
US20110189171; US7879329
5258



Proteins

SEQ ID NO: 34



RSV37
Heavy chain variable, F and G
clone 863
US20110189171; US7879329
5259



Proteins

SEQ ID NO: 35



RSV38
Heavy chain variable, F and G
clone 868
US20110189171; US7879329
5260



Proteins

SEQ ID NO: 36



RSV39
Heavy chain variable, F and G
clone 870
US20110189171; US7879329
5261



Proteins

SEQ ID NO: 37



RSV40
Heavy chain variable, F and G
clone 871
US20110189171; US7879329
5262



Proteins

SEQ ID NO: 38



RSV41
Heavy chain variable, F and G
clone 880
US20110189171; US7879329
5263



Proteins

SEQ ID NO: 39



RSV42
Heavy chain variable, F and G
clone 881
US20110189171; US7879329
5264



Proteins

SEQ ID NO: 40



RSV43
Heavy chain variable, F and G
clone 884
US20110189171; US7879329
5265



Proteins

SEQ ID NO: 41



RSV44
Heavy chain variable, F and G
clone 886
US20110189171; US7879329
5266



Proteins

SEQ ID NO: 42



RSV45
Heavy chain variable, F and G
clone 894
US20110189171; US7879329
5267



Proteins

SEQ ID NO: 44



RSV46
heavy chain variable, F protein
3210 variant 1
WO2013140247 SEQ ID NO:
5268



of RSV, MPV, or PVM

 13



RSV47
heavy chain variable, F protein
3210 variant 2,
WO2013140247 SEQ ID NO:
5269



of RSV, MPV, or PVM
3210 variant 3,
 17





3210 variant 6




RSV48
heavy chain variable, F protein
2430 variant 1
WO2013140247 SEQ ID NO:
5270



of RSV, MPV, or PVM

 29



RSV49
heavy chain variable, F protein
2430 variant 2,
WO2013140247 SEQ ID NO:
5271



of RSV, MPV, or PVM
2430 variant 5
 33



RSV50
heavy chain variable, F protein
3210 variant 4,
WO2013140247 SEQ ID NO:
5272



of RSV, MPV, or PVM
3210 variant 5
 49



RSV51
heavy chain variable, F protein
2430 variant 3,
WO2013140247 SEQ ID NO:
5273



of RSV, MPV, or PVM
2430 variant 4
 59



RSV52
Heavy chain variable, CDR

US20140093501 SEQ ID NO:
5274



Grafted, F Protein,

 31



RSV53
Heavy chain, F Protein
AM22
US8568726 SEQ ID NO: 16
5275


RSV54
Heavy chain, F Protein
RSVF2-5
US8221759 SEQ ID NO: 1
5276


RSV55
Heavy chain, F Protein

EP1259547; US8153133 SEQ
5277





ID NO: 4



RSV56
Heavy chain, F Protein
MEDI-
EP1259547; US8153133 SEQ
5278




493/Pavitizumab-
ID NO: 2





N-VL (Brand name






Synagis)




RSV57
Heavy chain, F Protein

EP1259547; US8153133 SEQ
5279





ID NO: 36



RSV58
Heavy chain, F Protein
clone 18
EP1259547; US8153133 SEQ
5280





ID NO: 37



RSV59
Heavy chain, F Protein
clone 19
EP1259547; US8153133 SEQ
5281





ID NO: 39



RSV60
Heavy chain, F Protein
clone 20
EP1259547; US8153133 SEQ
5282





ID NO: 41



RSV61
Heavy chain, F Protein
clone 21
EP1259547; US8153133 SEQ
5283





ID NO: 43



RSV62
Heavy chain, F Protein
clone 22
EP1259547; US8153133 SEQ
5284





ID NO: 45



RSV63
Heavy chain, F Protein
clone 23
EP1259547; US8153133 SEQ
5285





ID NO: 47



RSV64
Heavy chain, F Protein
clone 24
EP1259547; US8153133 SEQ
5286





ID NO: 49



RSV65
Heavy chain, F Protein
clone 25
EP1259547; US8153133 SEQ
5287





ID NO: 51



RSV66
Heavy chain, F Protein
clone 26
EP1259547; US8153133 SEQ
5288





ID NO: 53



RSV67
Heavy chain variable region, F

US20140093501 SEQ ID NO:
5289



Protein

 17



RSV68
Heavy chain variable region, F
MAb1308F
US20140093501 SEQ ID NO:
5290



Protein

 18



RSV69
Heavy chain variable region, F
huCOR
US20140093501 SEQ ID NO:
5291



Protein

 30



RSV70
Heavy chain variable region, F
MAb1129
US20140093501 SEQ ID NO:
5292



Protein

 32



RSV71
Heavy chain variable region, F
RSV G8
US7867497 SEQ ID NO: 2
5293



Protein





RSV72
Heavy chain variable region, F
Clone 1
US20120135006 SEQ ID NO:
5294



Protein

 18



RSV73
Heavy chain variable region, F
Clone 2
US20120135006 SEQ ID NO:
5295



Protein

 20



RSV74
Heavy chain variable region, F
Clone 3
US20120135006 SEQ ID NO:
5296



Protein

 22



RSV75
Heavy chain variable region, F
Clone 22
US20120135006 SEQ ID NO:
5297



Protein

 24



RSV76
Heavy chain variable region, F
Clone 23
US20120135006 SEQ ID NO:
5298



Protein

 26



RSV77
Heavy chain variable region, F
RSV13-9
WO2009088159 SEQ ID NO: 4
5299



Protein





RSV78
HV3 heavy chain variable, F

US20140093501 SEQ ID NO:
5300



Protein

 16



RSV79
Constant heavy region, F
B4HuVK
EP636182; WO1993020210;
5301



protein

SEQ ID NO: 6



RSV80
Constant heavy region, F
B13/B14HuVK
EP636182; WO1993020210;
5302



protein

SEQ ID NO: 8



RSV81
Heavy chain, F protein
58c5
US20140044719 SEQ ID NO: 1
5303


RSV82
Heavy chain, F protein
sc5
US20140044719 SEQ ID NO: 9
5304


RSV83
Heavy chain, F protein

US20110027294 SEQ ID NO:
5305





 74



RSV84
Heavy chain, F protein

US20110027294 SEQ ID NO:
5306





 75



RSV85
Heavy chain, F protein

US20110027294 SEQ ID NO:
5307





 76



RSV86
Heavy chain, F protein

US20110027294 SEQ ID NO:
5308





 77



RSV87
Heavy chain, F protein

US20110027294 SEQ ID NO:
5309





 78



RSV88
Heavy chain, F protein

US20110027294 SEQ ID NO:
5310





 79



RSV89
Heavy chain, F protein

US20110027294 SEQ ID NO:
531,1





 80



RSV90
Heavy chain, F protein
Gλ-1
US20050175986 SEQ ID NO: 5
5312


RSV91
Heavy chain, F protein
A construct
US20050175986 SEQ ID NO: 7
5313


RSV92
Heavy chain, F protein
B construct
US200501,75986 SEQ ID NO: 8
5314


RSV93
Heavy chain, F protein
hu19A
US20050019758;
5315





WO1998019704 SEQ ID NO: 5



RSV94
Heavy chain, F protein
hu19B
US20050019758;
5316





WO1998019704 SEQ ID NO: 6



RSV95
Heavy chain, F protein
hu19C
US20050019758;
5317





WO1998019704 SEQ ID NO: 7



RSV96
Heavy chain, F protein
hu19D
US20050019758;
5318





WO1998019704 SEQ ID NO: 8



RSV97
Heavy chain, F protein
B4HuVH
EP636182; WO1993020210;
5319





SEQ ID NO: 5



RSV98
Heavy chain, F protein
B13/B14HuVK
EP636182; WO1993020210;
5320





SEQ ID NO: 7



RSV99
Heavy chain, F protein
RSV19
EP636182; WO1993020210;
5321





SEQ ID NO: 10



RSV100
Heavy chain, F protein

WO19922004381
5322


RSV101
Heavy chain, F protein

WO19922004381
5323


RSV102
Heavy chain variable region, F
P1212
US20140044719 SEQ ID NO:
5324



Protein

 122



RSV103
Heavy chain variable region, F
P12f4
US20140044719 SEQ ID NO:
5325



Protein

 131



RSV104
Heavy chain variable region, F
P11d4
US20140044719 SEQ ID NO:
5326



Protein

 137



RSV105
Heavy chain variable region, F
A1e9
US20140044719 SEQ ID NO:
5327



Protein

 144



RSV106
Heavy chain variable region, F
A12a6
US20140044719 SEQ ID NO:
5328



Protein

 149



RSV107
Heavy chain variable region, F
A13c4
US20140044719 SEQ ID NO:
5329



Protein

 155



RSV108
Heavy chain variable region, F
A17d4
US20140044719 SEQ ID NO:
5330



Protein

 161



RSV109
Heavy chain variable region, F
A4B4
US20140044719 SEQ ID NO:
5331



Protein

 167



RSV110
Heavy chain variable region, F
A8c7
US20140044719 SEQ ID NO:
5332



Protein

 172



RSV111
Heavy chain variable region, F
IX-493L1R
US20140044719 SEQ ID NO:
5333



Protein

 176



RSV112
Heavy chain variable region, F
M3H9
US20140044719 SEQ ID NO:
5334



Protein

 181



RSV113
Heavy chain variable region, F
B21M
US20110027294 SEQ ID NO:
5335



Protein

 49



RSV114
Heavy chain variable region, F
101F
US20110027294 SEQ ID NO: 4
5336



Protein





RSV115
Heavy chain variable region, F
HNK20
EP1720908; WO2005079479
5337



Protein

SEQ ID NO: 1



RSV116
Heavy chain variable region, F
P1212
US20140044719 SEQ ID NO:
5338



Protein

 123



RSV117
Heavy chain variable region, F
P12f4
US20140044719 SEQ ID NO:
5339



Protein

 132



RSV118
Heavy chain variable region, F
P11d4
US20140044719 SEQ ID NO:
5340



Protein

 138



RSV119
Heavy chain variable region, F
A1e9
US20140044719 SEQ ID NO:
5341



Protein

 145



RSV120
Heavy chain variable region, F
A12a6
US20140044719 SEQ ID NO:
5342



Protein

 150



RSV121
Heavy chain variable region, F
A13c4
US20140044719 SEQ ID NO:
5343



Protein

 156



RSV122
Heavy chain variable region, F
A17d4
US20140044719 SEQ ID NO:
5344



Protein

 162



RSV123
Heavy chain variable region, F
A4B4
US20140044719 SEQ ID NO:
5345



Protein

 168



RSV124
Heavy chain variable region, F
A8c7
US20140044719 SEQ ID NO:
5346



Protein

 173



RSV125
Heavy chain variable region, F
IX-493L1FR
US20140044719 SEQ ID NO:
5347



Protein

 177



RSV126
Heavy chain variable region, F
H1 H3564P
WO2014159822 SEQ ID NO: 2
5348



Protein





RSV127
Heavy chain variable region, F
H1 H3565P
WO2014159822 SEQ ID NO:
5349



Protein

 18



RSV128
Heavy chain variable region, F
H1 H3566P
WO2014159822 SEQ ID NO:
5350



Protein

 34



RSV129
Heavy chain variable region, F
H1 H3567P
WO2014159822 SEQ ID NO:
5351



Protein

 50



RSV130
Heavy chain variable region, F
H1 H3581P
WO2014159822 SEQ ID NO:
5352



Protein

 66



RSV131
Heavy chain variable region, F
H1 H3583P
WO2014159822 SEQ ID NO:
5353



Protein

 82



RSV132
Heavy chain variable region, F
H1 H3589P
WO2014159822 SEQ ID NO:
5354



Protein

 98



RSV133
Heavy chain variable region, F
H1 H3591 P
WO2014159822 SEQ ID NO:
5355



Protein

 114



RSV134
Heavy chain variable region, F
H1 H3592P
WO2014159822 SEQ ID NO:
5356



Protein

 130



RSV135
Heavy chain variable region, F
H1 H3597P
WO2014159822 SEQ ID NO:
5357



Protein

 146



RSV136
Heavy chain variable region, F
H1 H3598P
WO2014159822 SEQ ID NO:
5358



Protein

 162



RSV137
Heavy chain variable region, F
H1 H3603P
WO2014159822 SEQ ID NO:
5359



Protein

 178



RSV138
Heavy chain variable region, F
H1 H3604P
WO2014159822 SEQ ID NO:
5360



Protein

 194



RSV139
Heavy chain variable region, F
H1 H3605P
WO2014159822 SEQ ID NO:
5361



Protein

 210



RSV140
Heavy chain variable region, F
H1 H3607P
WO2014159822 SEQ ID NO:
5362



Protein

 226



RSV141
Heavy chain variable region, F
H1 H3608P2
WO2014159822 SEQ ID NO:
5363



Protein

 242



RSV142
Heavy chain variable region, F
H1 H3592P2
WO2014159822 SEQ ID NO:
5364



Protein

 258



RSV143
Heavy chain variable region, F
H1 H3592P3
WO2014159822 SEQ ID NO:
5365



Protein

 274



RSV144
Heavy chain variable region, F
H1 M3621 N
WO2014159822 SEQ ID NO:
5366



Protein

 290



RSV145
Heavy chain variable region, F
H1 M3622N
WO2014159822 SEQ ID NO:
5367



Protein

 306



RSV146
Heavy chain variable region, F
H1 M2634N
WO2014159822 SEQ ID NO:
5368



Protein

 322



RSV147
Heavy chain variable region, F
H1 M3627N
WO2014159822 SEQ ID NO:
5369



Protein

 338



RSV148
Heavy chain variable region, F
Clone No. 735
US20120009623 SEQ ID NO: 1
5370



Protein





RSV149
Heavy chain variable region, F
Clone No. 736
US20120009623 SEQ ID NO: 2
5371



Protein





RSV150
Heavy chain variable region, F
Clone No. 744
US20120009623 SEQ ID NO: 3
5372



Protein





RSV151
Heavy chain variable region, F
Clone No. 793
US20120009623 SEQ ID NO: 4
5373



Protein





RSV152
Heavy chain variable region, F
Clone No. 795
US21120009623 SEQ ID NO: 5
5374



Protein





RSV153
Heavy chain variable region, F
Clone No. 796
US20120009623 SEQ ID NO: 6
5375



Protein





RSV154
Heavy chain variable region, F
Clone No. 799
US20120009623 SEQ ID NO: 7
5376



Protein





RSV155
Heavy chain variable region, F
Clone No. 800
US20120009623 SEQ ID NO: 8
5377



Protein





RSV156
Heavy chain variable region, F
Clone No. 801
US20120009623 SEQ ID NO: 9
5378



Protein





RSV157
Heavy chain variable region, F
Clone No. 804
US20120009623 SEQ ID NO:
5379



Protein

 10



RSV158
Heavy chain variable region, F
Clone No. 810
US20120009623 SEQ ID NO:
5380



Protein

 11



RSV159
Heavy chain variable region, F
Clone No. 811
US20120009623 SEQ ID NO:
5381



Protein

 12



RSV160
Heavy chain variable region, F
Clone No. 812
US20120009623 SEQ ID NO:
5382



Protein

 13



RSV161
Heavy chain variable region, F
Clone No. 814
US20120009623 SEQ ID NO:
5383



Protein

 14



RSV162
Heavy chain variable region, F
Clone No. 816
US20120009623 SEQ ID NO:
5384



Protein

 15



RSV163
Heavy chain variable region, F
Clone No. 817
US20120009623 SEQ ID NO:
5385



Protein

 16



RSV164
Heavy chain variable region, F
Clone No. 818
US20120009613 SEQ ID NO:
5386



Protein

 17



RSV165
Heavy chain variable region, F
Clone No. 819
US20120009 23 SEQ ID NO:
5387



Protein

 18



RSV166
Heavy chain variable region, F
Clone No. 824
US20120009623 SEQ ID NO:
5388



Protein

 19



RSV167
Heavy chain variable region, F
Clone No. 825
US20120009623 SEQ ID NO:
5389



Protein

 20



RSV168
Heavy chain variable region, F
Clone No. 827
US20120009623 SEQ ID NO:
5390



Protein

 21



RSV169
Heavy chain variable region, F
Clone No. 829
US20120009623 SEQ ID NO:
5391



Protein

 22



RSV170
Heavy chain variable region, F
Clone No. 830
US20120009623 SEQ ID NO:
5392



Protein

 23



RSV171
Heavy chain variable region, F
Clone No. 831
US20120009623 SEQ ID NO:
5393



Protein

 24



RSV172
Heavy chain variable region, F
Clone No. 835
US20120009623 SEQ ID NO:
5394



Protein

 25



RSV173
Heavy chain variable region, F
Clone No. 838
US20120009623 SEQ ID NO:
5395



Protein

 26



RSV174
Heavy chain variable region, F
Clone No. 841
US20120009623 SEQ ID NO:
5396



Protein

 27



RSV175
Heavy chain variable region, F
Clone No. 853
US20120009623 SEQ ID NO:
5397



Protein

 28



RSV176
Heavy chain variable region, F
Clone No. 855
US20120009623 SEQ ID NO:
5398



Protein

 29



RSV177
Heavy chain variable region, F
Clone No. 856
US20120009623 SEQ ID NO:
5399



Protein

 30



RSV178
Heavy chain variable region, F
Clone No. 857
US20120009623 SEQ ID NO:
5400



Protein

 31



RSV179
Heavy chain variable region, F
Clone No. 858
US20120009623 SEQ ID NO:
5401



Protein

 32



RSV180
Heavy chain variable region, F
Clone No. 859
US20120009623 SEQ ID NO:
5402



Protein

 33



RSV181
Heavy chain variable region, F
Clone No. 861
US20120009623 SEQ ID NO:
5403



Protein

 34



RSV182
Heavy chain variable region, F
Clone No. 863
US20120009623 SEQ ID NO:
5404



Protein

 35



RSV183
Heavy chain variable region, F
Clone No. 868
US20120009623 SEQ ID NO:
5405



Protein

 36



RSV184
Heavy chain variable region, F
Clone No. 870
US20120009623 SEQ ID NO:
5406



Protein

 37



RSV185
Heavy chain variable region, F
Clone No. 871
US20120009623 SEQ ID NO:
5407



Protein

 38



RSV186
Heavy chain variable region, F
Clone No. 880
US20120009623 SEQ ID NO:
5408



Protein

 39



RSV187
Heavy chain variable region, F
Clone No. 881
US20120009623 SEQ ID NO:
5409



Protein

 40



RSV188
Heavy chain variable region, F
Clone No. 884
US20120009623 SEQ ID NO:
5410



Protein

 41



RSV189
Heavy chain variable region, F
Clone No. 886
US20120009623 SEQ ID NO:
5411



Protein

 42



RSV190
Heavy chain variable region, F
Clone No. 888
US20120009623 SEQ ID NO:
5412



Protein

 43



RSV191
Heavy chain variable region, F
Clone No. 894
US20120009623 SEQ ID NO:
5413



Protein

 44



RSV192
Heavy chain variable region, F
Gλ-1
US20050175986 SEQ ID NO: 4
5414



Protein





RSV193
Super humanized heavy chain
SHVh1
EP1720908; WO2005079479
5415



based on HNK20, F protein

SEQ ID NO: 3



RSV194
Super humanized heavy chain
SHVh2
EP1720908; WO2005079479
5416



based on HNK20, F protein

SEQ ID NO: 4



RSV195
Super humanized heavy chain
SHVh3
EP1720908; WO2005079479
5417



based on HNK20, F protein

SEQ ID NO: 5



RSV196
Super humanized heavy chain
SHVh4
EP1720908; WO2005079479
5418



based on HNK20, F protein

SEQ ID NO: 6



RSV197
Super humanized heavy chain
SHVh5
EP1720908; WO2005079479
5419



based on HNK20, F protein

SEQ ID NO: 7



RSV198
Super humanized heavy chain
SHVh6
EP1720908; WO2005079479
5420



based on HNK20, F protein

SEQ ID NO: 8



RSV199
Super humanized heavy chain
SHVh7
EP1720908; WO2005079479
5421



based on HNK20, F protein

SEQ ID NO: 9



RSV200
Heavy chain variable region, F
B4
EP636182; WO1993020210;
5422



Protein

SEQ ID NO: 3



RSV201
Heavy chain variable region, F
B13/14
EP636182; WO1993020210;
5423



Protein

SEQ ID NO: 4



RSV202
Heavy chain variable region, F
RF-1
EP854730; WO1996040252;
5424



Protein

FIG. 7B



RSV203
Heavy chain variable region, F
RF-2
EP854730; WO1996040252;
5425



Protein

FIG. 8B



RSV204
Heavy chain, G Protein
1F12
US8273354 SEQ ID NO: 28
5426


RSV205
Heavy chain, G Protein
3G12
US8273354 SEQ ID NO: 29
5427


RSV206
Heavy chain, G Protein
1A5
US8273354 SEQ ID NO: 30
5428


RSV207
Heavy chain, G Protein
3D3
US8273354 SEQ ID NO: 31
5429


RSV208
Heavy chain, G Protein
1G1
US8273354 SEQ ID NO: 32
5430


RSV209
Heavy chain, G Protein
2B11
US8273354 SEQ ID NO: 33
5431


RSV210
Heavy chain, G Protein
5D8
US8273354 SEQ ID NO: 34
5432


RSV211
Heavy chain, G Protein
2D10
US8273354 SEQ ID NO: 35
5433


RSV212
Heavy chain, G Protein
3F9
US8273354 SEQ ID NO: 36
5434


RSV213
Heavy chain, G Protein
1D4
US8273354 SEQ ID NO: 37
5435


RSV214
Heavy chain, G Protein
1G8
US8273354 SEQ ID NO: 38
5436


RSV215
Heavy chain, G Protein
6A12
US8273354 SEQ ID NO: 39
5437


RSV216
Heavy chain, G Protein
10C6
US8273354 SEQ ID NO: 40
5438


RSV217
Heavy chain, G Protein
Hu 131-2G
US8273354 SEQ ID NO: 41
5439


RSV218
Heavy chain, G Protein
AT46
US20150004155 SEQ ID NO:
5440





 109



RSV219
Heavy chain, G Protein
AT32
US20150004155 SEQ ID NO:
5441





 110



RSV220
Heavy chain, G Protein
AT33
US20150004155 SEQ ID NO:
5442





 111



RSV221
Heavy chain, G Protein
AT34
US20150004155 SEQ ID NO:
5443





 112



RSV222
Heavy chain, G Protein
AT735
US20150004155 SEQ ID NO:
5444





 113



RSV223
Heavy chain, G Protein
AT36
US20150004155 SEQ ID NO:
5445





 114



RSV224
Heavy chain, G Protein
AT737
US20150004155 SEQ ID NO:
5446





 115



RSV225
Heavy chain, G Protein
AT39
US20150004155 SEQ ID NO:
5447





 116



RSV226
Heavy chain, G Protein
AT40
US20150004155 SEQ ID NO:
5448





 117



RSV227
Heavy chain, G Protein
AT42
US2010004155 SEQ ID NO:
5449





 118



RSV228
Heavy chain, G Protein
AT43
US20150004155 SEQ ID NO:
5450





 119



RSV229
Heavy chain, G Protein
AT44
US20150004155 SEQ ID NO:
5451





 120



RSV230
Heavy chain, G Protein
AT45
US20150004155 SEQ ID NO:
5452





 121



RSV231
Heavy chain, G Protein
AT47
US20150004155 SEQ ID NO:
5453





 122



RSV232
Heavy chain, G Protein
AT49
US20150004155 SEQ ID NO:
5454





 123



RSV233
Heavy chain, G Protein
AT50
US20150004155 SEQ ID NO:
5455





 124



RSV234
Heavy chain, G Protein
AT51
US20150004155 SEQ ID NO:
5456





 125



RSV235
Heavy chain variable region, G
CB058.1
WO2014170257 SEQ ID NO:
5457



Protein

 37



RSV236
Heavy chain variable region, G
CB048.3
WO2014170257 SEQ ID NO:
5458



Protein

 39



RSV237
Heavy chain variable region, G
CB010.7
WO2014170257 SEQ ID NO:
5459



Protein

 41



RSV238
Heavy chain variable region, G
CB003.1
WO2014170257 SEQ ID NO:
5460



Protein

 43



RSV239
Heavy chain variable region, G
CB028.2
WO2014170257 SEQ ID NO:
5461



Protein

 45



RSV240
Heavy chain variable region, G
CB002.1
WO2014170257 SEQ ID NO:
5462



Protein

 47



RSV241
Heavy chain variable region, G
CB017.3L
WO2014170258 SEQ ID NO:
5463



Protein

 73



RSV242
Heavy chain variable region, G
CB017.5L
WO2014170258 SEQ ID NO:
5464



Protein

 75



RSV243
Heavy chain variable region, G
CB028.1
WO2014170258 SEQ ID NO:
5465



Protein

 77



RSV244
Heavy chain variable region, G
CB030.1
WO2014170258 SEQ ID NO:
5466



Protein

 79



RSV245
Heavy chain variable region, G
CB047.1
WO2014170258 SEQ ID NO:
5467



Protein

 81



RSV246
Heavy chain variable region, G
CB04712
WO2014170258 SEQ ID NO:
5468



Protein

 83



RSV247
Heavy chain variable region, G
CB065.1
WO2014170258 SEQ ID NO:
5469



Protein

 85



RSV248
Heavy chain variable region, G
CB071.1L
WO2014170258 SEQ ID NO:
5470



Protein

 87



RSV249
Heavy chain variable region, G
CB072.1L
WO2014170258 SEQ ID NO:
5471



Protein

 89



RSV250
Heavy chain variable region, G
CB073.1L
WO2014170258 SEQ ID NO:
5472



Protein

 91



RSV251
Heavy chain variable region, G
CB076.2L
WO2014170258 SEQ ID NO:
5473



Protein

 93



RSV252
Heavy chain variable region, G
CB079.1
WO2014170258 SEQ ID NO:
5474



Protein

 95



RSV253
Heavy chain
AM14
US20140377279 SEQ ID NO:
5475





 78



RSV254
Heavy chain
AM16
US20140377279 SEQ ID NO:
5476





 85



RSV255
Heavy chain
AM23
US20140377279 SEQ ID NO:
5477





 92



RSV256
Heavy chain
D25
US20140377279 SEQ ID NO: 7
5478


RSV257
Heavy chain
AFFF
US7635568 SEQ ID NO: 210
5479


RSV258
Heavy chain
P12f2
US7635568 SEQ ID NO: 212
5480


RSV259
Heavy chain
P12f4
US7635568 SEQ ID NO: 214
5481


RSV260
Heavy chain
P11d4
US7635568 SEQ ID NO: 216
5482


RSV261
Heavy chain
Ale9
US7635568 SEQ ID NO: 218
5483


RSV262
Heavy chain
A12a6
US7635568 SEQ ID NO: 220
5484


RSV263
Heavy chain
A13c4
US7635568 SEQ ID NO: 222
5485


RSV264
Heavy chain
A17d4
US7635568 SEQ ID NO: 224
5486


RSV265
Heavy chain
A4B4
US7635568 SEQ ID NO: 226
5487


RSV266
Heavy chain
A8c7
US7635568 SEQ ID NO: 228
5488


RSV267
Heavy chain
1X-493L1FR
US7635568 SEQ ID NO: 230
5489


RSV268
Heavy chain
H3-3F4
US7635568 SEQ ID NO: 232
5490


RSV269
Heavy chain
M3H9
US7635568 SEQ ID NO: 234
5491


RSV270
Heavy chain
Y10H6
US7635568 SEQ ID NO: 236
5492


RSV271
Heavy chain
DG
US7635568 SEQ ID NO: 238
5493


RSV272
Heavy chain
AFFF(1)
US7635568 SEQ ID NO: 240
5494


RSV273
Heavy chain
6H8
US7635568 SEQ ID NO: 242
5495


RSV274
Heavy chain
L1-7E5
US7635568 SEQ ID NO: 244
5496


RSV275
Heavy chain
L2-15B10
US7635568 SEQ ID NO: 246
5497


RSV276
Heavy chain
A13a11
US7635568 SEQ ID NO: 248
5498


RSV277
Heavy chain
A1h5
US7635568 SEQ ID NO: 250
5499


RSV278
Heavy chain
A4B4(1)
US7635568 SEQ ID NO: 252
5500


RSV279
Heavy chain
A4B4L1FR-S28R
US7635568 SEQ ID NO: 254
5501




(MEDI-524,






Motavizumab,






Numax)




RSV280
Heavy chain
A4B4-F52S
US7635568 SEQ ID NO: 256
5502


RSV281
Heavy chain

US7364737 SEQ ID NO: 1
5503


RSV282
Heavy chain

US7364737 SEQ ID NO: 2
5504


RSV283
Heavy chain variable region
J variant
WO2015108967 SEQ ID NO:
5505





 12



RSV284
Heavy chainvariable region
L variant
WO2015108967 SEQ ID NO:
5506





 13



RSV285
Heavy chain variable region
LA variant
WO2015108967 SEQ ID NO:
5507





 14



RSV286
Heavy chain variable region
1G7
WO2015108967 SEQ ID NO:
5508





 15



RSV287
Heavy chain variable region
1F5
WO2015108967 SEQ ID NO:
5509





 16



RSV288
Heavy chain variable region
2D10
WO2015108967 SEQ ID NO:
5510





 17



RSV289
Heavy chain variable region
1G7-GLM
WO2015108967 SEQ ID NO:
5511





 18



RSV290
Heavy chain variable region
B12-1
WO2015108967 SEQ ID NO:
5512





 19



RSV291
Heavy chain variable region
E3-5
WO2015108967 SEQ ID NO:
5513





 20



RSV292
Heavy chain variable region
E9-2
WO2015108967 SEQ ID NO:
5514





 21



RSV293
Heavy chain variable region
1X-493L1FR
US7635568 SEQ ID NO: 7
5515


RSV294
Heavy chain variable region
AFFF, AFFF(1)
US7635568 SEQ ID NO: 9
5516


RSV295
Heavy chain variable region
P12f2
US7635568 SEQ ID NO: 17
5517


RSV296
Heavy chain variable region
P12f4
US7635568 SEQ ID NO: 24
5518


RSV297
Heavy chain variable region
P11d4
US7635568 SEQ ID NO: 28
5519


RSV298
Heavy chain variable region
Ale9, A1h5
US7635568 SEQ ID NO: 33
5520


RSV299
Heavy chain variable region
A12a6
US7635568 SEQ ID NO: 36
5521


RSV300
Heavy chain variable region
A13c4
US7635568 SEQ ID NO: 40
5522


RSV301
Heavy chain variable region
A17d4
US7635568 SEQ ID NO: 44
5523


RSV302
Heavy chain variable region
A4B4, A4B4(1),
US7635568 SEQ ID NO: 48
5524




A4B4L1FR-S28R






(MEDI-524,






Motavizumab,






Numax), A4B4-






F52S




RSV303
Heavy chain variable region
A8c7
US7635568 SEQ ID NO: 51
5525


RSV304
Heavy chain variable region
H3-3F4, M3H9,
US7635568 SEQ ID NO: 55
5526




Y10H6




RSV305
Heavy chain variable region
DG, 6H8, L1-7E5,
US7635568 SEQ ID NO: 78
5527




L2-15B10




RSV306
Heavy chain variable region
A13a11
US7635568 SEQ ID NO: 67
5528


RSV307
Heavy chain variable region

US7364742 SEQ ID NO: 7
5529


RSV308
Heavy chain variable region

US7364742 SEQ ID NO: 8
5530


RSV309
Heavy chain variable region
D2E7
EP1807111; WO2006041970
5531





SEQ ID NO: 2



RSV310
Heavy chain variable region
2SD4
EP1807111; WO2006041970
5532





SEQ ID NO: 10



RSV311
Heavy chain, human

Wen, X,, “Structure of the
5533



metapneumovirus fusion

human metapneumovirus fusion




protein with

protein with neutralizing




neutralizing antibody identifies

antibody identifies a




a pneumovirus antigenic site,

pneumovirus antigenic site”,






Nat. Struct. Mol. Biol. 19 (4),






461-463 (2012), NCBI






Accession # 4DAG_H(220 aa)



RSV312
Heavy chain variable, M2 1
8A4/G9-IgG
US20140348858 SEQ ID NO: 3
5534



antigen





RSV313
Heavy chain, Pre fusion RSV F
HMB2435
WO2015010792 SEQ ID NO:
5535



protein

 13



RSV314
Heavy chain, Pre fusion RSV F
HMB2437
WO2015010792 SEQ ID NO:
5536



protein

 29



RSV315
Heavy chain, Pre fusion RSV F
HMB2416
WO2015010792 SEQ ID NO:
5537



protein

 45



RSV316
Heavy chain, Pre fusion RSV F
HMB2437
WO2015010792 SEQ ID NO:
5538



protein,

 85



RSV317
Heavy chain, Pre fusion RSV F
CR9501
WO2014202570 SEQ ID NO:
5539



protein

 53



RSV318
Heavy chain, Pre fusion RSV F
CR9502
WO2014202570 SEQ ID NO:
5540



protein

 57



RSV319
Heavy chain 1, Pre fusion RSV
HMB2432
WO2015010792 SEQ ID NO:
5541



F protein

 61



RSV320
Heavy chain 2, Pre fusion RSV
HMB2432
WO2015010792 SEQ ID NO:
5542



F protein

 65



RSV321
Heavy chain FR LG, Pre
HMB2435
WO2015010792 SEQ ID NO:
5543



fusion RSV F protein

 75



RSV322
light chain, F and G Proteins
clone 735
US20110189171; US7879329
5544





SEQ ID NO: 89



RSV323
light chain, F and G Proteins
clone 736
US20110189171; US7879329
5545





SEQ ID NO: 90



RSV324
light chain, F and G Proteins
clone 744
US20110189171; US7879329
5546





SEQ ID NO: 91



RSV325
light chain, F and G Proteins
clone 793
US20110189171; US7879329
5547





SEQ ID NO: 92



RSV326
light chain, F and G Proteins
clone 795
US20110189171; US7879329
5548





SEQ ID NO: 93



RSV327
light chain, F and G Proteins
clone 796
US20110189171; US7879329
5549





SEQ ID NO: 94



RSV328
light chain, F and G Proteins
clone 799
US20110189171; US7879329
5550





SEQ ID NO: 95



RSV329
light chain, F and G Proteins
clone 800
US20110189171; US7879329
5551





SEQ ID NO: 96



RSV330
light chain, F and G Proteins
clone 801
US20110189171; US7879329
5552





SEQ ID NO: 97



RSV331
light chain, F and G Proteins
clone 804
US20110189171; US7879329
5553





SEQ ID NO: 98



RSV332
light chain, F and G Proteins
clone 810
US20110189171; US7879329
5554





SEQ ID NO: 99



RSV333
light chain, F and G Proteins
clone 811
US20110189171; US7879329
5555





SEQ ID NO: 100



RSV334
light chain, F and G Proteins
clone 812
US20110189171; US7879329
5556





SEQ ID NO: 101



RSV335
light chain, F and G Proteins
clone 814
US20110189171; US7879329
5557





SEQ ID NO: 102



RSV336
light chain, F and G Proteins
clone 816
US20110189171; US7879329
5558





SEQ ID NO: 103



RSV337
light chain, F and G Proteins
clone 817
US20110189171; US7879329
5559





SEQ ID NO: 104



RSV338
light chain, F and G Proteins
clone 818
US20110189171; US7879329
5560





SEQ ID NO: 105



RSV339
light chain, F and G Proteins
clone 819
US20110189171; US7879329
5561





SEQ ID NO: 106



RSV340
light chain, F and G Proteins
clone 824
US20110189171; US7879329
5562





SEQ ID NO: 107



RSV341
light chain, F and G Proteins
clone 825
US20110189171; US7879329
5563





SEQ ID NO: 108



RSV342
light chain, F and G Proteins
clone 827
US20110189171; US7879329
5564





SEQ ID NO: 109



RSV343
light chain, F and G Proteins
clone 829
US20110189171, US7879329
5565





SEQ ID NO: 110



RSV344
light chain, F and G Proteins
clone 830
US20110189171; US7879329
5566





SEQ ID NO: 111



RSV345
light chain, F and G Proteins
clone 831
US20110189171; US7879329
5567





SEQ ID NO: 112



RSV346
light chain, F and G Proteins
clone 835
US20110189171; US7879329
5568





SEQ ID NO, 113



RSV347
light chain, F and G Proteins
clone 838
US20110189171; US7879329
5569





SEQ ID NO: 114



RSV348
light chain, F and G Proteins
clone 841
US20110189171; US7879329
5570





SEQ ID NO: 115



RSV349
light chain, F and G Proteins
clone 853
US20110189171; US7879329
5571





SEQ ID NO: 116



RSV350
light chain, F and G Proteins
clone 855
US20110189171; US7879329
5572





SEQ ID NO: 117



RSV351
light chain, F and G Proteins
clone 856
US20110189171; US7879329
5573





SEQ ID NO: 118



RSV352
light chain, F and G Proteins
clone 857
US20110189171; US7879329
5574





SEQ ID NO: 119



RSV353
light chain, F and G Proteins
clone 858
US20110189171; US7879329
5575





SEQ ID NO: 120



RSV354
light chain, F and G Proteins
clone 859
US20110189171; US7879329
5576





SEQ ID NO: 121



RSV355
light chain, F and G Proteins
clone 861
US20110189171; US7879329
5577





SEQ ID NO: 122



RSV356
light chain, F and G Proteins
clone 863
US20110189171; US7879329
5578





SEQ ID NO: 123



RSV357
light chain, F and G Proteins
clone 868
US20110189171; US7879329
5579





SEQ ID NO: 124



RSV358
light chain, F and G Proteins
clone 870
US20110189171; US7879329
5580





SEQ ID NO: 125



RSV359
light chain, F and G Proteins
clone 871
US20110189171; US7879329
5581





SEQ ID NO: 126



RSV360
light chain, F and G Proteins
clone 880
US20110189171; US7879329
5582





SEQ ID NO: 127



RSV361
light chain, F and G Proteins
clone 881
US20110189171; US7879329
5383





SEQ ID NO: 128



RSV62
light chain, F and G Proteins
clone 884
US20110189171; US7879329
5584





SEQ ID NO: 129



RSV363
light chain, F and G Proteins
clone 886
US20110189171; US7879329
5585





SEQ ID NO: 130



RSV364
light chain, F and G Proteins
clone 888
US20110189171; US7879329
5586





SEQ ID NO: 131



RSV365
light chain, F and G Proteins
clone 894
US20110189171; US7879329
5587





SEQ ID NO: 132



RSV366
Light chain variable, F protein
3210 variant 1,
WO2013140247 SEQ ID NO:
5588



of RSV, MPV, or PVM
3210 variant 2,
 14





3210 variant 5




RSV367
Light chain variable, F protein
2430 variant 1,
WO2013140247 SEQ ID NO:
5589



of RSV, MPV, or PVM
2430 variant 2,
 30





2430 variant 4




RSV368
Light chain variable, F protein
3210 variant 3
WO2013140247 SEQ ID NO:
5590



of RSV, MPV, or PVM

 37



RSV369
Light chain variable, F protein
3210 variant 4,
WO20113140247 SEQ ID NO:
5591



of RSV, MPV, or PVM
3210 variant 6
 50



RSV370
Light chain variable, F protein
2430 variant 3,
WO2013140247 SEQ ID NO:
5592



of RSV, MPV, or PVM
2430 variant 5
 60



RSV371
Light chain, F Protein
clone 19
EP1259547; US8153133SEQ
5593





ID NO: 40



RSV372
Light chain variable region,

US20140093501 SEQ ID NO:
5594



CDR Grafted, F Protein

 20



RSV373
Light chain variable region,

US20140093501 SEQ ID NO:
5595



CDR Grafted, F Protein

 34



RSV374
Light chain, F Protein
AM22
US8568726 SEQ ID NO: 32
5596


RSV375
Light chain, F Protein
RSVF2-5
US8221759 SEQ ID NO: 9
5597


RSV376
Light chain, F Protein

EP1259547; US8153133 SEQ
5598





ID NO: 3



RSV377
Light chain, F Protein
MTDI-
EP1259547; US8153133 SEQ
5599




493/Pavilizumab-
ID NO: 1





N-VL (Brand name






Synagis)




RSV378
Light chain, F Protein

EP1259547; US8153133 SEQ
5600





ID NO: 35



RSV379
Light chain, F Protein
clone 18
EP1259547; US8153133 SEQ
5601





ID NO: 38



RSV380
Light chain, F Protein
clone 20
ER1259547; US8153133 SEQ
5602





ID NO: 42



RSV381
Light chain, F Protein
clone 21
EP1259547; US8153133 SEQ
5603





ID NO: 44



RSV382
Light chain, F Protein
clone 22
ER1259547; US8153133 SEQ
5604





ID NO: 46



RSV383
Light chain, F Protein
clone 23
EP1259547; US8153133 SEQ
5605





ID NO: 48



RSV384
Light chain, F Protein
clone 24
ER1259547; US8153133 SEQ
5606





ID NO: 50



RSV385
Light chain, F Protein
clone 25
EP1259547; US8153133 SEQ
5607





ID NO: 52



RSV386
Light chain, F Protein
clone 26
ER1259547; US8153133 SEQ
5608





ID NO: 54



RSV387
Light chain variable region, F
huK102
US20140093501 SEQ ID NO:
5609



Protein

 19



RSV388
Light chain variable region, F
huK102
US20140093501 SEQ ID NO:
5610



Protein

 33



RSV389
Light chain variable region, F
RSV G8
US7867497 SEQ ID NO: 4
5611



Protein





RSV390
Light chain variable region, F
Clone 1
US20120135006 SEQ ID NO:
5612



Protein

 17



RSV391
Light chain variable region, F
Clone 2
US20120135006 SEQ ID NO:
5613



Protein

 19



RSV392
Light chain variable region, F
Clone 3
US20120135006 SEQ ID NO:
5614



Protein

 21



RSV393
Light chain variable region, F
Clone 22
US20120135006 SEQ ID NO:
5615



Protein

 23



RSV394
Light chain variable region, F
Clone 23
US20120135006 SEQ ID NO:
5616



Protein

 25



RSV395
Light chain variable region, F
RSV13-9
WO2009088159 SEQ ID NO: 2
5617



Protein





RSV396
Light chain variable region, F
MAb1308F
US20140093501 SEQ ID NO:
5618



Protein

 21



RSV397
Light chain, F Protein
58c5
US20140044719 SEQ ID NO: 5
5619


RSV398
Light chain, F Protein
sc5
US20140044719 SEQ ID NO:
5620





 13



RSV399
Light chain, F Protein
Clone No. 735
US20120009623 SEQ ID NO:
5621





 89



RSV400
Light chain, F Protein
Clone No. 736
US20120009623 SEQ ID NO:
5622





 90



RSV401
Light chain, F Protein
Clone No. 744
US20120009623 SEQ ID NO:
5623





 91



RSV402
Light chain, F Protein
Clone No. 793
US20120009623 SEQ ID NO:
5624





 92



RSV403
Light chain, F Protein
Clone No. 795
US20120009623 SEQ ID NO:
5625





 93



RSV404
Light chain, F Protein
Clone No. 796
US20120009623 SEQ ID NO:
5626





 94



RSV405
Light chain, F Protein
Clone No. 799
US20120009623 SEQ ID NO:
5627





 95



RSV406
Light chain, F Protein
Clone No. 800
US20120009623 SEQ ID NO:
5628





 96



RSV407
Light chain, F Protein
Clone No. 801
US20120009623 SEQ ID NO:
5629





 97



RSV408
Light chain, F Protein
Clone No. 804
US20120009623 SEQ ID NO:
5630





 98



RSV409
Light chain, F Protein
Clone No. 810
US2012000923 SEQ ID NO:
5631





 99



RSV410
Light chain, F Protein
Clone No. 811
US20120009623 SEQ ID NO:
5632





 100



RSV411
Light chain, F Protein
Clone No. 812
US20120009623 SEQ ID NO:
5633





 101



RSV412
Light chain, F Protein
Clone No. 814
US20120009623 SEQ ID NO:
5634





 102



RSV413
Light chain, F Protein
Clone No. 816
US20120009623 SEQ ID NO:
5635





 103



RSV414
Light chain, F Protein
Clone No. 817
US20120009623 SEQ ID NO:
5636





 104



RSV415
Light chain, F Protein
Clone No. 818
US20120009623 SEQ ID NO:
5637





 105



RSV416
Light chain, F Protein
Clone No. 819
US20120009623 SEQ ID NO:
5638





 106



RSV417
Light chain, F Protein
Clone No. 824
US20120009623 SEQ ID NO:
5639





 107



RSV41,8
Light chain, F Protein
Clone No. 825
US20120009623 SEQ ID NO:
5640





 108



RSV419
Light chain, F Protein
Clone No. 827
US20120009623 SEQ ID NO:
5641





 109



RSV420
Light chain, F Protein
Clone No. 829
US20120009623 SEQ ID NO:
5642





 110



RSV421
Light chain, F Protein
Clone No. 830
US20120009623 SEQ ID NO:
5643





 111



RSV422
Light chain, F Protein
Clone No. 831
US20120009623 SEQ ID NO:
5644





 112



RSV23
Light chain, F Protein
Clone No. 835
US20120009623 SEQ ID NO:
5645





 113



RSV424
Light chain, F Protein
Clone No. 838
US20120009623 SEQ ID NO:
5646





 114



RSV42S
Light chain, F Protein
Clone No. 841
US20120009623 SEQ ID NO:
5647





 115



RSV426
Light chain, F Protein
Clone No. 853
US20120009623 SEQ ID NO:
5648





 116



RSV427
Light chain, F Protein
Clone No. 855
US20120009623 SEQ ID NO:
5649





 117



RSV428
Light chain, F Protein
Clone No. 856
US20120009623 SEQ ID NO:
5650





 118



RSV429
Light chain, F Protein
Clone No. 857
US20120009623 SEQ ID NO:
5651





 119



RSV430
Light chain, F Protein
Clone No. 858
US20120009623 SEQ ID NO:
5652





 120



RSV431
Light chain, F Protein
Clone No. 859
US20120009623 SEQ ID NO:
5653





 121



RSV432
Light chain, F Protein
Clone No. 861
US20120009623 SEQ ID NO:
5654





 122



RSV433
Light chain, F Protein
Clone No. 863
US20120009623 SEQ ID NO:
5655





 123



RSV434
Light chain, F Protein
Clone No. 868
US20120009623 SEQ ID NO:
5656





 124



RSV435
Light chain, F Protein
Clone No. 870
US20120009623 SEQ ID NO:
5657





 125



RSV436
Light chain, F Protein
Clone No. 871
US20120009623 SEQ ID NO:
5658





 126



RSV437
Light chain, F Protein
Clone No. 880
US2012000962 SEQ ID NO:
5659





 127



RSV438
Light chain, F Protein
Clone No. 881
US2012000923 SEQ ID NO:
5660





 128



RSV439
Light chain, F Protein
Clone No. 884
US20120009623 SEQ ID NO:
5661





 129



RSV440
Light chain, F Protein
Clone No. 886
US20120009623 SEQ ID NO:
5662





 130



RSV441
Light chain, F Protein
Clone No. 888
US20120009623 SEQ ID NO:
5663





 131



RSV442
Light chain, F Protein
Clone No. 894
US20120009623 SEQ ID NO:
5664





 132



RSV443
Light chain, F Protein

US20110027294 SEQ ID NO:
5665





 63



RSV444
Light chain, F Protein

US20110027294 SEQ ID NO:
5666





 64



RSV445
Light chain, F Protein

US20110027294 SEQ ID NO:
5667





 65



RSV446
Light chain, F Protein

US20110027294 SEQ ID NO:
5668





 66



RSV447
Light chain, F Protein

US20110027294 SEQ ID NO:
5669





 67



RSV448
Light chain, F Protein

US20110027294 SEQ ID NO:
5670





 68



RSV449
Light chain, F Protein

US20110027294 SEQ ID NO:
5671





 69



RSV450
Light chain, F Protein

US20110027294 SEQ ID NO:
5672





 70



RSV451
Light chain, F Protein

US20110027294 SEQ ID NO:
5673





 71



RSV452
Light chain, F Protein

US20110027294 SEQ ID NO:
5674





 72



RSV453
Light chain, F Protein

US20110027294 SEQ ID NO:
5675





 73



RSV454
Light chain, F Protein

US20110027294 SEQ ID NO:
5676





 81



RSV455
Light chain, F Protein

US20110027294 SEQ ID NO:
5677





 82



RSV456
Light chain, F Protein

US20110027294 SEQ ID NO:
5678





 83



RSV457
Light chain, F Protein

US20110027294 SEQ ID NO:
5679





 84



RSV458
Light chain, F Protein

US20110027294 SEQ ID NO:
5680





 85



RSV459
Light chain, F Protein

US20110027294 SEQ ID NO:
5681





 86



RSV460
Light chain, F Protein

US20110027294 SEQ ID NO:
5682





 87



RSV461
Light chain, F Protein

US20110027294 SEQ ID NO:
5683





 88



RSV462
Light chain, F Protein

US20110027294 SEQ ID NO:
5684





 89



RSV463
Light chain, F Protein

US20110027294 SEQ ID NO:
5685





 90



RSV464
Light chain, F Protein

US20110027294 SEQ ID NO:
5686





 91



RSV465
Light chain, F Protein

US20110027294 SEQ ID NO:
5687





 92



RSV466
Light chain, F Protein

US20110027294 SEQ ID NO:
5688





 93



RSV467
Light chain, F Protein

US20110027294 SEQ ID NO:
5689





 94



RSV468
Light chain, F Protein

US20110027294 SEQ ID NO:
5690





 95



RSV469
Light chain, F Protein

US20110027294 SEQ ID NO:
5691





 96



RSV470
Light chain, F Protein

US20110027294 SEQ ID NO:
5692





 97



RSV471
Light chain, F Protein

US20110027294 SEQ ID NO:
5693





 98



RSV472
Light chain, F Protein

US20110027294 SEQ ID NO:
5694





  99



RSV473
Light chain, F Protein

US20110027294 SEQ ID NO:
5695





 100



RSV474
Light chain, F Protein

US20110027294 SEQ ID NO:
5696





 101



RSV475
Light chain, F Protein

US20110027294 SEQ ID NO:
5697





 102



RSV476
Light chain, F Protein

US20110027294 SEQ ID NO:
5698





 103



RSV477
Light chain, F Protein

US20110027294 SEQ ID NO:
5699





 104



RSV478
Light chain, F Protein

US20110027294 SEQ ID NO:
5700





 105



RSV479
Light chain, F Protein

US20110027294 SEQ ID NO:
5701





 106



RSV480
Light chain, F Protein

US20110027294 SEQ ID NO:
5702





 107



RSV481
Light chain, F Protein

US20110027294 SEQ ID NO:
5703





 108



RSV482
Light chain, F Protein

US20110027294 SEQ ID NO:
5704





 109



RSV483
Light chain, F Protein

US20110027294 SEQ ID NO:
5705





 110



RSV484
Light chain, F Protein

US20110027294 SEQ ID NO:
5706





 111



RSV485
Light chain, F Protein

US20110027294 SEQ ID NO:
5707





 112



RSV486
Light chain, F Protein
Gλ-1A
US20050175986 SEQ ID NO: 9
5708


RSV487
Light chain, F Protein
A construct
US20050175986 SEQ ID NO:
5709





  11



RSV488
Light chain, F Protein
B construct
US20050175986 SEQ ID NO:
5710





  12



RSV489
Light chain, F Protein
hu19A
US20050019758;
5711





WO1998019704 SEQ ID NO:






  10



RSV490
Light chain, F Protein
hu19B
US20050019758;
5712





WO1998019704 SEQ ID NO:






  11



RSV491
Light chain, F Protein
hu19C
US20050019758;
5713





WO1998019704 SEQ ID NO:






  12



RSV492
Light chain, F Protein
hu19D
US20050019758;
5714





WO1998019704 SEQ ID NO:






  13



RSV493
Light chain, F Protein
RSV19
EP636182; WO1993020210;
5715





SEQ ID NO: 12



RSV494
Light chain, F Protein,

WO19922004381
5716


RSV495
Light chain variable region, F
P1212
US20140044719 SEQ ID NO:
5717



Protein

 127



RSV496
Light chain variable region, F
P12f4
US20140044719 SEQ ID NO:
5718



Protein

 134



RSV497
Light chain variable region, F
P11d4
US20140044719 SEQ ID NO:
5719



Protein

 140



RSV498
Light chain variable region, F
A1e9
US20140044719 SEQ ID NO:
5720



Protein

 146



RSV499
Light chain variable region, F
A12a6
US20140044719 SEQ ID NO:
5721



Protein

 152



RSV500
Light chain variable region, F
A13c4
US20140044719 SEQ ID NO:
5722



Protein

 158



RSV501
Light chain variable region, F
A17d4
US20140044719 SEQ ID NO:
5723



Protein

 164



RSV502
Light chain variable region, F
A4B4
US20140044719 SEQ ID NO:
5724



Protein

 169



RSV503
Light chain variable region, F
A8c7
US20140044719 SEQ ID NO:
5725



Protein

 174



RSV504
Light chain variable region, F
IX-493L1FR
US20140044719 SEQ ID NO:
5726



Protein

 178



RSV505
Light chain variable region, F
M3H9
US20140044719 SEQ ID NO:
5727



Protein

 180



RSV506
Light chain variable region, F
B21M
US20110027294 SEQ ID NO:
5728



Protein

  51



RSV507
Light chain variable region, F
101F
US20110027294 SEQ ID NO: 6
5729



Protein





RSV508
Light chain variable region, F
HNK20
EP1720908; WO2005079479
5730



Protein

SEQ ID NO: 2



RSV509
Light chain variable region, F
P1212
US20140044719 SEQ ID NO:
5731



Protein

 128



RSV510
Light chain variable region, F
P12f4
US20140044719 SEQ ID NO:
5732



Protein

 135



RSV511
Light chain variable region, F
P11d4
US20140044719 SEQ ID NO:
5733



Protein

 141



RSV512
Light chain variable region, F
A1e9
US20140044719 SEQ ID NO:
5734



Protein

 147



RSV513
Light chain variable region, F
A12a6
US20140044719 SEQ ID NO:
5735



Protein

 153



RSV514
Light chain variable region, F
A13c4
US20140044719 SEQ ID NO:
5736



Protein

 159



RSV515
Light chain variable region, F
A17d4
US20140044719 SEQ ID NO:
5737



Protein

 165



RSV516
Light chain variable region, F
A4B4
US20140044719 SEQ ID NO:
5738



Protein

 170



RSV517
Light chain variable region, F
A8c7
US20140044719 SEQ ID NO:
5739



Protein

 175



RSV518
Light chain variable region, F
IX-493L1FR
US20140044719 SEQ ID NO:
5740



Protein

 179



RSV519
Light chain variable region, F
H1 H3564P
WO2014159822 SEQ ID NO:
5741



Protein

 10



RSV520
Light chain variable region, F
H1 H3565P
WO2014159822 SEQ ID NO:
5742



Protein

 26



RSV521
Light chain variable region, F
H1 H3566P
WO2014159822 SEQ ID NO:
5743



Protein

 42



RSV522
Light chain variable region, F
H1 H3567P
WO2014159822 SEQ ID NO:
5744



Protein

 58



RSV523
Light chain variable region, F
H1 H3581 P
WO2014159822 SEQ ID NO:
5745



Protein

 74



RSV524
Light chain variable region, F
H1 H3583P
WO2014159822 SEQ ID NO:
5746



Protein

 90



RSV525
Light chain variable region, F
H1 H3589P
WO2014159822 SEQ ID NO:
5747



Protein

 106



RSV526
Light chain variable region, F
H1 H3591 P
WO2014159822 SEQ ID NO:
5748



Protein

 122



RSV527
Light chain variable region, F
H1 H3592P
WO2014159822 SEQ ID NO:
5749



Protein

 138



RSV528
Light chain variable region, F
H1 H3597P
WO2014159822 SEQ ID NO:
5750



Protein

 154



RSV529
Light chain variable region, F
H1 H3598P
WO2014159822 SEQ ID NO:
5751



Protein

 170



RSV530
Light chain variable region, F
H1 H3603P
WO2014159822 SEQ ID NO:
5752



Protein

 186



RSV531
Light chain variable region, F
H1 H3604P
WO2014159822 SEQ ID NO:
5753



Protein

 202



RSV532
Light chain variable region, F
H1 H3605P
WO2014159822 SEQ ID NO:
5754



Protein

 218



RSV533
Light chain variable region, F
H1 H3607P
WO2014159822 SEQ ID NO:
5755



Protein

 234



RSV534
Light chain variable region, F
H1 H3608P2
WO2014159822 SEQ ID NO:
5756



Protein

 250



RSV535
Light chain variable region, F
H1 H3592P2
WO2014159822 SEQ ID NO:
5757



Protein

 266



RSV536
Light chain variable region, F
H1 H3592P3
WO2014159822 SEQ ID NO:
5758



Protein

 282



RSV537
Light chain variable region, F
H1 M3621 N
WO2014159822 SEQ ID NO:
5759



Protein

 298



RSV538
Light chain variable region, F
H1 M3622N
WO2014159822 SEQ ID NO:
5760



Protein

 314



RSV539
Light chain variable region, F
H1 M2634N
WO2014159822 SEQ ID NO:
5761



Protein

 330



RSV540
Light chain variable region, F
H1 M3627N
WO2014159822 SEQ ID NO:
5762



Protein

 346



RSV541
Light chain variable region, F
Gλ-1
US20050175986 SEQ ID NO: 2
5763



Protein





RSV542
Light chain variable region, F
MAb1129
US20140093501 SEQ ID NO:
5764



Protein

 35



RSV543
super humanized kappa light
SHVl1
EP1720908; WO2005079479
5765



chain based on HNK20, F

SEQ ID NO: 10




protein





RSV544
super humanized kappa light
SHVl2
EP1720908; WO2005079479
5766



chain based on HNK20, F

SEQ ID NO: 11




protein





RSV545
super humanized kappa light
SHVl3
EP1720908; WO2005079479
5767



chain based on HNK20, F

SEQ ID NO: 12




protein





RSV546
super humanized kappa light
SHVl4
EP1720908; WO2005079479
5768



chain based on HNK20, F

SEQ ID NO: 13




protein





RSV547
super humanized kappa light
SHVl5
EP1720908; WO2005079479
5769



chain based on HNK20, F

SEQ ID NO: 14




protein





RSV548
super humanized kappa light
SHVl6
EP1720908; WO2005079479
5770



chain based on HNK20, F

SEQ ID NO: 15




protein





RSV549
Light chain variable region, F
B4
EP636182; WO1993020210;
5771



Protein

SEQ ID NO: 1



RSV550
Light chain variable region, F
B13/14
EP636182; WO1993020210;
5772



Protein

SEQ ID NO: 2



RSV551
Light chain variable region, F
RF-1
EP854730; WO1996040252;
5773



Protein

FIG. 7A



RSV552
Light chain variable region, F
RF-2
EP854730; WO1996040252;
5774



Protein

FIG. 8A



RSV553
Light chain variable region
CB058.1
WO2014170257 SEQ ID NO:
5775



Kappa, G protein

 38



RSV554
Light chain variable region
CB048.3
WO2014170257 SEQ ID NO:
5776



Kappa, G protein

 40



RSV555
Light chain variable region
CB010.7
WO2014170257 SEQ ID NO:
5777



Kappa, G protein

 42



RSV556
Light chain variable region
CB003.1
WO2014170257 SEQ ID NO:
5778



Kappa, G protein

 44



RSV557
Light chain variable region
CB028.2
WO2014170257 SEQ ID NO:
5779



Kappa, G protein

 46



RSV558
Light chain variable region
CB002.1
WO2014170257 SEQ ID NO:
5780



Kappa, G protein

 48



RSV559
Light chain, G Protein
1F12
US8273354 SEQ ID NO: 42
5781


RSV560
Light chain, G Protein
3G12
US8273354 SEQ ID NO: 43
5782


RSV561
Light chain, G Protein
1A5
US8273354 SEQ ID NO: 44
5783


RSV562
Light chain, G Protein
3D3
US8273354 SEQ ID NO: 45
5784


RSV563
Light chain, G Protein
1G1
US8273354 SEQ ID NO: 46
5785


RSV564
Light chain, G Protein
2B11
US8273354 SEQ ID NO: 47
5786


RSV565
Light chain, G Protein
5D8
US8273354 SEQ ID NO: 48
5787


RSV566
Light chain, G Protein
2D10
US8273354 SEQ ID NO: 49
5788


RSV567
Light chain, G Protein
3F9
US8273354 SEQ ID NO: 50
5789


RSV568
Light chain, G Protein
1D4
US8273354 SEQ ID NO: 51
5790


RSV569
Light chain, G Protein
1G8
US8273354 SEQ ID NO: 52
5791


RSV570
Light chain, G Protein
6A12
US8273354 SEQ ID NO: 53
5792


RSV571
Light chain, G Protein
10C6
US8273354 SEQ ID NO: 54
5793


RSV572
Light chain, G Protein
Hu 131-2G
US8273354 SEQ ID NO: 55
5794


RSV573
Light chain, G Protein
AT46
US20150004155 SEQ ID NO:
5795





 127



RSV574
Light chain, G Protein
AT32
US20150004155 SEQ ID NO:
5796





 128



RSV575
Light chain, G Protein
AT33
US20150004155 SEQ ID NO:
5797





 129



RSV576
Light chain, G Protein
AT34
US20150004155 SEQ ID NO:
5798





 130



RSV577
Light chain, G Protein
AT35
US20150004155 SEQ ID NO:
5799





 131



RSV578
Light chain, G Protein
AT36
US20150004155 SEQ ID NO:
5800





 132



RSV579
Light chain, G Protein
AT37
US20150004155 SEQ ID NO:
5801





 133



RSV580
Light chain, G Protein
AT39
US20150004155 SEQ ID NO:
5802





 134



RSV581
Light chain, G Protein
AT40
US20150004155 SEQ ID NO:
5803





 135



RSV582
Light chain, G Protein
AT42
US20150004155 SEQ ID NO:
5804





 136



RSV583
Light chain, G Protein
AT43
US20150004155 SEQ ID NO:
5805





 137



RSV584
Light chain, G Protein
AT44
US20150004155 SEQ ID NO:
5806





 138



RSV585
Light chain, G Protein
AT45
US20150004155 SEQ ID NO:
5807





 139



RSV586
Light chain, G Protein
AT47
US20150004155 SEQ ID NO:
5808





 140



RSV587
Light chain, G Protein
AT49
US20150004155 SEQ ID NO:
5809





 141



RSV588
Light chain, G Protein
AT50
US20150004155 SEQ ID NO:
5810





 142



RSV589
Light chain, G Protein
AT51
US20150004155 SEQ ID NO:
5811





 143



RSV590
Light chain variable region, G
CB017.3L
WO2014170258 SEQ ID NO:
5812



Protein

 74



RSV591
Light chain variable region, G
CB017.5L
WO2014170258 SEQ ID NO:
5813



Protein

 76



RSV592
Light chain variable region, G
CB028.1
WO2014170258 SEQ ID NO:
5814



Protein

 78



RSV593
Light chain variable region, G
CB030.1
WO2014170258 SEQ ID NO:
5815



Protein

 80



RSV594
Light chain variable region, G
CB047.1
WO2014170258 SEQ ID NO:
5816



Protein

 82



RSV595
Light chain variable region, G
CB047.2
WO2014170258 SEQ ID NO:
5817



Protein

 84



RSV596
Light chain variable region, G
CB065.1
WO2014170258 SEQ ID NO:
5818



Protein

 86



RSV597
Light chain variable region, G
CB071.1L
WO2014170258 SEQ ID NO:
5819



Protein

 88



RSV598
Light chain variable region, G
CB072.1L
WO2014170258 SEQ ID NO:
5820



Protein

 90



RSV599
Light chain variable region, G
CB073.1L
WO2014170258 SEQ ID NO:
5821



Protein

 92



RSV600
Light chain variable region, G
CB076.2L
WO2014170258 SEQ ID NO:
5822



Protein

 94



RSV601
Light chain variable region, G
CB079.1
WO2014170258 SEQ ID NO:
5823



Protein

 96



RSV602
Light chain, human

Wen,X., “Structure of the
5824



metapneumovirus fusion

human metapueumovirus fusion




protein with

protein with neutralizing




neutralizing antibody identifies

antibody identifies a




a pueumovirus antigenic site

pneumovirus antigenic site”,






Nat. Struct. Mol. Biol. 19 (4),






461-463 (2012), NCBI






Accession # 4DAG_L(213 aa)



RSV603
Light chain
AM14
US20140377279 SEQ ID NO:
5825





 79



RSV604
Light chain
AM16
US20140377279 SEQ ID NO:
5826





 86



RSV605
Light chain
AM23
US20140377279 SEQ ID NO:
5827





 93



RSV606
Light chain
D25
US20140377279 SEQ ID NO: 8
5828


RSV607
Light chain
AFFF
US7635568 SEQ ID NO: 211
5829


RSV608
Light chain
P12f2
US7635568 SEQ ID NO: 213
5830


RSV609
Light chain
P12f4
US7635568 SEQ ID NO: 215
5831


RSV610
Light chain
P11d4
US7635568 SEQ ID NO: 217
5832


RSV611
Light chain
Ale9
US7635568 SEQ ID NO: 219
5833


RSV612
Light chain
A12a6
US7635568 SEQ ID NO: 221
5834


RSV613
Light chain
A13c4
US7635568 SEQ ID NO: 223
5835


RSV614
Light chain
A17d4
US7635568 SEQ ID NO: 225
5836


RSV615
Light chain
A4B4
US7635568 SEQ ID NO: 227
5837


RSV616
Light chain
A8c7
US7635568 SEQ ID NO: 229
5838


RSV617
Light chain
1X-493-L1FR
US7635568 SEQ ID NO: 231
5839


RSV618
Light chain
H3-3F4, DG
US7635568 SEQ ID NO: 233
5840


RSV619
Light chain
M3H9
US7635568 SEQ ID NO: 235
5841


RSV620
Light chain
Y10H6
US7635568 SEQ ID NO: 237
5842


RSV621
Light chain
DG
US7635568 SEQ ID NO: 239
5843


RSV622
Light chain
AFFF(1)
US7635568 SEQ ID NO: 241
5844


RSV623
Light chain
6H8
US7635568 SEQ ID NO: 243
5845


RSV624
Light chain
L1-7E5
US7635568 SEQ ID NO: 245
5846


RSV625
Light chain
L2-15B10
US7635568 SEQ ID NO: 247
5847


RSV626
Light chain
A13a11
US7635568 SEQ ID NO: 249
5848


RSV627
Light chain
A1h5
US7635568 SEQ ID NO: 251
5849


RSV628
Light chain
A4B4(1)
US7635568 SEQ ID NO: 253
5850


RSV629
Light chain
A4B4L1FR-S28R
US7635568 SEQ ID NO: 255
5851


RSV630
Light chain
A4B4-F52S
US7635568 SEQ ID NO: 257
5852


RSV631
Light chain variable region
AFFF
US7635568 SEQ ID NO: 13
5853


RSV632
Light chain variable region
P12f2
US7635568 SEQ ID NO: 21
5854


RSV633
Light chain variable region
P12f4
US7635568 SEQ ID NO: 26
5855


RSV634
Light chain variable region
P11d4
US7635568 SEQ ID NO: 30
5856


RSV635
Light chain variable region
Ale9
US7635568 SEQ ID NO: 34
5857


RSV636
Light chain variable region
A12a6
US7635568 SEQ ID NO: 38
5858


RSV637
Light chain variable region
A13c4
US7635568 SEQ ID NO: 42
5859


RSV638
Light chain variable region
A17d4
US7635568 SEQ ID NO: 46
5860


RSV639
Light chain variable region
A4B4
US7635568 SEQ ID NO: 49
5861


RSV640
Light chain variable region
A8c7
US7635568 SEQ ID NO: 52
5862


RSV641
Light chain variable region
1X-493L1FR
US7635568 SEQ ID NO: 54
5863


RSV642
Light chain variable region
H3-3F4, DG
US7635568 SEQ ID NO: 56
5864


RSV643
Light chain variable region
M3H9
US7635568 SEQ ID NO: 70
5865


RSV644
Light chain variable region
Y10H6
US7635568 SEQ ID NO: 58
5866


RSV645
Light chain variable region
AFFF(1)
US7635568 SEQ ID NO: 60
5867


RSV646
Light chain variable region
6H8
US7635568 SEQ ID NO: 62
5868


RSV647
Light chain variable region
L1-7E5
US7635568 SEQ ID NO: 64
5869


RSV648
Light chain variable region
L2-15B10
US7635568 SEQ ID NO: 65
5870


RSV649
Light chain variable region
A13a11
US7635568 SEQ ID NO: 68
5871


RSV650
Light chain variable region
A1h5
US7635568 SEQ ID NO: 71
5872


RSV651
Light chain variable region
A4B4(1)
US7635568 SEQ ID NO: 74
5873


RSV652
Light chain variable region
A4B4L1FR-S28R
US7635568 SEQ ID NO: 11
5874


RSV653
Light chain variable region
A4B4-F52S
US7635568 SEQ ID NO: 76
5875


RSV654
Light chain variable region
6H; 11H; 21H;
US7364737 SEQ ID NO: 21
5876




22H; and 23H




RSV655
Light chain variable region
13H and 19H
US7364737 SEQ ID NO: 22
5877


RSV656
Light chain variable region
6L; 11L; 21L; and
US7364737 SEQ ID NO: 23
5878




22L




RSV657
Light chain variable region
23L
US7364737 SEQ ID NO: 24
5879


RSV658
Light chain variable region
13L and 19L
US7364737 SEQ ID NO: 25
5880


RSV659
Light chain variable region

US7364742 SEQ ID NO: 9
5881


RSV660
Light chain variable region

US7364742 SEQ ID NO: 10
5882


RSV661
Light chain variable region

US7364742 SEQ ID NO: 11
5883


RSV662
Light chain variable region

US7364742 SEQ ID NO: 12
5884


RSV663
Light chain variable region
D2E7
EP1807111; WO2006041970
5885





SEQ ID NO: 1



RSV664
Light chain variable region
2SD4
EP1807111; WO2006041970
5886





SEQ ID NO: 9



RSV665
Light chain variable, M2 1
8A4/G9-IgG
US20140348858 SEQ ID NO: 4
5887



antigen





RSV666
Light chain, Pre fusion RSV F
HMB2435
WO2015010792 SEQ ID NO:
5888



protein

 14



RSV667
Light chain, Pre fusion RSV F
HMB2437
WO2015010792 SEQ ID NO:
5889



protein

 30



RSV668
Light chain, Pre fusion RSV F
HMB2416
WO2015010792 SEQ ID NO:
5890



protein

 46



RSV669
Light chain, Pre fusion RSV F
HMB2437
WO2015010792 SEQ ID NO:
5891



protein

 86



RSV670
Light chain, Pre fusion RSV F
CR9501
WO2014202570 SEQ ID NO:
5892



protein

 61



RSV671
Light chain, Pre fusion RSV F
CR9502
WO2014202570 SEQ ID NO:
5893



protein

 65



RSV672
Light chain 1, Pre fusion RSV
HMB2432
WO2015010792 SEQ ID NO:
5894



F protein

 62



RSV673
Light chain FR GL, Pre fusion
HMB2432
WO2015010792 SEQ ID NO:
5895



RSV F protein

 66



RSV674
Light chain 2, Pre fusion RSV
HMB2435
WO2015010792 SEQ ID NO:
5896



F protein

 76



RSV675
derived Ig variable region
RSV19VH
EP636182; WO1993020210;
5897



amino acid sequence, F protein

SEQ ID NO: 13



RSV676
derived Ig variable region
pHuRSV19VH
EP636182; WO1993020210;
5898



amino acid sequence, F protein

SEQ ID NO: 14



RSV677
derived Ig variable region
pHuRSV19VHFNS
EP636182; WO1993020210;
5899



amino acid sequence, F protein

SEQ ID NO: 15



RSV678
derived Ig variable region
pHuRSV19VHNIK
EP636182; WO1993020210;
5900



amino acid sequence, F protein

SEQ ID NO: 16



RSV679
derived Ig variable region
pHuRSV19VK
EP636182; WO1993020210;
5901



amino acid sequence, F protein

SEQ ID NO: 17



RSV680
Nanobody binding to RSV F
LG202A10
US20110182897 SEQ ID NO:
5902



protein

 126



RSV681
Nanobody binding to RSV F
LG202A12
US20110182897 SEQ ID NO:
5903



protein

 127



RSV682
Nanobody binding to RSV F
LG202A5
US20110182897 SEQ ID NO:
5904



protein

 128



RSV683
Nanobody binding to RSV F
LG202A9
US20110182897 SEQ ID NO:
5905



protein

 129



RSV684
Nanobody binding to RSV F
LG202B10
US20110182897 SEQ ID NO:
5906



protein

 130



RSV685
Nanobody binding to RSV F
LG202B7
US20110182897 SEQ ID NO:
5907



protein

 131



RSV686
Nanobody binding to RSV F
LG202B8
US20110182897 SEQ ID NO:
5908



protein

 132



RSV687
Nanobody binding to RSV F
LG202B9
US20110182897 SEQ ID NO:
5909



protein

 133



RSV688
Nanobody binding to RSV F
LG202C1
US20110182897 SEQ ID NO:
5910



protein

 134



RSV689
Nanobody binding to RSV F
LG202C11
US20110182897 SEQ ID NO:
5911



protein

 135



RSV690
Nanobody binding to RSV F
LG202C2
US20110182897 SEQ ID NO:
5912



protein

 136



RSV691
Nanobody binding to RSV F
LG202C7
US20110182897 SEQ ID NO:
5913



protein

 137



RSV692
Nanobody binding to RSV F
LG202C8
US20110182897 SEQ ID NO:
5914



protein

 138



RSV693
Nanobody binding to RSV F
LG202C9
US20110182897 SEQ ID NO:
5915



protein

 139



RSV694
Nanobody binding to RSV F
LG202D5
US20110182897 SEQ ID NO:
5916



protein

 140



RSV695
Nanobody binding to RSV F
LG202D7
US20110182897 SEQ ID NO:
5917



protein

 141



RSV696
Nanobody binding to RSV F
LG202D8
US20110182897 SEQ ID NO:
5918



protein

 142



RSV697
Nanobody binding to RSV F
LG202E11
US20110182897 SEQ ID NO:
5919



protein

 143



RSV698
Nanobody binding to RSV F
LG202E2
US20110182897 SEQ ID NO:
5920



protein

 144



RSV699
Nanobody binding to RSV F
LG202E5
US20110182897 SEQ ID NO:
5921



protein

 145



RSV700
Nanobody binding to RSV F
LG202E6
US20110182897 SEQ ID NO:
5922



protein

 146



RSV701
Nanobody binding to RSV F
LG202E7
US20110182897 SEQ ID NO:
5923



protein

 147



RSV702
Nanobody binding to RSV F
LG202F10
US20110182897 SEQ ID NO:
5924



protein

 148



RSV703
Nanobody binding to RSV F
LG202F12
US20110182897 SEQ ID NO:
5925



protein

 149



RSV704
Nanobody binding to RSV F
LG202F3
US20110182897 SEQ ID NO:
5926



protein

 150



RSV705
Nanobody binding to RSV F
LG202F4
US20110182897 SEQ ID NO:
5927



protein

 151



RSV706
Nanobody binding to RSV F
LG202F8
US20110182897 SEQ ID NO:
5928



protein

 152



RSV707
Nanobody binding to RSV F
LG202G11
US20110182897 SEQ ID NO:
5929



protein

 153



RSV708
Nanobody binding to RSV F
LG202G3
US20110182897 SEQ ID NO:
5930



protein

 154



RSV709
Nanobody binding to RSV F
LG202G8
US20110182897 SEQ ID NO:
5931



protein

 155



RSV710
Nanobody binding to RSV F
LG202H2
US20110182897 SEQ ID NO:
5932



protein

 156



RSV711
Nanobody binding to RSV F
LG202H8
US20110182897 SEQ ID NO:
5933



protein

 157



RSV712
Nanobody binding to RSV F
LG191B9
US20110182897 SEQ ID NO:
5934



protein

 158



RSV713
Nanobody binding to RSV F
LG191D3
US20110182897 SEQ ID NO:
5935



protein

 159



RSV714
Nanobody binding to RSV F
LG192A8
US20110182897 SEQ ID NO:
5936



protein

 160



RSV715
Nanobody binding to RSV F
LG192B1
US20110182897 SEQ ID NO:
5937



protein

 161



RSV716
Nanobody binding to RSV F
LG192C10
US20110182897 SEQ ID NO:
5938



protein

 162



RSV717
Nanobody binding to RSV F
LG192C4
US20110182897 SEQ ID NO:
5939



protein

 163



RSV718
Nanobody binding to RSV F
LG192C6
US20110182897 SEQ ID NO:
5940



protein

 164



RSV719
Nanobody binding to RSV F
LG192D3
US20110182897 SEQ ID NO:
5941



protein

 165



RSV720
Nanobody binding to RSV F
LG191E4
US20110182897 SEQ ID NO:
5942



protein

 166



RSV721
Nanobody binding to RSV F
LG192F2
US20110182897 SEQ ID NO:
5943



protein

 167



RSV722
Nanobody binding to RSV F
LG192H1
US20110182897 SEQ ID NO:
5944



protein

 168



RSV723
Nanobody binding to RSV F
LG192H2
US20110182897 SEQ ID NO:
5945



protein

 169



RSV724
Nanobody binding to RSV F
LG20610B
US20110182897 SEQ ID NO:
5946



protein

 170



RSV725
Nanobody binding to RSV F
LG20610C
US20110182897 SEQ ID NO:
5947



protein

 171



RSV726
Nanobody binding to RSV F
LG20610D
US20110182897 SEQ ID NO:
5948



protein

 172



RSV727
Nanobody binding to RSV F
LG20610E
US20110182897 SEQ ID NO:
5949



protein

 173



RSV728
Nanobody binding to RSV F
LG20610F
US20110182897 SEQ ID NO:
5950



protein

 174



RSV729
Nanobody binding to RSV F
LG20611D
US20110182897 SEQ ID NO:
5951



protein

 175



RSV730
Nanobody binding to RSV F
LG20611H
US20110182897 SEQ ID NO:
5952



protein

 176



RSV731
Nanobody binding to RSV F
LG20612F
US20110182897 SEQ ID NO:
5953



protein

 177



RSV732
Nanobody binding to RSV F
LG2062A
US20110182897 SEQ ID NO:
5954



protein

 178



RSV733
Nanobody binding to RSV F
LG2062C
US20110182897 SEQ ID NO:
5955



protein

 179



RSV734
Nanobody binding to RSV F
LG2062E
US20110182897 SEQ ID NO:
5956



protein

 180



RSV735
Nanobody binding to RSV F
LG2062F
US20110182897 SEQ ID NO:
5957



protein

 181



RSV736
Nanobody binding to RSV F
LG2062G
US20110182897 SEQ ID NO:
5958



protein

 182



RSV737
Nanobody binding to RSV F
LG2062H
US20110182897 SEQ ID NO:
5959



protein

 183



RSV738
Nanobody binding to RSV F
LG2063A
US20110182897 SEQ ID NO:
5960



protein

 184



RSV739
Nanobody binding to RSV F
LG2063B
US20110182897 SEQ ID NO:
5961



protein

 185



RSV740
Nanobody binding to RSV F
LG2063C
US20110182897 SEQ ID NO:
5962



protein

 186



RSV741
Nanobody binding to RSV F
LG2063D
US20110182897 SEQ ID NO:
5963



protein

 187



RSV742
Nanobody binding to RSV F
LG2063E
US20110182897 SEQ ID NO:
5964



protein

 188



RSV743
Nanobody binding to RSV F
LG2063F
US20110182897 SEQ ID NO:
5965



protein

 189



RSV744
Nanobody binding to RSV F
LG2064D
US20110182897 SEQ ID NO:
5966



protein

 190



RSV745
Nanobody binding to RSV F
LG2064G
US20110182897 SEQ ID NO:
5967



protein

 191



RSV746
Nanobody binding to RSV F
LG2065A
US20110182897 SEQ ID NO:
5968



protein

 192



RSV747
Nanobody binding to RSV F
LG2065E
US20110182897 SEQ ID NO:
5969



protein

 193



RSV748
Nanobody binding to RSV F
LG2066A
US20110182897 SEQ ID NO:
5970



protein

 194



RSV749
Nanobody binding to RSV F
LG2066D
US20110182897 SEQ ID NO:
5971



protein

 195



RSV750
Nanobody binding to RSV F
LG2067B
US20110182897 SEQ ID NO:
5972



protein

 196



RSV751
Nanobody binding to RSV F
LG2067C
US20110182897 SEQ ID NO:
5973



protein

 197



RSV752
Nanobody binding to RSV F
LG2067E
US20110182897 SEQ ID NO:
5974



protein

 198



RSV753
Nanobody binding to RSV F
LG2067G
US20110182897 SEQ ID NO:
5975



protein

 199



RSV754
Nanobody binding to RSV F
LG2067H
US20110182897 SEQ ID NO:
5976



protein

 200



RSV755
Nanobody binding to RSV F
LG20711A
US20110182897 SEQ ID NO:
5977



protein

 201



RSV756
Nanobody binding to RSV F
LG20711B
US20110182897 SEQ ID NO:
5978



protein

 202



RSV757
Nanobody binding to RSV F
LG20711D
US20110182897 SEQ ID NO:
5979



protein

 203



RSV758
Nanobody binding to RSV F
LG20711E
US20110182897 SEQ ID NO:
5980



protein

 204



RSV759
Nanobody binding to RSV F
LG20711F
US20110182897 SEQ ID NO:
5981



protein

 205



RSV760
Nanobody binding to RSV F
LG20711G
US20110182897 SEQ ID NO:
5982



protein

 206



RSV761
Nanobody binding to RSV F
LG20711H
US20110182897 SEQ ID NO:
5983



protein

 207



RSV762
Nanobody binding to RSV F
LG2071A
US20110182897 SEQ ID NO:
5984



protein

 208



RSV763
Nanobody binding to RSV F
LG2071B
US20110182897 SEQ ID NO:
5985



protein

 209



RSV764
Nanobody binding to RSV F
LG2071C
US20110182897 SEQ ID NO:
5986



protein

 210



RSV765
Nanobody binding to RSV F
LG207D1
US20110182897 SEQ ID NO:
5987



protein

 211



RSV766
Nanobody binding to RSV F
LG2071E
US20110182897 SEQ ID NO:
5988



protein

 212



RSV767
Nanobody binding to RSV F
LG2071F
US20110182897 SEQ ID NO:
5989



protein

 213



RSV768
Nanobody binding to RSV F
LG2074A
US20110182897 SEQ ID NO:
5990



protein

 214



RSV769
Nanobody binding to RSV F
LG2074B
US20110182897 SEQ ID NO:
5991



protein

 215



RSV770
Nanobody binding to RSV F
LG2074D
US20110182897 SEQ ID NO:
5992



protein

 216



RSV771
Nanobody binding to RSV F
LG2074H
US20110182897 SEQ ID NO:
5993



protein

 217



RSV772
Nanobody binding to RSV F
LG2075A
US20110182897 SEQ ID NO:
5994



protein

 218



RSV773
Nanobody binding to RSV F
LG2075B
US20110182897 SEQ ID NO:
5995



protein

 219



RSV774
Nanobody binding to RSV F
LG2075C
US20110182897 SEQ ID NO:
5996



protein

 220



RSV775
Nanobody binding to RSV F
LG2075D
US20110182897 SEQ ID NO:
5997



protein

 221



RSV776
Nanobody binding to RSV F
LG2075E
US20110182897 SEQ ID NO:
5998



protein

 222



RSV777
Nanobody binding to RSV F
LG2076A
US20110182897 SEQ ID NO:
5999



protein

 223



RSV778
Nanobody binding to RSV F
LG2076B
US20110182897 SEQ ID NO:
6000



protein

 224



RSV779
Nanobody binding to RSV F
LG2076C
US20110182897 SEQ ID NO:
6001



protein

 225



RSV780
Nanobody binding to RSV F
LG2076D
US20110182897 SEQ ID NO:
6002



protein

 226



RSV781
Nanobody binding to RSV F
LG2076E
US20110182897 SEQ ID NO:
6003



protein

 227



RSV782
Nanobody binding to RSV F
LG2076F
US20110182897 SEQ ID NO:
6004



protein

 228



RSV783
Nanobody binding to RSV F
LG2079A
US20110182897 SEQ ID NO:
6005



protein

 229



RSV784
Nanobody binding to RSV F
LG2079B
US20110182897 SEQ ID NO:
6006



protein

 230



RSV785
Nanobody binding to RSV F
LG2079C
US20110182897 SEQ ID NO:
6007



protein

 231



RSV786
Nanobody binding to RSV F
LG2079D
US20110182897 SEQ ID NO:
6008



protein

 232



RSV787
Nanobody binding to RSV F
LG2079E
US20110182897 SEQ ID NO:
6009



protein

 233



RSV788
Nanobody binding to RSV F
LG2079F
US20110182897 SEQ ID NO:
6010



protein

 234



RSV789
Nanobody binding to RSV F
LG2079G
US20110182897 SEQ ID NO:
6011



protein

 235



RSV790
Nanobody binding to RSV F
LG2079H
US20110182897 SEQ ID NO:
6012



protein

 236



RSV791
Nanobody binding to RSV F
LG213B7
US20110182897 SEQ ID NO:
6013



protein

 237



RSV792
Nanobody binding to RSV F
LG213D6
US20110182897 SEQ ID NO:
6014



protein

 238



RSV793
Nanobody binding to RSV F
LG213D7
US20110182897 SEQ ID NO:
6015



protein

 239



RSV794
Nanobody binding to RSV F
LG213E6
US20110182897 SEQ ID NO:
6016



protein

 240



RSV795
Nanobody binding to RSV F
LG213H7
US20110182897 SEQ ID NO:
6017



protein

 241



RSV796
Nanobody binding to RSV F
LG214A8
US20110182897 SEQ ID NO:
6018



protein

 242



RSV797
Nanobody binding to RSV F
LG214C10
US20110182897 SEQ ID NO:
6019



protein

 243



RSV798
Nanobody binding to RSV F
LG214D10
US20110182897 SEQ ID NO:
6020



protein

 244



RSV799
Nanobody binding to RSV F
LG214E8
US20110182897 SEQ ID NO:
6021



protein

 245



RSV800
Nanobody binding to RSV F
LG214F8
US20110182897 SEQ ID NO:
6022



protein

 246



RSV801
Nanobody binding to RSV F
LG214H10
US20110182897 SEQ ID NO:
6023



protein

 247



RSV802
Nanobody binding to RSV F
RSVPMP5C1
US20110182897 SEQ ID NO:
6024



protein

 248



RSV803
Nanobody binding to RSV F
RSVPMP8A1
US20110182897 SEQ ID NO:
6025



protein

 249



RSV804
Nanobody binding to RSV F
RSVPMP8G1
US20110182897 SEQ ID NO:
6026



protein

 250



RSV805
Nanobody binding to RSV F
RSVPMP25B3
US20110182897 SEQ ID NO:
6027



protein

 251



RSV806
Nanobody binding to RSV F
RSVPMP8C8
US20110182897 SEQ ID NO:
6028



protein

 252



RSV807
Nanobody binding to RSV F
RSVPMP5A6
US20110182897 SEQ ID NO:
6029



protein

 253



RSV808
Nanobody binding to RSV F
RSVPMP8E11
US20110182897 SEQ ID NO:
6030



protein

 254



RSV809
Nanobody binding to RSV F
RSVPMP8F11
US20110182897 SEQ ID NO:
6031



protein

 255



RSV810
Nanobody binding to RSV F
RSVPMP13F11
US20110182897 SEQ ID NO:
6032



protein

 256



RSV811
Nanobody binding to RSV F
RSVPMP15B8
US20110182897 SEQ ID NO:
6033



protein

 257



RSV812
Nanobody binding to RSV F
RSVPMP15G11
US20110182897 SEQ ID NO:
6034



protein

 258



RSV813
Nanobody binding to RSV F
RSVPMP17C10
US20110182897 SEQ ID NO:
6035



protein

 259



RSV814
Nanobody binding to RSV F
RSVPMP21E7
US20110182897 SEQ ID NO:
6036



protein

 260



RSV815
Nanobody binding to RSV F
RSVPMP21F8
US20110182897 SEQ ID NO:
6037



protein

 261



RSV816
Nanobody binding to RSV F
RSVPMP5A2
US20110182897 SEQ ID NO:
6038



protein

 262



RSV817
Nanobody binding to RSV F
RSVPMP5B2
US20110182897 SEQ ID NO:
6039



protein

 263



RSV818
Nanobody binding to RSV F
RSVPMP5C3
US20110182897 SEQ ID NO:
6040



protein

 264



RSV819
Nanobody binding to RSV F
RSVPMP5D2
US20110182897 SEQ ID NO:
6041



protein

 265



RSV820
Nanobody binding to RSV F
RSVPMP5E2
US20110182897 SEQ ID NO:
6042



protein

 266



RSV821
Nanobody binding to RSV F
RSVPMP5F3
US20110182897 SEQ ID NO:
6043



protein

 267



RSV822
Nanobody binding to RSV F
RSVPMP5G3
US20110182897 SEQ ID NO:
6044



protein

 268



RSV823
Nanobody binding to RSV F
RSVPMP5H2
US20110182897 SEQ ID NO:
6045



protein

 269



RSV824
Nanobody binding to RSV F
RSVPMP5H3
US20110182897 SEQ ID NO:
6046



protein

 270



RSV825
Nanobody binding to RSV F
RSVPMP8C1
US20110182897 SEQ ID NO:
6047



protein

 271



RSV826
Nanobody binding to RSV F
RSVPMP8F2
US20110182897 SEQ ID NO:
6048



protein

 272



RSV827
Nanobody binding to RSV F
RSVPMP8G4
US20110182897 SEQ ID NO:
6049



protein

 273



RSV828
Nanobody binding to RSV F
RSVPMP13A1
US20110182897 SEQ ID NO:
6050



protein

 274



RSV829
Nanobody binding to RSV F
RSVPMP13A4
US20110182897 SEQ ID NO:
6051



protein

 275



RSV830
Nanobody binding to RSV F
RSVPMP13B1
US20110182897 SEQ ID NO:
6052



protein

 276



RSV831
Nanobody binding to RSV F
RSVPMP13B2
US20110182897 SEQ ID NO:
6053



protein

 277



RSV832
Nanobody binding to RSV F
RSVPMP13C1
US20110182897 SEQ ID NO:
6054



protein

 278



RSV833
Nanobody binding to RSV F
RSVPMP13C3
US20110182897 SEQ ID NO:
6055



protein

 279



RSV834
Nanobody binding to RSV F
RSVPMP13D6
US20110182897 SEQ ID NO:
6056



protein

 280



RSV835
Nanobody binding to RSV F
RSVPMP13E2
US20110182897 SEQ ID NO:
6057



protein

 281



RSV836
Nanobody binding to RSV F
RSVPMP13E3
US20110182897 SEQ ID NO:
6058



protein

 282



RSV837
Nanobody binding to RSV F
RSVPMP15A5
US20110182897 SEQ ID NO:
6059



protein

 283



RSV838
Nanobody binding to RSV F
RSVPMP15A6
US20110182897 SEQ ID NO:
6060



protein

 284



RSV839
Nanobody binding to RSV F
RSVPMP15B2
US20110182897 SEQ ID NO:
6061



protein

 285



RSV840
Nanobody binding to RSV F
RSVPMP15B3
US20110182897 SEQ ID NO:
6062



protein

 286



RSV841
Nanobody binding to RSV F
RSVPMP15E5
US20110182897 SEQ ID NO:
6063



protein

 287



RSV842
Nanobody binding to RSV F
RSVPMP17C2
US20110182897 SEQ ID NO:
6064



protein

 288



RSV843
Nanobody binding to RSV F
RSVPMP17D4
US20110182897 SEQ ID NO:
6065



protein

 289



RSV844
Nanobody binding to RSV F
RSVPMP17G4
US20110182897 SEQ ID NO:
6066



protein

 290



RSV845
Nanobody binding to RSV F
RSVPMP19B2
US20110182897 SEQ ID NO:
6067



protein

 291



RSV846
Nanobody binding to RSV F
RSVPMP25A4
US20110182897 SEQ ID NO:
6068



protein

 292



RSV847
Nanobody binding to RSV F
RSVPMP25A9
US20110182897 SEQ ID NO:
6069



protein

 293



RSV848
Nanobody binding to RSV F
RSVPMP25B5
US20110182897 SEQ ID NO:
6070



protein

 294



RSV849
Nanobody binding to RSV F
RSVPMP25G2
US20110182897 SEQ ID NO:
6071



protein

 295



RSV850
Nanobody binding to RSV F
RSVPMP25H5
US20110182897 SEQ ID NO:
6072



protein

 296



RSV851
Nanobody binding to RSV F
RSVPMP25E11
US20110182897 SEQ ID NO:
6073



protein

 297



RSV852
Nanobody binding to RSV F
RSVPMP8G3
US20110182897 SEQ ID NO:
6074



protein

 298



RSV853
Nanobody binding to RSV F
RSVPMP13B5
US20110182897 SEQ ID NO:
6075



protein

 299



RSV854
Nanobody binding to RSV F
RSVPMP15F2
US20110182897 SEQ ID NO:
6076



protein

 300



RSV855
Nanobody binding to RSV F
RSVPMP19E2
US20110182897 SEQ ID NO:
6077



protein

 301



RSV856
Nanobody binding to RSV F
RSVPMP25D1
US20110182897 SEQ ID NO:
6078



protein

 302



RSV857
Nanobody binding to RSV F
RSVPMP5A1
US20110182897 SEQ ID NO:
6079



protein

 303



RSV858
Nanobody binding to RSV F
RSVPMP5G2
US20110182897 SEQ ID NO:
6080



protein

 304



RSV859
Nanobody binding to RSV F
RSVPMP5H1
US20110182897 SEQ ID NO:
6081



protein

 305



RSV860
Nanobody binding to RSV F
RSVPMP6B1
US20110182897 SEQ ID NO:
6082



protein

 306



RSV861
Nanobody binding to RSV F
RSVPMP8H2
US20110182897 SEQ ID NO:
6083



protein

 307



RSV862
Nanobody binding to RSV F
RSVPMP8H3
US20110182897 SEQ ID NO:
6084



protein

 308



RSV863
Nanobody binding to RSV F
RSVPMP13A3
US20110182897 SEQ ID NO:
6085



protein

 309



RSV864
Nanobody binding to RSV F
RSVPMP13C5
US20110182897 SEQ ID NO:
6086



protein

 310



RSV865
Nanobody binding to RSV F
RSVPMP13H1
US20110182897 SEQ ID NO:
6087



protein

 311



RSV866
Nanobody binding to RSV F
RSVPMP13H2
US20110182897 SEQ ID NO:
6088



protein

 312



RSV867
Nanobody binding to RSV F
RSVPMP15E6
US20110182897 SEQ ID NO:
6089



protein

 313



RSV868
Nanobody binding to RSV F
RSVPMP17A3
US20110182897 SEQ ID NO:
6090



protein

 314



RSV869
Nanobody binding to RSV F
RSVPMP25G8
US20110182897 SEQ ID NO:
6091



protein

 315



RSV870
Nanobody binding to RSV F
RSVPMP6D1
US20110182897 SEQ ID NO:
6092



protein

 316



RSV871
Nanobody binding to RSV F
RSVPMP8D5
US20110182897 SEQ ID NO:
6093



protein

 317



RSV872
Nanobody binding to RSV F
RSVPMP13B4
US20110182897 SEQ ID NO:
6094



protein

 318



RSV873
Nanobody binding to RSV F
RSVPMP13B6
US20110182897 SEQ ID NO:
6095



protein

 319



RSV874
Nanobody binding to RSV F
RSVPMP13E6
US20110182897 SEQ ID NO:
6096



protein

 320



RSV875
Nanobody binding to RSV F
RSVPMP13F4
US20110182897 SEQ ID NO:
6097



protein

 321



RSV876
Nanobody binding to RSV F
RSVPMP15H3
US20110182897 SEQ ID NO:
6098



protein

 322



RSV877
Nanobody binding to RSV F
RSVPMP17E5
US20110182897 SEQ ID NO:
6099



protein

 323



RSV878
Nanobody binding to RSV F
RSVPMP19D3
US20110182897 SEQ ID NO:
6100



protein

 324



RSV879
Nanobody binding to RSV F
RSVPMP19F3
US20110182897 SEQ ID NO:
6101



protein

 325



RSV880
Nanobody binding to RSV F
RSVPMP25C4
US20110182897 SEQ ID NO:
6102



protein

 326



RSV881
Nanobody binding to RSV F
RSVPMP25E3
US20110182897 SEQ ID NO:
6103



protein

 327



RSV882
Nanobody binding to RSV F
RSVPMP5G4
US20110182897 SEQ ID NO:
6104



protein

 328



RSV883
Nanobody binding to RSV F
RSVPMP6G5
US20110182897 SEQ ID NO:
6105



protein

 329



RSV884
Nanobody binding to RSV F
RSVPMP8E6
US20110182897 SEQ ID NO:
6106



protein

 330



RSV885
Nanobody binding to RSV F
RSVPMP13A10
US20110182897 SEQ ID NO:
6107



protein

 331



RSV886
Nanobody binding to RSV F
RSVPMP21H10
US20110182897 SEQ ID NO:
6108



protein

 332



RSV887
Nanobody binding to RSV F
RSVPMP5A8
US20110182897 SEQ ID NO:
6109



protein

 333



RSV888
Nanobody binding to RSV F
RSVPMP5A10
US20110182897 SEQ ID NO:
6110



protein

 334



RSV889
Nanobody binding to RSV F
RSVPMPHA6
US20110182897 SEQ ID NO:
6111



protein

 335



RSV890
Nanobody binding to RSV F
RSVPMP16A6
US20110182897 SEQ ID NO:
6112



protein

 336



RSV891
Nanobody binding to RSV F
RSVPMP22D6
US20110182897 SEQ ID NO:
6113



protein

 337



RSV892
Nanobody binding to RSV F
RSVPMP8E2
US20110182897 SEQ ID NO:
6114



protein

 338



RSV893
Nanobody binding to RSV F
RSVPMP8C6
US20110182897 SEQ ID NO:
6115



protein

 339



RSV894
Nanobody binding to RSV F
RSVPMP5C6
US20110182897 SEQ ID NO:
6116



protein

 340



RSV895
Nanobody binding to RSV F
RSVPMP6D4
US20110182897 SEQ ID NO:
6117



protein

 341



RSV896
Nanobody binding to RSV F
RSVPMP8B10
US20110182897 SEQ ID NO:
6118



protein

 342



RSV897
Nanobody binding to RSV F
RSVPMP8E10
US20110182897 SEQ ID NO:
6119



protein

 343



RSV898
Nanobody binding to RSV F
RSVPMP15A7
US20110182897 SEQ ID NO:
6120



protein

 344



RSV899
Nanobody binding to RSV F
RSVPMP15E10
US20110182897 SEQ ID NO:
6121



protein

 345



RSV900
Nanobody binding to RSV F
RSVPMP13C7
US20110182897 SEQ ID NO:
6122



protein

 346



RSV901
Nanobody binding to RSV F
RSVPMP15A9
US20110182897 SEQ ID NO:
6123



protein

 347



RSV902
Nanobody binding to RSV F
RSVPMP15F11
US20110182897 SEQ ID NO:
6124



protein

 348



RSV903
Nanobody binding to RSV F
RSVPMP15A1
US20110182897 SEQ ID NO:
6125



protein

 349



RSV904
Nanobody binding to RSV F
RSVPMP6H2
US20110182897 SEQ ID NO:
6126



protein

 350



RSV905
Nanobody binding to RSV F
RSVPMP17A9
US20110182897 SEQ ID NO:
6127



protein

 351



RSV906
Nanobody binding to RSV F
RSVPMP7G1
US20110182897 SEQ ID NO:
6128



protein

 352



RSV907
Nanobody binding to RSV F
RSVPMP5A9
US20110182897 SEQ ID NO:
6129



protein

 353



RSV908
Nanobody binding to RSV F
RSVPMP7B2
US20110182897 SEQ ID NO:
6130



protein

 354



RSV909
Nanobody binding to RSV F
RSVPMP22A4
US20110182897 SEQ ID NO:
6131



protein

 355



RSV910
Nanobody binding to RSV F
RSVPMP22E10
US20110182897 SEQ ID NO:
6132



protein

 356



RSV911
Nanobody binding to RSV F
RSVPMP22H4
US20110182897 SEQ ID NO:
6133



protein

 357



RSV912
Nanobody binding to RSV F
RSVPMP15C5
US20110182897 SEQ ID NO:
6134



protein

 358



RSV913
Nanobody binding to RSV F
RSVNC39
US20110182897 SEQ ID NO:
6135



protein

 359



RSV914
Nanobody binding to RSV F
RSVPMP7B9
US20110182897 SEQ ID NO:
6136



protein

 360



RSV915
Nanobody binding to RSV F
RSVPMP15E11
US20110182897 SEQ ID NO:
6137



protein

 361



RSV916
Nanobody binding to RSV F
RSVPMP7E7
US20110182897 SEQ ID NO:
6138



protein

 362



RSV917
Nanobody binding to RSV F
RSVPMP14H3
US20110182897 SEQ ID NO:
6139



protein

 363



RSV918
Nanobody binding to RSV F
RSVPMP24D6
US20110182897 SEQ ID NO:
6140



protein

 364



RSV919
Nanobody binding to RSV F
RSVPMP23E5
US20110182897 SEQ ID NO:
6141



protein

 365



RSV920
Nanobody binding to RSV F
RSVPMP8A6
US20110182897 SEQ ID NO:
6142



protein

 366



RSV921
Nanobody binding to RSV F
RSVPMP14E2
US20110182897 SEQ ID NO:
6143



protein

 367



RSV922
Nanobody binding to RSV F
RSVPMP25F3
US20110182897 SEQ ID NO:
6144



protein

 368



RSV923
Nanobody binding to RSV F
RSVPMP19A6
US20110182897 SEQ ID NO:
6145



protein

 369



RSV924
Nanobody binding to RSV F
RSVPMP23G1
US20110182897 SEQ ID NO:
6146



protein

 370



RSV925
Nanobody binding to RSV F
RSVPMP15H8
US20110182897 SEQ ID NO:
6147



protein

 371



RSV926
Nanobody binding to RSV F
RSVNC41
US20110182897 SEQ ID NO:
6148



protein

 372



RSV927
Nanobody binding to RSV F
RSVPMP6A8
US20110182897 SEQ ID NO:
6149



protein

 373



RSV928
Nanobody binding to RSV F
RSVPMP25H9
US20110182897 SEQ ID NO:
6150



protein

 374



RSV929
Nanobody binding to RSV F
RSVPMP8B11
US20110182897 SEQ ID NO:
6151



protein

 375



RSV930
Nanobody binding to RSV F
RSVPMP17E1
US20110182897 SEQ ID NO:
6152



protein

 376



RSV931
Nanobody binding to RSV F
RSVPMP21A4
US20110182897 SEQ ID NO:
6153



protein

 377



RSV932
Nanobody binding to RSV F
RSVPMP25A11
US20110182897 SEQ ID NO:
6154



protein

 378



RSV933
Nanobody binding to RSV F
RSVPMP25C8
US20110182897 SEQ ID NO:
6155



protein

 379



RSV934
Nanobody binding to RSV F
RSVNC23
US20110182897 SEQ ID NO:
6156



protein

 380



RSV935
Nanobody binding to RSV F
RSVPMP20A11
US20110182897 SEQ ID NO:
6157



protein

 381



RSV936
Nanobody binding to RSV F
RSVPMP20A9
US20110182897 SEQ ID NO:
6158



protein

 382



RSV937
Nanobody binding to RSV F
RSVPMP1F7
US20110182897 SEQ ID NO:
6159



protein

 383



RSV938
Nanobody binding to RSV F
RSVPMP20D6
US20110182897 SEQ ID NO:
6160



protein

 384



RSV939
Nanobody binding to RSV F
RSVPMP1F1
US20110182897 SEQ ID NO:
6161



protein

 385



RSV940
Nanobody binding to RSV F
RSVPMP3D3
US20110182897 SEQ ID NO:
6162



protein

 386



RSV941
Nanobody binding to RSV F
RSVPMP3E6
US20110182897 SEQ ID NO:
6163



protein

 387



RSV942
Nanobody binding to RSV F
RSVPMP1C8
US20110182897 SEQ ID NO:
6164



protein

 388



RSV943
Nanobody binding to RSV F
RSVPMP1A2
US20110182897 SEQ ID NO:
6165



protein

 389



RSV944
Nanobody binding to RSV F
RSVPMP1C5
US20110182897 SEQ ID NO:
6166



protein

 390



RSV945
Nanobody binding to RSV F
RSVPMP20G5
US20110182897 SEQ ID NO:
6167



protein

 391



RSV946
Nanobody binding to RSV F
RSVPMP4D8
US20110182897 SEQ ID NO:
6168



protein

 392



RSV947
Nanobody binding to RSV F
RSVPMP20B6
US20110182897 SEQ ID NO:
6169



protein

 393



RSV948
Nanobody binding to RSV F
RSVPMP1D11
US20110182897 SEQ ID NO:
6170



protein

 394



RSV949
Nanobody binding to RSV F
RSVPMP20A8
US20110182897 SEQ ID NO:
6171



protein

 395



RSV950
Nanobody binding to RSV F
RSVPMP20E7
US20110182897 SEQ ID NO:
6172



protein

 396



RSV951
Nanobody binding to RSV F
RSVPMP20G8
US20110182897 SEQ ID NO:
6173



protein

 397



RSV952
Nanobody binding to RSV F
RSVPMP2D3
US20110182897 SEQ ID NO:
6174



protein

 398



RSV953
Nanobody binding to RSV F
RSVPMP2G5
US20110182897 SEQ ID NO:
6175



protein

 399



RSV954
Nanobody binding to RSV F
RSVPMP2A6
US20110182897 SEQ ID NO:
6176



protein

 400



RSV955
Nanobody binding to RSV F
RSVPMP3A2
US20110182897 SEQ ID NO:
6177



protein

 401



RSV956
Nanobody binding to RSV F
RSVPMP4A8
US20110182897 SEQ ID NO:
6178



protein

 402



RSV957
Nanobody binding to RSV F
RSVPMP4F9
US20110182897 SEQ ID NO:
6179



protein

 403



RSV958
Nanobody binding to RSV F
RSVPMP1A6
US20110182897 SEQ ID NO:
6180



protein

 404



RSV959
Nanobody binding to RSV F
RSVPMP3C2
US20110182897 SEQ ID NO:
6181



protein

 405



RSV960
Nanobody binding to RSV F
RSVPMP4H9
US20110182897 SEQ ID NO:
6182



protein

 406



RSV961
Nanobody binding to RSV F
RSVPMP4B10
US20110182897 SEQ ID NO:
6183



protein

 407



RSV962
Nanobody binding to RSV F
203B1
US20110182897 SEQ ID NO:
6184



protein

2431



RSV963
Nanobody binding to RSV F
203B2
US20110182897 SEQ ID NO:
6185



protein

2432



RSV964
Nanobody binding to RSV F
203G1
US20110182897 SEQ ID NO:
6186



protein

2433



RSV965
Nanobody binding to RSV F
203H1
US20110182897 SEQ ID NO:
6187



protein

2434



RSV966
Nanobody binding to RSV F
202E4
US20110182897 SEQ ID NO:
6188



protein

2435



RSV967
Nanobody binding to RSV F
189E2
US20110182897 SEQ ID NO:
6189



protein

2436



RSV968
Nanobody binding to RSV F
203A12
US20110182897 SEQ ID NO:
6190



protein

2437



RSV969
Nanobody binding to RSV F
203A9
US20110182897 SEQ ID NO:
6191



protein

2438



RSV970
Nanobody binding to RSV F
203B12
US20110182897 SEQ ID NO:
6192



protein

2439



RSV971
Nanobody binding to RSV F
203D2
US20110182897 SEQ ID NO:
6193



protein

2440



RSV972
Nanobody binding to RSV F
203D9
US20110182897 SEQ ID NO:
6194



protein

2441



RSV973
Nanobody binding to RSV F
203G3
US20110182897 SEQ ID NO:
6195



protein

2442



RSV974
Nanobody binding to RSV F
203G9
US20110182897 SEQ ID NO:
6196



protein

2443



RSV975
Nanobody binding to RSV F
203G10
US20110182897 SEQ ID NO:
6197



protein

2444



RSV976
Nanobody binding to RSV F
203H9
US20110182897 SEQ ID NO:
6198



protein

2445



RSV977
Nanobody binding to RSV F
203H10
US20110182897 SEQ ID NO:
6199



protein

2446



RSV978
Nanobody binding to RSV F
202E4
US20110182897 SEQ ID NO:
6200



protein

2447



RSV979
Nanobody binding to RSV F
189E2
US20110182897 SEQ ID NO:
6201



protein

2448



RSV980
Nanobody binding to RSV F
PRSVPMP20C3
US20110182897 SEQ ID NO:
6202



protein

2574



RSV981
Nanobody binding to RSV F
PRSVPMP20C5
US20110182897 SEQ ID NO:
6203



protein

2575



RSV982
Nanobody binding to RSV F
PRSVPMP20B2
US20110182897 SEQ ID NO:
6204



protein

2576



RSV983
Nanobody binding to RSV F
PRSVPMP20C1
US20110182897 SEQ ID NO:
6205



protein

2577



RSV984
Nanobody binding to RSV F
PRSVPMP1G8
US20110182897 SEQ ID NO:
6206



protein

2578



RSV985
Nanobody binding to RSV F
PRSVNMP1A4
US20110182897 SEQ ID NO:
6207



protein

2579



RSV986
Nanobody binding to RSV F
PRSVPMP13E12
US20110182897 SEQ ID NO:
6208



protein

2580



RSV987
Nanobody binding to RSV F
PRSVPMP5C6
US20110182897 SEQ ID NO:
6209



protein

2581



RSV988
Nanobody binding to RSV F
LG203E7
US20110182897 SEQ ID NO:
6210



protein

2682



RSV989
Nanobody binding to RSV F
LG203G8
US20110182897 SEQ ID NO:
6211



protein

2683



RSV990
Nanobody binding to RSV F
LG211A10
US20110182897 SEQ ID NO:
6212



protein

2684



RSV991
Nanobody binding to RSV F
LG211A8
US20110182897 SEQ ID NO:
6213



protein

2685



RSV992
Nanobody binding to RSV F
LG211B10
US20110182897 SEQ ID NO:
6214



protein

2686



RSV993
Nanobody binding to RSV F
LG211B8
US20110182897 SEQ ID NO:
6215



protein

2687



RSV994
Nanobody binding to RSV F
LG211C12
US20110182897 SEQ ID NO:
6216



protein

2688



RSV995
Nanobody binding to RSV F
LG211C8
US20110182897 SEQ ID NO:
6217



protein

2689



RSV996
Nanobody binding to RSV F
LG211D10
US20110182897 SEQ ID NO:
6218



protein

2690



RSV997
Nanobody binding to RSV F
LG211D8
US20110182897 SEQ ID NO:
6219



protein

2691



RSV998
Nanobody binding to RSV F
LG211E10
US20110182897 SEQ ID NO:
6220



protein

2692



RSV999
Nanobody binding to RSV F
LG211E12
US20110182897 SEQ ID NO:
6221



protein

2693



RSV1000
Nanobody binding to RSV F
LG211E8
US20110182897 SEQ ID NO:
6222



protein

2694



RSV1001
Nanobody binding to RSV F
LG211H8
US20110182897 SEQ ID NO:
6223



protein

2695



RSV1002
Nanobody binding to RSV F
LG212A10
US20110182897SEQ ID NO:
6224



protein

2696



RSV1003
Nanobody binding to RSV F
LG212A12
US20110182897 SEQ ID NO:
6225



protein

2697



RSV1004
Nanobody binding to RSV F
LG212A2
US20110182897 SEQ ID NO:
6226



protein

2698



RSV1005
Nanobody binding to RSV F
LG212A8
US20110182897 SEQ ID NO:
6227



protein

2699



RSV1006
Nanobody binding to RSV F
LG212B12
US20110182897 SEQ ID NO:
6228



protein

2700



RSV1007
Nanobody binding to RSV F
LG212B2
US20110182897 SEQ ID NO:
6229



protein

2701



RSV1008
Nanobody binding to RSV F
LG212C12
US20110182897 SEQ ID NO:
6230



protein

2702



RSV1009
Nanobody binding to RSV F
LG212D10
US20110182897 SEQ ID NO:
6231



protein

2703



RSV1010
Nanobody binding to RSV F
LG212D12
US20110182897 SEQ ID NO:
6232



protein

2704



RSV1011
Nanobody binding to RSV F
L0212D2
US20110182897 SEQ ID NO:
6233



protein

2705



RSV1012
Nanobody binding to RSV F
LG212E10
US20110182897 SEQ ID NO:
6234



protein

2706



RSV1013
Nanobody binding to RSV F
LG212E12
US20110182897 SEQ ID NO:
6235



protein

2707



RSV1014
Nanobody binding to RSV F
LG212E6
US20110182897 SEQ ID NO:
6236



protein

2708



RSV1015
Nanobody binding to RSV F
LG212F10
US20110182897 SEQ ID NO:
6237



protein

2709



RSV1016
Nanobody binding to RSV F
LG212F12
US20110182897 SEQ ID NO:
6238



protein

2710



RSV1017
Nanobody binding to RSV F
LG212F6
US20110182897 SEQ ID NO:
6239



protein

2711



RSV1018
Nanobody binding to RSV F
LG212F8
US20110182897 SEQ ID NO:
6240



protein

2712



RSV1019
Nanobody binding to RSV F
LG212G10
US20110182897 SEQ ID NO:
6241



protein

2713



RSV1020
Nanobody binding to RSV F
LG212G2
US20110182897 SEQ ID NO:
6242



protein

2714



RSV1021
Nanobody binding to RSV F
LG212H10
US20110182897 SEQ ID NO:
6243



protein

2715



RSV1022
Nanobody binding to RSV F
LG212H2
US20110182897 SEQ ID NO:
6244



protein

2716



RSVI023
Nanobody binding to RSV F
LG212H8
US20110182897 SEQ ID NO:
6245



protein

2717



RSV1024
Nanobody binding to RSV F
IV121
US20110182897 SEQ ID NO:
6246



protein

3064



RSV1025
Nanobody binding to RSV F
IV122
US20110182897 SEQ ID NO:
6247



protein

3065



RSV1026
Nanobody binding to RSV F
IV123
US20110182897 SEQ ID NO:
6248



protein

3066



RSV1027
Nanobody binding to RSV F
IV126
US20110182897 SEQ ID NO:
6249



protein

3067



RSV1028
Nanobody binding to RSV F
IV127
US20110182897 SEQ ID NO:
6250



protein

3068



RSV1029
Nanobody binding to RSV F
IV131
US20110182897 SEQ ID NO:
6251



protein

3069



RSV1030
Nanobody binding to RSV F
IV132
US20110182897 SEQ ID NO:
6252



protein

3070



RSV1031
Nanobody binding to RSV F
IV133
US20110182897 SEQ ID NO:
6253



protein

3071



RSV1032
Nanobody binding to RSV F
IV134
US20110182897 SEQ ID NO:
6254



protein

3072



RSV1033
Nanobody binding to RSV F
IV135
US20110182897 SEQ ID NO:
6255



protein

3073



RSV1034
Nanobody binding to RSV F
IV136
US20110182897 SEQ ID NO:
6256



protein

3074



RSV1035
Nanobody binding to RSV F
IV140
US20110182897 SEQ ID NO:
6257



protein

3075



RSV1036
Nanobody binding to RSV F
IV144
US20110182897 SEQ ID NO:
6258



protein

3076



RSV1037
Nanobody binding to RSV F
IV156
US20110182897 SEQ ID NO:
6259



protein

3077



RSV1038
Nanobody binding to RSV F
IV157
US20110182897 SEQ ID NO:
6260



protein

3078



RSV1039
Nanobody binding to RSV F
IV160
US20110182897 SEQ ID NO:
6261



protein

3079



RSV1040
Nanobody binding to RSV F
IV124
US20110182897 SEQ ID NO:
6262



protein

3080



RSV1041
Nanobody binding to RSV F
IV125
US20110182897 SEQ ID NO:
6263



protein

3081



RSV1042
Nanobody binding to RSV F
IV145
US20110182897 SEQ ID NO:
6264



protein

3082



RSV1043
Nanobody binding to RSV F
IV146
US20110182897 SEQ ID NO:
6265



protein

3083



RSV1044
Nanobody binding to RSV F
IV147
US20110182897 SEQ ID NO:
6266



protein

3084



RSV1045
Nanobody binding to RSV F
IV151
US20110182897 SEQ ID NO:
6267



protein

3085



RSV1046
Nanobody binding to RSV F
IV153
US20110182897 SEQ ID NO:
6268



protein

3086



RSV1047
Nanobody binding to RSV F
IV154
US20110182897 SEQ ID NO:
6269



protein

3087



RSV1048
Nanobody binding to RSV F
IV155
US20110182897 SEQ ID NO:
6270



protein

3088



RSV1049
Nanobody binding to RSV F
IV1
US20110182897 SEQ ID NO:
6271



protein

3089



RSV1050
Nanobody binding to RSV F
IV2
US20110182897 SEQ ID NO:
6272



protein

3090



RSV1051
Nanobody binding to RSV F
IV3
US20110182897 SEQ ID NO:
6273



protein

3091



RSV1052
Nanobody binding to RSV F
IV4
US20110182897 SEQ ID NO:
6274



protein

3092



RSV1053
Nanobody binding to RSV F
IV6
US20110182897 SEQ ID NO:
6275



protein

3093



RSV1054
Nanobody binding to RSV F
IV7
US20110182897 SEQ ID NO:
6276



protein

3094



RSV1055
Nanobody binding to RSV F
IV9
US20110182897 SEQ ID NO:
6277



protein

3095



RSV1056
Nanobody binding to RSV F
IV10
US20110182897 SEQ ID NO:
6278



protein

3096



RSV1057
Nanobody binding to RSV F
IV11
US20110182897 SEQ ID NO:
6279



protein

3097



RSV1058
Nanobody binding to RSV F
IV12
US20110182897 SEQ ID NO:
6280



protein

3098



RSV1059
Nanobody binding to RSV F
IV16
US20110182897 SEQ ID NO:
6281



protein

3099



RSV1060
Nanobody binding to RSV F
IV24
US20110182897 SEQ ID NO:
6282



protein

3100



RSV1061
Nanobody binding to RSV F
IV26
US20110182897 SEQ ID NO:
6283



protein

3101



RSV1062
Nanobody binding to RSV F
IV30
US20110182897 SEQ ID NO:
6284



protein

3102



RSV1063
Nanobody binding to RSV F
IV34
US20110182897 SEQ ID NO:
6285



protein

3103



RSV1064
Nanobody binding to RSV F
IV14
US20110182897 SEQ ID NO:
6286



protein

3104



RSV1065
Nanobody binding to RSV F
IV15
US20110182897 SEQ ID NO:
6287



protein

3105



RSV1066
Nanobody binding to RSV F
IV17
US20110182897 SEQ ID NO:
6288



protein

3106



RSV1067
Nanobody binding to RSV F
IV18
US20110182897 SEQ ID NO:
6289



protein

3107



RSV1068
Nanobody binding to RSV F
IV29
US20110182897 SEQ ID NO:
6290



protein

3108



RSV1069
Nanobody binding to RSV F
IV31
US20110182897 SEQ ID NO:
6291



protein

3109



RSV1070
Nanobody binding to RSV F
IV33
US20110182897 SEQ ID NO:
6292



protein

3110



RSV1071
Nanobody binding to RSV F
IV35
US20110182897 SEQ ID NO:
6293



protein

3111



RSV1072
Nanobody binding to RSV F
IV36
US20110182897 SEQ ID NO:
6294



protein

3112



RSV1073
Nanobody binding to RSV F
IV40
US20110182897 SEQ ID NO:
6295



protein

3113



RSV1074
Nanobody binding to RSV F
IV42
US20110182897 SEQ ID NO:
6296



protein

3114



RSV1075
Nanobody binding to RSV F
IV8
US20110182897 SEQ ID NO:
6297



protein

3115



RSV1076
Nanobody binding to RSV F
IV21
US20110182897 SEQ ID NO:
6298



protein

3116



RSV1077
Nanobody binding to RSV F
IV23
US20110182897 SEQ ID NO:
6299



protein

3117



RSV1078
Nanobody binding to RSV F
IV45
US20110182897 SEQ ID NO:
6300



protein

3118



RSV1079
Nanobody binding to RSV F
IV47
US20110182897 SEQ ID NO:
6301



protein

3119



RSV1080
Nanobody binding to RSV F
IV48
US20110182897 SEQ ID NO:
6302



protein

3120



RSV1081
Nanobody binding to RSV F
IV50
US20110182897 SEQ ID NO:
6303



protein

3121



RSV1082
Nanobody binding to RSV F
IV22
US20110182897 SEQ ID NO:
6304



protein

3122



RSV1083
Nanobody binding to RSV F
IV37
US20110182897 SEQ ID NO:
6305



protein

3123



RSV1084
Nanobody binding to RSV F
IV38
US20110182897 SEQ ID NO:
6306



protein

3124



RSV1085
Nanobody binding to RSV F
IV5
US20110182897 SEQ ID NO:
6307



protein

3125



RSV1086
Nanobody binding to RSV F
IV27
US20110182897 SEQ ID NO:
6308



protein

3126



RSV1087
Nanobody binding to RSV F
IV25
US20110182897 SEQ ID NO:
6309



protein

3127



RSV1088
Nanobody binding to RSV F
IV28
US20110182897 SEQ ID NO:
6310



protein

3128









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in US Publication No. US20140363427, and International Publication No. WO2004083373, the contents of each of which are herein incorporated by reference in their entirety, against RSV F or RSV G protein.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 23 against Hepatitis B, Hepatitis C and/or Hepatitis D.









TABLE 23







Antibodies against Hepatitis B, C, D viruses















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





HEPBD1
Anti-preS1

Park, S.G., et al., Hepatitis B virus-
6311



immunoglobulin,

neutralizing anti-pre-S1 human antibody




HBV Ab

fragments from large naive antibody phage






library; Antiviral Res. 68 (3), 109-115






(2005); NCBI Accession # AAW82034.1






(107aa)



HEPBD2
Anti-preS1

Park, S.G., et al., Hepatitis B virus-
6312



immunoglobulin,

neutralizing anti-pre-S1 human antibody




HBV Ab

fragments from large naive antibody phage






library; Antiviral Res. 68 (3), 109-115






(2005); NCBI Accession # AAW82035.1






(132aa)



HEPBD3
Anti-preS1

Park, S.G., et al., Hepatitis B virus-
6313



immunoglobulin,

neutralizing anti-pre-S1 human antibody




HBV Ab

fragments from large naive antibody phage






library; Antiviral Res. 68(3), 109-115






(2005); NCBI Accession #






AAW82033.1(111aa)



HEPBD4
Anti-preS1

Park, S.G., et al., Hepatitis B virus-
6314



immunoglobulin,

neutralizing anti-pre-S1 human antibody




HBV Ab

fragments from large naive antibody phage






library; Antiviral Res. 68(3), 109-115






(2005); NCBI Accession # AAW82032.1






(142aa)



HEPBD5
HCV Ab
Hu5b3.v3
Pantua, H., et al., Glycan shifting on
6315





hepatitis C virus(HCV) e2 glycoprotein is






a mechanism for escape from broadly






neutralizing antibodies; J. Mol. Biol. 425






(11), 1899-1914 (2013) NCBI Accession #






4HS8_H(228aa)



HEPBD6
HCV Ab
Igh526
Kong L., et al., Structure of Hepatitis C
6316





Virus Envelope Glycoprotein E1 Antigenic






Site 314-324 in Complex with Antibody






IGH526; J. Mol. Biol. 427 (16), 2617-2628






(2015) NCBI Accession #






4N0Y_H(231aa)



HEPBD7
Heavy chain partial,

Esposito, G., et al., Recombinant human
6317



HCV Ab

antibodies specific for hepatitis C virus






proteins; Arch. Virol. 142 (3), 601-610






(1997) NCBI Accession # CAA54914






(122aa)



HEPBD8
Heavy chain variable

EP0521348
6318



gene, Chimeric HBV






Ab





HEPBD9
Heavy chain variable

Keck, Z.Y., et al., Human monoclonal
6319



region partial, HCV

antibody to hepatitis C virUSE1




Ab

glycoprotein that blocks virus attachment






and viral infectivity; J. Virol. 78 (13),






7257-7263 (2004) NCBI Accession #






AAS47839 (142aa)



HEPBD10
Heavy chain variable
E183/A2
US20120308580 SEQ ID NO: 33; WO
6320



region, HBV Ab

2011062562; CN102781961, EP2501723



HEPBD11
Heavy chain variable

US20100260712 SEQ ID NO: 1;
6321



region, HBV Ab

WO2009069917



HEPBD12
Heavy chain variable

WO2015107126 SEQ ID NO: 2
6322



region, HBV Ab





HEPBD13
Heavy chain variable
HB48-33,
US8840895 SEQ ID NO: 1
6323



region, HBV Ab
HB48-35,






HB48-59




HEPBD14
Heavy chain variable
HFW141
US7435414 SEQ ID NO: 35;
6324



region, HBV Ab

US20060014937; WO2005100400;






CN1980956



HEPBD15
Heavy chain variable

US7112664 SEQ ID NO: 8; US6680053,
6325



region, HBV Ab

US6924368, US20020061581,






US20040191259, US20050249753,






WO2001092529



HEPBD16
Heavy chain variable
Ab17.1.4 1
USRE39586 SEQ ID NO: 4; US6146629;
6326



region, HBV Ab

WO1997047653



HEPBD17
Heavy chain variable
Ab 19.79.5
USRE40831 SEQ ID NO: 4
6327



region, HBV Ab





HEPBD18
Heavy chain variable

US20150232537 SEQ ID NO: 7;
6328



region, HB V Ab

WO2014048910; CA2884388;






CN104662041A; EP2900692



HEPBD19
Heavy chain variable

WO2013165972 SEQ ID NO: 45
6329



region, HBV Ab





HEPBD20
Heavy chain variable

WO2013165972 SEQ ID NO: 54
6330



region, HBV Ab





HEPBD21
Heavy chain variable

WO2013165972 SEQ ID NO: 63
6331



region, HBV Ab





HEPBD22
Heavy chain variable

WO2013165972 SEQ ID NO: 72
6332



region, HBV Ab





HEPBD23
Heavy chain variable

WO2013165972 SEQ ID NO: 81
6333



region, HBV Ab





HEPBD24
Heavy chain variable

WO2013165972 SEQ ID NO: 90
6334



region, HBV Ab





HEPBD25
Heavy chain variable

WO2013165972 SEQ ID NO: 99
6335



region, HBV Ab





HEPBD26
Heavy chain variable

WO2013165972 SEQ ID NO: 108
6336



region, HBV Ab





HEPBD27
Heavy chain variable

WO2013165972 SEQ ID NO: 117
6337



region, HBV Ab





HEPBD28
Heavy chain variable

WO2013165972 SEQ ID NO: 126
6338



region, HBV Ab





HEPBD29
Heavy chain variable

WO2013165972 SEQ ID NO: 135
6339



region, HBV Ab





HEPBD30
Heavy chain variable

WO2013165972 SEQ ID NO: 144
6340



region, HBV Ab





HEPBD31
Heavy chain variable

WO2013165972 SEQ ID NO: 153
6341



region, HBV Ab





HEPBD32
Heavy chain variable

WO2013165972 SEQ ID NO: 162
6342



region, HBV Ab





HEPBD33
Heavy chain variable

WO2013165972 SEQ ID NO: 171
6343



region, HBV Ab





HEPBD34
Heavy chain variable

WO2013165972 SEQ ID NO: 180
6344



region, HBV Ab





HEPBD35
Heavy chain variable

WO2013165972 SEQ ID NO: 189
6345



region, HBV Ab





HEPBD36
Heavy chain variable

WO2013165972 SEQ ID NO: 198
6346



region, HBV Ab





HEPBD37
Heavy chain variable

WO2013165972 SEQ ID NO: 207
6347



region, HBV Ab





HEPBD38
Heavy chain variable

WO2013165972 SEQ ID NO: 405
6348



region, HBV Ab





HEPBD39
Heavy chain variable

WO2013165972 SEQ ID NO: 409
6349



region, HBV Ab





HEPBD40
Heavy chain variable

WO2013165972 SEQ ID NO: 412
6350



region, HBV Ab





HEPBD41
Heavy chain variable

WO2013165972 SEQ ID NO: 418
6351



region, HBV Ab





HEPBD42
Heavy chain variable

WO2013165972 SEQ ID NO: 421
6352



region, HBV Ab





HEPBD43
Heavy chain variable

WO2009069916 SEQ ID NO: 1
6353



region, HBV Ab





HEPBD44
Heavy chain variable
PE1-1
WO1994011495
6354



region, HBV Ab





HEPBD45
Heavy chain variable
ZM1-1
WO1994011495
6355



region, HBV Ab





HEPBD46
Heavy chain variable
ZM1-2
WO1994011495
6356



region, HBV Ab





HEPBD47
Heavy chain variable
MD3-4
WO1994011495
6357



region, HBV Ab





HEPBD48
Heavy chain variable
A2E2
CN102757492 SEQ ID NO: 2
6358



region, HBV Ab





HEPBD49
Heavy chain variable
C9G9
CN102757492 SEQ ID NO: 6
6359



region, HBV Ab





HEPBD50
Heavy chain variable

CN104530228 SEQ ID NO: 3
6360



region, HBV Ab





HEPBD51
Heavy chain variable

CN104530228 SEQ ID NO: 4
6361



region, HBV Ab





HEPBD52
Heavy chain variable
Ab19
US8580256 SEQ ID NO: 2
6362



region, HBV Ab





HEPBD53
Heavy chain variable
Ab17
US8580256 SEQ ID NO: 4
6363



region, HBV Ab





HEPBD54
Heavy chain variable
KR127
US8420353 SEQ ID NO: 28
6364



region, HBV Ab





HEPBD55
Heavy chain variable
DP7
US8420353 SEQ ID NO: 32
6365



region, HBV Ab





HEPBD56
Heavy chain variable
HZ1
US8420353 SEQ ID NO: 36
6366



region, HBV Ab





HEPBD57
Heavy chain variable
MBL-HCV1
US8551484 SEQ ID NO: 1
6367



region, HCV Ab
(Antibody






produced by






clone 83-128)




HEPBD58
Heavy chain variable
MBL-HCV1
US8551484 SEQ ID NO: 3
6368



region, HCV Ab
(Antibody






produced by






clone 95-2)




HEPBD59
Heavy chain variable
MBL-HCV1
US8551484 SEQ ID NO: 5
6369



region, HCV Ab
(Antibody






produced by






clone 95-14)




HEPBD60
Heavy chain variable
Clone 13
US7250166 SEQ ID NO: 1
6370



region, HCV Ab





HEPBD61
Heavy chain variable
Clone 98
US7250166 SEQ ID NO: 3
6371



region, HCV Ab





HEPBD62
Heavy chain variable
Clone 1:4
US7250166 SEQ ID NO: 5
6372



region, HCV Ab





HEPBD63
Heavy chain variable
Clone 1:8
US7250166 SEQ ID NO: 7
6373



region, HCV Ab





HEPBD64
Heavy chain variable
Clone 1:9
US7250166 SEQ ID NO: 9
6374



region, HCV Ab





HEPBD65
Heavy chain variable
Clone 1:10
US7250166 SEQ ID NO: 11
6375



region, HCV Ab





HEPBD66
Heavy chain variable
Clone 4:6
US7250166 SEQ ID NO: 13
6376



region, HCV Ab





HEPBD67
Heavy chain variable
Clone 6a:5
US7250166 SEQ ID NO: 15
6377



region, HCV Ab





HEPBD68
Heavy chain variable
Clone2a:2
US7250166 SEQ ID NO: 17
6378



region, HCV Ab





HEPBD69
Heavy chain variable
Clone 2a:4
US7250166 SEQ ID NO: 19
6379



region, HCV Ab





HEPBD70
Heavy chain variable
Clone 2a:5
US7250166 SEQ ID NO: 21
6380



region, HCV Ab





HEPBD71
Heavy chain variable
Clone 2a:13
US7250166 SEQ ID NO: 23
6381



region, HCV Ab





HEPBD72
Heavy chain variable
Clone 2a:14
US7250166 SEQ ID NO: 25
6382



region, HCV Ab





HEPBD73
Heavy chain variable
Clone 2a:23
US7250166 SEQ ID NO: 27
6383



region, HCV Ab





HEPBD74
Heavy chain variable
Clone 2a:23
US7250166 SEQ ID NO: 29
6384



region, HCV Ab





HEPBD75
Heavy chain variable
Clone 2a:25
US7250166 SEQ ID NO: 31
6385



region, HCV Ab





HEPBD76
Heavy chain variable
Clone 2a:30
US7250166 SEQ ID NO: 33
6386



region, HCV Ab





HEPBD77
Heavy chain variable
Clone 2a:32
US7250166 SEQ ID NO: 35
6387



region, HCV Ab





HEPBD78
Heavy chain variable
Clone 2a:33
US7250166 SEQ ID NO: 37
6388



region, HCV Ab





HEPBD79
Heavy chain variable
Clone 2a:37
US7250166 SEQ ID NO: 39
6389



region, HCV Ab





HEPBD80
Heavy chain variable
Clone 2a:40
US7250166 SEQ ID NO: 41
6390



region, HCV Ab





HEPBD81
Heavy chain variable
Clone 2b:1
US7250166 SEQ ID NO: 43
6391



region, HCV Ab





HEPBD82
Heavy chain variable
Clone 2b:3
US7250166 SEQ ID NO: 45
6392



region, HCV Ab





HEPBD83
Heavy chain variable
Clone 2b:4
US7250166 SEQ ID NO: 47
6393



region, HCV Ab





HEPBD84
Heavy chain variable
Clone 2b:5
US7250166 SEQ ID NO: 49
6394



region, HCV Ab





HEPBD85
Heavy chain variable
Clone 2b:7
US7250166 SEQ ID NO: 51
6395



region, HCV Ab





HEPBD86
Heavy chain variable
Clone 2b:9
US7250166 SEQ ID NO: 53
6396



region, HCV Ab





HEPBD87
Heavy chain variable
Clone 2b:10
US7250166 SEQ ID NO: 55
6397



region, HCV Ab





HEPHD88
Heavy chain variable
anti-NS3 Fab
US7314919 SEQ ID NO: 1
6398



region, HCV Ab





HEPBD89
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 32
6399



region, HCV Ab
produced by






clone 95-14




HEPBD90
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 33
6400



region, HCV Ab
produced by






clone 95-38




HEPBD91
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 34
6401



region, HCV Ab
produced by






clone 95-25




HEPBD92
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 35
6402



region, HCV Ab
produced by






clone 95.42




HEPBD93
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 36
6403



region, HCV Ab
produced by






clone 95-43




HEPBD94
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 37
6404



region, HCV Ab
produced by






clone 95-49




HEPBD95
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 38
6405



region, HCV Ab
produced by






clone 95-54




HEPBD96
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 39
6406



region, HCV Ab
produced by






clone 95-58




HEPBD97
Heavy chain variable
Antibody
US8551484 SEQ ID NO: 40
6407



region, HCV Ab
produced by






clone 95-62




HEPBD98
Heavy chain variable
HC-84.1
US20130084301 SEQ ID NO: 55
6408



region, HCV Ab





HEPBD99
Heavy chain variable
HC-84.20
US20130084301 SEQ ID NO: 56
6409



region, HCV Ab





HEPBD100
Heavy chain variable
HC-84.21
US20130084301 SEQ ID NO: 57
6410



region, HCV Ab





HEPBD101
Heavy chain variable
HC-84.22
US20130084301 SEQ ID NO: 58
6411



region, HCV Ab





HEPBD102
Heavy chain variable
HC-23
US20130084301 SEQ ID NO: 59
6412



region, HCV Ab





HEPBD103
Heavy chain variable
HC-84.24
US20130084301 SEQ ID NO: 60
6413



region, HCV Ab





HEPBD104
Heavy chain variable
HC-84.25
US20130084301 SEQ ID NO: 61
6414



region, HCV Ab





HEPBD105
Heavy chain variable
HC-84.26
US20130084301 SEQ ID NO: 62
6415



region, HCV Ab





HEPBD106
Heavy chain variable
HC-84.27.
US20130084301 SEQ ID NO: 63
6416



region, HCV Ab





HEPBD107
Heavy chain variable
AOT3
US20120009196 SEQ ID NO: 1
6417



region, HCV Ab





HEPBD108
Heavy chain variable
C11-3
US20120009196 SEQ ID NO: 3
6418



region, HCV Ab





HEPBD109
Heavy chain variable
C11-7
US20120009196 SEQ ID NO: 5
6419



region, HCV Ab





HEPBDI10
Heavy chain variable
C11-9
US20120009196 SEQ ID NO: 7
6420



region, HCV Ab





HEPBD111
Heavy chain variable
C11-14
US20120009196 SEQ ID NO: 9
6421



region, HCV Ab





HEPBD112
Heavy chain variable

WO2014065822 SEQ ID NO: 3
6422



region, HCV Ab





HEPBD113
Heavy chain variable

WO2014065822 SEQ ID NO: 7
6423



region, HCV Ab





HEPBD114
Heavy chain variable
mPA-29
WO2007143701 SEQ ID NO: 2
6424



region, HCV Ab





HEPBD115
Heavy chain variable
Hc33.1
Li Y. et al., Structural basis for penetration
6425



region, HCV Ab

of the glycan shield of hepatitis C virUSe2






glycoprotein by a broadly neutralizing






human antibody; J. Biol. Chem. 290 (16),






10117-10125 (2015) NCBI Accession #






4XVJ_H (141aa)



HEPBD116
Heavy chain variable

Martin, F., et al., Affinity selection of a
6426



region, HCV Ab

camelized V(H) domain antibody inhibitor






of hepatitis C virUSNS3 protease; Protein






Eng. 10(5), 607-614 (1997NCBI






Accession # 1OL0_B (121aa)



HEPBD117
Heavy chain variable

US20150118242 SEQ ID NO: 2
6427



region, HCV Ab





HEPBD118
Heavy chain variable

US20150166637 SEQ ID NO: 1,
6428



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD119
Heavy chain variable

US20150166637 SEQ ID NO: 2;
6429



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD120
Heavy chain variable

US20150166637 SEQ ID NO: 3;
6430



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD121
Heavy chain variable

US20150166637 SEQ ID NO: 4;
6431



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD122
Heavy chain variable

US20150166637 SEQ ID NO: 5;
6432



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD123
Heavy chain variable
c18/A2
US20120308580 SEQ ID NO: 2; WO
6433



region, Monoclonal

2011062562; CN102781961, EP2501723




HBV antibody





HEPBD124
Heavy chain variable

US20110097270 SEQ ID NO: 1
6434



region, Neutralizing






monoclonal HBV






antibody





HEPBD125
Heavy chain, full

US20150232537 SEQ ID NO: 9;
6435



HBV Ab

WO2014048910; CA2884388;






CN104662041A; EP2900692



HEPBD126
Heavy chain, HBV Ab
HBFab21
CN103588874 SEQ ID NO: 2
6436


HEPBD127
Heavy chain, HCV Ab
Fab clone 1:5
US6747136 SEQ ID NO: 1
6437


HEPBD128
Heavy chain, HCV Ab
Fab clone 1:7
US6747136 SEQ ID NO: 2
6438


HEPBD129
Heavy chain, ACV Ab
Fab clone 1:11
US6747136 SEQ ID NO: 3
6439


HEPBD130
Heavy chain, HCV Ab
Fab clone L3
US6747136 SEQ ID NO: 4
6440


HEPBD131
Heavy chain, HCV Ab
Fab clone L1
US6747136 SEQ ID NO: 5
6441


HEPBD132
Heavy chain, HCV Ab
Fab clone A8
US6747136 SEQ ID NO: 6
6442


HEPBD133
Heavy chain, HCV Ab
Fab clone A12
US6747136 SEQ ID NO: 7
6443


HEPBD134
Heavy chain, HCV Ab
HCV-AB 68
US7241445 SEQ ID NO: 3
6444


HEPBD135
Heavy chain, HCV Ab
e8
US7727529 SEQ ID NO: 1
6445


HEPBD136
Heavy chain, HCV Ab
e10
US7727529 SEQ ID NO: 3
6446


HEPBD137
Heavy chain, HCV Ab
e20
US7727529 SEQ ID NO: 5
6447


HEPBD138
Heavy chain, HCV Ab
e137
US7727529 SEQ ID NO: 7
6448


HEPBD139
Heavy chain, HCV Ab
e301
US7727529 SEQ ID NO: 9
6449


HEPBD140
Heavy chain, HCV Ab
e509
US7727529 SEQ ID NO: 11
6450


HEPBD141
Heavy chain, HCV Ab
5D2
US20090104207 SEQ ID NO: 7
6451


HEPBD142
Heavy chain, HCV Ab
Mab V
WO2013186752 SEQ ID NO: 3
6452


HEPBD143
Heavy chain, HCV Ab
Mab VI
WO2013186752 SEQ ID NO: 5
6453


HEPBD144
Heavy chain, HCV Ab

WO2007143701 SEQ ID NO: 12
6454


HEPBD145
Heavy chain, HCV Ab
HuPA29VH#1
WO2007143701 SEQ ID NO: 15
6455


HEPBD146
Heavy chain, HCV Ab
HuPA29VH#2
WO2007143701 SEQ ID NO: 16
6456


HEPBD147
Heavy chain, HCV Ab
HuPA29VH#3
WO2007143701 SEQ ID NO: 17
6457


HEPBD148
Heavy chain, HCV Ab
PA29
WO2007143701 SEQ ID NO: 28
6458


HEPBD149
Heavy chain, HCV Ab
Ap33
Kong, L., et al., Structure of Hepatitis C
6459





Virus Envelope Glycoprotein E2 Antigenic






Site 412 to 423 in Complex with Antibody






AP33; J. Virol. 86 (23), 13085-13088






(2012) NCBI Accession # 4G6A _H






(224aa)



HEPBD50
Heavy chain, HCV Ab
Single Chain Fv
Gilmartin, A.A., et al., Protein Eng. Des.
6460




Fragment 1:7
Sel. 25 (2), 59-66 (2012) NCBI Accession






# 3U6R_A(149aa)



HEPBD151
Heavy Chain, HCV
Ar3c
Kong, L., etal., Hepatitis C virUSE2
6461



Fab

envelope glycoprotein core structure;






Science 342 (6162), 1090-1094 (2013)






NCBI Accession # 4MWF_A (233aa)



HEPBD152
Heavy Chain, HCV
Mrct10.v362
Pantua, H., et al., Glycan shifting on
6462



Fab

hepatitis C virus (HCV) e2 glycoprotein is






a mechanism for escape from broadly






neutralizing antibodies; J. Mol. Biol. 425






(11), 1899-1914 (2013) NCBI Accession #






HS6_H (226aa)



HEPBD153
Heavy Chain, Hcv1
Hcv1, P2(1)
Kong, L., et al., Structural basis of
6463



HCV Ab
Form
hepatitis C virus neutralization by broadly






neutralizing antibody HCV1; Proc. Natl.






Acad. Sci. U.S.A. 109 (24), 9499-9504






(2012) NCBI Accession # 4DGV_H






(226aa)



HEPBD154
Heavy Chain, Hcv1
Hcv1, C2 Form
Kong, L., etal., Structural basis of
6464



HCV Ab

hepatitis C virus neutralization by broadly






neutralizing antibody HCV1; Proc. Natl.






Acad. Sci. U.S.A. 109 (24), 9499-9504






(2012) NCBI Accession # 4DGY_H






(226aa)



HEPBD155
Heavy gamma chain
P18-9E
US8592559 SEQ ID NO: 13
6465



variable, HCV Ab





HEPBD156
Heavy-chain-only,
VHH D03
WO2014053634 SEQ ID NO: 4
6466



HCV Ab





HEPBD157
Heavy-chain-only,
VHH C09
WO2014053634 SEQ ID NO: 5
6467



HCV Ab





HEPBD158
Heavy-chain-only,
B1 1
WO2014053634 SEQ ID NO: 6
6468



HCV Ab





HEPBD159
Heavy-chain-only,
D04
WO2014053634 SEQ ID NO: 7
6469



HCV Ab





HEPBD160
Light chain full, HBV

US20150232537 SEQ ID NO: 10;
6470



Ab

WO2014048910; CA2884388;






CN104662041A; EP2900692



HEPBD161
Light chain kappa,

Esposito, C., et al., Recombinant human
6471



partial, HCV Ab

antibodies specific for hepatitis C virus






proteins; Arch. Virol. 142 (3), 601-610






(1997) NCBI Accession #






CAA54913.1(110aa)



HEPBD162
Light chain variable
c18/A2
US20120308580 SEQ ID NO: 1; WO
6472



domain, monoclonal

2011062562; CN102781961, EP2501723




HBV antibody





HEPBD163
Light chain variable

US20110097270 SEQ ID NO: 9
6473



domain, neutralizing






monoclonal HBV






antibody,





HEPBD164
Light chain variable

EP0521348
6474



gene, Chimeric HBV






Ab





HEPBD165
Light chain variable
E183/A2
US20120308580 SEQ ID NO: 32; WO
6475



region, HBV Ab

2011062562; CN102781961, EP2501723



HEPBD166
Light chain variable
HB48-33
US8840895 SEQ ID NO: 2
6476



region, HBV Ab





HEPBD167
Light chain variable
HB48-35
US8840895 SEQ ID NO: 3
6477



region, HBV Ab





HEPBD168
Light chain variable
HB48-59
US8840895 SEQ ID NO: 4
6478



region, HBV Ab





HEPBD169
Light chain variable
LFW22-31
US7435414 SEQ ID NO: 36;
6479



region, HBV Ab

US20060014937; WO2005100400;






CN1980956



HEPBD170
Light chain variable
LFW22-312
US7435414 SEQ ID NO: 37;
6480



region, HBV Ab

US20060014937; WO2005100400;






CN1980956



HEPBD171
Light chain variable

WO2013165972 SEQ ID NO: 216
6481



region, HBV Ab





HEPBD172
Light chain variable

WO2013165972 SEQ ID NO: 225
6482



region, HBV Ab





HEPBD173
Light chain variable

WO2013165972 SEQ ID NO: 234
6483



region, HBV Ab





HEPBD174
Light chain variable

WO2013165972 SEQ ID NO: 243
6484



region, HBV Ab





HEPBD175
Light chain variable

WO2013165972 SEQ ID NO: 252
6485



region, HBV Ab





HEPBD176
Light chain variable

WO2013165972 SEQ ID NO: 261
6486



region, HBV Ab





HEPBD177
Light chain variable

WO2013165972 SEQ ID NO: 270
6487



region, HBV Ab





HEPBD178
Light chain variable

WO2013165972 SEQ ID NO: 279
6488



region, HBV Ab





HEPBD179
Light chain variable

WO2013165972 SEQ ID NO: 288
6489



region, HBV Ab





HEPBD180
Light chain variable

WO2013165972 SEQ ID NO: 297
6490



region, HBV Ab





HEPBD181
Light chain variable

WO2013165972 SEQ ID NO: 306
6491



region, HBV Ab





HEPBD182
Light chain variable

WO2013165972 SEQ ID NO: 315
6492



region, HBV Ab





HEPBD183
Light chain variable

WO2013165972 SEQ ID NO: 324
6493



region, HBV Ab





HEPBD184
Light chain variable

WO2013165972 SEQ ID NO: 333
6494



region, HBV Ab





HEPBD185
Light chain variable

WO2013165972 SEQ ID NO: 342 and 351
6495



region, HBV Ab





HEPBD186
Light chain variable

WO2013165972 SEQ ID NO: 360
6496



region, HBV Ab





HEPBD187
Light chain variable

WO2013165972 SEQ ID NO: 369
6497



region, HBV Ab





HEPBD188
Light chain variable

WO2013165972 SEQ ID NO: 378
6498



region, HBV Ab





HEPBD189
Light chain variable

WO2013165972 SEQ ID NO: 387
6499



region, HBV Ab





HEPBD190
Light chain variable

WO2013165972 SEQ ID NO: 396
6500



region, HBV Ab





HEPBD191
Light chain variable

WO2009069916 SEQ ID NO: 2
6501



region, HBV Ab





HEPBD192
Light chain variable
PE1-1
WO1994011495
6502



region, HBV Ab





HEPBD193
Light chain variable
ZM1-1
WO1994011495
6503



region, HBV Ab





HEPBD194
Light chain variable
ZM1-2
WO1994011495
6504



region, HB V Ab





HEPBD195
Light chain variable
MD3 -4
WO1994011495
6505



region, HBV Ab





HEPBD196
Light chain variable
A2E2
CN102757492 SEQ ID NO: 4
6506



region, HBV Ab





HEPBD197
Light chain variable
C9G9
CN102757492 SEQ ID NO: 8
6507



region, HBV Ab





HEPBD198
Light chain variable

CN104530228 SEQ ID NO: 1
6508



region, HBV Ab





HEPBD199
Light chain variable

CN104530228 SEQ ID NO: 2
6509



region, HBV Ab





HEPBD200
Light chain variable
Ab19
US8580256 SEQ ID NO: 1
6510



region, HBV Ab





HEPBD201
Light chain variable
Ab17
US8580256 SEQ ID NO: 3
6511



region, HBV Ab





HEPBD202
Light chain variable
KR127
US8420353 SEQ ID NO: 4
6512



region, HBV Ab





HEPBD203
Light chain variable
KR127
US8420353 SEQ ID NO: 2
6513



region, HBV Ab





HEPBD204
Light chain variable
KR127
US8420353 SEQ ID NO: 30
6514



region, HBV Ab





HEPBD205
Light chain variable
DPK12
US8420353 SEQ ID NO: 34
6515



region, HBV Ab





HEPBD206
Light chain variable
HZI
US8420353 SEQ ID NO: 38
6516



region, HBV Ab





HEPBD207
Light chain variable

US7112664 SEQ ID NO: 7; US6680053,
6517



region, HBV Ab

US6924368, US20020061581,






US20040191259, US20050249753,






WO2001092529



HEPBD208
Light chain variable
Ab17.1.4 1
USRE39586 SEQ ID NO: 2; US6146629;
6518



region, HBV Ab

WO1997047653



HEPBD209
Light chain variable
Ab 19.79.5
USRE40831 SEQ ID NO: 2
6519



region, HBV Ab





HEPBD210
Light chain variable

US20150232537 SEQ ID NO: 8;
6520



region, HBV Ab

WO2014048910; CA2884388;






CN104662041A; EP2900692



HEPBD211
Light chain variable

US20100260712 SEQ ID NO: 2;
6521



region, HBV Ab

WO2009069917



HEPBD212
Light chain variable

WO2015107126 SEQ ID NO: 4
6522



region, HBV Ab





HEPBD213
Light chain variable
MBL-HCV1
US8551484 SEQ ID NO: 2
6523



region, HCV Ab
(Antibody






produced by






clone 83-128)




HEPBD214
Light chain variable
MBL-HCV1
US8551484 SEQ ID NO: 4
6524



region, HCV Ab
(Antibody






produced by






clone 95-2)




HEPBD215
Light chain variable
MBL-HV1
US8551484 SEQ ID NO: 6
6525



region, HCV Ab
(Antibody






produced by






clone 073-1)




HEPBD216
Light chain variable
Clone 13
US7250166 SEQ ID NO: 2
6526



region, HCV Ab





HEPBD217
Light chain variable
Clone 98
US7250166 SEQ ID NO: 4
6527



region, HCV Ab





HEPBD218
Light chain variable
Clone 1:4
US7250166 SEQ ID NO: 6
6528



region, HCV Ab





HEPBD219
Light chain variable
Clone 1:8
US7250166 SEQ ID NO: 8
6529



region, HCV Ab





HEPBD220
Light chain variable
Clone 1:9
US7250166 SEQ ID NO: 10
6530



region, HCV Ab





HEPBD221
Light chain variable
Clone 1:10
US7250166 SEQ ID NO: 12
6531



region, HCV Ab





HEPBD222
Light chain variable
Clone 4:6
US7250166 SEQ ID NO: 14
6532



region, HCV Ab





HEPBD223
Light chain variable
Clone 6a:5
US7250166 SEQ ID NO: 16
6533



region, HCV Ab





HEPBD224
Light chain variable
Clone 2a:2
US7250166 SEQ ID NO: 18
6534



region, HCV Ab





HEPBD225
Light chain variable
Clone 2a:4
US7250166 SEQ ID NO: 20
6535



region, HCV Ab





HEPBD226
Light chain variable
Clone 2a:5
US7250166 SEQ ID NO: 22
6536



region, HCV Ab





HEPBD227
Light chain variable
Clone 2a:13
US7250166 SEQ ID NO: 24
6537



region, HCV Ab





HEPBD228
Light chain variable
Clone 2a:14
US7250166 SEQ ID NO: 26
6538



region, HCV Ab





HEPBD229
Light chain variable
Clone 2a:23
US7250166 SEQ ID NO: 28
6539



region, HCV Ab





HEPBD230
Light chain variable
Clone 2a:23
US7250166 SEQ ID NO: 30
6540



region, HCV Ab





HEPBD231
Light chain variable
Clone 2a:25
US7250166 SEQ ID NO: 32
6541



region, HCV Ab





HEPBD232
Light chain variable
Clone 2a:30
US7250166 SEQ ID NO: 34
6542



region, HCV Ab





HEPBD233
Light chain variable
Clone 2a:32
US7250166 SEQ ID NO: 36
6543



region, HCV Ab





HEPBD234
Light chain variable
Clone 2a:33
US7250166 SEQ ID NO: 38
6544



region, HCV Ab





HEPBD235
light chain variable
Clone 2a:37
US7250166 SEQ ID NO: 40
6545



region, HCV Ab





HEPBD236
Light chain variable
Clone 2a:40
US7250166 SEQ ID NO: 42
6546



region, HCV Ab





HEPBD237
Light chain variable
Clone 2b:1
US7250166 SEQ ID NO: 44
6547



region, HCV Ab





HEPBD238
Light chain variable
Clone 2b:3
US7250166 SEQ ID NO: 46
6548



region, HCV Ab





HEPBD239
Light chain variable
Clone 2b:4
US7250166 SEQ ID NO: 48
6549



region, HCV Ab





HEPBD240
Light chain variable
Clone 2b:5
US7250166 SEQ ID NO: 50
6550



region, HCV Ab





HEPBD241
Light chain variable
Clone 2b:7
US7250166 SEQ ID NO: 52
6551



region, HCV Ab





HEPBD242
Light chain variable
Clone 2b:9
US7250166 SEQ ID NO: 54
6552



region, HCV Ab





HEPBD243
Light chain variable
Clone 2b:10
US7250166 SEQ ID NO: 56
6553



region, HCV Ab





HEPBD244
Light chain variable
anti-NS3 Fab
US7314919 SEQ ID NO: 6
6554



region, HCV Ab





HEPBD245
Light chain variable

US7507408 SEQ ID NO: 2
6555



region, HCV Ab





HEPBD246
Light chain variable

US7507408 SEQ ID NO: 4
6556



region, HCV Ab





HEPBD247
Light chain variable

US7507408 SEQ ID NO: 6
6557



region, HCV Ab





HEPBD248
Light chain variable
Antibody
US8551484 SEQ ID NO: 44
6558



region, HCV Ab
produced by






clone 95-14




HEPBD249
Light chain variable
Antibody
US8551484 SEQ ID NO: 53
6559



region, HCV Ab
produced by






clone 95-38




HEPBD250
Light chain variable
HC-84.1
US20130084301 SEQ ID NO: 64
6560



region, HCV Ab





HEPBD251
Light chain variable
HC-84.20
US20130084301 SEQ ID NO: 65
6561



region, HCV Ab





HEPBD252
Light chain variable
HC-84.21
US20130084301 SEQ ID NO: 66
6562



region, HCV Ab





HEPBD253
Light chain variable
HC-84.22
US20130084301 SEQ ID NO: 67
6563



region, HCV Ab





HEPBD254
Light chain variable
HC-23
US20130084301 SEQ ID NO: 68
6564



region, HCV Ab





HEPBD255
Light chain variable
HC-84.24
US20130084301 SEQ ID NO: 69
6565



region, HCV Ab





HEPBD256
Light chain variable
HC-84.25
US20130084301 SEQ ID NO: 70
6566



region, HCV Ab





HEPBD257
Light chain variable
HC-84,26
US20130084301 SEQ ID NO: 71
6567



region, HCV Ab





HEPBD258
Light chain variable
HC-84.27.
US20130084301 SEQ ID NO. 72
6568



region, HCV Ab





HEPBD259
Light chain variable
AOT3
US20120009196 SEQ ID NO: 2
6569



region, HCV Ab





HEPBD260
Light chain variable
C11-3
US20120009196 SEQ ID NO: 4
6570



region, HCV Ab





HEPBD261
Light chain variable
C11-7
US20120009196 SEQ ID NO: 6
6571



region, HCV Ab





HEPBD262
Light chainvariable
C11-9
US20120009196 SEQ ID NO: 8
6572



region, HCV Ab





HEPBD263
Light chain variable
C11-14
US20120009196 SEQ ID NO: 10
6573



region, HCV Ab





HEPBD264
Light chain variable

WO2014065822 SEQ ID NO: 5
6574



region, HCV Ab





HEPBD265
Light chain variable

WO2014065822 SEQ ID NO: 9
6575



region, HCV Ab





HEPBD266
Light chain variable
Antibody light
WO2007143701 SEQ ID NO: 1
6576



region, HCV Ab
chain from






WO2007143701




HEPBD267
Light chain variable
Hc33.1
Li Y. et al., Structural basis for penetration
6577



region, HCV Ab

of the glycan shield of hepatitis C virUSe2






glycoprotein by a broadly neutralizing






human antibody; J. Biol. Chem. 290 (16),






10117-10125 (2015) NCBI Accession #






4XVJ_L (115aa)



HEPBD268
Light chain variable

US20150118242 SEQ ID NO: 3
6578



region, HCV Ab





HEPBD269
Light chain variable

US20150166637 SEQ ID NO: 6;
6579



region, Human HVB

WO2014010890; CA2878155,




antibody that binds to

CN104487090; EP2858674




the surface antigen






(HBsAg)





HEPBD270
Light chain variable

US20150166637 SEQ ID NO: 7;
6580



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD271
Light chain variable

US20150166637 SEQ ID NO: 8;
6581



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD272
Light chain variable

US20150166637 SEQ ID NO: 9;
6582



region, Human HBV

WO2014010890; CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD273
Light chain variable

US20150166637 SEQ ID NO: 10;
6583



region, Human HBV

WO2014010890, CA2878155,




antibody that binds to

CN104487090, EP2858674




the surface antigen






(HBsAg)





HEPBD274
Light chain variable

Keck, Z.Y., et al., Human monoclonal
6584



region, partial, HCV

antibody to hepatitis C virUSE1




Ab

glycoprotein that blocks virus attachment






and viral infectivity; J. Virol. 78(13),






7257-7263 (2004) NCBI Accession #






AAS47840 (147aa)



HEPBD275
Light chain, HCV Ab
Hu5b3.v3
Pantua, B., et al., Glycan shifting on
6585





hepatitis C virus (HCV) e2 glycoprotein is






a mechanism for escape from broadly






neutralizing antibodies; J. Mol. Biol. 425






(11), 1899-1914 (2013) NCBI Accession #






4HS8_L (218aa)



HEPBD276
Light chain, HCV Ab
Ap33
Kong, L., et al., Structure of Hepatitis C
6586





Virus Envelope Glycoprotein E2 Antigenic






Site 412 to 423 in Complex with Antibody






AP33; J. Virol. 86 (23), 13085-13088






(2012) NCBI Accession # 4G6A_L






(218aa)



HEPBD277
Light chain, HBV Ab
HBFab21
CN103588874 SEQ ID NO: 1
6587


HEPBD278
Light chain, HBV Ab
Fab clone 1:5
US6747136 SEQ ID NO: 8
6588


HEPBD279
Light chain, HCV Ab
Fab clone 1:7
US6747136 SEQ ID NO: 9
6589


HEPBD280
Light chain, HCV Ab
Fab clone 1:11
US6747136 SEQ ID NO: 10
6590


HEPBD281
Light chain, HCV Ab
Fab clone L3
US6747136 SEQ ID NO: 11
6591


HEPBD282
Light chain, HCV Ab
Fab clone L1
US6747136 SEQ ID NO: 12
6592


HEPBD283
Light chain, HCV Ab
Fab clone A8
US6747136 SEQ ID NO: 13
6593


HEPBD284
Light chain, HCV Ab
Fab clone A12
US6747136 SEQ ID NO: 14
6594


HEPBD285
Light chain, HCV Ab
HCV#1
US6924362 SEQ ID NO: 1
6595


HEPBD286
Light chain, HCV Ab
HCV#4
US6924362 SEQ ID NO: 2
6596


HEPBD287
Light chain, HCV Ab
HCV#7
US6924362 SEQ ID NO: 3
6597


HEPBD288
Light chain, HEV Ab
HCV#12
US6924362 SEQ ID NO: 4
6598


HEPBD289
Light chain, HCV Ab
HGV#13
US6924362 SEQ ID NO: 5
6599


HEPBD290
Light chain, HCV Ab
HCV-AB 68
US7241445 SEQ ID NO: 4
6600


HEPBD291
Light chain, HCV Ab
e8
US7727529 SEQ ID NO: 2
6601


HEPBD292
Light chain, HCV Ab
e10
US7727529 SEQ ID NO: 4
6602


HEPBD293
Light chain, HEV Ab
e20
US7727529 SEQ ID NO: 6
6603


HEPBD294
Light chain, HCV Ab
e137
US7727529 SEQ ID NO: 8
6604


HEPBD295
Light chain, HCV Ab
e301
US7727529 SEQ ID NO: 10
6605


HEPBD296
Light chain, HCV Ab
e509
US7727529 SEQ ID NO: 12
6606


HEPBD297
Light chain, HCV Ab
5D2
US20090104207 SEQ ID NO: 8
6607


HEPBD298
Light chain, HCV Ab
MabV
WO2013186752 SEQ ID NO: 4
6608


HEPBD299
Light chain, HCV Ab
Mab VI
WO2013186752 SEQ ID NO: 6
6609


HEPBD300
Light chain, HCV Ab

WO2007143701 SEQ ID NO: 11
6610


HEPBD301
Light chain, HCV Ab
HuPA29VH#1
WO2007143701 SEQ ID NO: 18
6611


HEPBD302
Light chain, HCV Ab
HuPA29VH#2
WO2007143701 SEQ ID NO: 19
6612


HEPBD303
Light chain, HCV Ab
PA29
WO2007143701 SEQ ID NO: 29
6613


HEPBD304
Light chain, HCV Ab
Single Chain Fv
Gilmartin, A.A., et al., Protein Eng. Des.
6614




Fragment 1:7
Sel. 25 (2), 59-66 (2012) NCBI Accession






# 3U6R_B (143aa)



HEPBD305
Light chain, HCV Ab
Igh526
Kong L., et al., Structure of Hepatitis C
6615





Virus Envelope Glycoprotein E1 Antigenic






Site 314-324 in Complex with Antibody






1GH526; J. Mol. Biol. 427 (16), 2617-2628






(2015) NCBI Accession # 4N0Y_L






(218aa)



HEPBD306
Light chain, HCV Fab
Ar3c
Kong, L., et al., Hepatitis C virUSE2
6616





envelope glycoprotein core structure;






Science 342 (6162), 1090-1094 (2013)






NCBI Accession # 4MWF_B (214aa)



HEPBD307
Light chain, HCV Fab
Mrct10.v362
Pantua, H., et al., Glycan shifting on
6617





hepatitis C virus (HCV) e2 glycoprotein is






a mechanism for escape from broadly






neutralizing antibodies; J. Mol. Biol. 425






(11), 1899-1914 (2013) NCBI Accession #






4HS6_L (218aa)



HEPBD308
Light chain, Hcv1
Hcv1, C2 Form
Kong, L., et al., Structural basis of
6618



HCV Ab

hepatitis C virus neutralization by broadly






neutralizing antibody HCV1; Proc. Natl.






Acad. Sci, U.S.A. 109 (24), 9499-9504






(2012) NCBI Accession # 4DGY_L






(213aa)



HEPBD309
Light chain, Hcv1
Hcv1, P2(1)
Kong, L., et al., Structural basis of
6619



HCV Ab
Form
hepatitis C virus neutralization by broadly






neutralizing antibody HCV1; Proc. Natl.






Acad. Sci, U.S.A. 109 (24), 9499-9504






(2012) NCBI Accession # 4DGV_L






(213aa)



HEPBD310
Light kappa chain
P18-9E
US8592559 SEQ ID NO: 14
6620



variable, HCV Ab





HEPBD311
PEGylated anti-E2

WO2006028634 SEQ ID NO: 1
6621



heavy chain, HCV Ab





HEPBD312
PEGylated anti-E2

WO2006028634 SEQ ID NO: 2
6622



heavy chain, HCV Ab





HEPBD313
PEGylated anti-E2

WO2006028634 SEQ ID NO: 3
6623



heavy chain, HCV Ab





HEPBD314
PEGylated anti-E2

WO2006028634 SEQ ID NO: 4
6624



heavy chain, HCV Ab





HEPBD315
PEGylated anti-E2

WO2006028634 SEQ ID NO: 8
6625



heavy chain, HCV Ab





HEPBD316
single chain, HBV Ab

US6562599 SEQ ID NO: 4
6626


HEPBD317
single chain, HBV Ab

US6562599 SEQ ID NO: 6
6627









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in U.S. Pat. Nos. 7,241,445, and 8,858,947, the contents of each of which are herein incorporated by reference in their entirety, against HCV.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in US Publication No. US20150072885 and US20110046354, U.S. Pat. No. 5,204,095, European Publication No. EP0232921, EP0038642, and EP0186371, and International Publication No. WO1994011495, the contents of each of which are herein incorporated by reference in their entirety, against HBV.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in U.S. Pat. No. 6,020,195, the contents of which are herein incorporated by reference in their entirety, against HGV (hepatitis G virus).


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 24 against Herpes Virus.









TABLE 24







Antibodies against Herpesvirus















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO





HERP1
Chain A, HSV
E317 Fab
Lee, C. et al., “Structural basis for the
6628





antibody neutralization of herpes simplex






virus” Acta Crystallogr. D Biol. Crystallogr.






69 (PT 10), 1935-1945 (2013), NCBI






Accession # 3W9D_A



HERP2
Chain B, HSV
E317 Fab
Lee, C. et al., “Structural basis for the
6629





antibody neutralization of herpes simplex






virus” Acta Crystallogr. D Biol. Clystallogr.






69 (PT 10), 1935-1945 (2013), NCBI






Accession # 3W9D_B



HERP3
Chain C, HSV
E317 Fab
Lee, C. et al., “Structural basis for the
6630





antibody neutralization of herpes simplex






virus” Acta Crystatlogr. D Biol. Crystallogr.






69 (PT 10), 1935-1945 (2013), NCBI






Accession # 3W9D_C



HERP4
Chain D, HSV
E317 Fab
Lee, C. et al., “Structural basis for the
6631





antibody neutralization of herpes simplex






virus” Acta Crystallogr. D Biol. Clystallogr.






69 (PT 10), 1935-1945 (2013), NCBI






Accession # 3W9D_D



HERP5
Chimeric anti-

Tanner, J.E., “Peptides Designed To Spatially
6632



EBVs

Depict the Epstein-Barr Virus Major Virion




gp350 antibody

Glycoprotein gp350 Neutralization Epitope






Elicit Antibodies That Block Virus-






Neutralizing Antibody 72A1 Interaction with






the Native gp350 Molecule””, J. Virol. 89 (9),






4932-4911(2015), NCBI Accession






#AJR20276



HERP6
Chimeric anti-

Tanner, J.E., “Peptides Designed To Spatially
6633



EBVs

Depict the Epstein-Barr Virus Major Virion




gp350 antibody

Glycoprotein gp350 Neutralization Epitope






Elicit Antibodies That Block Virus-






Neutralizing Antibody 72A1 Interaction with






the Native gp350 Molecule””, J. Virol. 89 (9),






4932-4941 (2015), NCBI Accession






#AJR20275



HERP7
CMV
AE11F/3-20L1
Lantto, J. et al., Binding characteristics
6634





determine the neutralizing potential of






antibody fragments specific for antigenic






domain 2 on glycoprotein B of human






cytomegalovirus, Virology 305 (1), 201-209






(2003), NCBI Accession # AAN87569.1 (256






aa)



HERP8
Fv, EBV
G5
Fang, C.Y., “Modulation of Epstein-Barr virus
6635





latent membrane protein 1 activity by






intrabodies”, Intervirology 50 (4), 254-263






(2007), NCBI Accession #ABA55015



HERP9
Fv, EBV
A4
Fang, C.Y., “Modulation of Epstein-Barr virus
6636





latent membrane protein 1 activity by






intrabodies”, Intervirology 50(4), 254-263






(2007), NCBI Accession #ABA55014



HERP10
Fv, EBV
B8
Fang, CY., “Modulation of Epstein-Barr virus
6637





latent membrane protein 1 activity by






intrabodies”, Intervirology 50 (4), 254-263






(2007), NCBI Accession #ABA55013



HERP11
Fv, EBV
F5
Fang, C.Y., “Modulation of Epstein-Barr virus
6638





latent membrane protein 1 activity by






intrabodies”, Intervirology 50(4), 254-263






(2007), NCBI Accession #ABA55012



HERP12
Fv, EBV
E2
Fang, C.Y., “Modulation of Epstein-Barr virus
6639





latent membrane protein 1 activity by






intrabodies”, Intervirology 50 (4), 254-263






(2007), NCBI Accession #ABA55011



HERP13
Fv, EBV
H3
Fang, C,Y., “Modulation of Epstein-Barr virus
6640





latent membrane protein 1 activity by






intrabodies”, Intervirology 50 (4), 254-263






(2007), NCBI Accession #ABA55010



HERP14
Heavy chain,
DDF-VZV1
US20100074906 SEQ ID NO: 20
6641



FLAGhis tagged






sequence, VZV





HERP15
Heavy chain
ACHDV1
Burioni, R. et al. “Recombinant human Fab to
6642



variable domain,

glycoprotein D neutralizes infectivity and




clone 11, HSV

prevents cell-to-cell transmission of herpes






simplex viruses 1 and 2 in vitro”, Proc. Natl.






Acad. Sci. U.S.A. 91 ( 1), 355-359 (1994),






NCBI Accession # AAB29447



HERP16
Heavy chain
ACHDV1
Burioni, R. et al. “Recombinant human Fab to
6643



variable domain,

glycoprotein D neutralizes infectivity and




clone 13, HSV

prevents cell-to-cell transmission of herpes






simplex viruses 1 and 2 in vitro”, Proc. Natl.






Acad. Sci. U.S.A. 91 ( 1), 355-359 (1994),






NCBI Accession # AAB29449



HERP17
Heavy chain
ACHDV2
Burioni, R, et al, “Recombinant human Fab to
6644



variable domain,

glycoprotein D neutralizes infectivity and




clone 15, HSV

prevents cell-to-cell transmission of herpes






simplex viruses 1 and 2 in vitro”, Proc. Natl.






Acad. Sci. U.S.A. 91 ( 1), 355-359 (1994),






NCBI Accession # AAB29456



HERP18
Heavy chain
ACHDV1
Burioni, R. et al. “Recombinant human Fab to
6645



variable domain,

glycoprotein D neutralizes infectivity and




clone 15, HSV

prevents cell-to-cell transmission of herpes






simplex viruses 1 and 2 in vitro”, Proc. Natl.






Acad. Sci. U.S.A. 91 (1), 355-359 (1994,)






NCBI Accession # AAB29450



HERP19
Heavy chain
ACHDV1
Burioni, R. et al. “Recombinant human Fab to
6646



variable domain,

glycoprotein D neutralizes infectivity and




clone 18, HSV

prevents cell-to-cell transmission of herpes






simplex viruses 1 and 2 in vitro”, Proc. Natl.






Acad. Sci. U.S.A. 91 (1), 355-359 (1994,)






NCBI Accession # AAB29448



HERP20
Heavy chain
ACHDV1
Burioni, R. et al. “Recombinant human Fab to
6647



variable domain,

glycoprotein D neutralizes infectivity and




clone 2, HSV

prevents cell-to-cell transmission of herpes






simplex viruses 1 and 2 in vitro”, Proc. Natl.






Acad. Sci. U.S.A. 91 (1), 355-359 (1994),






NCBI Accession # AAB29455



HERP21
Heavy chain
1F7
US8202518 SEQ ID NO: 5
6648



variable region,






CMV





HERP22
Heavy chain
Humanized 57.4
WO2014200898 SEQ ID NO: 633
6649



variable region,






CMV





HERP23
Heavy chain
Humanized 57.4
WO2014200898 SEQ ID NO: 634
6650



variable region,






CMV





HERP24
Heavy chain
Humanized 58.5
WO2014200898 SEQ ID NO: 637
6651



variable region,






CMV





HERP25
Heavy chain
Humanized 58.5
WO2014200898 SEQ ID NO: 638
6652



variable region,






CMV





HERP26
Heavy chain
Humanized
WO2014200898 SEQ ID NO: 641
6653



variable region,
272.7





CMV





HERP27
Heavy chain
Humanized
WO2014200898 SEQ ID NO: 644
6654



variable region,
276.10





CMV





HERP28
Heavy chain
Humanized
WO2014200898 SEQ ID NO: 645
6655



variable region,
276.10





CMV





HERP29
Heavy chain
Sm5-1
Li, B., Construction and characterization of a
6656



variable region,

high-affinity humanized SMS-1 monoclonal




CMV

antibody, Biochem. Biophys. Res. Commun.






357 (4), 951-956 (2007), NCBI Accession #






ABI22831.1



HERP30
Heavy chain

Schoppel, K. et al., Antibodies specific for the
6657



variable region,

antigenic domain 1 of glycoprotein B




CMV

(gpUL55) of human cytomegalovirus bind to






different substructures, Virology 216 (1), 133-






145 (1996), NCBI Accession # AAB26953.1






(163 aa)



HERP1
Heavy chain

Schoppel, K. et al., Antibodies specific for the
6658



variable region,

antigenic domain 1 of glycoprotein B




CMV

(gpUL55) of human cytomegalovirus bind to






different substructures, Virology 216 (1), 133-






145 (1996), NCBI Accession # AAB26952.1






(161 aa)



HERP32
Heavy chain

Schoppel, K. et al., Antibodies specific for the
6659



variable region,

antigenic domain 1 of glycoprotein B




CMV

(gpUL55) of human cytomegalovirus bind to






different substructures, Virology 216 (1), 133-






145 (1996), NCBI Accession # AAB26951.1






(158 aa)



HERP33
Heavy chain

Potzsch, S., B Cell Repertoire Analysis
6660



variable region,

Identifies New Antigenic Domains on




CMV

Glycoprotein B of Human Cytomegalovirus






which Are Target of Neutralizing Antibodies,






NCBI Accession # AEF33814.1



HERP34
Heavy chain
1F11
US9149524 SEQ ID NO: 7
6661



variable region,






CMV, a complex






of human






cytomegalovirus






(hCMV) proteins






UL130 and






UL131A





HERP35
Heavy chain
2F4
US9149524 SEQ ID NO: 17
6662



variable region,






CMV, a complex






of human






cytomegalovirus






(hCMV) proteins






UL130 and






UL131A





HERP36
Heavy chain
5A2
US9149524 SEQ ID NO: 39
6663



variable region,






CMV, a complex






of human






cytomegalovirus






(hCMV) proteins






UL130 and






UL131A





HERP37
Heavy chain
EV2038
US8492529 SEQ ID NO: 10
6664



variable region,






CMV, AD1






region of HMV






glycoprotein gB





HERP38
Heavy chain

US20150064174 SEQ ID 1
6665



variable region,






EBV





HERP39
Heavy chain

US20150064174 SEQ ID 2
6666



variable region,






EBV





HERP40
Heavy chain
HCMV16
WO1994009136, FIG. 1
6667



variable region,






gH glycoprotein






of HCMV





HERP41
Heavy chain

Nejatollahi, F. and Bagheri, V., “Isolation of
6668



variable region,

neutralizing human specific single-chain




HSV

antibodies against Herpes Simplex Virus type






1 glycoproiein D”, unpublished, NCBI






Accession # AGO59015



HERP42
Heavy chain
E317
US8431118 SEQ ID NO: 1; US8252906
6669



variable region,






HSV 1&2





HERP43
Heavy chain
E425
US8431118 SEQ ID NO: 3; US8252906
6670



variable region,






HSV 1&2





HERP44
Heavy chain
Y571
US8431118 SEQ ID NO: 41; US8252906
6671



variable region,






HSV 1&2





HERP45
Heavy chain

US5506132 SEQ ID NO: 4
6672



variable region,






VZV





HERP46
Heavy chain
DDF-VZV2
US20100074906 SEQ ID NO: 26
6673



variable region,






VZV





HERP47
Heavy chain
EV2038
US8492529 SEQ ID NO: 6
6674



without a signal






sequence, CMV,






AD1 region of






HCMV






glycoprote in gB





HERP48
Heavy chain,
8f9
McLean, G.R. et al., Recognition of human
6675



CMV

cytomegalovirus by human primary






immunoglobulins identifies an innate






foundation to an adaptive immune response, J.






Immunol. 174 (8), 4768-4778 (2005), NCBI






Accession # CAE54374.1



HERP49
Heavy chain,
Mab 109
Simpson, J.A. et al., Neutralizing monoclonal
6676



CMV

antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationally distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24505.1 (119 aa)



HERP50
Heavy chain,
Mab 115
Simpson, J.A. et al., Neutralizing monoclonal
6677



CMV

antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationaly distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24504.1 (117 aa)



HERP51
Heavy chain,
Mab 33
Simpson, J.A. et al., Neutralizing monoclonal
6678



CMV

antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationally distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24503.1 (120 aa)



HERP52
Heavy chain,
Mab 5
Simpson, J.A. et at, Neutralizing monoclonal
6679



CMV

antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationaly distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24502.1 (120 aa)



HERP53
Heavy chain,
6G4
WO2010007463 SEQ ID NO: 7
6680



CMV, a






combination of






the hCMV






proteins UL128,






UL130 and






UL131A





HERP54
Heavy chain,

US20140093526 SEQ ID 12
6681



HHV-6





HERP55
Heavy chain,
FabHS V 8.
US6156313 SEQ ID NO: 2
6682



HSV 1&2





HERP56
Heavy chain,
64-683
US5646041 SEQ ID NO: 2; EP876478
6683



HSV 1&2





HERP57
Heavy chain,
H005157
US20140302062 SEQ ID NO: 3
6684



HSV 1&2





HERP58
Heavy chain,
H005158
US20140302062 SEQ ID NO: 4
6685



HSV 1&2





HERP59
Heavy chain,
H005159
US20140302062 SEQ ID NO: 5
6686



HSV 1&2





HERP60
Heavy chain,
H005160
US20140302062 SEQ ID NO: 6
6687



HSV 1&2





HERP61
Heavy chain,
H005188
US20140302062 SEQ ID NO: 7
6688



HSV 1&2





HERP62
Heavy chain,
H005190
US20140302062 SEQ ID NO: 8
6689



HSV 1&2





HERP63
Heavy chain,
H005192
US20140302062 SEQ ID NO: 9
6690



HSV 1&2





HERP64
Light chain
HCMV16
WO1994009136, FIG. 2
6691



variable region,






gH glycoprotein






of HCMV





HERP65
Light chain
DDF-VZV1
US20100074906 SEQ ID NO: 22
6692



recombinant,






VZV





HERP66
Light chain
1F7
US8202518 SEQ ID NO: 10
6693



variable region,






CMV





HERP67
Light chain
Humanized 57.4
WO2014200898 SEQ ID NO: 631
6694



variable region,






CMV





HERP68
Light chain
Humanized 57.4
WO2014200898 SEQ ID NO: 632
6695



variable region,






CMV





HERP69
Light chain
Humanized 58.5
WO2014200898 SEQ ID NO: 635
6696



variable region,






CMV





HERP70
Light chain
Humanized 58.5
WO2014200898 SEQ ID NO: 636
6697



variable region,






CMV





HERP71
Light chain
Humanized
WO2014200898 SEQ ID NO: 639
6698



variable region,
272.7





CMV





HERP72
Light chain
Humanized
WO2014200898 SEQ ID NO: 640
6699



variable region,
272.7





CMV





HERP73
Light chain
Humanized
WO2014200898 SEQ ID NO: 642
6700



variable region,
276.10





CMV





HERP74
Light chain
Humanized
WO2014200898 SEQ ID NO: 643
6701



variable region,
276.10





CMV





HERP75
Light chain
Sm5-1
Li, B., Construction and characterization of a
6702



variable region,

high-affinity humanized SM5-1 monoclonal




CMV

antibody, Biochem. Biophys. Res. Commun.






357 (4), 951-956 (2007), NCBI Accession #






AB122832.1



HERP76
Light chain
8f9
Schoppel, K. et al., Antibodies specific for the
6703



variable region,

antigenic domain 1 of glycoprotein B




CMV

(gpUL55) of human cytomegalovirus bind to






different substructures, Virology 216 (1), 133-






145 (1996), NCBI Accession # AAB26956.1






(146 aa)



HERP77
Light chain

Schoppel, K. et al., Antibodies specific for the
6704



variable region,

antigenic domain 1 of glycoprotein B




CMV

(gpUL55) of human cytomegalovirus bind to






different substructures, Virology 216 (1), 133-






145 (1996), NCBI Accession # AAB26955.1






(141 aa)



HERP78
Light chain

Schoppel, K. et al., Antibodies specific for the
6705



variable region,

antigenic domain 1 of glycoprotein B




CMV

(gpUL55) of human cytomegalovirus bind to






different substructures, Virology 216 (1), 133-






45 (1996), NCBI Accession # AAB26954.1






(152 aa)



HERP79
Light chain

Potzsch, S., B Cell Repertoire Analysis
6706



variable region,

Identifies New Antigenic Domains on




CMV

Glycoprotein B of Human Cytomegalovirus






which Are Target of Neutralizing Antibodies,






NCBI Accession # AEF33824.1



HERP80
Light chain
1F11
US9149524 SEQ ID NO: 8
6707



variable region,






CMV, a






combination of






the hCMV






proteins UL128,






UL130 and






UL131A





HERP81
Light chain
2F4
US9149524 SEQ ID NO: 18
6708



variable region,






CMV, a






combination of






the hCMV






proteins UL128,






ULL30 and






UL131A





HERP82
Light chain
5A2
US9149524 SEQ ID NO: 40
6709



variable region,






CMV, a






combination of






the hCMV






proteins IUL128,






UL130 and






UL131A





HERP83
Light chain
EV2038
US8492529 SEQ ID NO. 12
6710



variable region,






CMV, AD1






region of HCMV






glycoprotein gB





HERP84
Light chain

US20150064174 SEQ ID 3
6711



variable region,






EBV





HERP85
Light chain

US20150064174 SEQ ID 4
6712



variable region,






EBV





HERP86
Light chain

Nejatollahi, F. and Bagheri, V., “Isolation of
6713



variable region,

neutralizing human specific single-chain




HSV

antibodies against Herpes Simplex Virus type






1 glycoprotein D”, unpublished”, NCBI






Accession # AGO59016



HERP87
Light chain
E317
US8431118 SEQ ID NO: 2; US8252906
6714



variable region,






HSV 1&2





HERP88
Light chain
E425
US8431118 SEQ ID NO: 4; US8252906
6715



variable region,






HSV 1&2





HERP89
Light chain
Y571
US8431118 SEQ ID NO: 42; US8252906
6716



variable region,






HSV 1&2





HERP90
Light chain

US5506132 SEQ ID NO: 2
6717



variable region,






VZV





HERP91
Light chain
DDF-VZV2
US20100074906 SEQ ID NO: 24
6718



variable region,






VZV





HERP92
Light chain
EV2038
US8492529 SEQ ID NO: 8
6719



without a signal






sequence, CMV,






AD1 region of






HCMV






glycoprotein gB





HERP93
Light chain, CMV
8f9
McLean, G.R. et al., Recognition of human
6720





cytomegalovirus by human primary






immunoglobulins identifies an innate






foundation to an adaptive immune response, J.






Immunol. 174 (8), 4768-4778 (2005), NCBI






Accession # CAE54366.1



HERP94
Light chain, CMV
Mab 109
Simpson, J.A. et al., Neutralizing monoclonal
6721





antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationally distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # A AB24501.1 (111 aa)



HERP95
Light chain, CMV
Mab 115
Simpson, J.A. et al., Neutralizing monoclonal
6722





antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationaly distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24500.1 (107 aa)



HERP96
Light chain, CMV
Mab 33
Simpson, J.A. et al., Neutralizing monoclonal
6723





antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationally distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24499.1 (107 aa)



HERP97
Light chain, CMV
Mab 5
Simpson, J.A. et al., Neutralizing monoclonal
6724





antibodies that distinguish three antigenic sites






on human cytomegalovirus glycoprotein H






have conformationally distinct binding sites, J.






Virol. 67 (1), 489-496 (1993), NCBI






Accession # AAB24498.1 (107 aa)



HERP98
Light chain,
6G4
WO2010007463 SEQ ID NO: 8
6725



CMV, a






combination of






the hCMV






proteins UL128,






UL130 and






UL131A





HERP99
Light chain,

US20140093526 SEQ ID 10
6726



HHV-6





HERP100
Light chain, HSV
64-683
US5646041 SEQ ID NO: 4; EP876478
6727



1&2





HERP101
Light chain, HSV
K003927
US20140302062 SEQ ID NO: 10
6728



1&2





HERP102
Light chain, HSV
K003928
US20140302062 SEQ ID NO: 11
6729



1&2





HERP103
Light chain, HSV
K003929
US20140302062 SEQ ID NO: 12
6730



1&2





HERP104
Light chain, HSV
K003930
US20140302062 SEQ ID NO: 13
6731



1&2





HERP105
Light chain, HSV
K003946
US20140302062 SEQ ID NO: 14
6732



1&2





HERP106
Light chain, HSV
K003948
US20140302062 SEQ ID NO: 15
6733



1&2





HERP107
Light chain, HSV
K003949
US20140302062 SEQ ID NO: 16
6734



1&2





HERP108
Light chain, HSV
L00184-4
US20140302062 SEQ ID NO: 17
6735



1&2





HERP109
Single chain Fv

Lantto, J. et al., Non-germ-line encoded
6736



antibody,

residues are critical for effective antibody




glycoprotein B

recognition of a poorly immunogenic




recombinant,

neutralization epitope on glycoprotein B of




CMV

human cytomegalovirus, Eur. J. Immunol. 32






(6), 1659-1669 (2002), NCBI Accession #






AAM92769.1 (255 aa)









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in International Publication No. WO2010109874, and WO1997026329, the contents of each of which are herein incorporated by reference in their entirety, against HSV.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in International Publication No. WO1995031546, the contents of which are herein incorporated by reference in their entirety, against VZV.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody poly peptides listed in Table 25 against Coronavirus.









TABLE 25







Antibodies against Coronaviruses















SEQ


Antibody

Antibody
Reference
ID


No.
Description
Name
Information
NO





CORV1
Heavy chain partial sequence,

Liu, J., unpublished, NCBI
6737



Human anti-SARS antibody, Ig

Accession # BAE94186.1(228aa)



CORV2
Heavy chain partial sequence
H12
AAX19356.1(127aa)
6738



Human SARS neutralization






antibody, Ig





CORV3
Heavy chain variable partial

Leung et at., PLoS Med. 3 (7),
6739



sequence, Human neutralizing

E237 (2006), NCBI Accession #




SARS antibody

ABA54614.1(113aa)



CORV4
Heavy chain variable region,
M396
Prabakaran etal., J. Biol. Chem.
6740



Human anti-SARS antibody

281 (23), 15829-15836 (2006),






NCBI Accession # 2G75_D






(213aa)



CORV5
Heavy chain variable region,

Prabakaran etal., J. Biol. Chem.
6741



Human neutralizing SARS

281 (23), 15829-15836 (2006),




antibody

NCBI Accession # 2DD8_L






(213aa)



CORV6
Heavy chain variable region,

CN103864924 SEQ ID NO: 1
6742



Humanized neutralizing murine






monoclonal MERS





CORV7
Heavy chain variable region,

CN104447986 SEQ ID NO: 1
6743



MERs





CORV8
Heavy chain variable region,

US7750123 SEQ ID NO: 12;
6744



Neutralizing antibody (binds to

WO2005060520; CN1914226;




the spike protein (5) of SARS-

US20050249739




cov)





CORV9
Heavy chain variable region,
s110.4
US20110159001 SEQ ID NO: 62;
6745



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV10
Heavy chain variable region,
s124.5
US20110159001 SEQ ID NO: 66;
6746



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV11
Heavy chain variable region,
s215.17
US20110159001 SEQ ID NO: 70;
6747



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV12
Heavy chain variable region,
s218.9
US20110159001 SEQ ID NO: 74;
6748



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV13
Heavy chain variable region,
s223.4
US20110159001 SEQ ID NO: 78;
6749



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV14
Heavy chain variable region,
s22512
US20110159001 SEQ ID NO: 82;
6750



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV15
Heavy chain variable region,
s231.19
US20110159001 SEQ ID NO: 86;
6751



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV16
Heavy chain variable region,
s230.14 + 15
US20110159001 SEQ ID NO: 90;
6752



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV17
Heavy chain variable region,
s227. 14
US20110159001 SEQ ID NO: 94;
6753



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV18
Heavy chain variable region,
s109.8
US20110159001 SEQ ID NO: 98;
6754



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV19
Heavy chain variable region,
Fab58
CN1513874
6755



SARS antibody





CORV20
Heavy chain variable region,
Fab59
CN1513874
6756



SARS antibody





CORV21
Heavy chain variable region,
3C7
US7728110 SEQ ID NO: 60;
6757



SARS human monoclonal

WO2008060331; EP2035454A2,




antibody

US20080248043



CORV22
Heavy chain variable region,
F26G18
US7622112 SEQ ID NO: 5;
6758



SARS human monoclonal

WO2005054469;




antibody

US20080248043; US20080081047



CORV23
Heavy chain variable region A,

WO2006095180 SEQ ID NO: 24
6759



humanized antibody binding to






S2 domain of SARS





CORV24
Heavy chain Humanized

CN103864924 SEQ ID NO: 3
6760



neutralizing murine monoclonal






MERS





CORV25
Heavy chain, MERS
m336
WO2015057942 SEQ ID NO: 1
6761


CORV26
Heavy chain, MERS
m337
WO2015057942 SEQ ID NO: 9
6762


CORV27
Fleavy chain, MERS
m338
WO2015057942 SEQ ID NO: 16
6763


CORV28
Heavy chain, MERS
2e 6
CN104447986 SEQ ID NO: 3
6764


CORV29
Heavy chain, MERS
M336
Ying et al., Nat Commun 6, 8223
6765





(2015), NCBI Accession #






4XAK_H(252aa)



CORV30
Human anti-SARS antibody

Leung et al., PLoS Med. 3 (7),
6766





E237 (2006), NCBI Accession #






ABA54613.1(117aa)



CORV31
Human monoclonal MERS
Mers-27
CN104628848 SEQ ID NO: 1
6767


CORV32
Human monoclonal MERS
Mers-27
CN104628848 SEQ ID NO. 3
6768


CORV33
Human monoclonal MERS
Mers-4
CN104628849 SEQ ID NO: 1
6769


CORV34
Human monoclonal MERS
Mers-4
CN104628849 SEQ ID NO: 3
6770


CORV35
Kappa light chain partial
H12
AX19355.1(108aa)
6771



sequence, human SARS






neutralization antibody, Ig





CORV36
Light chain partial sequence,

Liu, J., unpublished, NCBI
6772



Human anti-SARS antibody, Ig

Accession # BAE94187.1(219aa)



CORV37
Light chain variable domain,

CN104447986 SEQ ID NO: 2
6773



MERS





CORV38
Light chain variable partial
80R
Hwang et al., J. Biol. Chem. 281
6774



sequence, Human neutralizing

(45), 34610-34616 (2006), NCBI




SARS antibody

Accession # 2GHW_D (247aa)



CORV39
Light chain variable region, A

WO2006095180 SEQ ID NO: 25
6775



humanized antibody binding to






S2 domain of SARS





CORV40
Light chain variable region,
M396
Prabakaran et al., J. Biol. Chem.
6776



human anti-SARS antibody

281 (23), 15829-15836 (2006),






NCBI Accession # 2G75_C






(245aa)



CORV41
Light chain variable region,

Prabakaran et al., J. Biol. Chem.
6777



Human neutralizing SARS

281 (23), 15829-15836 (2006),




antibody

NCBI Accession #






2DD8_H(245aa)



CORV42
Light chain variable region,

CN103864924 SEQ ID NO: 2
6778



Humanized neutralizing murine






monoclonal MERS





CORV43
Light chain variable region,

US7750123 SEQ ID NO: 20;
6779



neutralizing antibody (binds to

WO2005060520; CN1914226;




the spike protein (S) of SARS-

US20050249739




cov)





CORV44
Light chain variable region,
s110.4
US20110159001 SEQ ID NO: 64;
6780



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV45
Light chain variable region,
s124.5
US20110159001 SEQ ID NO: 68;
6781



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV46
Light chain variable region,
s215.17
US20110159001 SEQ ID NO: 72;
6782



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV47
Light chain variable region,
s218.9
US20110159001 SEQ ID NO: 76;
6783



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV48
Light chain variable region,
s223.4
US20110159001 SEQ ID NO: 80;
6784



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV49
Light chain variable region,
s225.1.2
US20110159001 SEQ ID NO: 84;
6785



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV50
Light chain variable region,
s231.19
US20110159001 SEQ ID NO: 88;
6786



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV51
Light chain variable region,
s230.14 + 15
US20110159001 SEQ ID NO: 92;
6787



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV52
Light chain variable region,
s227.14
US20110159001 SEQ ID NO: 96;
6788



SARS antibody

WO2009128963; EP2242768;






CN102015767



CORV53
Light chain variable region,
s109.8
US20110159001 SEQ ID NO:
6789



SARS antibody

101; WO2009128963; EP2242768;






CN102015767



CORV54
Light chain variable region,
Fab58
CN1513874
6790



SARS antibody





CORV55
Light chain variable region,
Fab59
CN1513874
6791



SARS antibody





CORN56
Light chain variable region,
3C7
US7728110 SEQ ID NO: 58;
6792



SARS human monoclonal

WO2008060331; EP2035454A2,




antibody

US20080248043



CORV57
Light chain variable region,
F26G18
US7622112 SEQ ID NO: 14;
6793



SARS human monoclonal

WO2005054469;




antibody

US20080248043; US20080081047



CORV58
Light chain, Humanized

CN103864924 SEQ ID NO: 4
6794



neutralizing murine monoclonal






MERS





CORV59
Light chain, MERS
m336
WO2015057942 SEQ ID NO: 2
6795


CORV60
Light chain, MERS
m337
WO2015057942 SEQ ID NO: 10
6796


CORV61
Light chain, MERS
m338
WO2015057942 SEQ ID NO: 17
6797


CORV62
Light chain, MERS
2E 6
CN104447986 SEQ ID NO: 4
6798


CORV63
Light chain, MERS
M336
Ying et al., Nat Commun 6, 8223
6799





(2015), NCBI Accession #






4XAK_L (214aa)



CORV64
Variable heavy chain-constant
4C2Fab
CN103864924 SEQ ID NO: 7
6800



heavy chain 1, Humanized






neutralizing murine monoclonal






MERS





CORV65
Variable light chain-constant
4C2Fab
CN103864924 SEQ ID NO: 9
6801



light chain 1, Humanized






neutralizing murine monoclonal






MERS









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in U.S. Pat. No. 7,629,443, US Publication No US20080254440, Chinese Publication No. CN103613666. CN1570638, CN101522208, CN1673231, CN1590409, CN1557838, and CN1488645, the contents of each of which are herein incorporated by reference in their entirety, against SARS.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 26 against John Cunningham Virus.









TABLE 26







Antibodies against John Cunningham Virus











Anti-



SEQ


body

Antibody
Reference
ID


No.
Description
Name
Information
NO





JCV1
Heavy chain
14G8
US20150056188
6802





SEQ ID NO: 1



JCV2
Heavy chain
16H5
US20150056188
6803





SEQ ID NO: 5



JCV3
Heavy chain
18C9
US20150056188
6804





SEQ ID NO: 9



JCV4
Heavy chain
34C6
US20150056188
6805





SEQ ID NO: 13



JCV5
Heavy chain
18C9 N55S
US20150056188
6806





SEQ ID NO: 16



JCV6
Heavy chain
18C9 N55Q
US20150056188
6807





SEQ ID NO: 18



JCV7
Heavy chain
18C9 N55D
US20150056188
6808





SEQ ID NO: 20



JCV8
Heavy chain
18C9 N55H
US20150056188
6809





SEQ ID NO: 22



JCV9
Heavy chain
18C9 N55T
US20150056188
6810





SEQ ID NO: 24



JCV10
Heavy chain
18C9 N55A
US20150056188
6811





SEQ ID NO: 26



JCV11
Heavy chain
18C9 N55L
US20150056188
6812





SEQ ID NO: 28



JCV12
Heavy chain
18C9 N55X
US20150056188
6813





SEQ ID NO: 30



JCV13
Heavy chain
18C9 G56A
US20150056188
6814





SEQ ID NO: 32



JCV14
Heavy chain
18C9 G56V
US20150056188
6815





SEQ ID NO: 34



JCV15
Heavy chain
18C9 G56P
US20150056188
6816





SEQ ID NO: 36



JCV16
Heavy chain
18C9 G56X
US20150056188
6817





SEQ ID NO: 38



JCV17
Heavy chain
399-h (C35A
US20150050271
6818




V50A)
SEQ ID NO: 20



JCV18
Heavy chain
Antibody from
US20150050271
6819




US20150050271
SEQ ID NO: 66



JCV19
Heavy chain
H0
US20150050271
6820





SEQ ID NO: 51



JCV20
Heavy chain
H1
US20150050271
6821





SEQ ID NO: 52



JCV21
Heavy chain
H3
US20150050271
6822





SEQ ID NO: 54



JCV22
Heavy chain
H4
US20150050271
6823





SEQ ID NO: 55



JCV23
Heavy chain
H5
US20150050271
6824





SEQ ID NO: 56



JCV24
Heavy chain
H6
US20150050271
6825





SEQ ID NO: 57



JCV25
Heavy chain
H7
US20150050271
6826





SEQ ID NO: 58



JCV26
Heavy chain
H8
US20150050271
6827





SEQ ID NO: 59



JCV27
Heavy chain
H9
US20150050271
6828





SEQ ID NO: 60



JCV28
Heavy chain
L0
US20150050271
6829





SEQ ID NO: 48



JCV29
Heavy chain
jcv411_vh
US20150050271
6830





SEQ ID NO: 43



JCV30
Heavy chain
IGHV3-30-3x01
US20150050271
6831





SEQ ID NO: 44



JCV31
Heavy chain
H0
US20150050271
6832





SEQ ID NO: 19



JCV32
Heavy chain
H0 V50G
US20150050271
6833





SEQ ID NO: 21



JCV33
Heavy chain
H1
US20150050271
6834





SEQ ID NO: 22



JCV34
Heavy chain
H2
US20150050271
6835





SEQ ID NO: 23



JCV35
Heavy chain
H3
US20150050271
6836





SEQ ID NO: 24



JCV36
Heavy chain
H4
US20150050271
6837





SEQ ID NO: 25



JCV37
Heavy chain
H5
US20150050271
6838





SEQ ID NO: 26



JCV38
Heavy chain
H6
US20150050271
6839





SEQ ID NO: 27



JCV39
Heavy chain
H7
US20150050271
6840





SEQ ID NO: 28



JCV40
Heavy chain
H8
US20150050271
6841





SEQ ID NO: 29



JCV41
Heavy chain
H9
US20150050271
6842





SEQ ID NO: 30



JCV42
Heavy chain
GRE1
US20150191530
6843



variable

SEQ ID NO: 1




region





JCV43
Heavy chain
R399
US20150050271
6844



variable

SEQ ID NO: 6




region





JCV44
Light chain
14G8
US20150056188
6845





SEQ ID NO: 3



JCV45
Light chain
16H5
US20150056188
6846





SEQ ID NO: 7



JCV46
Light chain
18C9
US20150056188
6847





SEQ ID NO: 11



JCV47
Light chain
34C6
US20150056188
6848





SEQ ID NO: 14



JCV48
Light chain
18C9 C96L
US20150056188
6849





SEQ ID NO: 40



JCV49
Light chain
18C9 C96S
US20150056188
6850





SEQ ID NO: 42



JCV50
Light chain
18C9 C96A
US20150056188
6851





SEQ ID NO: 44



JCV51
Light chain
18C9 C96X
US20150056188
6852





SEQ ID NO: 46



JCV52
Light chain
399-1 (N31G),
US20150050271
6853




L
SEQ ID NO: 15



JCV53
Light chain
Antibody from
US20150050271
6854




US20150050271
SEQ ID NO: 67



JCV54
Light chain
H2
US20150050271
6855





SEQ ID NO: 53



JCV55
Light chain
L1
US20150050271
6856





SEQ ID NO: 49



JCV56
Light chain
L2
US20150050271
6857





SEQ ID NO: 50



JCV57
Light chain
1GKV1D-13x01
US20150050271
6858





SEQ ID NO: 39



JCV58
Light chain
L0
US20150050271
6859





SEQ ID NO: 11



JCV59
Light chain
L1
US20150050271
6860





SEQ ID NO: 12



JCV60
Light chain
L2
US20150050271
6861





SEQ ID NO: 13



JCV61
Light chain
L2 N31A
US20150050271
6862





SEQ ID NO: 14



JCV62
Heavy chain
GRE1
US20150191530
6863



variable

SEQ ID NO: 2




region





JCV63
Heavy chain
R399
US20150050271
6864



variable

SEQ ID NO: 1




region





JCV64
Heavy chain
R411.jcv411_vh
US20150050271
6865



variable

SEQ ID NO: 38




region









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 27 against Poxvirus.









TABLE 27







Antibodies against Poxvirus











Antibody

Antibody
Reference
SEQ ID


No.
Description
Name
Information
NO





POXV1
Heavy chain
B5R binding
US8623370
6866



variable region,
antibody
SEQ ID NO: 2




B5R envelope






protein





POXV2
Heavy chain
B5R binding
US8623370
6867



variable region,
antibody
SEQ ID NO: 6




B5R envelope






protein





POXV3
Heavy chain
B5R binding
US8623370
6868



variable region,
antibody
SEQ ID NO:




B5R envelope

10




protein





POXV4
Heavy chain
B5R binding
US8623370
6869



variable region,
antibody
SEQ ID NO:




B5R envelope

14




protein





POXV5
Heavy chain,
H3L binding
US20140186370
6870



H3L envelope
antibody
SEQ ID




protein

NO: 14



POXV6
Light chain variable
B5R binding
US8623370
6871



region, B5R
antibody
SEQ ID NO: 4




envelope protein





POXV7
Light chain variable
B5R binding
US8623370
6872



region, B5R
antibody
SEQ ID NO: 8




envelope protein





POXV8
Light chain variable
B5R binding
US8623370
6873



region, B5R

SEQ ID NO:




envelope protein
antibody
12



POXV9
Light chain variable
B5R binding
US8623370
6874



region, B5R

SEQ ID NO:




envelope protein
antibody
16



POXV10
Light chain,
H3L binding
US20140186370
6875



H3L envelope
antibody
SEQ ID




protein

NO: 16









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 28 against Enterovirus 71.









TABLE 28







Antibodies against Enterovirus 71















SEQ


Antibody


Reference
ID


No.
Description
Antibody Name
Information
NO





ENTV1
Heavy chain

CN102718864A
6876



variable region

SEQ ID NO: 2



ENTV2
Heavy chain
E18
WO2015092668
6877



variable region

SEQ ID NO: 1



ENTV3
Heavy chain
E19
WO2015092668
6878



variable region

SEQ ID NO: 3



ENTV4
Heavy chain
E20
WO2015092668
6879



variable region

SEQ ID NO: 5



ENTV5
Heavy chain
E19 humanized
WO2015092668
6880



variable region
VH1
SEQ ID NO: 19



ENTV6
Heavy chain
E19 humanized
WO2015092668
6881



variable region
VH2
SEQ ID NO: 20



ENTV7
Heavy chain
E19 humanized
WO2015092668
6882



variable region
VH3
SEQ ID NO: 21



ENTV8
Heavy chain
E19 humanized
WO2015092668
6883



variable region
VH4
SEQ ID NO: 22



ENTV9
Light chain

CN102718864A
6884



variable region

SEQ ID NO: 1



ENTV10
Light chain
E18
WO2015092668
6885



variable region

SEQ ID NO: 2



ENTV11
Light chain
E19
WO2015092668
6886



variable region

SEQ ID NO: 4



ENTV12
Light chain
E20
WO2015092668
6887



variable region

SEQ ID NO: 6



ENTV13
Light chain
E18 VL2
WO2015092668
6888



variable region

SEQ ID NO: 15



ENTV14
Light chain
E19 humanized
WO2015092668
6889



variable region
VL1
SEQ ID NO: 16



ENTV15
Light chain
E19 humanized
WO2015092668
6890



variable region
VL2
SEQ ID NO: 17



ENTV16
Light chain
E19 humanized
WO2015092668
6891



variable region
VL3
SEQ ID NO: 18









In one embodiment, the payload region of the AA particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in Chinese Publication No. CN104357400, the contents of which are herein incorporated by reference in their entirety, against EV71.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants encoding MAB979, fragments or variants thereof for treating a disease and/or disorder or preventing a disease and/or disorder. As a non-limiting example, the disease and/or disorder is EV71.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 29 against Rubella Virus.









TABLE 29







Antibodies against Rubella Virus











Antibody

Antibody

SEQ ID


No.
Description
Name
Reference Information
NO





RUBV1
Heavy chain
DDF-RuV1
US20100143376
6892



variable region

SEQ ID NO: 2



RUBV2
Heavy chain
DDF-RuV2
US20100143376
6893



variable region

SEQ ID NO: 9



RUBV3
Light chain
DDF-RuV1
US20100143376
6894



variable region

SEQ ID NO: 7



RUBV4
Light chain
DDF-RuV2
US20100143376
6895



variable region

SEQ ID NO: 14









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 30 against Human Papilloma Virus.









TABLE 30







Antibodies against Human Papilloma Virus










Antibody


SEQ


No.
Description
Reference Information
ID NO





HPV1
Heavy chain
WO2015096269 SEQ ID NO: 1
6896



variable region




HPV2
Light chain
WO2015096269 SEQ ID NO: 2
6897



variable region









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in US Publication No. US20130337438, the contents of which are herein incorporated by reference in their entirety, against HBV.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the broadly neutralizing payload antibody polypeptides listed in Table 31 against viruses.









TABLE 31







Broadly Neutralizing Antibodies for Viruses











Anti-



SEQ


body

Antibody
Reference
ID


No.
Description
Name
Information
NO





VIR1
Heavy chain variable
3G4
US7611704
6898



region, hepatitis, influenza,

SEQ ID




HIV, herpes,

NO: 2




paramyxovirus, poxvirus,






rhabdovirus or arenavirus





VIR2
Heavy chain variable
3G4
US7611704
6899



region, hepatitis, influenza,

SEQ ID




HIV, herpes,

NO: 4




paramyxovirus, poxvirus,






rhabdovirus or arenavirus





VIR3
Heavy chain variable
679
US7429381
6900



region, HIV, herpes,

SEQ ID




cytomegalovirus, rabies,

NO: 4




influenza, hepatitis B,






Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster, light






chain variable region,






Dengue, rubella, measles,






adenovirus, human T-cell






leukemias, Epstein-






Barr, murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis, wart






and blue tongue





VIR4
Heavy chain variable
Mu-9V
US7429381
6901



region, HIV, herpes,

SEQ ID




cytomegalovirus, rabies,

NO: 10




influenza, hepatitis B,






Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster,






Dengue, rubella, measles,






adenovirus, human T-






cell leukemias, Epstein-Barr,






murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis,






wart and blue






tongue, light chain






variable region





VIR5
Heavy chain variable
humanized
US7429381
6902



region, HIV, herpes,
Mu-9
SEQ ID




cytomegalovirus, rabies,

NO: 14




influenza, hepatitis B,






Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster,






Dengue, rubella, measles,






adenovirus, human T-






cell leukemias, Epstein-Barr,






murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis,






wart and blue






tongue, light chain






variable region





VIR6
Heavy chain variable
Fab-2
US20120269801
6903



region, Human
Clone3
SEQ




cytomegalovirus, HCMV,

ID NO: 6




human T-cell leukemia






virus type 1, HIV-1,






simian immunodeficiency






virus, Ebola virus,






Herpesvirus saimiri virus,






influenza virus, and






vaccinia virus





VIR7
Heavy chain variable
Fab-3
US20120269801
6904



region, Human
Clone 7
SEQ




cytomegalovirus, HCMV,

ID NO: 10




human T-cell leukemia






virus type 1, HIV-1,






simian immunodeficiency






virus, Ebola virus,






Herpesvirus saimiri virus,






influenza virus, and






vaccinia virus





VIR8
Light chain variable
Mu-9V
US7429381
6905



region, HIV, herpes,

SEQ ID




cytomegalovirus, rabies,

NO: 8




influenza, hepatitis B,






Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster,






Dengue, rubella, measles,






adenovirus, human T-






cell leukemias, Epstein-Bair,






murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis,






wart and blue






tongue, light chain






variable region





VIR9
Light chain variable
humanized
US7429381
6906



region, HIV, herpes,
Mu-9
SEQ ID




cytomegalovirus, rabies,

NO: 12




influenza, hepatitis B,






Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster,






Dengue, rubella, measles,






adenovirus, human T-






cell leukemias, Epstein-Barr,






murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis,






wart and blue






tongue, light chain






variable region





VIR10
Light chain variable
679
US7429381
6907



region, HIV, herpes,

SEQ ID




cytomegalovirus, rabies,

NO: 2




influenza, hepatitis B,






Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster,






Dengue, rubella, measles,






adenovirus, human T-






cell leukemias, Epstein-Barr,






murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis,






wart and blue






tongue





VIR11
Light chain variable
Fab-3
US20120269801
6908



region, Human
Clone 7
SEQ




cytomegalovirus, HCMV,

ID NO: 8




human T-cell leukemia






virus type 1, HIV-1,






simian immunodeficiency






virus, Ebola virus,






Herpesvirus saimiri virus,






influenza virus, and






vaccinia virus





VIR12
Light chain variable,
Fab-2
US20120269801
6909



Human cytomegalovirus,
Clone3
SEQ




HCMV, human T-cell

ID NO: 4




leukemia virus type 1,






HIV-1, simian






immunodeficiency






virus, Ebola






virus, Herpesvirus saimiri






virus, influenza virus,






and vaccinia virus, region





VIR13
ScFv, hepatitis, influenza,
3A2
US7611704
6910



HIV, herpes,

SEQ ID




paramyxovirus, poxvirus,

NO: 6




rhabdovirus or






arenavirus





VIR14
ScFv, HIV, herpes,
679
US7429381
6911



cytomegalovirus, rabies,

SEQ ID




influenza, hepatitis B,

NO: 6




Sendai, feline leukemia,






Reo, polio, human serum






parvo-like, simian 40,






respiratory syncytial,






mouse mammary tumor,






Varicella-Zoster, Dengue,






rubella, measles,






adenovirus, human






T-cell leukemias, Epstein-






Barr, murine leukemia,






mumps, vesicular






stomatitis, Sindbis,






lymphocytic






choriomeningitis, wart






and blue tongue









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 32 against Pseudomonas aeruginosa









TABLE 32







Antibodies against Pseudomonas Aeruginosa











Anti-



SEQ


body


Reference
ID


No.
Description
Antibody Name
Information
NO





PSEU1
Bivalent
260 (1E11-
US20150044215
6912



nanobody
40GS-2B10)
SEQ ID NO: 118



PSEU2
Bivalent
272 (11B09-
US20150044215
6913



nanobody
40GS-
SEQ ID NO: 119





10C05)




PSEU3
Bivalent
308 (6B05-
US20150044215
6914



nanobody
40GS-1E11)
SEQ ID NO: 120



PSEU4
Bivalent
264 (1E11-
US20150044215
6915



nanobody
40GS-2B02)
SEQ ID NO: 121



PSEU5
Bivalent
302 (5H01-
US20150044215
6916



nanobody
40GS-7C10)
SEQ ID NO: 122



PSEU6
Bivalent
234 (7C10-
US20150044215
6917



nanobody
40GS-5H01)
SEQ ID NO: 123



PSEU7
Bivalent
064 (13F07-
US20150044215
6918



nanobody
40GS-7C10)
SEQ ID NO: 124



PSEU8
Bivalent
275 (2G09-
US20150044215
6919



nanobody
40GC-5H10)
SEQ ID NO: 125



PSEU9
Bivalent
083 (7C10-
US20150044215
6920



nanobody
40GS-11B09)
SEQ ID NO: 126



PSEU10
Bivalent
087 (1E11-
US20150044215
6921



nanobody
40GS-7C10)
SEQ ID NO: 127



PSEU11
Bivalent
269 (6B05-
US20150044215
6922



nanobody
40GS-13F07)
SEQ ID NO: 128



PSEU12
Bivalent
256 (13F07-
US20150044215
6923



nanobody
40GS-5H01)
SEQ ID NO: 129



PSEU13
Bivalent
277 (5H01-
US20150044215
6924



nanobody
40GS-11B09)
SEQ ID NO: 130



PSEU14
Bivalent
257 (13F07-
US20150044215
6925



nanobody
40GS-2B10)
SEQ ID NO: 131



PSEU15
Bivalent
285 (13F07-
US20150044215
6926



nanobody
40GS-2B02)
SEQ ID NO: 132



PSEU16
Bivalent
115 (11B09-
US20150044215
6927



nanobody
40GS-13F07)
SEQ ID NO: 133



PSEU17
Bivalent
258 (13F07-
US20150044215
6928



nanobody
40GS-14E10)
SEQ ID NO: 134



PSEU18
Bivalent
283 (7E09-
US20150044215
6929



nanobody
40G5-6B05)
SEQ ID NO: 135



PSEU19
Bivalent
271 (7C10-
US20150044215
6930



nanobody
40GS-14E10)
SEQ ID NO: 136



PSEU20
Bivalent
259 (1E11-
US20150044215
6931



nanobody
40GS-5H01)
SEQ ID NO: 137



PSEU21
Bivalent
319 (13F07-
US20150044215
6932



nanobody
40GS-6B05)
SEQ ID NO: 138



PSEU22
Bivalent
335 (5H01-
US20150044215
6933



nanobody
40G5-1E11)
SEQ ID NO: 139



PSEU23
Bivalent
261 (5H01-
US20150044215
6934



nanobody
40GS-2B10)
SEQ ID NO: 140



PSEU24
Bivalent
262 (7E09-
US20150044215
6935



nanobody
40GS-7C10)
SEQ ID NO: 141



PSEU25
Constant

US20150044215
6936



heavy chain

SEQ ID NO: 148



PSEU26
Constant

US20150044215
6937



light chain

SEQ ID NO: 149



PSEU27
Heavy chain
Panobacumab
US8197816
6938





SEQ ID NO: 8



PSEU28
Heavy chain

US20130156696
6939





SEQ ID NO: 2



PSEU29
Heavy chain

US7494653
6940





SEQ ID NO: 2



PSEU30
Heavy chain
KB0001
US8044181
6941



variable

SEQ ID NO: 3




region





PSEU31
Heavy chain
KB0001
US8044181
6942



variable

SEQ ID NO: 5




region





PSEU32
Heavy chain
KB0001
US8044181
6943



variable

SEQ ID NO: 7




region





PSEU33
Heavy chain
KB0001
US8044181
6944



variable

SEQ ID NO: 9




region





PSEU34
Heavy chain
KB0001
US8044181
6945



variable

SEQ ID NO: 11




region





PSEU35
Heavy chain
1F3
US9085611
6946



variable

SEQ ID NO: 11




region





PSEU36
Heavy chain
2A4
US9085611
6947



variable

SEQ ID NO: 13




region





PSEU37
Heavy chain

US9085611
6948



variable

SEQ ID NO: 27




region





PSEU38
Heavy chain
mAbs LST-001
US8653242
6949



variable

SEQ ID NO: 29




region





PSEU39
Heavy chain
rnAbs LST-002
US8653242
6950



variable

SEQ ID NO: 49




region





PSEU40
Heavy chain
mAbs LST-005
US8653242
6951



variable

SEQ ID NO: 52




region





PSEU41
Heavy chain
rnAbs LST-006
US8653242
6952



variable

SEQ ID NO: 54




region





PSEU42
Heavy chain
mAbs LST-007
US8653242
6953



variable

SEQ ID NO: 13




region





PSEU43
Heavy chain
mAbs LST-008
US8653242
6954



variable

SEQ ID NO: 15




region





PSEU44
Heavy chain
310BO6
US7597893
6955



variable

SEQ ID NO: 8




region





PSEU45
Heavy chain
Cam-003
US20140227285
6956



variable

SEQ ID NO: 1




region





PSEU46
Heavy chain
Cam-004
US20140227285
6957



variable

SEQ ID NO: 3




region





PSEU47
Heavy chain
Cam-005
US20140227285
6958



variable

SEQ ID NO: 4




region





PSEU48
Heavy chain
WapR-001
US20140227285
6959



variable

SEQ ID NO: 5




region





PSEU49
Heavy chain
WapR-002
US20140227285
6960



variable

SEQ ID NO: 7




region





PSEU50
Heavy chain
WapR-003
US20140227285
6961



variable

SEQ ID NO: 9




region





PSEU51
Heavy chain
WapR-004
US20140227285
6962



variable

SEQ ID NO: 11




region





PSEU52
Heavy chain
WapR-007
US20140227285
6963



variable

SEQ ID NO: 13




region





PSEU53
Heavy chain
WapR-016
US20140227285
6964



variable

SEQ ID NO: 15





region




PSEU54
Heavy chain
1584
US20130045207
6965



variable

SEQ ID NO: 8




region





PSEU55
Heavy chain
1573
US20130045207
6966



variable

SEQ ID NO: 16




region





PSEU56
Heavy chain
1572
US20130045207
6967



variable

SEQ ID NO: 24




region





PSEU57
Heavy chain
1587
US20130045207
6968



variable

SEQ ID NO: 32




region





PSEU58
Heavy chain
3099
US20130022604
6969



variable

SEQ ID NO: 8




region





PSEU59
Heavy chain
2745
US20130022604
6970



variable

SEQ ID NO: 16




region





PSEU60
Heavy chain
2459
US20130022604
6971



variable

SEQ ID NO: 24




region





PSEU61
Heavy chain
2316
US20130022606
6972



variable

SEQ ID NO: 8




region





PSEU62
Heavy chain
1838
US20130022606
6973



variable

SEQ ID NO: 16




region





PSEU63
Heavy chain
2314
US20130022606
6974



variable

SEQ ID NO: 24




region





PSEU64
Heavy chain
2326
US20130022606
6975



variable

SEQ ID NO: 32




region





PSEU65
Heavy chain
2328
US20130022606
6976



variable

SEQ ID NO: 40




region





PSEU66
Heavy chain
2438
US20130022606
6977



variable

SEQ ID NO: 48




region





PSEU67
Heavy chain
1774
US20130004500
6978



variable

SEQ ID NO: 8




region





PSEU68
Heavy chain
1660
US20130004500
6979



variable

SEQ ID NO: 16




region





PSEU69
Heavy chain
1923
US20130004500
6980



variable

SEQ ID NO: 24




region





PSEU70
Heavy chain
1656
US20130004499
6981



variable

SEQ ID NO: 8




region





PSEU71
Heavy chain
1640
US20130004499
6982



variable

SEQ ID NO: 16




region





PSEU72
Heavy chain
2459
US20130004499
6983



variable

SEQ ID NO: 24




region





PSEU73
Heavy chain

US20120114657
6984



variable

SEQ ID NO: 8




region





PSEU74
Heavy chain
Anti-It-2
US20110177087
6985



variable

SEQ ID NO: 13




region





PSEU75
Heavy chain
Anti-It-3
US20110177087
6986



variable

SEQ ID NO: 14




region





PSEU76
Heavy chain
Anti-It-4
US20110177087
6987



variable

SEQ ID NO: 15




region





PSEU77
Heavy chain
Anti-It-5
US20110177087
6988



variable

SEQ ID NO: 16




region





PSEU78
Heavy chain
Anti-It-6
US20110177087
6989



variable

SEQ ID NO: 17




region





PSEU79
Heavy chain
Anti-170003
US20110177087
6990



variable

SEQ ID NO: 18




region





PSEU80
Heavy chain
Anti-170006
US20110177087
6991



variable

SEQ ID NO: 19




region





PSEU81
Heavy chain
Anti-Pa01
US20110177087
6992



variable

SEQ ID NO: 20




region





PSEU82
Heavy chain
Anti-IATS016
US20110177087
6993



variable

SEQ ID NO: 21




region





PSEU83
Heavy chain

US20090191186
6994



variable

SEQ ID NO: 1




region





PSEU84
Heavy chain

US20090191186
6995



variable

SEQ ID NO: 11




region





PSEU85
Heavy chain

US20090191186
6996



variable

SEQ ID NO: 3




region





PSEU86
Heavy chain

US20090191186
6997



variable

SEQ ID NO: 7




region





PSEU87
Heavy chain

US20090191186
6998



variable

SEQ ID NO: 9




region





PSEU88
Heavy chain

US20090191186
6999



variable

SEQ ID NO: 5




region





PSEU89
Heavy chain

US20090191186
7000



variable

SEQ ID NO: 13




region





PSEU90
Heavy chain

US20090191186
7001



variable

SEQ ID NO: 21




region





PSEU91
Heavy chain

US20090191186
7002



variable

SEQ ID NO: 17




region





PSEU92
Heavy chain

US20090191186
7003



variable

SEQ ID NO: 26




region





PSEU93
Heavy chain

US20090191186
7004



variable

SEQ ID NO: 25




region





PSEU94
Heavy chain

US20090191186
7005



variable

SEQ ID NO: 23




region





PSEU95
Heavy chain

US20090191186
7006



variable

SEQ ID NO: 29




region





PSEU96
Heavy chain

US20090191186
7007



variable

SEQ ID NO: 35




region





PSEU97
Heavy chain
V2L2
WO2014074528
7008



variable

SEQ ID NO: 216




region





PSEU98
Heavy chain
V2L2-MD
WO2014074528
7009



variable

SEQ ID NO: 255




region





PSEU99
Heavy chain
V2L2-MD
WO2O14074528
7010



variable
and V2L2-
SEQ ID NO: 256




region
GL




PSEU100
Heavy chain
V2L2-GL
WO2014074528
7011



variable

SEQ ID NO: 257




region





PSEU101
Heavy chain
2409
WO2013024905
7012



variable

SEQ ID NO: 16




region





PSEU102
Heavy chain
2453
WO2013024905
7013



variable

SEQ ID NO: 24




region





PSEU103
Heavy chain
S20
US7972845
7014



variable

SEQ ID NO: 2




region





PSEU104
Heavy chain
Fab 13.37
US20150044215
7015



variable

SEQ ID NO: 142




region





PSEU105
Heavy chain
Fab 26.24
US20150044215
7016



variable

SEQ ID NO: 144




region





PSEU106
Heavy chain
Fab 35.36
US20150044215
7017



variable

SEQ ID NO: 146




region





PSEU107
Heavy chain
KB0001
US8044181
7018



variable

SEQ ID NO: 1




region





PSEU108
Heavy

Horn., M.P. et al.
7019



chain, LPS

“Preclinical In




serotype

Vitro and In Vivo




IATS-O11.

characterization






of the fully human






monoclonal






IgM antibody






KBPA101 specific






for Pseudomonas







aeruginosa







serotype IATS-






O11”, Antimicrob.






Agents Chemother.






54 (6), 2338-






2344 (2010)



PSEU109
J chain
Panobacumab

7020


PSEU110
Light chain
Panobacumab
US8197816
7021





SEQ ID NO: 7



PSEU111
Light chain

US20130156696
7022





SEQ ID NO: 4



PSEU112
Light chain

US7494653
7023





SEQ ID NO: 4



PSEU113
Light chain
1F3
US9085611
7024



variable

SEQ ID NO: 2




region





PSEU114
Light chain
2A4
US9085611
7025



variable

SEQ ID NO: 4




region





PSEU115
Light chain

US9085611
7026



variable

SEQ ID NO: 28




region





PSEU116
Light chain
mAbS LST-001
US8653242
7027



variable

SEQ ID NO: 18




region





PSEU117
Light chain
mAbs LST-006
US8653242
7028



variable

SEQ ID NO: 53




region





PSEU118
Light chain
mAbs LST-008
US8653242
7029



variable

SEQ ID NO: 14




region





PSEU119
Light chain
mAbs LST-008
US8653242
7030



variable

SEQ ID NO: 16




region





PSEU120
Light chain
310BO6
US7597893
7031



variable

SEQ ID NO: 7




region





PSEU121
Light chain
Cam-003,
US20140227285
7032



variable
Cam-004,
SEQ ID NO: 2




region
Cam-005




PSEU122
Light chain
WapR-001
US20140227285
7033



variable

SEQ ID NO: 6




region





PSEU123
Light chain
WapR-002
US20140227285
7034



variable

SEQ ID NO: 8




region





PSEU124
Light chain
WapR-003
US20140227285
7035



variable

SEQ ID NO: 10




region





PSEU125
Light chain
WapR-004,
US20140227285
7036



variable
WapR-
SEQ ID NO: 12




region
004-RAD




PSEU126
Light chain
WapR-007
US20140227285
7037



variable

SEQ ID NO: 14




region





PSEU127
Light chain
WapR-016
US20140227285
7038



variable

SEQ ID NO: 16




region





PSEU128
Light chain
1584
US20130045207
7039



variable

SEQ ID NO: 7




region





PSEU129
Light chain
1573
US20130045207
7040



variable

SEQ ID NO: 5




region





PSEU130
Light chain
1572
US20130045207
7041



variable

SEQ ID NO: 23




region





PSEU131
Light chain
1587
US20130045207
7042



variable

SEQ ID NO: 31




region





PSEU132
Light chain
3099
US20130022604
7043



variable

SEQ ID NO: 7




region





PSEU133
Light chain
2745
US20130022604
7044



variable

SEQ ID NO: 15




region





PSEU134
Light chain
2459
US20130022604
7045



variable

SEQ ID NO: 23




region





PSEU135
Light chain
2316
US20130022606
7046



variable

SEQ ID NO: 7




region





PSEU136
Light chain
1838
US20130022606
7047



variable

SEQ ID NO: 15




region





PSEU137
Light chain
2314
US20130022606
7048



variable

SEQ ID NO: 23




region





PSEU138
Light chain
2326
US20130022606
7049



variable

SEQ ID NO: 31




region





PSEU139
Light chain
2328
US20130022606
7050



variable

SEQ ID NO: 39




region





PSEU140
Light chain
2438
US20130022606
7051



variable

SEQ ID NO: 47




region





PSEU141
Light chain
1774
US20130004500
7052



variable

SEQ ID NO: 7




region





PSEU142
Light chain
1660
US20130004500
7053



variable

SEQ ID NO: 15




region





PSEU143
Light chain
1923
US20130004500
7054



variable

SEQ ID NO: 23




region





PSEU144
Light chain
1656
US20130004499
7055



variable

SEQ ID NO: 7




region





PSEU145
Light chain
1640
US20130004499
7056



variable

SEQ ID NO: 5




region





PSEU146
Light chain
2459
US20130004499
7057



variable

SEQ ID NO: 23




region





PSEU147
Light chain

US20120114657
7058



variable

SEQ ID NO: 7




region





PSEU148
Light chain
Anti-It-2
US20110177087
7059



variable

SEQ ID NO: 22




region





PSEU149
Light chain
Anti-It-3
US20110177087
7060



variable

SEQ ID NO: 23




region





PSEU150
Light chain
Anti-It-4
US20110177087
7061



variable

SEQ ID NO: 24




region





PSEU151
Light chain
Anti-It-5
US20110177087
7062



variable

SEQ ID NO: 25




region





PSEU152
Light chain
Anti-It-6
US20110177087
7063



variable

SEQ ID NO: 26




region





PSEU153
Light chain
Anti-170003
US20110177087
7064



variable

SEQ ID NO: 27




region





PSEU154
Light chain
Anti-170006
US20110177087
7065



variable

SEQ ID NO: 28




region





PSEU155
Light chain
Anti-Pa01
US20110177087
7066



variable

SEQ ID NO: 29




region





PSEU156
Light chain
Anti-
US20110177087
7067



variable
IATS016
SEQ ID NO: 30




region





PSEU157
Light chain

US20090191186
7068



variable

SEQ ID NO: 2




region





PSEU158
Light chain

US20090191186
7069



variable

SEQ ID NO: 12




region





PSEU159
Light chain

US20090191186
7070



variable

SEQ ID NO: 8




region





PSEU160
Light chain

US20090191186
7071



variable

SEQ ID NO: 10




region





PSEU161
Light chain

US20090191186
7072



variable

SEQ ID NO: 6




region





PSEU162
Light chain

US20090191186
7073



variable

SEQ ID NO: 37




region





PSEU163
Light chain

US20090191186
7074



variable

SEQ ID NO: 18




region





PSEU164
Light chain

US20090191186
7075



variable

SEQ ID NO: 24




region





PSEU165
Light chain

US20090191186
7076



variable

SEQ ID NO: 20




region





PSEU166
Light chain

US20090191186
7077



variable

SEQ ID NO: 36




region





PSEU167
Light chain

US20090191186
7078



variable

SEQ ID NO: 28




region





PSEU168
Light chain

US20090191186
7079



variable

SEQ ID NO: 30




region





PSEU169
Light chain

US20090191186
7080



variable

SEQ ID NO: 34




region





PSEU170
Light chain

US20090191186
7081



variable

SEQ ID NO: 32




region





PSEU171
Light chain
V2L2
WO2014074528
7082



variable

SEQ ID NO: 217




region





PSEU172
Light chain
2409
WO2013024905
7083



variable

SEQ ID NO: 15




region





PSEU173
Light chain
2453
WO2013024905
7084



variable

SEQ ID NO: 23




region





PSEU174
Light chain
S20
US7972845
7085



variable

SEQ ID NO: 4




region





PSEU175
Light chain
Fab 13.37
US20150044215
7086



variable

SEQ ID NO: 143




region





PSEU176
Light chain
Fab 26.24
US20150044215
7087



variable

SEQ ID NO: 45




region





PSEU177
Light chain
Fab 35.36
US20150044215
7088



variable

SEQ ID NO: 147




region





PSEU178
Light chain
mAbs
US8653242
7089



variable
LST-002
SEQ ID NO: 32




region






majority





PSEU179
Light chain
mAbs
US8653242
7090



variable
LST-006
SEQ ID NO: 55




region






majority





PSEU180
Light chain
mAbs
US8653242
7091



variable
LST-002
SEQ ID NO: 51




region minority





PSEU181
Light chain
mAbs LST-007
US8653242
7092



variable

SEQ ID NO: 56




region minority





PSEU182
Light chain,

Horn, M.P. et al.
7093



Anti-P.

“Preclinical In




Aeuginosa LPS

Vitro and in Vivo




serotype

characterization




IATS-O11,

of the fully human






monoclonal






IgM antibody






KBPA101 specific






for Pseudomonas







aeruginosa







serotype IATS-O11”,






Antimicrob.






Agents Chemother.






54 (6), 2338-






2344 (2010)



PSEU183
Light kappa
KB0001
US8044181
7094



chain

SEQ ID NO: 10




variable






region





PSEU184
Light kappa
KB0001
US8044181
7095



chain

SEQ ID NO: 2




variable






region





PSEU185
Light kappa
KB0001
US8044181
7096



chain

SEQ ID NO: 4




variable






region





PSEU186
Light kappa
KB0001
US8044181
7097



chain

SEQ ID NO: 6




variable






region





PSEU187
Light kappa
KB0001
US8044181
7098



chain

SEQ ID NO: 8




variable






region





PSEU188
Monovalent
5H01
US20150044215
7099



nanobody

SEQ ID NO: 1



PSEU189
Monovalent
7C10
US20150044215
7100



nanobody

SEQ ID NO: 2



PSEU190
Monovalent
1E11
US20150044215
7101



nanobody

SEQ ID NO: 3



PSEU191
Monovalent
2B02
US20150044215
7102



nanobody

SEQ ID NO: 4



PSEU192
Monovalent
2B10
US20150044215
7103



nanobody

SEQ ID NO: 5



PSEU193
Monovalent
2G09
US20150044215
7104



nanobody

SEQ ID NO: 6



PSEU194
Monovalent
6B05
US20150044215
7105



nanobody

SEQ ID NO: 7



PSEU195
Monovalent
10C05
US20150044215
7106



nanobody

SEQ ID NO: 8



PSEU196
Monovalent
11B09
US20150044215
7107



nanobody

SEQ ID NO: 9



PSEU197
Monovalent
14E10
US20150044215
7108



nanobody

SEQ ID NO: 10



PSEU198
Monovalent
7E09
US20150044215
7109



nanobody

SEQ ID NO: 11



PSEU199
Monovalent
13F07
US20150044215
7110



nanobody

SEQ ID NO: 12



PSEU200
Monovalent
3B11
US20150044215
7111



nanobody

SEQ ID NO: 13



PSEU201
Monovalent
4C03
US20150044215
7112



nanobody

SEQ ID NO: 14



PSEU202
Monovalent
4G10
US20150044215
7113



nanobody

SEQ ID NO: 15



PSEU203
Monovalent
12B02
US20150044215
7114



nanobody

SEQ ID NO: 16



PSEU204
Monovalent
14B10
US20150044215
7115



nanobody

SEQ ID NO: 17



PSEU205
Monovalent
3E10
US20150044215
7116



nanobody

SEQ ID NO: 18



PSEU206
Monovalent
5E02
US20150044215
7117



nanobody

SEQ ID NO: 19



PSEU207
Scfv-Fc
W4-M1
WO2014074528
7118





SEQ ID NO: 78



PSEU208
Scfv-Fc
W4-M5
WO2014074528
7119





SEQ ID NO: 79



PSEU209
Scfv-Fc
W4-M6
WO2014074528
7120





SEQ ID NO: 80



PSEU210
Scfv-Fc
W4-M7
WO2014074528
7121





SEQ ID NO: 81



PSEU211
Scfv-Fc
W4-M8
WO2014074528
7122





SEQ ID NO: 82



PSEU212
Scfv-Fc
W4-M9
WO2014074528
7123





SEQ ID NO: 83



PSEU213
Scfv-Fc
W4-M11
WO2014074528
7124





SEQ ID NO: 84



PSEU214
Scfv-Fc
W4-M12
WO2014074528
7125





SEQ ID NO: 85



PSEU215
Scfv-Fc
W4-M14
WO2014074528
7126





SEQ ID NO: 86



PSEU216
Scfv-Fc
W4-M15
WO2014074528
7127





SEQ ID NO: 87



PSEU217
Scfv-Fc
W4-M16
WO2014074528
7128





SEQ ID NO: 88



PSEU218
Scfv-Fc
W4-M17
WO2014074528
7129





SEQ ID NO: 89



PSEU219
Scfv-Fc
W4-M19
WO2014074528
7130





SEQ ID NO: 90



PSEU220
Scfv-Fc
W4-M20
WO2014074528
7131





SEQ ID NO: 91



PSEU221
Sefv-Fc
W4-M4
WO2014074528
7132





SEQ ID NO: 92



PSEU222
Scfv-Fc
W4-M10
WO2014074528
7133





SEQ ID NO: 93



PSEU223
Scfv-Fc
W4-HC1-LCP
WO2014074528
7134





SEQ ID NO: 94



PSEU224
Scfv-Fc
W4-HC1-LC7
WO2014074528
7135





SEQ ID NO: 95



PSEU225
Scfv-Fc
W4-HC2-LC7
WO2014074528
7136





SEQ ID NO: 96



PSEU226
Scfv-Fc
W4-HC3-LCP
WO2014074528
7137





SEQ ID NO: 97



PSEU227
Scfv-Fc
W4-HC4-LCP
WO2014074528
7138





SEQ ID NO: 98



PSEU228
Scfv-Fc
W4-HC5-LCP
WO2014074528
7139





SEQ ID NO: 99



PSEU229
Scfv-Fc
W4-HC5-LC7
WO2014074528
7140





SEQ ID NO: 100



PSEU230
Scfv-Fc
W4-HC7-LCP
WO2014074528
7141





SEQ ID NO: 101



PSEU231
Scfv-Fc
W4-VH1-VL8
WO2014074528
7142





SEQ ID NO: 102



PSEU232
Scfv-Fc
W4-VH2-VLP
WO2014074528
7143





SEQ ID NO: 103



PSEU233
Scfv-Fc
W4-VH2-VL8
WO2014074528
7144





SEQ ID NO: 104



PSEU234
Scfv-Fc
W4-VH3-VL7
WO2014074528
7145





SEQ ID NO: 105



PSEU235
Scfv-Fc
W4-VH3-VL8
WO2014074528
7146





SEQ ID NO: 106



PSEU236
Scfv-Fc
W4-VH5-VL8
WO2014074528
7147





SEQ ID NO: 107



PSEU237
Scfv-Fc
W4-VH6-VL7
WO2014074528
7148





SEQ ID NO: 108



PSEU238
Scfv-Fc
W4-VH6-VL8
WO2014074528
7149





SEQ ID NO: 109



PSEU239
Scfv-Fc
W4-VH6-VLP
WO2014074528
7150





SEQ ID NO: 110



PSEU240
Scfv-Fc
W4-VH7-VLP
WO2014074528
7151





SEQ ID NO: 111



PSEU241
Scfv-Fc
W4-VH7-VL7
WO2014074528
7152





SEQ ID NO: 112



PSEU242
Scfv-Fc
W4-VH7-VL8
WO2014074528
7153





SEQ ID NO: 113



PSEU243
Scfv-Fc
W4-VH9-VLP
WO2014074528
7154





SEQ ID NO: 114



PSEU244
Scfv-Fc
W4-VH10-VLP
WO2014074528
7155





SEQ ID NO: 115



PSEU245
Scfv-Fc
W4-VH11-VLP
WO2014074528
7156





SEQ ID NO: 116



PSEU246
Scfv-Fc
W4-VH12-VLP
WO2014074528
7157





SEQ ID NO: 117



PSEU247
Scfv-Fc
W4-VH15-VLP
WO2014074528
7158





SEQ ID NO: 118



PSEU248
Scfv-Fc
W4-VH16-VLP
WO2014074528
7159





SEQ ID NO: 119



PSEU249
Scfv-Fc
W4-VH20-VLP
WO2014074528
7160





SEQ ID NO: 120



PSEU250
Scfv-Fc
W4-VH31-VLP
WO2014074528
7161





SEQ ID NO: 121



PSEU251
Scfv-Fc
W4-VH37-VLP
WO2014074528
7162





SEQ ID NO: 122



PSEU252
Scfv-Fc
W4-VH41-VLP
WO2014074528
7163





SEQ ID NO: 123



PSEU253
Scfv-Fc
W4-VH42-VLP
WO2014074528
7164





SEQ ID NO: 124



PSEU254
Scfv-Fc
W4-VH35-VLP
WO2014074528
7165





SEQ ID NO: 125



PSEU255
Scfv-Fc
W4-VH36-VLP
WO2014074528
7166





SEQ ID NO: 126



PSEU256
Scfv-Fc
W4-VH52-VLP
WO2014074528
7167





SEQ ID NO: 127



PSEU257
Scfv-Fc
W4-VH53-VLP
WO2014074528
7168





SEQ ID NO: 128



PSEU258
Scfv-Fc
W4-VH54-VLP
WO2014074528
7169





SEQ ID NO: 129



PSEU259
Scfv-Fc
W4-VH55-VLP
WO2014074528
7170





SEQ ID NO: 130



PSEU260
Scfv-Fc
W4-VH56-VLP
WO2014074528
7171





SEQ ID NO: 131



PSEU261
Scfv-Fc
W4-VH57-VLP
WO2014074528
7172





SEQ ID NO: 132



PSEU262
Scfv-Fc
W4-VH58-VLP
WO2014074528
7173





SEQ ID NO: 133



PSEU263
Scfv-Fc
W4-VH60-VLP
WO2014074528
7174





SEQ ID NO: 134



PSEU264
Scfv-Fc
W4-VH61-VLP
WO2014074528
7175





SEQ ID NO: 135



PSEU265
Scfv-Fc
W4-VH62-VLP
WO2014074528
7176





SEQ ID NO: 136



PSEU266
Scfv-Fc
W4-VH63-VLP
WO2014074528
7177





SEQ ID NO: 137



PSEU267
Scfv-Fc
W4-VH64-VLP
WO2014074528
7178





SEQ ID NO: 138



PSEU268
Scfv-Fc
W4-VH65-VLP
WO2014074528
7179





SEQ ID NO: 139



PSEU269
Scfv-Fc
W4-VH66-VLP
WO2014074528
7180





SEQ ID NO: 140



PSEU270
Scfv-Fc
W4-VH67-VLP
WO2014074528
7181





SEQ ID NO: 141



PSEU271
Scfv-Fc
W4-VH69-VLP
WO2014074528
7182





SEQ ID NO: 142



PSEU272
Scfv-Fc
W4-VH70-VLP
WO2014074528
7183





SEQ ID NO: 143



PSEU273
Scfv-Fc
W4-VH72-VLP
WO2014074528
7184





SEQ ID NO: 144



PSEU274
Scfv-Fc
W4-VH79-VLP
WO2014074528
7185





SEQ ID NO: 145



PSEU275
Scfv-Fc
W4-VH80-VLP
WO2014074528
7186





SEQ ID NO: 146



PSEU276
Scfv-Fc
W4-M9
WO2014074528
7187





SEQ ID NO: 152



PSEU277
Scfv-Fc
Psl0170
WO2014074528
7188





SEQ ID NO: 245



PSEU278
Scfv-Fc
Psl0304
WO2014074528
7189





SEQ ID NO: 246



PSEU279
Scfv-Fc
Psl0348
WO2014074528
7190





SEQ ID NO: 247



PSEU280
Scfv-Fc
Psl0573
WO2014074528
7191





SEQ ID NO: 248



PSEU281
Scfv-Fc
Psl0574
WO2014074528
7192





SEQ ID NO: 249



PSEU282
Scfv-Fc
Psl0582
WO2014074528
7193





SEQ ID NO: 250



PSEU283
Scfv-Fc
Psl0584
WO2014074528
7194





SEQ ID NO: 251



PSEU284
Scfv-Fc
Psl0585
WO2014074528
7195





SEQ ID NO: 252



PSEU285
Scfv-Fc
Psl0589
WO2014074528
7196





SEQ ID NO: 253









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 33 against Streptococcus bacteria.









TABLE 33







Antibodies against Streptococcus bacteria











Anti-



SEQ


body

Antibody
Reference
ID


No.
Description
Name
Information
NO





STRP1
Heavy chair

US7625561
7197



variable region,

SEQ ID NO: 5




Diabody for







Streptococcus






STRP2
Heavy chain

US7625561
7198



variable region,

SEQ ID NO: 3




Diabody for







Streptococcus






STRP3
Heavy chain

US7625561
7199



variable region,

SEQ ID NO: 7




Diabody for







Streptococcus






STRP4
Heavy chain
DP-54
Lucas, A.H.
7200



variable region,

“Combinatorial




partial,

library





Streptococcus


cloning of human





pneumoniae


antibodies to







Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation of






Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48823



STRP5
Heavy chain
DP-35
Lucas, A.H.
7201



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pueumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F,” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48825



STRP6
Heavy chain
DP-47
Lucas, A.H.
7202



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48827



S'I7RP7
Heavy chain
DP-47
Lucas, A.H.
7203



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001,)






NCBI Accession #






AAD48828



S'IRP8
Heavy chain
LSG-6 1
Lucas, A.H.
7204



variable

“Combinatorial




region,

library




partial,

cloning of hurnan





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48830



STRP9
Heavy chain
LSG6.1
Lucas, A.H.
7205



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48832



STRP10
Heavy chain
DP-47
Lucas, A.H.
7206



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48835



STRP11
Heavy chain
humanized
US7429381
6902



variable region,
Mu-9
SEQ ID NO: 14





Streptococcus








agalactiae,







Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,








Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B.








Treponema








pallidum, Lyme






disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis.





STRP12
Heavy chain
Anti-PsaA
US20070003561
7207



variable region.
7-1G9
SEQ ID NO: 16





Streptococcus








pneumoniae






STRP13
Heavy chain
Anti-PsaA
US20070003561
7208



variable region,
1-15E5
SEQ ID NO: 32





Streptococcus








pneumoniae






STRP14
Heavy chain
Anti-PsaA
US20070003561
7209



variable region,
9A7
SEQ ID NO: 48





Streptococcus








pneumoniae






STRP15
Heavy chain
23f Fab
Bryson, S.,
7210



variable region,
023.102,
“Multitasking





Streptococcus

chain B
immimoglobulin





pneumoniae


V-Genes And






Somatic Div Cdr3






Loops Generate






Binding Sites For






Chemically Di






Antigens From






Bacterial And. Viral






Pathogens”






Unpublished″, NCBI






Accession #






4HIE B



STRP16
Heavy chain
5.12.14
US5686070
7211



variable region,

SEQ ID NO: 22





Streptococcus








pneumoniae,







Escherichia coli, or







Pseudomonas








aeruginosa






SIRP17
Heavy chain
6G4.2.5
US5686070
7212



variable region,

SEQ ID NO: 50





Streptococcus








pneumoniae,







Escherichia coli, or







Pseudomonas








aeruginosa






STRP18
Heavy chain
chimeric
US5686070
7213



variable region,
6G4.2.5
SEQ ID NO: 58





Streptococcus








pneumoniae








Escherichia coli, or







Pseudomonas








aeruginosa






STRP19
Heavy chain,
Mab6679
US7429381
6900




Streptococcus


SEQ ID NO: 4





agalactiae,







Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,







Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B,







Treponema








palliduni Lyrae







disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis.





STRP20
Light chain

US7625561
7214



variable region,

SEQ ID NO: 6




Diabody for







Streptococcus






STRP21
Light chain

US7625561
7215



variable region,

SEQ ID NO: 8




Diabody for







Streptococcus






STRP22
Light chain

US7625561
7216



variable region,

SEQ ID NO: 4




Diabody for







Streptococcus






STRP23
Light chain
A2
Lucas, A.H.
7217



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48824



STRP24
Light chain
133
Lucas, A.H.
7218



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48822



STRP25
Light chain
A23
Lucas, A.H.
7219



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48826



STRP26
Light chain
L2
Lucas, A.H.
7220



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48829



STRP27
Light chain
DPL5
Lucas, A.H.
7221



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48831



STRP28
Light chain
DPL5
Lucas, A.H.
7222



variable

“Combinatorial




region,

library




partial,

cloning of human





Streptococcus


antibodies to





pneumoniae



Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48833



STRP29
Light chain
L2
Lucas, A.H.
7223



variable region,

“Combinatorial




partial,

library





Streptococcus


cloning of human





pneumoniae


antibodies to







Streptococcus








pneumoniae capsular






polysaccharides:






variable region






primary structures






and evidence for






somatic mutation






of Fab fragments






specific for capsular






serotypes 6B,






14, and 23F” Infect.






Immun. 69 (2),






853-864 (2001),






NCBI Accession #






AAD48834



STRP30
Light chain
Anti-PsaA
US20070003561
7224



variable region,
7-1G9
SEQ ID NO: 8





Streptococcus








pneumoniae






STRP31
Light chain
Anti-PsaA
US20070003561
7225



variable region,
1-15E5
SEQ ID NO: 24





Streptococcus








pneumoniae






STRP32
Light chain
Anti-pSaA
US20070003561
7226



variable region,
9A7
SEQ ID NO: 40





Streptococcus








pneumoniae






STRP33
Light chain
5.12.14
US5686070
7227



variable region,

SEQ ID NO: 20





Streptococcus








pneumoniae,







Escherichia coli, or







Pseudomonas








aeruginosa






STRP34
Light chain
6G4.2.5
US5686070
7228



variable region,

SEQ ID NO: 48





Streptococcus








pneumoniae,







Escherichia coli, or







Pseudomonas








aeruginosa






STRP35
Light chain
chimeric
US5686070
7229



variable region,
6G4.2.5
SEQ ID NO: 56





Streptococcus








pneumoniae,







Escherichia coli, or







Pseudomonas








aeruginosa






STRP36
Light chain,
Mab679
US7429381
6907




Streptococcus


SEQ ID NO: 2





agalactiae,







Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,







Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B,







Treponema








pallidum, Lyme






disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis






STRP37
scFv, Streptococcus
Mab679
US7429381
6911




agalactiae,

SEQ ID NO: 6





Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,








Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B,







Treponema








pallidum, Lyme






disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis






STRP38
scFv, Streptococcus
Mu-9V
US7429381
6905




agalactiae,

SEQ ID NO: 8





Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,








Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B,







Treponema








pallidum, Lyme






disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis






STRP39
scFv, Streptococcus
Mu-9V
US7429381
6901




agalactiae,

SEQ ID NO: 10





Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,








Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B,







Treponema








pallidum, Lyme






disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis






STRP40
scFv, Streptococcus
humanized
US7429381
6906




agalactiae,
Mu-9
SEQ ID NO: 12





Legionella








pneumophilia,







Streptococcus








pyogenes,







Escherichia coli,








Neisseria








gonorrhoeae,








Neisseria








meningitidis,








Pneumococcus,








Hemophilis








influenzae B,







Treponema








pallidum, Lyme






disease







spirochetes,








Pseudomonas








aeruginosa,








Mycobacterium








leprae, Brucella








abortus and







Mycobacterium








tuberculosis










In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in US Pub No. US20040198960 and US20130195876, the contents of each of which are herein incorporated by reference in their entirety, against Streptococcus pneumoniae infection.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants encoding Afelimomab, fragments or variants thereof for treating a disease and/or disorder or preventing a disease and/or disorder. As a non-limiting example, the disease and/or disorder is sepsis.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants encoding Nebacumab, fragments or variants thereof for treating a disease and/or disorder or preventing a disease and/or disorder. As a non-limiting example, the disease and/or disorder is sepsis.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 34 against Staphylococcal bacteria and related bacteria.









TABLE 34







Antibodies against Staphylococcal bacteria and related bacteria















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO














STPH1
Heavy chain variable region, S. aureus

U.S. Pat. No. 8,609,102
7230





SEQ ID NO: 2


STPH2
Heavy chain variable region, S. aureus

U.S. Pat. No. 8,609,102
7231





SEQ ID NO: 6


STPH3
Heavy chain variable region, S. aureus
SAR279356
U.S. Pat. No. 7,786,255
7232



or S. epidermidis, E. coli, Yersinia

SEQ ID NO: 1




pestis (Y. pestis), Y. entercolitica,




Xanthomnonas axonopodis (X.




axonopodis), Pseudonmonas




fuorescerns (P.




fluorescens), Actinobacillus




actinomycetemcomitans (A.




actinomycetemcomitans), A.




pleuropneumoniae, Ralstonia




solanacearum (R.




solanacearum), Bordetella pertussis (B.




pertussis), B. parapertussis or B.




bronchiseptica



STPH4
Heavy chain variable region, S. aureus
SAR279356
US20110002932 SEQ ID
7233



or S. epidermidis, E. coli, Yersinia

NO: 1




pestis (Y. pestis), Y. entercolitica,




Xanthomnonas axonopodis (X.




axonopodis), Pseudonmonas




fuorescerns (P.




fluorescens), Actinobacillus




actinomycetemcomitans (A.




actinomycetemcomitans), A.




pleuropneumoniae, Ralstonia




solanacearum (R.




solanacearum), Bordetella pertussis (B.




pertussis), B. parapertussis or B.




bronchiseptica



STPH5
Heavy chain variable region, S.
108-1
U.S. Pat. No. 8,475,798
7234




epidermidis


SEQ ID NO: 18


STPH6
Heavy chain variable region, S.
108-36
U.S. Pat. No. 8,475,798
7235




epidermidis


SEQ ID NO: 22


STPH7
Heavy chain variable region, S.
110-15
U.S. Pat. No. 8,475,798
7236




epidermidis


SEQ ID NO: 26


STPH8
Heavy chain variable region, S.
108-1VH-
U.S. Pat. No. 8,475,798
7237




epidermidis

Hu
SEQ ID NO: 28


STPH9
Heavy chain variable region, S.
108-36VH-
U.S. Pat. No. 8,475,798
7238




epidermidis

Hu
SEQ ID NO: 30


STPH10
Heavy chain variable region, S.
110-15VH-
U.S. Pat. No. 8,475,798
7239




epidermidis

Hu
SEQ ID NO: 32


STPH11
Heavy chain variable region,
Pagibaximab
U.S. Pat. No. 8,372,958
7240



Staphylococcal sepsis

SEQ ID NO: 87


STPH12
Heavy chain variable region,
Pagibaximab
U.S. Pat. No. 8,372,958
7241



Staphylococcal sepsis

SEQ ID NO: 12


STPH13
Heavy chain variable region,
Pagibaximab
U.S. Pat. No. 8,372,958
7242



Staphylococcal sepsis

SEQ ID NO: 17


STPH14
Heavy chain variable region,
F628
U.S. Pat. No. 8,912,314
7243



Staphylococci such as S. aureus and S.

SEQ ID NO: 3




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH15
Heavy chain variable region,
F630
U.S. Pat. No. 8,912,314
7244



Staphylococci such as S. aureus and S.

SEQ ID NO: 5




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH16
Heavy chain variable region,
F598
U.S. Pat. No. 8,912,314
7245



Staphylococci such as S. aureus and S.

SEQ ID NO: 55




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH17
Heavy chain variable region,
F628
U.S. Pat. No. 8,912,314
7246



Staphylococci such as S. aureus and S.

SEQ ID NO: 58




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH18
Heavy chain variable region,
F598
U.S. Pat. No. 8,912,314
7247



Staphylococci such as S. aureus and S.

SEQ ID NO: 1




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH19
Heavy chain variable region,
108-3BVH-
U.S. Pat. No. 8,475,798
7248




Staphylococcus epidermidis

Hu
SEQ ID NO: 34


STPH20
Heavy chain, MRSA, MSSA
2B2
U.S. Pat. No. 8,735,554
7249





SEQ ID NO: 3


STPH21
Heavy chain, MRSA, MSSA
2G7
U.S. Pat. No. 8,735,554
7250





SEQ ID NO: 5


STPH22
Heavy chain, MRSA, MSSA
3B12
U.S. Pat. No. 8,735,554
7251





SEQ ID NO: 7


STPH23
Heavy chain, S. aureus
DF1.1
U.S. Pat. No. 8,715,673
7252





SEQ ID NO: 2


STPH24
Heavy chain, S. aureus
DF1
U.S. Pat. No. 8,715,673
7253





SEQ ID NO: 4


STPH25
Heavy chain, S. aureus
DF2
U.S. Pat. No. 8,715,673
7254





SEQ ID NO: 35


STPH26
Heavy chain, S. aureus
DF3
U.S. Pat. No. 8,715,673
7255





SEQ ID NO: 36


STPH27
Heavy chain, S. aureus
DF4
U.S. Pat. No. 8,715,673
7256





SEQ ID NO: 37


STPH28
Heavy chain, S. aureus
DF5
U.S. Pat. No. 8,715,673
7257





SEQ ID NO: 38


STPH29
Heavy chain, S. aureus
DF6
U.S. Pat. No. 8,715,673
7258





SEQ ID NO: 39


STPH30
Heavy chain, S. aureus
DF7
U.S. Pat. No. 8,715,673
7259





SEQ ID NO: 40


STPH31
Heavy chain, S. aureus
DF8
U.S. Pat. No. 8,715,673
7260





SEQ ID NO: 41


STPH32
Heavy chain, S. aureus
DF9
U.S. Pat. No. 8,715,673
7261





SEQ ID NO: 42


STPH33
Heavy chain, S. aureus
DF10
U.S. Pat. No. 8,715,673
7262





SEQ ID NO: 43


STPH34
Heavy chain, S. aureus
DF11
U.S. Pat. No. 8,715,673
7263





SEQ ID NO: 44


STPH35
Heavy chain, S. aureus
DF12
U.S. Pat. No. 8,715,673
7264





SEQ ID NO: 45


STPH36
Heavy chain, S. aureus
DF13
U.S. Pat. No. 8,715,673
7265





SEQ ID NO: 46


STPH37
Heavy chain, S. aureus
DF14
U.S. Pat. No. 8,715,673
7266





SEQ ID NO: 47


STPH38
Heavy chain, S. aureus
DF15
U.S. Pat. No. 8,715,673
7267





SEQ ID NO: 48


STPH39
Heavy chain, S. aureus
DF16
U.S. Pat. No. 8,715,673
7268





SEQ ID NO: 49


STPH40
Heavy chain, S. aureus
DF17
U.S. Pat. No. 8,715,673
7269





SEQ ID NO: 50


STPH41
Heavy chain, S. aureus
DF18
U.S. Pat. No. 8,715,673
7270





SEQ ID NO: 51


STPH42
Heavy chain, S. aureus
DF19
U.S. Pat. No. 8,715,673
7271





SEQ ID NO: 52


STPH43
Heavy chain, S. aureus
DF20
U.S. Pat. No. 8,715,673
7272





SEQ ID NO: 53


STPH44
Heavy chain, S. aureus and S.
CR2430
U.S. Pat. No. 8,460,666
7273




epidermidis


SEQ ID NO: 26


STPH45
Heavy chain, S. aureus and S.
CR5132
U.S. Pat. No. 8,460,666
7274




epidermidis


SEQ ID NO: 28


STPH46
Heavy chain, S. aureus and S.
CR5133
U.S. Pat. No. 8,460,666
7275




epidermidis


SEQ ID NO: 30


STPH47
Heavy chain, S. aureus and S.
CR6166
U.S. Pat. No. 8,460,666
7276




epidermidis


SEQ ID NO: 117


STPH48
Heavy chain, S. aureus and S.
CR6171
U.S. Pat. No. 8,460,666
7277




epidermidis


SEQ ID NO: 119


STPH49
Heavy chain, S. aureus and S.
CR6176
U.S. Pat. No. 8,460,666
7278




epidermidis


SEQ ID NO: 121


STPH50
Heavy chain, S. aureus and S.
CR6187
U.S. Pat. No. 8,460,666
7279




epidermidis


SEQ ID NO: 123


STPH51
Heavy chain, S. aureus and S.
CR6193
U.S. Pat. No. 8,460,666
7280




epidermidis


SEQ ID NO: 125


STPH52
Heavy chain, S. aureus and S.
CR6249
U.S. Pat. No. 8,460,666
7281




epidermidis


SEQ ID NO: 127


STPH53
Heavy chain, S. aureus and S.
CR6273
U.S. Pat. No. 8,460,666
7282




epidermidis


SEQ ID NO: 129


STPH54
Heavy chain, S. aureus and S.
CR6389
U.S. Pat. No. 8,460,666
7283




epidermidis


SEQ ID NO: 131


STPH55
Heavy chain, S. aureus and S.
CR6403
U.S. Pat. No. 8,460,666
7284




epidermidis


SEQ ID NO: 133


STPH56
Heavy chain, S. aureus and S.
CR6406
U.S. Pat. No. 8,460,666
7285




epidermidis


SEQ ID NO: 135


STPH57
Heavy chain, S. aureus and S.
CR6410
U.S. Pat. No. 8,460,666
7286




epidermidis


SEQ ID NO: 137


STPH58
Heavy chain, S. aureus and S.
CR6446
U.S. Pat. No. 8,460,666
7287




epidermidis


SEQ ID NO: 139


STPH59
Heavy chain, S. aureus and S.
CR6450
U.S. Pat. No. 8,460,666
7288




epidermidis


SEQ ID NO: 141


STPH60
Heavy chain, S. aureus and S.
CR6452
U.S. Pat. No. 8,460,666
7289




epidermidis


SEQ ID NO: 143


STPH61
Heavy chain, S. aureus and S.
CR6453
U.S. Pat. No. 8,460,666
7290




epidermidis


SEQ ID NO: 145


STPH62
Heavy chain, S. aureus and S.
CR6464
U.S. Pat. No. 8,460,666
7291




epidermidis


SEQ ID NO: 147


STPH63
Heavy chain, S. aureus and S.
CR6471
U.S. Pat. No. 8,460,666
7292




epidermidis


SEQ ID NO: 149


STPH64
Heavy chain, S. aureus and S.
CR6516
U.S. Pat. No. 8,460,666
7293




epidermidis


SEQ ID NO: 151


STPH65
Heavy chain, S. aureus and S.
CR6517
U.S. Pat. No. 8,460,666
7294




epidermidis


SEQ ID NO: 153


STPH66
Heavy chain, S. aureus and S.
CR6526
U.S. Pat. No. 8,460,666
7295




epidermidis


SEQ ID NO: 155


STPH67
Heavy chain, S. aureus and S.
CR6528
U.S. Pat. No. 8,460,666
7296




epidermidis


SEQ ID NO: 157


STPH68
Heavy chain, S. aureus and S.
CR6531
U.S. Pat. No. 8,460,666
7297




epidermidis


SEQ ID NO: 159


STPH69
Heavy chain, S. aureus and S.
CR6533
U.S. Pat. No. 8,460,666
7298




epidermidis


SEQ ID NO: 161


STPH70
Heavy chain, S. aureus and S.
CR6536
U.S. Pat. No. 8,460,666
7299




epidermidis


SEQ ID NO: 163


STPH71
Heavy chain, S. aureus and S.
CR6537
U.S. Pat. No. 8,460,666
7300




epidermidis


SEQ ID NO: 165


STPH72
Heavy chain, S. aureus and S.
CR6538
U.S. Pat. No. 8,460,666
7301




epidermidis


SEQ ID NO: 167


STPH73
Heavy chain, S. aureus and S.
CR6540
U.S. Pat. No. 8,460,666
7302




epidermidis


SEQ ID NO: 169


STPH74
Heavy chain, S. aureus and S.
CR6544
U.S. Pat. No. 8,460,666
7303




epidermidis


SEQ ID NO: 171


STPH75
Heavy chain, S. aureus and S.
CR6566
U.S. Pat. No. 8,460,666
7304




epidermidis


SEQ ID NO: 173


STPH76
Heavy chain, S. aureus and S.
CR6625
U.S. Pat. No. 8,460,666
7305




epidermidis


SEQ ID NO: 175


STPH77
Heavy chain, S. aureus, Enterococcus
CR5140
U.S. Pat. No. 8,628,776
7306





SEQ ID NO: 395


STPH78
Heavy chain, S. aureus, Enterococcus
CR5159
U.S. Pat. No. 8,628,776
7307





SEQ ID NO: 82


STPH79
Heavy chain, S. aureus, Enterococcus
CR5179
U.S. Pat. No. 8,628,776
7308





SEQ ID NO: 399


STPH80
Heavy chain, S. aureus, Enterococcus
CR6016
U.S. Pat. No. 8,628,776
7309





SEQ ID NO: 88


STPH81
Heavy chain, S. aureus, Enterococcus
CR6049
U.S. Pat. No. 8,628,776
7310





SEQ ID NO: 92


STPH82
Heavy chain, S. aureus. Enterococcus
CR6071
U.S. Pat. No. 8,628,776
7311





SEQ ID NO: 94


STPH83
Heavy chain, S. aureus, Enterococcus
CR6078
U.S. Pat. No. 8,628,776
7312





SEQ ID NO: 96


STPH84
Heavy chain, S. aureus, Enterococcus
CR6086
U.S. Pat. No. 8,628,776
7313





SEQ ID NO: 407


STPH85
Heavy chain, S. aureus, Enterococcus
CR6089
U.S. Pat. No. 8,628,776
7314





SEQ ID NO: 213


STPH86
Heavy chain, S. aureus, Enterococcus
CR6191
UU.S. Pat. No. 8,628,776
7315





SEQ ID NO: 411


STPH87
Heavy chain, S. aureus, Enterococcus
CR6198
U.S. Pat. No. 8,628,776
7316





SEQ ID NO: 415


STPH88
Heavy chain, S. aureus, Enterococcus
CR6242
U.S. Pat. No. 8,628,776
7317





SEQ ID NO: 417


STPH89
Heavy chain, S. aureus, Enterococcus
CR6252
U.S. Pat. No. 8,628,776
7318





SEQ ID NO: 100


STPH90
Heavy chain, S. aureus, Enterococcus
CR6389
0U.S. Pat. No. 8,628,776
7319





SEQ ID NO: 423


STPH91
Heavy chain, S. aureus, Enterococcus
CR6402
U.S. Pat. No. 8,628,776
7320





SEQ ID NO: 427


STPH92
Heavy chain, S. aureus, Enterococcus
CR6415
U.S. Pat. No. 8,628,776
7321





SEQ ID NO: 431


STPH93
Heavy chain, S. aureus, Enterococcus
CR6429
U.S. Pat. No. 8,628,776
7322





SEQ ID NO: 435


STPH94
Heavy chain, S. aureus, Enterococcus
CR5140
U.S. Pat. No. 8,628,776
7323





SEQ ID NO: 439


STPH95
Heavy chain, S. aureus, Enterococcus
CR5159
U.S. Pat. No. 8,628,776
7324





SEQ ID NO: 102


STPH96
Heavy chain, S. aureus, Enterococcus
CR5179
U.S. Pat. No. 8,628,776
7325





SEQ ID NO: 443


STPH97
Heavy chain, S. aureus, Enterococcus
CR6016
U.S. Pat. No. 8,628,776
7326





SEQ ID NO: 108


STPH98
Heavy chain, S. aureus, Enterococcus
CR6049
U.S. Pat. No. 8,628,776
7327





SEQ ID NO: 112


STPH99
Heavy chain, S. aureus, Enterococcus
CR6071
U.S. Pat. No. 8,628,776
7328





SEQ ID NO: 114


STPH100
Heavy chain, S. aureus, Enterococcus
CR6078
U.S. Pat. No. 8,628,776
7329





SEQ ID NO: 116


STPH101
Heavy chain, S. aureus, Enterococcus
CR6086
U.S. Pat. No. 8,628,776
7330





SEQ ID NO: 451


STPH102
Heavy chain, S. aureus, Enterococcus
CR6089
U.S. Pat. No. 8,628,776
7331





SEQ ID NO: 217


STPH103
Heavy chain, S. aureus, Enterococcus
CR6191
U.S. Pat. No. 8,628,776
7332





SEQ ID NO: 455


STPH104
Heavy chain, S. aureus, Enterococcus
CR6198
U.S. Pat. No. 8,628,776
7333





SEQ ID NO: 459


STPH105
Heavy chain, S. aureus, Enterococcus
CR6242
U.S. Pat. No. 8,628,776
7334





SEQ ID NO: 461


STPH106
Heavy chain, S. aureus, Enterococcus
CR6252
U.S. Pat. No. 8,628,776
7335





SEQ ID NO: 120


STPH107
Heavy chain, S. aureus, Enterococcus
CR6389
U.S. Pat. No. 8,628,776
7336





SEQ ID NO: 467


STPH108
Heavy chain, S. aureus, Enterococcus
CR6402
U.S. Pat. No. 8,628,776
7337





SEQ ID NO: 471


STPH109
Heavy chain, S. aureus, Enterococcus
CR6415
U.S. Pat. No. 8,628,776
7338





SEQ ID NO: 475


STPH110
Heavy chain, S. aureus, Enterococcus
CR6429
U.S. Pat. No. 8,628,776
7339





SEQ ID NO: 479


STPH111
Heavy chain, S. aureus, S. epidermidis,
F1 antibody
U.S. Pat. No. 8,617,556
7340




S. caprae, S. saprophyticus, S. capitis, or
variant
SEQ ID NO: 7



methicillin-resistant S. aureus (MRSA)


STPH112
Heavy chain, S. aureus, S. epidermidis,
F1 antibody
U.S. Pat. No. 8,617,556
7341




S. caprae, S. saprophyticus, S. capitis, or
variant
SEQ ID NO: 9



methicillin-resistant S. aureus (MRSA)


STPH113
Heavy chain, S. aureus, S. epidermidis,
rF1
U.S. Pat. No. 8,617,556
7342




S. caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 55



methicillin-resistant S. aureus (MRSA)


STPH114
Heavy chain, S. aureus, S. epidermidis,
rF1 A114C
U.S. Pat. No. 8,617,556
7343




S. caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 56



methicillin-resistant S. aureus (MRSA)


STPH115
Heavy chain, S. aureus, S. epidermidis,
rF1
U.S. Pat. No. 8,617,556
7344




S. caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 63



methicillin-resistant S. aureus (MRSA)


STPH116
Heavy chain, S. aureus, S. epidermidis,
rF1 A114C
U.S. Pat. No. 8,617,556
7345




S. caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 62



methicillin-resistant S. aureus (MRSA)


STPH117
Light chain

U.S. Pat. No. 8,609,102
7346





SEQ ID NO: 4


STPH118
Light chain variable region, S. aureus

U.S. Pat. No. 8,609,102
7347





SEQ ID NO: 8


STPH119
Light chain variable region, S. aureus or
SAR279356
U.S. Pat. No. 7,786,255
7348




S. epidermidis, E. coli, Yersinia

SEQ ID NO: 2




pestis (Y. pestis), Y. entercolitica,




Xanthomnonas axonopodis (X.




axonopodis), Pseudonmonas




fuorescerns (P.




fluorescens), Actinobacillus




actinomycetemcomitans (A.




actinomycetemcomitans), A.




pleuropneumoniae, Ralstonia




solanacearum (R.




solanacearum), Bordetella pertussis (B.




pertussis), B. parapertussis or B.




bronchiseptica



STPH120
Light chain variable region, S. aureus or
SAR279356
US20110002932 SEQ ID
7349




S. epidermidis, E. coli, Yersinia

NO: 2




pestis (Y. pestis), Y. entercolitica,




Xanthomnonas axonopodis (X.




axonopodis), Pseudonmonas




fuorescerns (P.




fluorescens), Actinobacillus




actinomycetemcomitans (A.




actinomycetemcomitans), A.




pleuropneumoniae, Ralstonia




solanacearum (R.




solanacearum), Bordetella pertussis (B.




pertussis), B. parapertussis or B.




bronchiseptica



STPH121
Light chain variable region, S.
108-1
U.S. Pat. No. 8,475,798
7350




epidermidis


SEQ ID NO: 16


STPH122
Light chain variable region, S.
108-36
U.S. Pat. No. 8,475,798
7351




epidermidis


SEQ ID NO: 20


STPH123
Light chain variable region, S.
110-15
U.S. Pat. No. 8,475,798
7352




epidermidis


SEQ ID NO: 24


STPH124
Light chain variable region, S.
108-1VL-
U.S. Pat. No. 8,475,798
7353




epidermidis

Hu
SEQ ID NO: 27


STPH125
Light chain variable region, S.
108-36VL-
U.S. Pat. No. 8,475,798
7354




epidermidis

Hu
SEQ ID NO: 29


STPH126
Light chain variable region, S.
110-15VL-
U.S. Pat. No. 8,475,798
7355




epidermidis

Hu
SEQ ID NO: 31


STPH127
Light chain variable region,
Pagibaximab
U.S. Pat. No. 8,372,958
7356



Staphylococcal sepsis

SEQ ID NO: 89


STPH128
Light chain variable region,
Pagibaximab
U.S. Pat. No. 8,372,958
7357



Staphylococcal sepsis

SEQ ID NO: 10


STPH129
Light chain variable region,
Pagibaximab
U.S. Pat. No. 8,372,958
7358



Staphylococcal sepsis

SEQ ID NO: 16


STPH130
Light chain variable region,
F598
U.S. Pat. No. 8,912,314
7359



Staphylococci such as S. aureus and S.

SEQ ID NO: 2




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH131
Light chain variable region,
F628
U.S. Pat. No. 8,912,314
7360



Staphylococci such as S. aureus and S.

SEQ ID NO: 4




epidermidis, E. coli such as E.




coli strains O157: H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH132
Light chain variable region,
F630
U.S. Pat. No. 8,912,314
7361



Staphylococci such as S. aureus and S.

SEQ ID NO: 6




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH133
Light chain variable region,
F598
U.S. Pat. No. 8,912,314
7362



Staphylococci such as S. aureus and S.

SEQ ID NO: 57




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH134
Light chain variable region,
F630
U.S. Pat. No. 8,912,314
7363



Staphylococci such as S. aureus and S.

SEQ ID NO: 60




epidermidis, E. coli such as E.




coli strains O157:H7 and



CFT073, Yersinia pestis, Yersinia




entercolitica, Xanthomonas axonopodis,




Pseudomonas fluorescens (all of which



are sequenced species with complete



pgaABCD loci), and Actinobacillus




actinomycetemcomitans (AA),




Actinobacillus pleuropneumoniae (Ap),




Ralstonia solanacearum (e.g., megaplasmid



form), Bordetella pertussis, Bordetella




parapertussis and Bordetella




bronchiseptica



STPH135
Light chain, MRSA, MSSA
2B2
U.S. Pat. No. 8,735,554
7364





SEQ ID NO: 2


STPH136
Light chain. MRSA, MSSA
2G7
U.S. Pat. No. 8,735,554
7365





SEQ ID NO: 4


STPH137
Light chain, MRSA, MSSA
3B12
U.S. Pat. No. 8,735,554
7366





SEQ ID NO: 6


STPH138
Light chain, S. aureus
DFLI
U.S. Pat. No. 8,715,673
7367





SEQ ID NO: 1


STPH139
Light chain, S. aureus
DF1-DF20
U.S. Pat. No. 8,715,673
7368





SEQ ID NO: 3


STPH140
Light chain, S. aureus and S. epidermidis
CR2430
U.S. Pat. No. 8,460,666
7369





SEQ ID NO: 32


STPH141
Light chain, S. aureus and S. epidermidis
CR5132
U.S. Pat. No. 8,460,666
7370





SEQ ID NO: 34


STPH142
Light chain, S. aureus and S. epidermidis
CR5133
U.S. Pat. No. 8,460,666
7371





SEQ ID NO: 36


STPH143
Light chain, S. aureus and S. epidermidis
CR6166
U.S. Pat. No. 8,460,666
7372





SEQ ID NO: 177


STPH144
Light chain, S. aureus and S. epidermidis
CR6171
U.S. Pat. No. 8,460,666
7373





SEQ ID NO: 179


STPH145
Light chain, S. aureus and S. epidermidis
CR6176
U.S. Pat. No. 8,460,666
7374





SEQ ID NO: 181


STPH146
Light chain, S. aureus and S. epidermidis
CR6187
U.S. Pat. No. 8,460,666
7375





SEQ ID NO: 183


STPH147
Light chain, S. aureus and S. epidermidis
CR6193
U.S. Pat. No. 8,460,666
7376





SEQ ID NO: 185


STPH148
Light chain, S. aureus and S. epidermidis
CR6249
U.S. Pat. No. 8,460,666
7377





SEQ ID NO: 187


STPH149
Light chain, S. aureus and S. epidermidis
CR6273
U.S. Pat. No. 8,460,666
7378





SEQ ID NO: 189


STPH150
Light chain, S. aureus and S. epidermidis
CR6389
U.S. Pat. No. 8,460,666
7379





SEQ ID NO: 191


STPH151
Light chain, S. aureus and S. epidermidis
CR6403
U.S. Pat. No. 8,460,666
7380





SEQ ID NO: 193


STPH152
Light chain, S. aureus and S. epidermidis
CR6406
U.S. Pat. No. 8,460,666
7381





SEQ ID NO: 195


STPH153
Light chain, S. aureus and S. epidermidis
CR6410
U.S. Pat. No. 8,460,666
7382





SEQ ID NO: 197


STPH154
Light chain, S. aureus and S. epidermidis
CR6446
U.S. Pat. No. 8,460,666
7383





SEQ ID NO: 199


STPH155
Light chain, S. aureus and S. epidermidis
CR6450
U.S. Pat. No. 8,460,666
7384





SEQ ID NO: 201


STPH156
Light chain, S. aureus and S. epidermidis
CR6452
U.S. Pat. No. 8,460,666
7385





SEQ ID NO: 203


STPH157
Light chain, S. aureus and S. epidermidis
CR6453
U.S. Pat. No. 8,460,666
7386





SEQ ID NO: 205


STPH158
Light chain, S. aureus and S. epidermidis
CR6464
U.S. Pat. No. 8,460,666
7387





SEQ ID NO: 207


STPH159
Light chain, S. aureus and S. epidermidis
CR6471
U.S. Pat. No. 8,460,666
7388





SEQ ID NO: 209


STPH160
Light chain, S. aureus and S. epidermidis
CR6516
U.S. Pat. No. 8,460,666
7389





SEQ ID NO: 211


STPH161
Light chain, S. aureus and S. epidermidis
CR6517
U.S. Pat. No. 8,460,666
7390





SEQ ID NO: 213


STPH162
Light chain, S. aureus and S. epidermidis
CR6526
U.S. Pat. No. 8,460,666
7391





SEQ ID NO: 215


STPH163
Light chain, S. aureus and S. epidermidis
CR6528
U.S. Pat. No. 8,460,666
7392





SEQ ID NO: 217


STPH164
Light chain, S. aureus and S. epidermidis
CR6531
U.S. Pat. No. 8,460,666
7393





SEQ ID NO: 219


STPH165
Light chain, S. aureus and S. epidermidis
CR6533
U.S. Pat. No. 8,460,666
7394





SEQ ID NO: 221


STPH166
Light chain, S. aureus and S. epidermidis
CR6536
U.S. Pat. No. 8,460,666
7395





SEQ ID NO: 223


STPH167
Light chain, S. aureus and S. epidermidis
CR6537
U.S. Pat. No. 8,460,666
7396





SEQ ID NO: 225


STPH168
Light chain, S. aureus and S. epidermidis
CR6538
U.S. Pat. No. 8,460,666
7397





SEQ ID NO: 227


STPH169
Light chain, S. aureus and S. epidermidis
CR6540
U.S. Pat. No. 8,460,666
7398





SEQ ID NO: 229


STPH170
Light chain, S. aureus and S. epidermidis
CR6544
U.S. Pat. No. 8,460,666
7399





SEQ ID NO: 231


STPH171
Light chain, S. aureus and S. epidermidis
CR6566
U.S. Pat. No. 8,460,666
7400





SEQ ID NO: 233


STPH172
Light chain, S. aureus and S. epidermidis
CR6625
U.S. Pat. No. 8,460,666
7401





SEQ ID NO: 235


STPH173
Light chain, S. aureus, Enterococcus
CR6157
U.S. Pat. No. 8,628,776
7402





SEQ ID NO: 397


STPH174
Light chain, S. aureus, Enterococcus
CR5166
U.S. Pat. No. 8,628,776
7403





SEQ ID NO: 84


STPH175
Light chain, S. aureus, Enterococcus
CR5187
U.S. Pat. No. 8,628,776
7404





SEQ ID NO: 86


STPH176
Light chain, S. aureus, Enterococcus
CR6043
U.S. Pat. No. 8,628,776
7405





SEQ ID NO: 90


STPH177
Light chain, S. aureus, Enterococcus
CR6050
U.S. Pat. No. 8,628,776
7406





SEQ ID NO: 401


STPH178
Light chain, S. aureus, Enterococcus
CR6077
U.S. Pat. No. 8,628,776
7407





SEQ ID NO: 403


STPH179
Light chain, S. aureus, Enterococcus
CR6079
U.S. Pat. No. 8,628,776
7408





SEQ ID NO: 405


STPH180
Light chain, S. aureus, Enterococcus
CR6087
U.S. Pat. No. 8,628,776
7409





SEQ ID NO: 211


STPH181
Light chain, S. aureus, Enterococcus
CR6092
U.S. Pat. No. 8,628,776
7410





SEQ ID NO: 409


STPH182
Light chain, S. aureus, Enterococcus
CR6195
U.S. Pat. No. 8,628,776
7411





SEQ ID NO: 413


STPH183
Light chain, S. aureus, Enterococcus
CR6241
U.S. Pat. No. 8,628,776
7412





SEQ ID NO: 98


STPH184
Light chain, S. aureus, Enterococcus
CR6246
U.S. Pat. No. 8,628,776
7413





SEQ ID NO: 419


STPH185
Light chain, S. aureus, Enterococcus
CR6388
U.S. Pat. No. 8,628,776
7414





SEQ ID NO: 421


STPH186
Light chain, S. aureus, Enterococcus
CR6396
U.S. Pat. No. 8,628,776
7415





SEQ ID NO: 425


STPH187
Light chain, S. aureus, Enterococcus
CR6409
U.S. Pat. No. 8,628,776
7416





SEQ ID NO: 429


STPH188
Light chain, S. aureus, Enterococcus
CR6421
U.S. Pat. No. 8,628,776
7417





SEQ ID NO: 433


STPH189
Light chain, S. aureus, Enterococcus
CR6432
U.S. Pat. No. 8,628,776
7418





SEQ ID NO: 437


STPH190
Light chain, S. aureus, Enterococcus
CR5157
U.S. Pat. No. 8,628,776
7419





SEQ ID NO: 441


STPH191
Light chain, S. aureus, Enterococcus
CR5166
U.S. Pat. No. 8,628,776
7420





SEQ ID NO: 104


STPH192
Light chain, S. aureus, Enterococcus
CR5187
U.S. Pat. No. 8,628,776
7421





SEQ ID NO: 106


STPH193
Light chain, S. aureus, Enterococcus
CR6043
U.S. Pat. No. 8,628,776
7422





SEQ ID NO: 110


STPH194
Light chain, S. aureus, Enterococcus
CR6050
U.S. Pat. No. 8,628,776
7423





SEQ ID NO: 445


STPH195
Light chain, S. aureus, Enterococcus
CR6077
U.S. Pat. No. 8,628,776
7424





SEQ ID NO: 447


STPH196
Light chain, S. aureus, Enterococcus
CR6079
U.S. Pat. No. 8,628,776
7425





SEQ ID NO: 449


STPH197
Light chain, S. aureus, Enterococcus
CR6087
U.S. Pat. No. 8,628,776
7426





SEQ ID NO: 215


STPH198
Light chain, S. aureus, Enterococcus
CR6092
U.S. Pat. No. 8,628,776
7427





SEQ ID NO: 453


STPH199
Light chain, S. aureus, Enterococcus
CR6195
U.S. Pat. No. 8,628,776
7428





SEQ ID NO: 457


STPH200
Light chain, S. aureus, Enterococcus
CR6241
U.S. Pat. No. 8,628,776
7429





SEQ ID NO: 118


STPH201
Light chain, S. aureus, Enterococcus
CR6246
U.S. Pat. No. 8,628,776
7430





SEQ ID NO: 463


STPH202
Light chain, S. aureus, Enterococcus
CR6388
U.S. Pat. No. 8,628,776
7431





SEQ ID NO: 465


STPH203
Light chain, S. aureus, Enterococcus
CR6396
U.S. Pat. No. 8,628,776
7432





SEQ ID NO: 469


STPH204
Light chain, S. aureus, Enterococcus
CR6409
U.S. Pat. No. 8,628,776
7433





SEQ ID NO: 473


STPH205
Light chain, S. aureus, Enterococcus
CR6421
U.S. Pat. No. 8,628,776
7434





SEQ ID NO: 477


STPH206
Light chain, S. aureus, Enterococcus
CR6432
U.S. Pat. No. 8,628,776
7435





SEQ ID NO: 481


STPH207
Light chain, S. aureus, S. epidermidis, S.
F1 antibody
U.S. Pat. No. 8,617,556
7436




caprae, S. saprophyticus, S. capitis, or
variant
SEQ ID NO: 8



methicillin-resistant S. aureus (MRSA)


STPH208
Light chain, S. aureus, S. epidermidis, S.
F1 antibody
U.S. Pat. No. 8,617,556
7437




caprae, S. saprophyticus, S. capitis, or
variant
SEQ ID NO: 10



methicillin-resistant S. aureus (MRSA)


STPH209
Light chain, S. aureus, S. epidermidis, S.
F1 antibody
U.S. Pat. No. 8,617,556
7438




caprae, S. saprophyticus, S. capitis, or
variant
SEQ ID NO: 11



methicillin-resistant S. aureus (MRSA)


STPH210
Light chain, S. aureus, S. epidermidis, S.
rF1
U.S. Pat. No. 8,617,556
7439




caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 57



methicillin-resistant S. aureus (MRSA)


STPH211
Light chain, S. aureus, S. epidermidis, S.
rF1 V205C
U.S. Pat. No. 8,617,556
7440




caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 58



methicillin-resistant S. aureus (MRSA)


STPH212
Light chain, S. aureus, S. epidermidis, S.
rF1
U.S. Pat. No. 8,617,556
7441




caprae, S. saprophyticus, S. capitis, or

SEQ ID NO: 64



methicillin-resistant S. aureus (MRSA)


STPH213
ScFv, S. aureus and S. epidermidis
SC02-430
U.S. Pat. No. 8,460,666
7442





SEQ ID NO: 20


STPH214
ScFv, S. aureus and S. epidermidis
SC05-132
U.S. Pat. No. 8,460,666
7443





SEQ ID NO: 22


STPH215
ScFv, S. aureus and S. epidermidis
SC05-133
U.S. Pat. No. 8,460,666
7444





SEQ ID NO: 24


STPH216
ScFv, S. aureus, Enterococcus
SC05-140
U.S. Pat. No. 8,628,776
7445





SEQ ID NO: 351


STPH217
ScFv, S. aureus, Enterococcus
SC05-157
U.S. Pat. No. 8,628,776
7446





SEQ ID NO: 353


STPH218
ScFv, S. aureus, Enterococcus
SC05-159
U.S. Pat. No. 8,628,776
7447





SEQ ID NO: 62


STPH219
ScFv, S. aureus, Enterococcus
SC05-166
U.S. Pat. No. 8,628,776
7448





SEQ ID NO: 64


STPH220
ScFv, S. aureus, Enterococcus
SC05-179
U.S. Pat. No. 8,628,776
7449





SEQ ID NO: 355


STPH221
ScFv, S. aureus, Enterococcus
SC05-187
U.S. Pat. No. 8,628,776
7450





SEQ ID NO: 66


STPH222
ScFv, S. aureus, Enterococcus
SC06-016
U.S. Pat. No. 8,628,776
7451





SEQ ID NO: 68


STPH223
ScFv, S. aureus, Enterococcus
SC06-043
U.S. Pat. No. 8,628,776
7452





SEQ ID NO: 70


STPH224
ScFv, S. aureus, Enterococcus
SC06-049
U.S. Pat. No. 8,628,776
7453





SEQ ID NO: 72


STPH225
ScFv, S. aureus, Enterococcus
SC06-050
U.S. Pat. No. 8,628,776
7454





SEQ ID NO: 357


STPH226
ScFv, S. aureus, Enterococcus
SC06-071
U.S. Pat. No. 8,628,776
7455





SEQ ID NO: 74


STPH227
ScFv, S. aureus, Enterococcus
SC06-077
U.S. Pat. No. 8,628,776
7456





SEQ ID NO: 359


STPH228
ScFv, S. aureus, Enterococcus
SC06-078
U.S. Pat. No. 8,628,776
7457





SEQ ID NO: 76


STPH229
ScFv, S. aureus, Enterococcus
SC06-079
U.S. Pat. No. 8,628,776
7458





SEQ ID NO: 361


STPH230
ScFv, S. aureus, Enterococcus
SC06-086
U.S. Pat. No. 8,628,776
7459





SEQ ID NO: 363


STPH231
ScFv, S. aureus, Enterococcus
SC06-087
U.S. Pat. No. 8,628,776
7460





SEQ ID NO: 207


STPH232
ScFv, S. aureus, Enterococcus
SC06-089
U.S. Pat. No. 8,628,776
7461





SEQ ID NO: 209


STPH233
ScFv, S. aureus, Enterococcus
SC06-092
U.S. Pat. No. 8,628,776
7462





SEQ ID NO: 365


STPH234
ScFv, S. aureus, Enterococcus
SC06-091
U.S. Pat. No. 8,628,776
7463





SEQ ID NO: 367


STPH235
ScFv, S. aureus, Enterococcus
SC06-195
U.S. Pat. No. 8,628,776
7464





SEQ ID NO: 369


STPH236
ScFv, S. aureus, Enterococcus
SC06-198
U.S. Pat. No. 8,628,776
7465





SEQ ID NO: 371


STPH237
ScFv, S. aureus, Enterococcus
SC06-241
U.S. Pat. No. 8,628,776
7466





SEQ ID NO: 78


STPH238
ScFv, S. aureus, Enterococcus
SC06-242
U.S. Pat. No. 8,628,776
7467





SEQ ID NO: 373


STPH239
ScFv, S. aureus, Enterococcus
SC06-246
U.S. Pat. No. 8,628,776
7468





SEQ ID NO: 375


STPH240
ScFv, S. aureus, Enterococcus
SC06-252
U.S. Pat. No. 8,628,776
7469





SEQ ID NO: 80


STPH241
ScFv, S. aureus, Enterococcus
SC06-388
U.S. Pat. No. 8,628,776
7470





SEQ ID NO: 377


STPH242
ScFv, S. aureus, Enterococcus
SC06-389
U.S. Pat. No. 8,628,776
7471





SEQ ID NO: 379


STPH243
ScFv, S. aureus, Enterococcus
SC06-396
U.S. Pat. No. 8,628,776
7472





SEQ ID NO: 381


STPH244
ScFv, S. aureus, Enterococcus
SC06-402
U.S. Pat. No. 8,628,776
7473





SEQ ID NO: 383


STPH245
ScFv, S. aureus, Enterococcus
SC06-409
U.S. Pat. No. 8,628,776
7474





SEQ ID NO: 385


STPH246
ScFv, S. aureus, Enterococcus
SC06-415
U.S. Pat. No. 8,628,776
7475





SEQ ID NO: 387


STPH247
ScFv, S. aureus, Enterococcus
SC06-421
U.S. Pat. No. 8,628,776
7476





SEQ ID NO: 389


STPH248
ScFv, S. aureus, Enterococcus
SC06-429
U.S. Pat. No. 8,628,776
7477





SEQ ID NO: 391


STPH249
ScFv, S. aureus, Enterococcus
SC06-432
U.S. Pat. No. 8,628,776
7478





SEQ ID NO: 393









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in International Publication No. WO2000071585, WO2013162751, WO2015089502, WO2015088346 (e.g., SEQ ID NO: 17), US Pub No. US20030224000, US20080014202, US20140037650, US20140170134, U.S. Pat. No. 8,460,666, the contents of each of which are herein incorporated by reference in their entirety, against Staphylococcus infection.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 35 against Clostridium tetani.









TABLE 35







Antibodies against Clostridium Tetani















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO














CTET1
Heavy chain

Sims, G. P. “Tetanus toxoid specific antibody heavy chain
7479



partial

V-gene sequence”, Unpublished, CNBI Accession #





AAC69189.1


CTET2
Heavy chain
F5-20
Sims, G. P. “Tetanus toxoid specific antibody heavy chain
7480



variable region

V-gene sequence”, Unpublished, CNBI Accession #





AAB50736.1


CTET3
Heavy chain

Larrick, J. W., “Therapeutic human antibodies derived
7481



variable region

from PCR amplification of B-cell variable regions”,





Immunol. Rev. 130, 69-85 (1992), CNBI Accession #





AAB25318.1


CTET4
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7482



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36976.1


CTET5
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7483



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36975.1


CTET6
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7484



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36974.1


CTET7
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7485



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36973.1


CTET8
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7486



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36972.1


CTET9
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7487



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36971.1


CTET10
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7488



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36970.1


CTET11
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7489



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36969.1


CTET12
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7490



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36968.1


CTET13
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7491



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol, Biol,



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36967.1


CTET14
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7492



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36966.1


CTET15
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7493



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36965.1


CTET16
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7494



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36964.1


CTET17
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7495



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36963.1


CTET18
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7496



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36962.1


CTET19
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7497



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36961.1


CTET20
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7498



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36960.1


CTET21
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7499



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36958.1


CTET22
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7500



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36959.1


CTET23
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7501



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36957.1


CTET24
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7502



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36956.1


CTET25
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7503



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36955.1


CTET26
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7504



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36954.1


CTET27
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7505



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36953.1


CTET28
Heavy chain

de Kruif, J, et al., “Human immunoglobulin repertoires
7506



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36952.1


CTET29
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7507



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36951.1


CTET30
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7508



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36950.1


CTET31
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7509



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36949.1


CTET32
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7510



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36948.1


CTET33
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7511



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36947.1


CTET34
Heavy chain

de Kruif, J, et al., “Human immunoglobulin repertoires
7512



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36946.1


CTET35
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7513



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36924.1


CTET36
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7514



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36925.1


CTET37
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7515



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36926.1


CTET38
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7516



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36927.1


CTET39
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7517



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36928.1


CTET40
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7518



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J, Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36929.1


CTET41
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7519



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36930.1


CTET42
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7520



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36931.1


CTET43
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7521



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36932.1


CTET44
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7522



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36933.1


CTET45
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7523



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36934.1


CTET46
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7524



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36935.1


CTET47
Heavy chain

de Kruif, J. et al., “Human immunoglobulin repertoires
7525



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36936.1


CTET48
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7526



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36937.1


CTET49
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7527



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36938.1


CTET50
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7528



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36939.1


CTET51
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7529



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36940.1


CTET52
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7530



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36941.1


CTET53
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7531



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36943.1


CTET54
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7532



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36942.1


CTET55
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7533



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36944.1


CTET56
Heavy chain

e Kruif, J. et al., “Human immunoglobulin repertoires
7534



variable region,

against tetanus toxoid contain a large and diverse fraction



Human

of high-affinity promiscuous V(H) genes”, J. Mol. Biol.



immunoglobulin

387 (3), 548-558 (2009), CNBI Accession # ACL36945.1


CTET57
Light chain

Larrick, J. W.. “Therapeutic human antibodies derived
7535



variable region

from PCR amplification of B-cell variable regions”,





Immunol. Rev. 130, 69-85 (1992), CNBI Accession #





AAB25319.1









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 36 against Bordetella pertussis and/or Bordetella parapertussis.









TABLE 36







Antibodies against Bordetella Pertussis and Bordetella Parapertussis















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference information
NO














BORT1
Heavy chain
42.1 1.D4
WO2014160098 SEQ ID NO: 47
7536


BORT2
Heavy chain
42.12.G2
WO2014160098 SEQ ID NO: 51
7537


BORT3
Heavy chain
42.12.A12
WO2014160098 SEQ ID NO: 55
7538


BORT4
Heavy chain
42.12.A9
WO2014160098 SEQ ID NO: 59
7539


BORT5
Heavy chain
42.18.E12
WO2014160098 SEQ ID NO: 63
7540


BORT6
Heavy chain
55.12.A8
WO2014160098 SEQ ID NO: 67
7541


BORT7
Heavy chain
55.15.H5
WO2014160098 SEQ ID NO: 71
7542


BORT8
Heavy chain
55.17.D8
WO2014160098 SEQ ID NO: 75
7543


BORT9
Heavy chain
55.22.E7
WO2014160098 SEQ ID NO: 79
7544


BORT10
Light chain
42,1 1.D4
WO2014160098 SEQ ID NO: 49
7545


BORT11
Light chain
42.12.G2
WO2014160098 SEQ ID NO: 53
7546


BORT12
Light chain
42.12.A12
WO2014160098 SEQ ID NO: 57
7547


BORT13
Light chain
42.12.A9
WO2014160098 SEQ ID NO: 61
7548


BORT14
Light chain
42.18.E12
WO2014160098 SEQ ID NO: 65
7549


BORT15
Light chain
55.12.A8
WO2014160098 SEQ ID NO: 69
7550


BORT16
Light chain
55.15.H5
WO2014160098 SEQ ID NO: 73
7551


BORT17
Light chain
55.17.D8
WO2014160098 SEQ ID NO: 77
7552


BORT18
Light chain
55.22.E7
WO2014160098 SEQ ID NO: 81
7553


BORT19
Single chain variable

Hussein, A. H. et al. “Construction and
7554



fragment antibody type

characterization of single-chain variable



1 a1, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13478.1


BORT20
Single chain variable

Hussein, A. H. et al. “Construction and
7555



fragment antibody type

characterization of single-chain variable



18 a18, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13483.1


BORT21
Single chain variable

Hussein, A. H, el al. “Construction and
7556



fragment antibody type

characterization of single-chain variable



2 a2, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13479.1


BORT22
Single chain variable

Hussein, A. H. et al. “Construction and
7557



fragment antibody type

characterization of single-chain variable



4 b4, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13480.1


BORT23
Single chain variable

Hussein, A. H. et al. “Construction and
7558



fragment antibody type

characterization of single-chain variable



5 c5, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13481.1


BORT24
Single chain variable

Hussein, A. H. et al. “Construction and
7559



fragment antibody type

characterization of single-chain variable



6 d6, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13482.1


BORT25
Single chain variable

Hussein, A. H. et al. “Construction and
7560



fragment antibody type

characterization of single-chain variable



7 e, single chain

fragment antibodies directed against the



variable region


Bordetella pertussis surface adhesins





filamentous hemagglutinin and pertactin”





Infect. Immun. 75 (11), 5476-5482 (2007),





NCBI Accession # ABB13484.1









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 37 against Mycobacteria









TABLE 37







Antibodies against Mycobacteria















SEQ


Antibody

Antibody

ID


No,
Description
Name
Reference Information
NO














MYCO1
Autod2 Single-chain variable

Berger et al., Microbes Infect, 9
7561



fragment antibody, Tb antibody, anti-

(8), 963-970 (2007), NCBI



neutrophil cytoplasmic antibodies

Accession # ABI81486.1



cross-react with mycobacterium avium



subsp. Paratuberculosis antigens


MYCO2
autoh1 single-chain variable fragment

Berger et al., Microbes Infect. 9
7562



antibody, Tb antibody, anti-neutrophil

(8), 963-970 (2007), NCBI



cytoplasmic antibodies cross-react

Accession # ABI81485.1



with mycobacterium avium subsp.




Paratuberculosis antigens,


MYCO3
Heavy chain constant region,
moG2a/
US20130309237 SEQ ID NO:
7563



Mycobacteria
moG2afull
10


MYCO4
Heavy chain constant region,
hG1mG2a
US20130309237 SEQ ID NO:
7564



Mycobacteria

11


MYCO5
Heavy chain constant region,
hG3mG2a
US20130309237 SEQ ID NO:
7565



Mycobacteria

12


MYCO6
Heavy chain constant region,
huG1full
US20130309237 SEQ ID NO:
7566



Mycobacteria

13


MYCO7
Heavy chain constant region,
huG3full
US20130309237 SEQ ID NO:
7567



Mycobacteria

14


MYCO8
Heavy chain variable region,
2F12 IgGs
US20130309237 SEQ ID NO:
7568



Mycobacteria

15


MYCO9
Heavy chain variable region,
2F12 IgGs
US20130309237 SEQ ID NO:
7569



Mycobacteria

18


MYCO10
Heavy chain variable region, partial
16a1
Al-sayyed et al., Tuberculosis
7570



sequence, Tb antibody, mouse

(Edinb) 87 (6), 489-497 (2007),



monoclonal mpt51

NCBI Accession # ABS20005.1


MYCO11
Light chain constant region,
HuCK
US20130309237 SEQ ID NO:
7571



Mycobacteria

16


MYCO12
Light chain variable region,
MoCK
US20130309237 SEQ ID NO:
7572



Mycobacteria

17


MYCO13
Light chain variable region, partial
16a1
Al-sayyed el al., Tuberculosis
7573



sequence, Tb antibody, mouse

(Edinb) 87 (6), 489-497 (2007),



monoclonal mpt51

NCBI Accession # ABS20006.1


MYC014
Scfv, Tb antibody, an engineered

US20060229438 SEQ ID NO: 3
7574



single chain antibody


MYC015
Scfv, Tb antibody, an engineered

US20060229438 SEQ ID NO: 4
7575



single chain antibody


MYC016
Scfv, Tb antibody, an engineered

US20060229438 SEQ ID NO: 2
7576



single chain antibody









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 38 against Francisella tularensis.









TABLE 38







Antibodies against Francisella Tularensis















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO














FRAN1
Chain H
Ab-52
Rynkiewicz, M. J. et al., “Structural Analysis of a Protective
7577





Epitope of the Francisella tularensis O-Polysaccharide”,





Biochemistry- 51 (28), 5684-5694 (2012), NCBI Accession #





3UJT_H


FRAN2
Chain H
N62
Lu, Z., et al., “The binding sites of monoclonal antibodies to
7578





the non-reducing end of Francisella tularensis O-antigen





accommodate mainly the terminal saccharide”, Immunology





140 (3), 374-389 (2013), NCBI Accession # 4KPH_H


FRAN3
Chain H
Ab64
Lu, Z. et al., “B-cell epitopes in GroEL of Francisella
7579






tularensis”, PLoS ONE 9 (6), E99847 (2014), NCBI





Accession # 4PB9_H


FRAN4
Chain H
Ab53
Lu, Z, et al., “B-cell epitopes in GroEL of Francisella
7580






tularensis”, PLoS ONE 9 (6), E99847 (2014), NCBI





Accession # 4PB0_H


FRAN5
Chain H
N203
Lu, Z. et al., “Functional and Structural Characterization of
7581






Francisella tularensis O-Antigen Antibodies at the Low End





of Antigen Reactivity”, Monoclonal Antib Immunodiagn





Immunother 33 (4), 235-245 (2014), NCBI Accession #





4OTX_H


FRAN6
Chain I
Ab-52
Rynkiewicz, M. J., et al., “Structural Analysis of a Protective
7582





Epitope of the Francisella tularensis O-Polysaccharide”,





Biochemistry 51 (28), 5684-5694 (2012), NCBI Accession #





3UJT_I


FRAN7
Chain I
N62
Lu, Z., et al., “The binding sites of monoclonal antibodies to
7583





the non-reducing end of Francisella tularensis O-antigen





accommodate mainly the terminal saccharide”, Immunology





140 (3), 374-389 (2013), NCBI Accession # 4KPH_I


FRAN8
Chain I
N203
Lu, Z. et al., “Functional and Structural Characterization of
7584






Francisella tularensis O-Antigen Antibodies at the Low End





of Antigen Reactivity”, Monoclonal Antib Immunodiagn





Immunother 33 (4), 235-245 (2014), NCBI Accession #





4OTX_I


FRAN9
Chain L
Ab-52
Rynkiewicz, M. J., et al., “Structural Analysis of a Protective
7585





Epitope of the Francisella tularensis O-Polysaccharide”,





Biochemistry 51 (28), 5684-5694 (2012), NCBI Accession #





3UJT_L


FRAN10
Chain L
N62
Lu, Z., et al., “The binding sites of monoclonal antibodies to
7586





the non-reducing end of Francisella tularensis O-antigen





accommodate mainly the terminal saccharide”, Immunology





140 (3), 374-389 (2013), NCBI Accession # 4KPH_L


FRAN11
Chain L
Ab64
Lu, Z. et al., “B-cell epitopes in GroEL of Francisella
7587






tularensis”, PLoS ONE 9 (6), E99847 (2014), NCBI





Accession # 4PB9_L


FRAN12
Chain L
Ab53
Lu, Z. et al., “B-cell epitopes in GroEL of Francisella
7588






tularensis”, PLoS ONE 9 (6), E99847 (2014), NCBI





Accession # 4PB0_L


FRAN13
Chain L
N203
Lu, Z, et al., “Functional and Structural Characterization of
7589






Francisella tularensis O-Antigen Antibodies at the Low End





of Antigen Reactivity”, Monoclonal Antib Immunodiagn





Immunother 33 (4), 235-245 (2014), NCBI Accession #





4OTX_L


FRAN14
Chain M
Ab-52
Rynkiewicz, M. J. et al., “Structural Analysis of a Protective
7590





Epitope of the Francisella tularensis O-Polysaccharide”,





Biochemistry 51 (28), 5684-5694 (2012), NCBI Accession #





3UJT_M


FRAN15
Chain M
N62
Lu, Z., et al., “The binding sites of monoclonal antibodies to
7591





the non-reducing end of Francisella tularensis O-antigen





accommodate mainly the terminal saccharide”, Immunology





140 (3), 374-389 (2013), NCBI Accession # 4KPH_M


FRAN16
Chain M
N203
Lu, Z, et al., “Functional and Structural Characterization of
7592






Francisella tularensis O-Antigen Antibodies at the Low End





of Antigen Reactivity”, Monoclonal Antib Immunodiagn





Immunother 33 (4), 235-245 (2014), NCBI Accession #





4OTX_M









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 39 against Bacteria.









TABLE 39







Antibodies against Bacteria















SEQ


Antibody



ID


No.
Description
Antibody Name
Reference Information
NO














BACI1
Heavy chain variable

US20080038266 SEQ ID NO: 1
7593



region, Enterococcus




faecium, Enterococcus




faecalis, Clostridium




difficile



BACI2
Heavy chain variable
Naid60
US20060073139 SEQ ID NO: 5
7594



region, Neisseria




meningitidis,


BACI3
Heavy chain, Neisseria

Fernandez de Cossio, M. E., et al.
7595




meningitidis,

“Human monoclonal antibodies against





an epitope on the class 5c outer





membrane protein common to many





pathogenic strains of Neisseria






meningitidis”, J. Infect. Dis. 166 (6),





1322-1328 (1992), AAB18935


BACI4
Heavy chain, Neisseria

Fernandez de Cossio, M. E., et al.
7596




meningitidis,

“Human monoclonal antibodies against





an epitope on the class 5c outer





membrane protein common to many





pathogenic strains of Neisseria






meningitidis”, J. Infect. Dis. 166 (6),





1322-1328 (1992), AAB18934


BACI5
Heavy chain, Septic
Edobacomab,

7597



shock, meningococcal
E5, XMMEN-



septic shock
0E5


BACI6
Ig kappa chain V-I

Goni, F. and Frangione, B., “Amino acid
7598



region WEA,

sequence of the Fv region of a human




Klebsiella bacteria

monoclonal IgM (protein WEA) with





antibody activity against 3,4-pyruvylated





galactose in Klebsiella polysaccharides





K30 and K33”, Proc. Natl. Acad. Sci.





U.S.A. 80 (15), 4837-4841 (1983).





P01610


BACI7
Ig kappa chain V-I

Goni, F. and Frangione, B., “Amino acid
7599



region WEA,

sequence of the Fv region of a human




Klebsiella bacteria

monoclonal IgM (protein WEA) with





antibody activity against 3,4-pyruvylated





galactose in Klebsiella polysaccharides





K30 and K33”, Proc. Natl. Acad. Sci.





U.S.A. 80 (15), 4837-4841 (1983),





P01763


BACI8
Light chain variable

US20080038266 SEQ ID NO: 16
7600



region, Enterococcus




faecium, Enterococcus




faecalis, Clostridium




difficile



BACI9
Light chain variable
Naid60
US20060073139 SEQ ID NO: 6
7601



region, Neisseria




meningitidis



BACI10
Light chain, Septic
Edobacomab,

7602



shock, meningococcal
E5, XMMEN-



septic shock,
0E5


BACI11
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7603




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ABI97022.1


BACI12
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7604




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ABI97023.1


BACI13
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7605




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ABI97021.1


BACI14
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7606




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ABI97018.1


BACI15
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7607




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ABI97024.1


BACI16
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7608




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ACZ65033.1


BACI17
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7609




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ACZ65032.1


BACI18
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7610




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ACZ65031.1


BACI19
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7611




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ACZ65030.1


BACI20
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain. Fv
7612




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ACZ65029.1


BACI21
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7613




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ACZ65028.1


BAC122
scFv antibody, Anti-

Zou, N,, et al. “Human Single-Chain Fv
7614




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





AB197020.1


BACI23
scFv antibody, Anti-

Zou, N., et al. “Human Single-Chain Fv
7615




Burkholderia mallei


Antibodies against Burkholderia mallei





and Burkholderia pseudomallei”,





unpublished, NCBI Accession #





ABI97019.1


BACI24
Single chain variable,
CB515
LaRocca, T. J., et al. “Bactericidal action
7616




Borrelia,

of a complement-independent relapsing





fever Borrelia resides in its variable





region”, J. Immunol. 180 (9), 6222-6228





(2008), NCBI Accession # ABV22509









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants encoding Doxorubicin, fragments or variants thereof for treating a disease and/or disorder or preventing a disease and/or disorder. As a non-limiting example, the disease and/or disorder is bacterial infection.


In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 40 against Toxoplasma gondii.









TABLE 40







Antibodies against Toxoplasma gondii











Antibody



SEQ ID


No.
Description
Antibody Name
Reference Information
NO














TOXO1
4f11e12
Fab Heavy Chain Variable
Graille, M. et al., J. Mol. Biol. 354
7617




Region, Surface antigen 1
(2), 447-458 (2005), NCBI Accession




(SAG1)
# 1YNT_D (218aa)


TOXO2
4f11e12
Fab Light Chain Variable
Graille, M. et al., J. Mol, Biol. 354
7618




Region, Surface antigen 1
(2), 447-458 (2005), NCBI Accession




(SAG1)
# 1YNT_C (213aa)









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 41 against Candida Yeast









TABLE 41







Antibodies against Candida Yeast












Antibody


SEQ ID



No.
Description
Antibody Name
NO







CAND1
Efungumab

Candida

7619










In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences encoding one or more of the payload antibody polypeptides listed in Table 42.









TABLE 42







HIV Antibodies















SEQ


Antibody

Antibody

ID


No.
Description
Name
Reference Information
NO














HIV1
4e10 Antibody
4e10antibody
NCBI Accession # 4OB5_H (127aa)
7620



Germline Precursor 7



Heavy Chain Fv


HIV2
4e10 Antibody
4e10antibody
NCBI Accession # 4OB5_L (114aa)
7621



Germline Precursor 7



Light Chain Fv


HIV3
Antigen Binding
Ch103
Liao et al., Co-evolution of a broadly
7622



Fragment Of Heavy

neutralizing HIV-1 antibody and founder virus;



Chain

Nature 496 (7446), 469-476 (2013), NCBI





Accession # 4JAM_H (226aa)


HIV4
Antigen Binding
Ch103
Liao et al., Co-evolution of a broadly
7623



Fragment Of Light

neutralizing HIV-1 antibody and founder virus;



Chain

Nature 496 (7446), 469-476 (2013), NCBI





Accession # 4JAM_L (209aa)


HIV5
Fab Fragment, Heavy
N12-i15
NCBI Accession # 3QEH_G (232aa)
7624



Chain


HIV6
Fab Fragment, Light
N12-i15
NCBI Accession # 3QEH_H (218aa)
7625



Chain


HIV7
Fab Heavy Chain
35o22
Huang et al., Broad and potent HIV-1
7626





neutralization by a human antibody that binds





the gp41-gp120 interface; Nature 515 (7525),





138-142 (2014), NCBI Accession # 4TOY_H





(243 aa)


HIV8
Fab Heavy Chain
8anc195
Scharf, L., et al., Cell Rep 7 (3), 785-795
7627





(2014), NCBI Accession # 4P9H_H (244aa)


HIV9
Fab Heavy Chain
B13
Chen L. et al., Science 326 (5956), 1123-1127
7628





(2009), NCBI Accession # 3IDY_B (231aa)


HIV10
Fab Heavy Chain
Ch58
Liao et al., vaccine Induction of Antibodies
7629





against a Structurally Heterogeneous Site of





Immune Pressure within HIV-1 Envelope





Protein Variable region 1 and 2; Immunity 38





(1), 176-186 (2013), NCBI Accession #





4HQQ_H (231aa)


HIV11
Fab Heavy Chain
Ch59
Liao et al., vaccine Induction of Antibodies
7630





against a Structurally Heterogeneous Site of





Immune Pressure within HIV-1 Envelope





Protein Variable region 1 and 2; Immunity 38





(1), 176-186 (2013), NCBI Accession #





4HPY_H (225aa)


HIV12
Fab Heavy Chain
E51
Huang C et al., Proc. Natl, Acad. Sci. U.S.A.
7631





101 (9), 2706-2711 (2004), NCBI Accession #





1RZF_H (235aa)


HIV13
Fab Heavy Chain
N26-i1 Fab
NCBI Accession # 4FZE_H(232aa)
7632


HIV14
Fab Heavy Chain
Pgt145
McLellan, J. S. et al., Structure of HIV-1 gp120
7633





V1 V2 domain with broadly neutralizing





antibody PG9; Nature 480 (7377), 336-343





(2011), NCBI Accession # 3U1S_H (267aa)


HIV15
Fab Heavy Chain Of
A32 Fab
NCBI Accession # 3TNM_A (231aa)
7634



Human Anti-hiv-1



Env Antibody A32


HIV16
Fab Heavy Chain Of
C11 Fab
NCBI Accession # 4FZ8_H (237aa)
7635



Human Anti-hiv-1



Env Antibody C11


HIV17
Fab Light Chain
35o22
Huang et al., Broad and potent HIV-1
7636





neutralization by a human antibody that binds





the gp41-gp120 interface; Nature 515 (7525),





138-142 (2014), NCBI Accession # 4TOY_L





(216aa)


HIV18
Fab Light Chain
8anc195
Scharf, L., et al., Cell Rep 7 (3), 785-795
7637





(2014), NCBI Accession # 4P9H_L (215aa)


HIV19
Fab Light Chain
B13
Chen L. et al., Science 326 (5956), 1123-1127
7638





(2009), NCBI Accession # 3IDY_C (215aa)


HIV20
Fab Light Chain
Ch58
Liao et al., vaccine Induction of Antibodies
7639





against a Structurally Heterogeneous Site of





Immune Pressure within HIV-1 Envelope





Protein Variable region 1 and 2; Immunity 38





(1), 176-186 (2013), NCBI Accession #





4HQQ_L (216aa)


HIV21
Fab Light Chain
Ch59
Liao et al., vaccine Induction of Antibodies
7640





against a Structurally Heterogeneous Site of





Immune Pressure within HIV-1 Envelope





Protein Variable region 1 and 2; Immunity 38





(1), 176-186 (2013), NCBI Accession #





4HPY_L (215aa)


HIV22
Fab Light Chain
E51
Huang C et al., Proc. Natl. Acad. Sci. U.S.A.
7641





101 (9), 2706-2711 (2004), NCBI Accession #





1RZF_L (213aa)


HIV23
Fab Light Chain
Monoclonal
Bartesaghi, A. et al., Perfusion structure of
7642




Antibody
trimeric HIV-1 envelope glycoprotein




Vrc03
determined by cryo-electron microscopy; Nat.





Struct. Mol. Biol. 20 (12), 1352-1357 (2013),





NCBI Accession # 4CC8_L (209aa)


HIV24
Fab Light Chain
N26-i1 Fab
NCBI Accession# 4FZE_L (212aa)
7643


HIV25
Fab Light Chain
Pgt145
McLellan, J. S. et al., Structure of HIV-1 gp120
7644





V1 V2 domain with broadly neutralizing





antibody PG9; Nature 480 (7377), 336-343





(2011), NCBI Accession # 3U1S_L (239aa)


HIV26
Fab Light Chain Of
A32 Fab
NCBI Accession # 3TNM_B (216aa)
7645



Human Anti-hiv-1



Env Antibody A32


HIV27
Fab Light Chain Of
C11 Fab
NCBI Accession # 4FZ8_L (218aa)
7646



Human Anti-hiv-1



Env Antibody C11


HIV28
Fab Region Of The
Fab 2558
Gorny et al., PLoS ONE 6 (12), E27780 (2011),
7647



Heavy Chain

NCBI Accession # 3UJI_H (223aa)


HIV29
Fab Region Of The
Fab 4025
Gorny et al., PLoS ONE 6 (12), E27780 (2011),
7648



Heavy Chain

NCBI Accession # 3UJJ_H (230aa)


HIV30
Fab, Heavy Chain
3bnc60
Scheid, J. F., et al,. Science 333 (6049), 1633-
7649





1637 (2011), NCBI Accession # 3RPI_A





(229aa)


HIV31
Fab, Heavy Chain
48d
Huang C C et al., Proc. Natl. Acad. Sci. U.S.A.
7650





101 (9), 2706-2711 (2004), NCBI Accession #





1R27_H (219aa)


HIV32
Fab, Heavy Chain
4e10Fab
Bird et al., Nat. Struct. Mol. Biol. (2014), NCBI
7651





Accession # 4NGH_H (228aa)


HIV33
Fab, Heavy Chain
Ch58-ua
Nicely et al. Ebiomedicine 2 (2015), NCBI
7652





Accession # 4RIS_H (230aa)


HIV34
Fab, Heavy chain
Mab 2909
Spurrier, B., et al., Structure 19 (5), 691-699
7653





(2011), NCBI Accession # 3Q6F_J (233aa)


HIV35
Fab, Heavy Chain
Monoclonal
Bartesaghi, A. et al., Perfusion structure of
7654




Antibody
trimeric HIV-1 envelope glycoprotein




Vrc03
determined by cryo-electron microscopy; Nat.





Struct. Mol. Biol. 20 (12), 1352-1357 (2013),





NCBI Accession # 4CC8_I (233aa)


HIV36
Fab, light chain
3bnc60
Scheid, J. F., et al., Science 333 (6049), 1633-
7655





1637 (2011), NCBI Accession # 3RPI_B





(206aa)


HIV37
Fab, Light Chain
48d
Huang C C et al., Proc. Natl. Acad. Sci. U.S.A.
7656





101 (9), 2706-2711. (2004), NCBI Accession #





1RZ7_L (212aa)


HIV38
Fab, Light Chain
4e10Fab
Bird et al., Nat. Struct. Mol. Biol. (2014), NCBI
7657





Accession # 4NGH_L (215aa)


HIV39
Fab, Light Chain
Ch58-ua
Nicely et al. Ebiomedicine 2 (2015), NCBI
7658





Accession # 4RIS_L (216aa)


HIV40
Fab, light Chain
Mab 2909
Spurrier, B., et al., Structure 19 (5), 691-699
7659





(2011), NCBI Accession # 3Q6F_K (213aa)


HIV41
Gamma heavy chain
1443_C16
U.S. Pat. No. 9,051,362 SEQ ID NO: 12
7660


HIV42
Gamma heavy chain
1471 M23
U.S. Pat. No. 9,051,362 SEQ ID NO: 139
7661


HIV43
Gamma heavy chain
1489_I13
U.S. Pat. No. 9,051,362 SEQ ID NO: 59
7662


HIV44
Gamma heavy chain
1503_H05
U.S. Pat. No. 9,051,362 SEQ ID NO: 53
7663


HIV45
Gamma heavy chain
1456_A12
U.S. Pat. No. 9,051,362 SEQ ID NO: 48
7664



variable region


HIV46
Gamma heavy chain
1456_P20
U.S. Pat. No. 9,051,362 SEQ ID NO: 33
7665



variable region


HIV47
Gamma heavy chain
1460_G14
U.S. Pat. No. 9,051,362 SEQ ID NO: 35
7666



variable region


HIV48
Gamma heavy chain
1470_M23
U.S. Pat. No. 9,051,362 SEQ ID NO: 140
7667



variable region


HIV49
Gamma heavy chain
1480_I08
U.S. Pat. No. 9,051,362 SEQ ID NO: 31
7668



variable region


HIV50
Gamma heavy chain
1480_I08
U.S. Pat. No. 9,051,362 SEQ ID NO: 65
7669



variable region


HIV51
Gamma heavy chain
1489_I13
U.S. Pat. No. 9,051,362 SEQ ID NO: 60
7670



variable region


HIV52
Gamma heavy chain
1495_C14
U.S. Pat. No. 9,051,362 SEQ ID NO: 37
7671



variable region


HIV53
Gamma heavy chain
1503_H05
U.S. Pat. No. 9,051,362 SEQ ID NO: 54
7672



variable region


HIV54
Gamma heavy chain
1496_C09
U.S. Pat. No. 9,051,362 SEQ ID NO: 39
7673



variable region


HIV55
Gamma heavy chain
1456_A12
U.S. Pat. No. 9,051,362 SEQ ID NO: 47
7674


HIV56
Gamma heavy chain
1460_G14
U.S. Pat. No. 9,051,362 SEQ ID NO: 20
7675


HIV57
Gamma heavy chain
1495_C14
U.S. Pat. No. 9,051,362 SEQ ID NO: 24
7676


HIV58
Gamma heavy chain
1496_C09
U.S. Pat. No. 9,051,362 SEQ ID NO: 28
7677


HIV59
Gamma heavy
1456_P20
U.S. Pat. No. 9,051,362 SEQ ID NO: 16
7678


HIV60
Gp41-specific

US20140348785 SEQ ID NO: 11
7679



antibody, heavy chain


HIV61
Gp41-specific

US20140348785 SEQ ID NO: 146
7680



antibody, heavy chain



consensus


HIV62
Gp41-specific

US20140348785 SEQ ID NO: 187
7681



antibody, heavy chain



consensus variable



region


HIV63
Gp41-specific

US20140348785 SEQ ID NO: 188
7682



antibody, heavy chain



consensus variable



region


HIV64
Gp41-specific

US20140348785 SEQ ID NO: 153
7683



antibody, heavy chain



variable region


HIV65
Gp41-specific

US20140348785 SEQ ID NO: 154
7684



antibody, heavy chain



variable region


HIV66
Gp41-specific

US20140348785 SEQ ID NO: 155
7685



antibody, heavy chain



variable region


HIV67
Gp41-specific

US20140348785 SEQ ID NO: 156
7686



antibody, heavy chain



variable region


HIV68
Gp41-specific

US20140348785 SEQ ID NO: 157
7687



antibody, heavy chain



variable region


HIV69
Gp41-specific

US20140348785 SEQ ID NO: 158
7688



antibody, heavy chain



variable region


HIV70
Gp41-specific

US20140348785 SEQ ID NO: 159
7689



antibody, heavy chain



variable region


HIV71
Gp41-specific

US20140348785 SEQ ID NO: 160
7690



antibody, heavy chain



variable region


HIV72
Gp41-specific

US20140348785 SEQ ID NO: 161
7691



antibody, heavy chain



variable region


HIV73
Gp41-specific

US20140348785 SEQ ID NO: 162
7692



antibody, heavy chain



variable region


HIV74
Gp41 -specific

US20140348785 SEQ ID NO: 163
7693



antibody, heavy chain



variable region


HIV75
Gp41-specific

US20140348785 SEQ ID NO: 189
7694



antibody, heavy chain



variable region


HIV76
Gp41-specific

US20140348785 SEQ ID NO: 190
7695



antibody, heavy chain



variable region


HIV77
Gp41-specific

US20140348785 SEQ ID NO: 191
7696



antibody, heavy chain



variable region


HIV78
Gp41-specific

US20140348785 SEQ ID NO: 192
7697



antibody, heavy chain



variable region


HIV79
Gp41-specific

US20140348785 SEQ ID NO: 200
7698



antibody, heavy chain



variable region


HIV80
Gp41-specific

US20140348785 SEQ ID NO: 201
7699



antibody, heavy chain



variable region


HIV81
Gp41-specific

US20140348785 SEQ ID NO: 202
7700



antibody, heavy chain



variable region


HIV82
Gp41-specific

US20140348785 SEQ ID NO: 203
7701



antibody, heavy chain



variable region


HIV83
Gp41-specific

US20140348785 SEQ ID NO: 204
7702



antibody, heavy chain



variable region


HIV84
Gp41-specific

US20140348785 SEQ ID NO: 205
7703



antibody, heavy chain



variable region


HIV85
Gp41-specific

US20140348785 SEQ ID NO: 206
7704



antibody, heavy chain



variable region


HIV86
Gp41-specific

US20140348785 SEQ ID NO: 207
7705



antibody, heavy chain



variable region


HIV87
Gp41-specific

US20140348785 SEQ ID NO: 208
7706



antibody, heavy chain



variable region


HIV88
Gp41-specific

US20140348785 SEQ ID NO: 209
7707



antibody, heavy chain



variable region


HIV89
Gp41-specific

US20140348785 SEQ ID NO: 12
7708



antibody, light chain



variable region


HIV90
Gp41-specific

US20140348785 SEQ ID NO: 164
7709



antibody, light chain



variable region


HIV91
Gp41-specific

US20140348785 SEQ ID NO: 165
7710



antibody, light chain



variable region


HIV92
Gp41-specific

US20140348785 SEQ ID NO: 166
7711



antibody, light chain



variable region


HIV93
Gp41-specific

US20140348785 SEQ ID NO: 167
7712



antibody, light chain



variable region


HIV94
Gp41-specific

US20140348785 SEQ ID NO: 168
7713



antibody, light chain



variable region


HIV95
Gp41-specific

US20140348785 SEQ ID NO: 169
7714



antibody, light chain



variable region


HIV96
Gp41-specific

US20140348785 SEQ ID NO: 170
7715



antibody, light chain



variable region


HIV97
Gp41-specific

US20140348785 SEQ ID NO: 171
7716



antibody, light chain



variable region


HIV98
Gp41-specific

US20140348785 SEQ ID NO: 172
7717



antibody, light chain



variable region


HIV99
Gp41-specific

US20140348785 SEQ ID NO: 173
7718



antibody, light chain



variable region


HIV100
Gp41-specific

US20140348785 SEQ ID NO: 174
7719



antibody, light chain



variable region


HIV101
Gp41-specific

US20140348785 SEQ ID NO: 175
7720



antibody, light chain



variable region


HIV102
Gp41-specific

US20140348785 SEQ ID NO: 176
7721



antibody, light chain



variable region


HIV103
Gp41-specific

US20140348785 SEQ ID NO: 177
7722



antibody, light chain



variable region


HIV104
Gp41-specific

US20140348785 SEQ ID NO: 178
7723



antibody, light chain



variable region


HIV105
Gp41-specific

US20140348785 SEQ ID NO: 179
7724



antibody, light chain



variable region


HIV106
Gp41-specific

US20140348785 SEQ ID NO: 180
7725



antibody, light chain



variable region


HIV107
Gp41-specific

US20140348785 SEQ ID NO: 181
7726



antibody, light chain



variable region


HIV108
Gp41-specific

US20140348785 SEQ ID NO: 182
7727



antibody, light chain



variable region


HIV109
Gp41-specific

US20140348785 SEQ ID NO: 183
7728



antibody, light chain



variable region


HIV110
Gp41-specific

US20140348785 SEQ ID NO: 184
7729



antibody, light chain



variable region


HIV111
Gp41-specific

US20140348785 SEQ ID NO: 185
7730



antibody, light chain



variable region


HIV112
Gp41-specific

US20140348785 SEQ ID NO: 186
7731



antibody, light chain



variable region


HIV113
Gp41-specific

US20140348785 SEQ ID NO: 197
7732



antibody, light chain



variable region


HIV114
Gp41-specific

US20140348785 SEQ ID NO: 198
7733



antibody, light chain



variable region


HIV115
Gp41-specific

US20140348785 SEQ ID NO: 199
7734



antibody, light chain



variable region


HIV116
Heavy chain
Vrc06b
Wu, X., et al., Maturation and Diversity of the
7735





VRC01-Antibody Lineage over 15 Years of





Chronic HIV-1 Infection; Cell 161 (3), 470-485





(2015), NCBI Accession # 4XNZ_E (234aa)


HIV117
Heavy Chain
2424
Kumar, R., et al., Functional and Structural
7736





Characterization of Human V3-Specific





Monoclonal Antibody 2424 with Neutralizing





Activity against HIV-1 JRFL; J. Virol. 89 (17),





9090-9102 (2015), NCBI Accession #





4XML_H(223aa)


HIV118
Heavy chain
5827
US20140205607 Table S13
7737


HIV119
Heavy chain
7863
US20140205607 Table S13
7738


HIV120
Heavy Chain
8062
Gustchina, E., PLoS ONE 8 (11), E78187
7739





(2013), NCBI Accession # 4KHX_H(245aa)


HIV121
Heavy chain
18761
US20140205607 Table S13
7740


HIV122
Heavy chain
19891
US20140205607 Table S13
7741


HIV123
Heavy chain
22425
US20140205607 Table S13
7742


HIV124
Heavy chain
28241
US20140205607 Table S13
7743


HIV125
Heavy chain
61272
US20140205607 Table S13
7744


HIV126
Heavy chain
61822
US20140205607 Table S13
7745


HIV127
Heavy chain
65030
US20140205607 Table S13
7746


HIV128
Heavy chain
70085
US20140205607 Table S13
7747


HIV129
Heavy chain
70542
US20140205607 Table S13
7748


HIV130
Heavy chain
80585
US20140205607 Table S13
7749


HIV131
Heavy chain
87722
US20140205607 Table S13
7750


HIV132
Heavy chain
96362
US20140205607 Table S13
7751


HIV133
Heavy chain
103787
US20140205607 Table S13
7752


HIV134
Heavy chain
146940
US20140205607 Table S13
7753


HIV135
Heavy chain
153849
US20140205607 Table S13
7754


HIV136
Heavy chain
1.00E+09
US20140348785 SEQ ID NO: 1
7755


HIV137
Heavy chain
104625_2
US20140205607 Table S14
7756


HIV138
Heavy chain
105239_4
US20140205607 Table S14
7757


HIV139
Heavy chain
10731_1
US20140205607 Table S14
7758


HIV140
Heavy Chain
10e8
Huang J et al., Nature 491 (7424), 406-412
7759




(monoclonal)
(2012), NCBI Accession # 4G6F_B (236aa)


HIV141
Heavy chain
120119_4
US20140205607 Table S14
7760


HIV142
Heavy chain
121325_4
US20140205607 Table S14
7761


HIV143
Heavy chain
12467_3
US20140205607 Table S14
7762


HIV144
Heavy chain
124918_2
US20140205607 Table S14
7763


HIV145
Heavy chain
127586_4
US20140205607 Table S14
7764


HIV146
Heavy chain
12A10HC
US20140328862 SEQ ID NO: 147
7765


HIV147
Heavy chain
12A12HC
US20140328862 SEQ ID NO: 148
7766


HIV148
Heavy chain
12A13HC
US20140328862 SEQ ID NO: 149
7767


HIV149
Heavy chain
12A16HC
US20140328862 SEQ ID NO: 150
7768


HIV150
Heavy chain
12A17HC
US20140328862 SEQ ID NO: 151
7769


HIV151
Heavy chain
12A1HC
US20140328862 SEQ ID NO: 152
7770


HIV152
Heavy chain
12A20HC
US20140328862 SEQ ID NO: 153
7771


HIV153
Heavy Chain
12a21
NCBI Accession # 4JPW_H (225aa)
7772


HIV154
Heavy chain
12A21HC
US20140328862 SEQ ID NO: 154
7773


HIV155
Heavy chain
I2A22HC
US20140328862 SEQ ID NO: 155
7774


HIV156
Heavy chain
12A23HC
US20140328862 SEQ ID NO: 156
7775


HIV157
Heavy chain
12A27HC
US20140328862 SEQ ID NO: 157
7776


HIV158
Heavy chain
12A2HC
US20140328862 SEQ ID NO: 158
7777


HIV159
Heavy chain
12A30HC
US20140328862 SEQ ID NO: 159
7778


HIV160
Heavy chain
12A37HC
US20140328862 SEQ ID NO: 160
7779


HIV161
Heavy chain
12A46HC
US20140328862 SEQ ID NO: 161
7780


HIV162
Heavy chain
12A4HC
US20140328862 SEQ ID NO: 162
7781


HIV163
Heavy chain
12A55HC
US20140328862 SEQ ID NO: 163
7782


HIV164
Heavy chain
12A56HC
US20140328862 SEQ ID NO: 164
7783


HIV165
Heavy chain
12A6HC
US20140328862 SEQ ID NO: 165
7784


HIV166
Heavy chain
12A7HC
US20140328862 SEQ ID NO: 166
7785


HIV167
Heavy chain
12A9HC
US20140328862 SEQ ID NO: 167
7786


HIV168
Heavy chain
132797_4
US20140205607 Table S14
7787


HIV169
Heavy chain
135083_3
US20140205607 Table S14
7788


HIV170
Heavy chain
13826_2
US20140205607 Table S14
7789


HIV171
Heavy chain
143251_3
US20140205607 Table S14
7790


HIV172
Heavy chain
149590_4
US20140205607 Table S14
7791


HIV173
Heavy chain
149768_4
US20140205607 Table S14
7792


HIV174
Heavy chain
151901_4
US20140205607 Table S14
7793


HIV175
Heavy chain
156858_3
US20140205607 Table S14
7794


HIV176
Heavy chain
164202_3
US20140205607 Table S14
7795


HIV177
Heavy chain
164922_3
US20140205607 Table S14
7796


HIV178
Heavy chain
165478_2
US20140205607 Table S14
7797


HIV179
Heavy chain
166726_3
US20140205607 Table S14
7798


HIV180
Heavy chain
167612_4
US20140205607 Table S14
7799


HIV181
Heavy chain
168509_2
US20140205607 Table S14
7800


HIV182
Heavy chain
169094_4
US20140205607 Table S14
7801


HIV183
Heavy chain
17720_4
US20140205607 Table S14
7802


HIV184
Heavy chain
178037_3
US20140205607 Table S14
7803


HIV185
Heavy chain
179400_4
US20140205607 Table S14
7804


HIV186
Heavy chain
179500_4
US20140205607 Table S14
7805


HIV187
Heavy chain
179888_3
US20140205607 Table S14
7806


HIV188
Heavy Chain
17b
Kwong, P. D., et al., structure of an HIV gp120
7807





envelope glycoprotein in complex with the CD4





receptor and a neutralizing human antibody;





Nature 393 (6686), 648-659 (1998), NCBI





Accession# 1G9M_H (229aa)


HIV189
Heavy chain
18278_1
US20140205607 Table S14
7808


HIV190
Heavy chain
184939_4
US20140205607 Table S14
7809


HIV191
Heavy chain
185961_4
US20140205607 Table S14
7810


HIV192
Heavy chain
186066_4
US20140205607 Table S14
7811


HIV193
Heavy chain
186275_2
US20140205607 Table S14
7812


HIV194
Heavy chain
186640_2
US20140205607 Table S14
7813


HIV195
Heavy chain
190244_4
US20140205607 Table S14
7814


HIV196
Heavy chain
193526_4
US20140205607 Table S14
7815


HIV197
Heavy chain
193896_4
US20140205607 Table S14
7816


HIV198
Heavy chain
195462_4
US20140205607 Table S14
7817


HIV199
Heavy chain
196147_4
US20140205607 Table S14
7818


HIV200
Heavy chain
196283_4
US20140205607 Table S14
7819


HIV201
Heavy Chain
1b2530
Zhou T el al., Structural Repertoire of HIV-1-
7820





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YFL_H





(227aa)


HIV202
Heavy chain
1F7
U.S. Pat. No. 6,057,421A FIG. 8
7821


HIV203
Heavy chain
1NC9
WO2012154312 SEQ ID NO: 2471
7822


HIV204
Heavy Chain
2.2C
Acharya, P., et al., Structural Definition of an
7823





Antibody-Dependent Cellular Cytotoxicity





Response Implicated in Reduced Risk for HIV-





1 Infection; J. Virol. 88 (21), 12895-12906





(2014), NCBI Accession # 4R4N_H (220aa)


HIV205
Heavy chain
24972_4
US20140205607 Table S14
7824


HIV206
Heavy chain
28936_1
US20140205607 Table S14
7825


HIV207
Heavy chain
2F5
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 5
7826


HIV208
Heavy chain
2F5 F100BW
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 7
7827


HIV209
Heavy chain
2F5 L100AW
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 6
7828


HIV210
Heavy chain
2F5
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 9
7829




L100AW-




V100DW


HIV211
Heavy chain
2F5
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 8
7830




V100DW


HIV212
Heavy chain
30263_2
US20140205607 Table S14
7831


HIV213
Heavy chain
3040HC
WO2015117008 SEQ ID NO: 14
7832


HIV214
Heavy chain
3044HC
WO20S5117008 SEQ ID NO: 17
7833


HIV215
Heavy chain
31458_3
US20140205607 Table S14
7834


HIV216
Heavy chain
3430HC
WO2015117008 SEQ ID NO: 15
7835


HIV217
Heavy chain
3484HC
WO2015117008 SEQ ID NO: 16
7836


HIV218
Heavy chain
3630HC
WO2015117008 SEQ ID NO: 18
7837


HIV219
Heavy chain
3A124HC
US20140328862 SEQ ID NO: 261
7838


HIV220
Heavy chain
3A125HC
US20140328862 SEQ ID NO: 262
7839


HIV221
Heavy chain
3A140HC
US20140328862 SEQ ID NO: 263
7840


HIV222
Heavy chain
3A144HC
US20140328862 SEQ ID NO: 264
7841


HIV223
Heavy chain
3A160HC
US20140328862 SEQ ID NO: 265
7842


HIV224
Heavy chain
3A18HC
US20140328862 SEQ ID NO: 266
7843


HIV225
Heavy chain
3A204HC
US20140328862 SEQ ID NO: 267
7844


HIV226
Heavy chain
3A228HC
US20140328862 SEQ ID NO: 268
7845


HIV227
Heavy chain
3A233HC
US20140328862 SEQ ID NO: 269
7846


HIV228
Heavy chain
3A244HC
US20140328862 SEQ ID NO: 270
7847


HIV229
Heavy chain
3A255HC
US20140328862 SEQ ID NO: 271
7848


HIV230
Heavy chain
3A296HC
US20140328862 SEQ ID NO: 272
7849


HIV231
Heavy chain
3A334HC
US20140328862 SEQ ID NO: 273
7850


HIV232
Heavy chain
3A366HC
US20140328862 SEQ ID NO: 274
7851


HIV233
Heavy chain
3A381HC
US20140328862 SEQ ID NO: 275
7852


HIV234
Heavy chain
3A384HC
US20140328862 SEQ ID NO: 276
7853


HIV235
Heavy chain
3A419HC
US20140328862 SEQ ID NO: 277
7854


HIV236
Heavy chain
3a426hc
US20140328862 SEQ ID NO: 343
7855


HIV237
Heavy chain
3A461HC
US20140328862 SEQ ID NO: 278
7856


HIV238
Heavy chain
3A474HC
US20140328862 SEQ ID NO: 279
7857


HIV239
Heavy chain
3a515hc
US20140328862 SEQ ID NO: 344
7858


HIV240
Heavy chain
3A518HC
US20140328862 SEQ ID NO: 280
7859


HIV241
Heavy chain
3A539HC
US20140328862 SEQ ID NO: 281
7860


HIV242
Heavy chain
3A576HC
US20140328862 SEQ ID NO: 282
7861


HIV243
Heavy chain
3A613HC
US20140328862 SEQ ID NO: 283
7862


HIV244
Heavy chain
3A64HC
US20140328862 SEQ ID NO: 284
7863


HIV245
Heavy chain
3A650HC
US20140328862 SEQ ID NO: 285
7864


HIV246
Heavy chain
3A67HC
US20140328862 SEQ ID NO: 286
7865


HIV247
Heavy chain
3A779HC
US20140328862 SEQ ID NO: 287
7866


HIV248
Heavy chain
3A816HC
US20140328862 SEQ ID NO: 288
7867


HIV249
Heavy chain
3A869HC
US20140328862 SEQ ID NO: 289
7868


HIV250
Heavy chain
3A93HC
US20140328862 SEQ ID NO: 290
7869


HIV251
Heavy chain
3A966HC
US20140328862 SEQ ID NO: 291
7870


HIV252
Heavy chain
3A978HC
US20140328862 SEQ ID NO: 292
7871


HIV253
Heavy chain
3ANC32HC
US20140328862 SEQ ID NO: 346
7872


HIV254
Heavy chain
3ANC3HC
US20140328862 SEQ ID NO: 293
7873


HIV255
Heavy chain
3ANC3HC
US20140328862 SEQ ID NO: 347
7874


HIV256
Heavy chain
3ANC41HC
US20140328862 SEQ ID NO: 348
7875


HIV257
Heavy chain
3ANC42HC
US20140328862 SEQ ID NO: 294
7876


HIV258
Heavy chain
3ANC42HC
US20140328862 SEQ ID NO: 349
7877


HIV259
Heavy chain
3ANC66HC
US20140328862 SEQ ID NO: 295
7878


HIV260
Heavy chain
3ANC66HC
US20140328862 SEQ ID NO: 350
7879


HIV261
Heavy chain
3ANC70HC
US20140328862 SEQ ID NO: 351
7880


HIV262
Heavy chain
3ANC75HC
US20140328862 SEQ ID NO: 352
7881


HIV263
Heavy chain
3ANC79HC
US20140328862 SEQ ID NO: 296
7882


HIV264
Heavy chain
3ANC79HC
US20140328862 SEQ ID NO: 353
7883


HIV265
Heavy chain
3ANC87HC
US20140328862 SEQ ID NO: 354
7884


HIV266
Heavy chain
3ANC8HC
US20140328862 SEQ ID NO: 355
7885


HIV267
Heavy chain
3ANC96HC
US20140328862 SEQ ID NO: 356
7886


HIV268
Heavy chain
3B106HC
US20140328862 SEQ ID NO: 357
7887


HIV269
Heavy chain
3B10HC
US20140328862 SEQ ID NO: 297
7888


HIV270
Heavy chain
3B120HC
US20140328862 SEQ ID NO: 298
7889


HIV271
Heavy chain
3B126HC
US20140328862 SEQ ID NO: 299
7890


HIV272
Heavy chain
3B129HC
US20140328862 SEQ ID NO: 300
7891


HIV273
Heavy chain
3B142HC
US20140328862 SEQ ID NO: 301
7892


HIV274
Heavy chain
3B154HC
US20140328862 SEQ ID NO: 302
7893


HIV275
Heavy chain
3B165HC
US20140328862 SEQ ID NO: 303
7894


HIV276
Heavy chain
3B16HC
US20140328862 SEQ ID NO: 358
7895


HIV277
Heavy chain
3B171HC
US20140328862 SEQ ID NO: 304
7896


HIV278
Heavy chain
3B17HC
US20140328862 SEQ ID NO: 305
7897


HIV279
Heavy chain
3B180HC
US20140328862 SEQ ID NO: 359
7898


HIV280
Heavy chain
3B183HC
US20140328862 SEQ ID NO: 360
7899


HIV281
Heavy chain
3B186HC
US20140328862 SEQ ID NO: 306
7900


HIV282
Heavy chain
3B191HC
US20140328862 SEQ ID NO: 361
7901


HIV283
Heavy chain
3B193HC
US20140328862 SEQ ID NO: 307
7902


HIV284
Heavy chain
3B21HC
US20140328862 SEQ ID NO: 362
7903


HIV285
Heavy chain
3B22HC
US20140328862 SEQ ID NO: 308
7904


HIV286
Heavy chain
3B27HC
US20140328862 SEQ ID NO: 309
7905


HIV287
Heavy chain
3B29HC
US20140328862 SEQ ID NO: 310
7906


HIV288
Heavy chain
3B2HC
US20140328862 SEQ ID NO: 311
7907


HIV289
Heavy chain
3B31HC
US20140328862 SEQ ID NO: 312
7908


HIV290
Heavy chain
3B33HC
US20140328862 SEQ ID NO: 313
7909


HIV291
Heavy chain
3B40HC
US20140328862 SEQ ID NO: 314
7910


HIV292
Heavy chain
3B41HC
US20140328862 SEQ ID NO: 315
7911


HIV293
Heavy chain
3B44HC
US20140328862 SEQ ID NO: 316
7912


HIV294
Heavy chain
3B45HC
US20140328862 SEQ ID NO: 317
7913


HIV295
Heavy chain
3b46HC
US20140328862 SEQ ID NO: 345
7914


HIV296
Heavy chain
3B48HC
US20140328862 SEQ ID NO: 318
7915


HIV297
Heavy chain
3B50HC
US20140328862 SEQ ID NO: 319
7916


HIV298
Heavy chain
3B51HC
US20140328862 SEQ ID NO: 320
7917


HIV299
Heavy chain
3B56HC
US20140328862 SEQ ID NO: 321
7918


HIV300
Heavy chain
3B57HC
US20140328862 SEQ ID NO: 322
7919


HIV301
Heavy chain
3B5HC
US20140328862 SEQ ID NO: 323
7920


HIV302
Heavy chain
3B61HC
US20140328862 SEQ ID NO: 324
7921


HIV303
Heavy chain
3B6HC
US20140328862 SEQ ID NO: 325
7922


HIV304
Heavy chain
3B77HC
US20140328862 SEQ ID NO: 326
7923


HIV305
Heavy chain
3B79HC
US20140328862 SEQ ID NO: 327
7924


HIV306
Heavy chain
3B84HC
US20140328862 SEQ ID NO: 328
7925


HIV307
Heavy chain
3B86HC
US20140328862 SEQ ID NO: 329
7926


HIV308
Heavy chain
3B8HC
US20140328862 SEQ ID NO: 330
7927


HIV309
Heavy chain
3B93HC
US20140328862 SEQ ID NO: 331
7928


HIV310
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 363
7929


HIV311
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 364
7930


HIV312
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 365
7931


HIV313
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 366
7932


HIV314
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 367
7933


HIV315
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 368
7934


HIV316
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 369
7935


HIV317
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 370
7936


HIV318
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 371
7937


HIV319
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 372
7938


HIV320
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 373
7939


HIV321
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 374
7940


HIV322
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 375
7941


HIV323
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 376
7942


HIV324
Heavy chain
3BBM60
US20140328862 SEQ ID NO: 377
7943


HIV325
Heavy chain
3BNC101HC
US20140328862 SEQ ID NO: 332
7944


HIV326
Heavy chain
3BNC101HC
US20140328862 SEQ ID NO: 378
7945


HIV327
Heavy chain
3BNC102HC
US20140328862 SEQ ID NO: 379
7946


HIV328
Heavy chain
3BNC104HC
US20140328862 SEQ ID NO: 380
7947


HIV329
Heavy chain
3BNC105HC
US20140328862 SEQ ID NO: 381
7948


HIV330
Heavy chain
3BNC106HC
US20140328862 SEQ ID NO: 382
7949


HIV331
Heavy chain
3BNC107HC
US20140328862 SEQ ID NO: 383
7950


HIV332
Heavy chain
3BNC108HC
US20140328862 SEQ ID NO: 384
7951


HIV333
Heavy chain
3BNC10HC
US20140328862 SEQ ID NO: 385
7952


HIV334
Heavy chain
3BNC114HC
US20140328862 SEQ ID NO: 386
7953


HIV335
Heavy Chain
3bnc117
Zhou T et al., Immunity 39 (2), 245-258 (2013),
7954





NCBI Accession # 4LSV_H (226aa)


HIV336
Heavy chain
3BNC117HC
US20140328862 SEQ ID NO: 387
7955


HIV337
Heavy chain
3BNC124HC
US20140328862 SEQ ID NO: 333
7956


HIV338
Heavy chain
3BNC126HC
US20140328862 SEQ ID NO: 388
7957


HIV339
Heavy chain
3BNC127HC
US20140328862 SEQ ID NO: 389
7958


HIV340
Heavy chain
3BNC130HC
US20140328862 SEQ ID NO: 334
7959


HIV341
Heavy chain
3BNC134HC
US20140328862 SEQ ID NO: 390
7960


HIV342
Heavy chain
3BNC140HC
US20140328862 SEQ ID NO: 391
7961


HIV343
Heavy chain
3BNC141HC
US20140328862 SEQ ID NO: 392
7962


HIV344
Heavy chain
3BNC142HC
US20140328862 SEQ ID NO: 393
7963


HIV345
Heavy chain
3BNC148HC
US20140328862 SEQ ID NO: 394
7964


HIV346
Heavy chain
3BNC149HC
US20140328862 SEQ ID NO: 335
7965


HIV347
Heavy chain
3BNC149HC
US20140328862 SEQ ID NO: 395
7966


HIV348
Heavy chain
3BNC151HC
US20140328862 SEQ ID NO: 396
7967


HIV349
Heavy chain
3BNC153HC
US20140328862 SEQ ID NO: 397
7968


HIV350
Heavy chain
3BNC156HC
US20140328862 SEQ ID NO: 398
7969


HIV351
Heavy chain
3BNC158HC
US20140328862 SEQ ID NO: 399
7970


HIV352
Heavy chain
3BNC159HC
US20140328862 SEQ ID NO: 400
7971


HIV353
Heavy chain
3BNC15HC
US20140328862 SEQ ID NO: 401
7972


HIV354
Heavy chain
3BNC173HC
US20140328862 SEQ ID NO: 402
7973


HIV355
Heavy chain
3BNC175HC
US20140328862 SEQ ID NO: 403
7974


HIV356
Heavy chain
3BNC176HC
US20140328862 SEQ ID NO: 404
7975


HIV357
Heavy chain
3BNC177HC
US20140328862 SEQ ID NO: 336
7976


HIV358
Heavy chain
3BNC17HC
US20140328862 SEQ ID NO: 337
7977


HIV359
Heavy chain
3BNC181HC
US20140328862 SEQ ID NO: 405
7978


HIV360
Heavy chain
3BNC186HC
US20140328862 SEQ ID NO: 406
7979


HIV361
Heavy chain
3BNC18HC
US20140328862 SEQ ID NO: 407
7980


HIV362
Heavy chain
3BNC193HC
US20140328862 SEQ ID NO: 408
7981


HIV363
Heavy chain
3BNC196HC
US20140328862 SEQ ID NO: 409
7982


HIV364
Heavy chain
3BNC20HC
US20140328862 SEQ ID NO: 410
7983


HIV365
Heavy chain
3BNC29HC
US20140328862 SEQ ID NO: 411
7984


HIV366
Heavy chain
3BNC31HC
US20140328862 SEQ ID NO: 412
7985


HIV367
Heavy chain
3BNC33HC
US20140328862 SEQ ID NO: 413
7986


HIV368
Heavy chain
3BNC42HC
US20140328862 SEQ ID NO: 414
7987


HIV369
Heavy chain
3BNC44HC
US20140328862 SEQ ID NO: 415
7988


HIV370
Heavy chain
3BNC45HC
US20140328862 SEQ ID NO: 416
7989


HIV371
Heavy chain
3BNC48HC
US20140328862 SEQ ID NO: 338
7990


HIV372
Heavy chain
3BNC53HC
US20140328862 SEQ ID NO: 417
7991


HIV373
Heavy chain
3BNC54HC
US20140328862 SEQ ID NO: 418
7992


HIV374
Heavy chain
3BNC55HC
US20140328862 SEQ ID NO: 419
7993


HIV375
Heavy chain
3BNC58HC
US20140328862 SEQ ID NO: 339
7994


HIV376
Heavy chain
3BNC59HC
US20140328862 SEQ ID NO: 420
7995


HIV377
Heavy chain
3BNC60HC
US20140328862 SEQ ID NO: 421
7996


HIV378
Heavy chain
3BNC62HC
US20140328862 SEQ ID NO: 422
7997


HIV379
Heavy chain
3BNC64HC
US20140328862 SEQ ID NO: 423
7998


HIV380
Heavy chain
3BNC65HC
US20140328862 SEQ ID NO: 424
7999


HIV381
Heavy chain
3BNC66HC
US20140328862 SEQ ID NO: 425
8000


HIV382
Heavy chain
3BNC6HC
US20140328862 SEQ ID NO: 426
8001


HIV383
Heavy chain
3BNC72HC
US20140328862 SEQ ID NO: 427
8002


HIV384
Heavy chain
3BNC75HC
US20140328862 SEQ ID NO: 428
8003


HIV385
Heavy chain
3BNC78HC
US20140328862 SEQ ID NO: 340
8004


HIV386
Heavy chain
3BNC79HC
US20140328862 SEQ ID NO: 429
8005


HIV387
Heavy chain
3BNC81HC
US20140328862 SEQ ID NO: 430
8006


HIV388
Heavy chain
3BNC82HC
US20140328862 SEQ ID NO: 341
8007


HIV389
Heavy chain
3BNC84HC
US20140328862 SEQ ID NO: 431
8008


HIV390
Heavy chain
3BNC86HC
US20140328862 SEQ ID NO: 432
8009


HIV391
Heavy chain
3BNC87HC
US20140328862 SEQ ID NO: 433
8010


HIV392
Heavy chain
3BNC89HC
US20140328862 SEQ ID NO: 434
8011


HIV393
Heavy chain
3BNC8HC
US20140328862 SEQ ID NO: 342
8012


HIV394
Heavy chain
3BNC91HC
US20140328862 SEQ ID NO: 435
8013


HIV395
Heavy chain
3BNC92HC
US20140328862 SEQ ID NO: 436
8014


HIV396
Heavy chain
3BNC94HC
US20140328862 SEQ ID NO: 437
8015


HIV397
Heavy chain
3BNC95HC
US20140328862 SEQ ID NO: 438
8016


HIV398
Heavy Chain
412d
Huang et al., Science 317 (5846), 1930-1934
8017





(2007), NCBI Accession # 2QAD_H (231aa)


HIV399
Heavy chain
43243_3
US20140205607 Table S14
8018


HIV400
Heavy chain
43359_2
US20140205607 Table S14
8019


HIV401
Heavy chain
43555_1
US20140205607 Table S14
8020


HIV402
Heavy chain
43567_2
US20140205607 Table S14
8021


HIV403
Heavy Chain
44-vrc13.01
Zhou T et al., Structural Repertoire of HIV-1-
8022





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession #





4YDJ_A(238aa)


HIV404
Heavy chain
45-46m2
Diskin, R., et al., Restricting HIV-1 pathways
8023





for escape using rationally designed anti-HIV-1





antibodies; J. Exp. Med. 210 (6), 1235-1249





(2013), NCBI Accession # 4JKP_H (229aa)


HIV405
Heavy chain
46260_1
US20140205607 Table S14
8024


HIV406
Heavy chain
47890_1
US20140205607 Table S14
8025


HIV407
Heavy Chain
4e10 Fv
Finton, K. A., et al., PLoS Pathol. 9 (9),
8026





E1003639 (2013), NCBI Accession # 4LLV_A





(129aa)


HIV408
Heavy chain
53821_1
US20140205607 Table S14
8027


HIV409
Heavy chain
57729_2
US20140205607 Table S14
8028


HIV410
Heavy chain
61048_1
US20140205607 Table S14
8029


HIV411
Heavy chain
69713_1
US20140205607 Table S14
8030


HIV412
Heavy chain
70679_1
US20140205607 Table S14
8031


HIV413
Heavy chain
71632_2
US20140205607 Table S14
8032


HIV414
Heavy chain
74400_3
US20140205607 Table S14
8033


HIV415
Heavy chain
74511_1
US20140205607 Table S14
8034


HIV416
Heavy chain
76927_2
US20140205607 Table S14
8035


HIV417
Heavy Chain
7b2
Santra, S., et al., PLoS Pathol. 11 (8),
8036





E1005042 (2015), NCBI Accession # 4YDV_H





(252aa)


HIV418
Heavy chain
7H6
US20140348785 SEQ ID NO: 3
8037


HIV419
Heavy chain
7N16
US20140348785 SEQ ID NO: 5
8038


HIV420
Heavy chain
8460_4
US20140205607 Table S14
8039


HIV421
Heavy chain
86277_2
US20140205607 Table S14
8040


HIV422
Heavy chain
86343_1
US20140205607 Table S14
8041


HIV423
Heavy chain
86984_2
US20140205607 Table S14
8042


HIV424
Heavy chain
89680_4
US20140205607 Table S14
8043


HIV425
Heavy chain
8A253HC
US20140328862 SEQ ID NO: 5
8044


HIV426
Heavy chain
8A275HC
US20140328862 SEQ ID NO: 6
8045


HIV427
Heavy chain
8ABM11
US20140328862 SEQ ID NO: 7
8046


HIV428
Heavy chain
8ABM12
US20140328862 SEQ ID NO: 8
8047


HIV429
Heavy chain
8ABM13
US20140328862 SEQ ID NO: 9
8048


HIV430
Heavy chain
8ABM14
US20140328862 SEQ ID NO: 10
8049


HIV431
Heavy chain
8ABM20
US20140328862 SEQ ID NO: 11
8050


HIV432
Heavy chain
8ABM24
US20140328862 SEQ ID NO: 12
8051


HIV433
Heavy chain
8ABM26
US20140328862 SEQ ID NO: 13
8052


HIV434
Heavy chain
8ABM27
US20140328862 SEQ ID NO: 14
8053


HIV435
Heavy chain
8ANC103HC
US20140328862 SEQ ID NO: 36
8054


HIV436
Heavy chain
8ANC105HC
US20140328862 SEQ ID NO: 15
8055


HIV437
Heavy chain
8ANC106HC
US20140328862 SEQ ID NO: 37
8056


HIV438
Heavy chain
8ANC107HC
US20140328862 SEQ ID NO: 38
8057


HIV439
Heavy chain
8ANC108HC
US20140328862 SEQ ID NO: 39
8058


HIV440
Heavy chain
8ANC109HC
US20140328862 SEQ ID NO: 40
8059


HIV441
Heavy chain
8ANC10HC
US20140328862 SEQ ID NO: 41
8060


HIV442
Heavy chain
8ANC111HC
US20140328862 SEQ ID NO: 42
8061


HIV443
Heavy chain
8ANC112HC
US20140328862 SEQ ID NO: 43
8062


HIV444
Heavy chain
8ANC113HC
US20140328862 SEQ ID NO: 44
8063


HIV445
Heavy chain
8ANC114HC
US20140328862 SEQ ID NO: 45
8064


HIV446
Heavy chain
8ANC115HC
US20140328862 SEQ ID NO: 46
8065


HIV447
Heavy chain
8ANC116HC
US20140328862 SEQ ID NO: 16
8066


HIV448
Heavy chain
8ANC117HC
US20140328862 SEQ ID NO: 47
8067


HIV449
Heavy chain
8ANC11HC
US20140328862 SEQ ID NO: 48
8068


HIV450
Heavy chain
8ANC121HC
US20140328862 SEQ ID NO: 49
8069


HIV451
Heavy chain
8ANC126HC
US20140328862 SEQ ID NO: 50
8070


HIV452
Heavy chain
8ANC127HC
US20140328862 SEQ ID NO: 17
8071


HIV453
Heavy chain
8ANC130HC
US20140328862 SEQ ID NO: 51
8072


HIV454
Heavy Chain
8anc131
Zhou T et al., Structural Repertoire of HIV-1-
8073





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4RWY_H





(227aa)


HIV455
Heavy chain
8ANC131HC
US20140328862 SEQ ID NO: 18
8074


HIV456
Heavy chain
8ANC132HC
US20140328862 SEQ ID NO: 52
8075


HIV457
Heavy chain
8ANC133HC
US20140328862 SEQ ID NO: 53
8076


HIV458
Heavy Chain
8anc134
Zhou T et al., Structural Repertoire of HIV-1-
8077





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4RX4_H





(229aa)


HIV459
Heavy chain
8ANC134HC
US20140328862 SEQ ID NO: 19
8078


HIV460
Heavy chain
8ANC136HC
US20140328862 SEQ ID NO: 54
8079


HIV461
Heavy chain
8ANC137HC
US20140328862 SEQ ID NO: 55
8080


HIV462
Heavy chain
8ANC139HC
US20140328862 SEQ ID NO: 56
8081


HIV463
Heavy chain
8ANC13HC
US20140328862 SEQ ID NO: 20
8082


HIV464
Heavy chain
8ANC140HC
US20140328862 SEQ ID NO: 57
8083


HIV465
Heavy chain
8ANC142HC
US20140328862 SEQ ID NO: 58
8084


HIV466
Heavy chain
8ANC143HC
US20140328862 SEQ ID NO: 59
8085


HIV467
Heavy chain
8ANC144HC
US20140328862 SEQ ID NO: 60
8086


HIV468
Heavy chain
8ANC145HC
US20140328862 SEQ ID NO: 61
8087


HIV469
Heavy chain
8ANC146HC
US20140328862 SEQ ID NO: 62
8088


HIV470
Heavy chain
8ANC147HC
US20140328862 SEQ ID NO: 63
8089


HIV471
Heavy chain
8ANC148HC
US20140328862 SEQ ID NO: 64
8090


HIV472
Heavy chain
8ANC149HC
US20140328862 SEQ ID NO: 65
8091


HIV473
Heavy chain
8ANC14HC
US20140328862 SEQ ID NO: 66
8092


HIV474
Heavy chain
8ANC150HC
US20140328862 SEQ ID NO: 67
8093


HIV475
Heavy chain
8ANC151HC
US20140328862 SEQ ID NO: 68
8094


HIV476
Heavy chain
8ANC153HC
US20140328862 SEQ ID NO: 69
8095


HIV477
Heavy chain
8ANC154HC
US20140328862 SEQ ID NO: 70
8096


HIV478
Heavy chain
8ANC155HC
US20140328862 SEQ ID NO: 71
8097


HIV479
Heavy chain
8ANC156HC
US20140328862 SEQ ID NO: 72
8098


HIV480
Heavy chain
8ANC157HC
US20140328862 SEQ ID NO: 73
8099


HIV481
Heavy chain
8ANC158HC
US20140328862 SEQ ID NO: 74
8100


HIV482
Heavy chain
8ANC160HC
US20140328862 SEQ ID NO: 75
8101


HIV483
Heavy chain
8ANC161HC
US20140328862 SEQ ID NO: 76
8102


HIV484
Heavy chain
8ANC162HC
US20140328862 SEQ ID NO: 77
8103


HIV485
Heavy chain
8ANC163HC
US20140328862 SEQ ID NO: 78
8104


HIV486
Heavy chain
8ANC164HC
US20140328862 SEQ ID NO: 79
8105


HIV487
Heavy chain
8ANC165HC
US20140328862 SEQ ID NO: 80
8106


HIV488
Heavy chain
8ANC166HC
US20140328862 SEQ ID NO: 81
8107


HIV489
Heavy chain
8ANC168HC
US20140328862 SEQ ID NO: 82
8108


HIV490
Heavy chain
8ANC169HC
US20140328862 SEQ ID NO: 83
8109


HIV491
Heavy chain
8ANC16HC
US20140328862 SEQ ID NO: 84
8110


HIV492
Heavy chain
8ANC171HC
US20140328862 SEQ ID NO: 21
8111


HIV493
Heavy chain
8ANC173HC
US20140328862 SEQ ID NO: 85
8112


HIV494
Heavy chain
8ANC174HC
US20140328862 SEQ ID NO: 86
8113


HIV495
Heavy chain
8ANC175HC
US20140328862 SEQ ID NO: 87
8114


HIV496
Heavy chain
8ANC176HC
US20140328862 SEQ ID NO: 88
8115


HIV497
Heavy chain
8ANC177HC
US20140328862 SEQ ID NO: 89
8116


HIV498
Heavy chain
8ANC178HC
US20140328862 SEQ ID NO: 90
8117


HIV499
Heavy chain
8ANC179HC
US20140328862 SEQ ID NO: 91
8118


HIV500
Heavy chain
8ANC17HC
US20140328862 SEQ ID NO: 92
8119


HIV501
Heavy chain
8ANC18
US20140328862 SEQ ID NO: 22
8120


HIV502
Heavy chain
8ANC180HC
US20140328862 SEQ ID NO: 93
8121


HIV503
Heavy chain
8ANC181HC
US20140328862 SEQ ID NO: 94
8122


HIV504
Heavy chain
8ANC182HC
US20140328862 SEQ ID NO: 23
8123


HIV505
Heavy chain
8ANC184HC
US20140328862 SEQ ID NO: 95
8124


HIV506
Heavy chain
8ANC185HC
US20140328862 SEQ ID NO: 96
8125


HIV507
Heavy chain
8ANC186HC
US20140328862 SEQ ID NO: 97
8126


HIV508
Heavy chain
8ANC187HC
US20140328862 SEQ ID NO: 98
8127


HIV509
Heavy chain
8ANC188HC
US20140328862 SEQ ID NO: 99
8128


HIV510
Heavy chain
8ANC191HC
US20140328862 SEQ ID NO: 100
8129


HIV511
Heavy chain
8ANC192HC
US20140328862 SEQ ID NO: 24
8130


HIV512
Heavy chain
8ANC193HC
US20140328862 SEQ ID NO: 101
8131


HIV513
Heavy chain
8ANC194HC
US20140328862 SEQ ID NO: 102
8132


HIV514
Heavy chain
8ANC195HC
US20140328862 SEQ ID NO: 103
8133


HIV515
Heavy chain
8ANC196HC
US20140328862 SEQ ID NO: 104
8134


HIV516
Heavy chain
8ANC20HC
US20140328862 SEQ ID NO: 105
8135


HIV517
Heavy chain
8ANC21HC
US20140328862 SEQ ID NO: 106
8136


HIV518
Heavy chain
8ANC22HC
US20140328862 SEQ ID NO: 25
8137


HIV519
Heavy chain
8ANC24HC
US20140328862 SEQ ID NO: 107
8138


HIV520
Heavy chain
8ANC25HC
US20140328862 SEQ ID NO: 108
8139


HIV521
Heavy chain
8ANC26HC
US20140328862 SEQ ID NO: 26
8140


HIV522
Heavy chain
8ANC27HC
US20140328862 SEQ ID NO: 109
8141


HIV523
Heavy chain
8ANC2HC
US20140328862 SEQ ID NO: 27
8142


HIV524
Heavy chain
8ANC30HC
US20140328862 SEQ ID NO: 28
8143


HIV525
Heavy chain
8ANC31HC
US20140328862 SEQ ID NO: 110
8144


HIV526
Heavy chain
8ANC33HC
US20140328862 SEQ ID NO: 111
8145


HIV527
Heavy chain
8ANC34HC
US20140328862 SEQ ID NO: 112
8146


HIV528
Heavy chain
8ANC36HC
US20140328862 SEQ ID NO: 113
8147


HIV529
Heavy chain
8ANC37HC
US20140328862 SEQ ID NO: 29
8148


HIV530
Heavy chain
8ANC38HC
US20140328862 SEQ ID NO: 114
8149


HIV531
Heavy chain
8ANC39HC
US20140328862 SEQ ID NO: 115
8150


HIV532
Heavy chain
8ANC3HC
US20140328862 SEQ ID NO: 116
8151


HIV533
Heavy chain
8ANC40HC
US20140328862 SEQ ID NO: 30
8152


HIV534
Heavy chain
8ANC41HC
US20140328862 SEQ ID NO: 31
8153


HIV535
Heavy chain
8ANC43HC
US20140328862 SEQ ID NO: 117
8154


HIV536
Heavy chain
8ANC45HC
US20140328862 SEQ ID NO: 32
8155


HIV537
Heavy chain
8ANC46HC
US20140328862 SEQ ID NO: 118
8156


HIV538
Heavy chain
8ANC48HC
US20140328862 SEQ ID NO: 119
8157


HIV539
Heavy chain
8ANC49HC
US20140328862 SEQ ID NO: 120
8158


HIV540
Heavy chain
8ANC50HC
US20140328862 SEQ ID NO: 33
8159


HIV541
Heavy chain
8ANC51HC
US20140328862 SEQ ID NO: 121
8160


HIV542
Heavy chain
8ANC53HC
US20140328862 SEQ ID NO: 34
8161


HIV543
Heavy chain
8ANC57HC
US20140328862 SEQ ID NO: 122
8162


HIV544
Heavy chain
8ANC58HC
US20140328862 SEQ ID NO: 123
8163


HIV545
Heavy chain
8ANC5HC
US20140328862 SEQ ID NO: 124
8164


HIV546
Heavy chain
8ANC60HC
US20140328862 SEQ ID NO: 125
8165


HIV547
Heavy chain
8ANC63HC
US20140328862 SEQ ID NO: 126
8166


HIV548
Heavy chain
8ANC65HC
US20140328862 SEQ ID NO: 127
8167


HIV549
Heavy chain
8ANC67HC
US20140328862 SEQ ID NO: 128
8168


HIV550
Heavy chain
8ANC69HC
US20140328862 SEQ ID NO: 129
8169


HIV551
Heavy chain
8ANC6HC
US20140328862 SEQ ID NO: 130
8170


HIV552
Heavy chain
8ANC70HC
US20140328862 SEQ ID NO: 131
8171


HIV553
Heavy chain
8ANC71HC
US20140328862 SEQ ID NO: 132
8172


HIV554
Heavy chain
8ANC72HC
US20140328862 SEQ ID NO: 133
8173


HIV555
Heavy chain
8ANC74HC
US20140328862 SEQ ID NO: 134
8174


HIV556
Heavy chain
8ANC75HC
US20140328862 SEQ ID NO: 135
8175


HIV557
Heavy chain
8ANC76HC
US20140328862 SEQ ID NO: 136
8176


HIV558
Heavy chain
8ANC78HC
US20140328862 SEQ ID NO: 137
8177


HIV559
Heavy chain
8ANC79HC
US20140328862 SEQ ID NO: 138
8178


HIV560
Heavy chain
8ANC7HC
US20140328862 SEQ ID NO: 139
8179


HIV561
Heavy chain
8ANC80HC
US20140328862 SEQ ID NO: 140
8180


HIV562
Heavy chain
8ANC82HC
US20140328862 SEQ ID NO: 141
8181


HIV563
Heavy chain
8ANC83HC
US20140328862 SEQ ID NO: 142
8182


HIV564
Heavy chain
8ANC88HC
US20140328862 SEQ ID NO: 35
8183


HIV565
Heavy chain
8ANC91HC
US20140328862 SEQ ID NO: 143
8184


HIV566
Heavy chain
8ANC92HC
US20140328862 SEQ ID NO: 144
8185


HIV567
Heavy chain
8ANC93HC
US20140328862 SEQ ID NO: 145
8186


HIV568
Heavy chain
8ANC9HC
US20140328862 SEQ ID NO: 146
8187


HIV569
Heavy chain
94565_1
US20140205607 Table S14
8188


HIV570
Heavy chain
95589_2
US20140205607 Table S14
8189


HIV571
Heavy chain
96298_1
US20140205607 Table S14
8190


HIV572
Heavy chain
9815_2
US20140205607 Table S14
8191


HIV573
Heavy chain
99473_3
US20140205607 Table S14
8192


HIV574
Heavy chain
99989_1
US20140205607 Table S14
8193


HIV575
Heavy chain
Antibody
US20140328862 SEQ ID NO: 439
8194


HIV576
Heavy chain
Anti-HcG
Fotinou C. et al “Structure of an Fab fragment
8195





against a C-terminal peptide of hCG at 2.0 A





resolution” J. Biol. Chem. 273 (35), 22515-





22518 (1998); NCBI Accession # 1SBS_H


HIV577
Heavy Chain
B12
Zhou T et al., Structural definition of a
8196





conserved neutralization epitope on HIV-1





gp120; Nature 445 (7129), 732-737 (2007),





NCBI Accession # 2NY7_H (230aa)


HIV578
Heavy Chain
C38-vrc16.01
Zhou T et al., Structural Repertoire of HIV-1-
8197





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YDK_H





(234aa)


HIV579
Heavy Chain
C38-vrc18.02
Zhou T et al., Structural Repertoire of HIV-1-
8198





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YDL_H





(226aa)


HIV580
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 13
8199




VRC26.01


HIV581
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 17
8200




VRC26.02


HIV582
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 21
8201




VRC26.03


HIV583
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 25
8202




VRC26.04


HIV584
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 29
8203




VRC26.05


HIV585
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 33
8204




VRC26.06


HIV586
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 37
8205




VRC26.07


HIV587
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 41
8206




VRC26.08


HIV588
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 45
8207




VRC26.09


HIV589
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 49
8208




VRC26.10


HIV590
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 53
8209




VRC26.11


HIV591
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 57
8210




VRC26.12


HIV592
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 170
8211




VRC26.25


HIV593
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 178
8212




VRC26.26


HIV594
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 186
8213




VRC26.27


HIV595
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 5
8214




VRC26-I1


HIV596
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 9
8215




VRC26-I2.


HIV597
Heavy chain
CAP256-
WO2015128846 SEQ ID NO: 1
8216




VRC26-




UCA.


HIV598
Heavy chain
construct
WO2015013390 SEQ ID NO: 3
8217




#2816, #2859


HIV599
Heavy chain
construct
WO2015013390 SEQ ID NO: 4
8218




#2817


HIV600
Heavy chain
construct
WO2015013390 SEQ ID NO: 8
8219




#2858, #2860


HIV601
Heavy Chain
Fab 2219
Stanfield, R. L., et al., J. Virol. 80 (12), 6093-
8220





6105 (2006), NCBI Accession # 2B0S_H





(226aa)


HIV602
Heavy Chain
Fab 2g12
Doores. K. J., et al., J. Virol. 84 (20), 10690-
8221





10699 (2010), NCBI Accession # 3OAU_H





(225aa)


HIV603
Heavy Chain
Fab 2g12
Stanfield, R. L. et al., Crystal structure of the
8222





HIV neutralizing antibody 2G12 in complex





with a bacterial oligosaccharide analog of





mammalian oligomannose; Glycobiology 25





(4), 412-419 (2015), NCBI Accession #





4RBP_H (224aa)


HIV604
Heavy Chain
Fab F425-
Bell et al., J. Mol. Biol. 375 (4), 969-978
8223




b4e8
(2008), NCBI Accession # 2QSC_H (222aa)


HIV605
Heavy chain
fusion protein
US20080038280 SEQ ID NO: 5
8224




of A32 and




m9


HIV606
Heavy chain
g20
WO2015117008 SEQ ID NO: 4
8225


HIV607
Heavy chain
g22
WO2015117008 SEQ ID NO: 7
8226


HIV608
Heavy chain
g23
WO2015117008 SEQ ID NO: 2
8227


HIV609
Heavy chain
g3
WO2015117008 SEQ ID NO: 13
8228


HIV610
Heavy chain
g4
WO2015117008 SEQ ID NO: 9
8229


HIV611
Heavy chain
g44
WO2015117008 SEQ ID NO: 11
8230


HIV612
Heavy chain
g46
WO2015117008 SEQ ID NO: 10
8231


HIV613
Heavy chain
G4D
US20130195881 SEQ ID NO: 9
8232


HIV614
Heavy chain
G4H
US20130195881 SEQ ID NO: 8
8233


HIV615
Heavy chain
g50
WO2015117008 SEQ ID NO: 12
8234


HIV616
Heavy chain
g52
WO2015117008 SEQ ID NO: 1
8235


HIV617
Heavy chain
g59
WO2015117008 SEQ ID NO: 5
8236


HIV618
Heavy chain
g62
WO2015117008 SEQ ID NO: 6
8237


HIV619
Heavy chain
g8
WO2015117008 SEQ ID NO: 3
8238


HIV620
Heavy chain
gl5
WO2015117008 SEQ ID NO: 8
8239


HIV621
Heavy chain
gVRC-
WO2013090644 SEQ ID NO: 45
8240




H5(d74)/VR




C-PG04LC


HIV622
Heavy chain
gVRCOH12(D74)/
WO2013090644 SEQ ID NO: 46
8241




VRC-




PG04LC


HIV623
Heavy Chain
I2 (unbound)
Fera, D. et al., Affinity maturation in an HIV
8242




From Ch103
broadly neutralizing B-cell lineage through




Lineage
reorientation of variable domains; Proc. Natl.





Acad. Sci. U.S.A. 111 (28), 10275-10280





(2014), NCBI Accession # 4QHN_A (232aa)


HIV624
Heavy chain
IGHV3-
US20140348785 SEQ ID NO: 7
8243




15*05


HIV625
Heavy chain
LSSB2055HC
US20140328862 SEQ ID NO: 229
8244


HIV626
Heavy chain
LSSB2066HC
US20140328862 SEQ ID NO: 230
8245


HIV627
Heavy chain
LSSB2068HC
US20140328862 SEQ ID NO: 231
8246


HIV628
Heavy chain
LSSB2080HC
US20140328862 SEQ ID NO: 232
8247


HIV629
Heavy chain
LSSB2133HC
US20140328862 SEQ ID NO: 233
8248


HIV630
Heavy chain
LSSB2182HC
US20140328862 SEQ ID NO: 234
8249


HIV631
Heavy chain
LSSB218HC
US20140328862 SEQ ID NO: 235
8250


HIV632
Heavy chain
LSSB2277HC
US20140328862 SEQ ID NO: 236
8251


HIV633
Heavy chain
LSSB2288HC
US20140328862 SEQ ID NO: 237
8252


HIV634
Heavy chain
LSSB2339HC
US20140328862 SEQ ID NO: 168
8253


HIV635
Heavy chain
LSSB2351HC
US20140328862 SEQ ID NO: 169
8254


HIV636
Heavy chain
LSSB2361HC
US20140328862 SEQ ID NO: 170
8255


HIV637
Heavy chain
LSSB2364HC
US20140328862 SEQ ID NO: 171
8256


HIV638
Heavy chain
LSSB2367HC
US20140328862 SEQ ID NO: 172
8257


HIV639
Heavy chain
LSSB2416HC
US20140328862 SEQ ID NO: 173
8258


HIV640
Heavy chain
LSSB2434HC
US20140328862 SEQ ID NO: 174
8259


HIV641
Heavy chain
LSSB2483HC
US20140328862 SEQ ID NO: 175
8260


HIV642
Heavy chain
LSSB2490HC
US20140328862 SEQ ID NO: 176
8261


HIV643
Heavy chain
LSSB2503HC
US20140328862 SEQ ID NO: 177
8262


HIV644
Heavy chain
LSSB2525HC
US20140328862 SEQ ID NO: 178
8263


HIV645
Heavy chain
LSSB2530HC
US20140328862 SEQ ID NO: 179
8264


HIV646
Heavy chain
LSSB2538HC
US20140328862 SEQ ID NO: 180
8265


HIV647
Heavy chain
LSSB2554HC
US20140328862 SEQ ID NO: 181
8266


HIV648
Heavy chain
LSSB2573HC
US20140328862 SEQ ID NO: 182
8267


HIV649
Heavy chain
LSSB2578HC
US20140328862 SEQ ID NO: 183
8268


HIV650
Heavy chain
LSSB2586HC
US20140328862 SEQ ID NO: 184
8269


HIV651
Heavy chain
LSSB2609HC
US20140328862 SEQ ID NO: 185
8270


HIV652
Heavy chain
LSSB2612HC
US20140328862 SEQ ID NO: 186
8271


HIV653
Heavy chain
LSSB2630HC
US20140328862 SEQ ID NO: 187
8272


HIV654
Heavy chain
LSSB2640HC
US20S40328862 SEQ ID NO: 188
8273


HIV655
Heavy chain
LSSB2644HC
US20140328862 SEQ ID NO: 189
8274


HIV656
Heavy chain
LSSB2665HC
US20S40328862 SEQ ID NO: 190
8275


HIV657
Heavy chain
LSSB2666HC
US20140328862 SEQ ID NO: 191
8276


HIV658
Heavy chain
LSSB2669HC
US20S40328862 SEQ ID NO: 192
8277


HIV659
Heavy chain
LSSB2680HC
US20140328862 SEQ ID NO: 193
8278


HIV660
Heavy chain
LSSB2683HC
US20S40328862 SEQ ID NO: 194
8279


HIV661
Heavy chain
LSSB331HC
US20140328862 SEQ ID NO: 238
8280


HIV662
Heavy chain
LSSB344HC
US20140328862 SEQ ID NO: 195
8281


HIV663
Heavy chain
LSSNEC101HC
US20140328862 SEQ ID NO: 239
8282


HIV664
Heavy chain
LSSNEC106HC
US20140328862 SEQ ID NO: 240
8283


HIV665
Heavy chain
LSSNEC107HC
US20140328862 SEQ ID NO: 196
8284


HIV666
Heavy chain
LSSNEC108HC
US20140328862 SEQ ID NO: 197
8285


HIV667
Heavy chain
LSSNEC109HC
US20140328862 SEQ ID NO: 198
8286


HIV668
Heavy chain
LSSNEC110HC
US20140328862 SEQ ID NO: 199
8287


HIV669
Heavy chain
LSSNEC112HC
US20140328862 SEQ ID NO: 241
8288


HIV670
Heavy chain
LSSNEC115HC
US20140328862 SEQ ID NO: 242
8289


HIV671
Heavy chain
LSSNEC116HC
US20140328862 SEQ ID NO: 200
8290


HIV672
Heavy chain
LSSNEC117HC
US20140328862 SEQ ID NO: 201
8291


HIV673
Heavy chain
LSSNEC118HC
US20140328862 SEQ ID NO: 202
8292


HIV674
Heavy chain
LSSNEC11HC
US20140328862 SEQ ID NO: 203
8293


HIV675
Heavy chain
LSSNEC122HC
US20140328862 SEQ ID NO: 204
8294


HIV676
Heavy chain
LSSNEC123HC
US20140328862 SEQ ID NO: 205
8295


HIV677
Heavy chain
LSSNEC124HC
US20140328862 SEQ ID NO: 243
8296


HIV678
Heavy chain
LSSNEC125HC
US20140328862 SEQ ID NO: 244
8297


HIV679
Heavy chain
LSSNEC126HC
US20140328862 SEQ ID NO: 245
8298


HIV680
Heavy chain
LSSNEC127HC
US20140328862 SEQ ID NO: 206
8299


HIV681
Heavy chain
LSSNEC14HC
US20140328862 SEQ ID NO: 246
8300


HIV682
Heavy chain
LSSNEC16HC
US20140328862 SEQ ID NO: 247
8301


HIV683
Heavy chain
LSSNEC18HC
US20140328862 SEQ ID NO: 207
8302


HIV684
Heavy chain
LSSNEC21HC
US20140328862 SEQ ID NO: 248
8303


HIV685
Heavy chain
LSSNEC24HC
US20140328862 SEQ ID NO: 208
8304


HIV686
Heavy chain
LSSNEC29HC
US20140328862 SEQ ID NO: 209
8305


HIV687
Heavy chain
LSSNEC2HC
US20140328862 SEQ ID NO: 210
8306


HIV688
Heavy chain
LSSNEC30HC
US20140328862 SEQ ID NO: 249
8307


HIV689
Heavy chain
LSSNEC33HC
US20140328862 SEQ ID NO: 211
8308


HIV690
Heavy chain
LSSNEC34HC
US20140328862 SEQ ID NO: 212
8309


HIV691
Heavy chain
LSSNEC3HC
US20140328862 SEQ ID NO: 213
8310


HIV692
Heavy chain
LSSNEC46HC
US20140328862 SEQ ID NO: 214
8311


HIV693
Heavy chain
LSSNEC48HC
US20140328862 SEQ ID NO: 215
8312


HIV694
Heavy chain
LSSNEC49HC
US20140328862 SEQ ID NO: 250
8313


HIV695
Heavy chain
LSSNEC52HC
US20140328862 SEQ ID NO: 216
8314


HIV696
Heavy chain
LSSNEC54HC
US20140328862 SEQ ID NO: 251
8315


HIV697
Heavy chain
LSSNEC55HC
US20140328862 SEQ ID NO: 252
8316


HIV698
Heavy chain
LSSNEC56HC
US20140328862 SEQ ID NO: 217
8317


HIV699
Heavy chain
LSSNEC57HC
US20140328862 SEQ ID NO: 253
8318


HIV700
Heavy chain
LSSNEC5HC
US20140328862 SEQ ID NO: 254
8319


HIV701
Heavy chain
LSSNEC60HC
US20140328862 SEQ ID NO: 218
8320


HIV702
Heavy chain
LSSNEC66HC
US20140328862 SEQ ID NO: 219
8321


HIV703
Heavy chain
LSSNEC67HC
US20140328862 SEQ ID NO: 255
8322


HIV704
Heavy chain
LSSNEC70HC
US20140328862 SEQ ID NO: 220
8323


HIV705
Heavy chain
LSSNEC72HC
US20140328862 SEQ ID NO: 221
8324


HIV706
Heavy chain
LSSNEC74HC
US20140328862 SEQ ID NO: 256
8325


HIV707
Heavy chain
LSSNEC77HC
US20140328862 SEQ ID NO: 257
8326


HIV708
Heavy chain
LSSNEC7HC
US20140328862 SEQ ID NO: 222
8327


HIV709
Heavy chain
LSSNEC82HC
US20140328862 SEQ ID NO: 223
8328


HIV710
Heavy chain
LSSNEC85HC
US20140328862 SEQ ID NO: 258
8329


HIV711
Heavy chain
LSSNEC89HC
US20140328862 SEQ ID NO: 224
8330


HIV712
Heavy chain
LSSNEC8HC
US20140328862 SEQ ID NO: 225
8331


HIV713
Heavy chain
LSSNEC91HC
US20140328862 SEQ ID NO: 259
8332


HIV714
Heavy chain
LSSNEC92HC
US20140328862 SEQ ID NO: 260
8333


HIV715
Heavy chain
LSSNEC94HC
US20140328862 SEQ ID NO: 226
8334


HIV716
Heavy chain
LSSNEC95HC
US20140328862 SEQ ID NO: 227
8335


HIV717
Heavy chain
LSSNEC9HC
US20140328862 SEQ ID NO: 228
8336


HIV718
Heavy chain
m12_Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 3
8337


HIV719
Heavy chain
m14-Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 1
8338


HIV720
Heavy chain
m16-Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 4
8339


HIV721
Heavy chain
m18 Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 2
8340


HIV722
Heavy Chain
M66
Ofek, G., et al., Structural Basis for HIV-1
8341





Neutralization by 2F5-Like Antibodies m66





and m66.6; J. Virol. 88 (5), 2426-2441 (2014),





NCBI Accession # 4NRY_L (220aa)


HIV723
Heavy Chain
M66.6
Ofek, G., et al., Structural Basis for HIV-1
8342





Neutralization by 2F5-Like Antibodies m66





and m66.6; J. Virol. 88 (5), 2426-2441 (2014),





NCBI Accession # 4NRZ_H (234aa)


HIV724
Heavy Chain
Mab 2158
Spurrier, B., et al., Functional Implications of
8343





the Binding Mode of a Human Conformation-





Dependent V2 Monoclonal Antibody against





HIV; J. Virol, 88 (8), 4100-4112 (2014), NCBI





Accession # 4OAW_D (236aa)


HIV725
Heavy chain
MV1
US20130195881 SEQ ID NO: 10
8344


HIV726
Heavy Chain
Pg16 Fab
Pancera, M., et al., Nat. Struct. Mol. Biol. 20
8345





(7), 804-813 (2013), NCBI Accession #





4DQO_H (246aa)


HIV727
Heavy Chain
Pg9
Willis, J. R., et al., J. Clin. Invest. 125 (6), 2523-
8346





2531 (2015), NCBI Accession #





4YAQ_H(248aa)


HIV728
Heavy Chain
Pgt121-Gl
Mouquet H et al., Complex-type N-glycan
8347




Fab
recognition by potent broadly neutralizing HIV





antibodies; Proc Natl Acad Sci USA. 2012





Nov. 20; 109(47): E3268-77, NCBI Accession #





4FQQ_B (244aa)


HIV729
Heavy Chain
Pgt122
Julien, J. P., et al., PLoS Pathol. 9 (5),
8348





E1003342 (2013), NCBI Accession # 4JY5_H





(235aa)


HIV730
Heavy Chain
Pgt123
Julien, J. P., et al., PLoS Pathol. 9 (5),
8349





E1003342 (2013), NCBI Accession # 4JY6_B





(235aa)


HIV731
Heavy Chain
Pgt124
Garces, F., et al., Structural Evolution of
8350





Glycan Recognition by a Family of Potent HIV





Antibodies; Cell 159 (1), 69-79 (2014), NCBI





Accession # 4R26_H (236aa)


HIV732
Heavy Chain
Pgt130
Doores, K. J., et al., J. Virol. 89 (2), 1105-1118
8351





(2015), NCBI Accession # 4RNR_A (233aa)


HIV733
Heavy Chain
Pgt135
Grover et al., Science 343 (6171), 656-661
8352





(2014), NCBI Accession # 4NZR_H (234aa)


HIV734
Heavy chain
S19
US20110059015 SEQ ID NO: 6
8353


HIV735
Heavy chain
S20
US20110059015 SEQ ID NO: 8
8354


HIV736
Heavy chain
S8
US20110059015 SEQ ID NO: 4
8355


HIV737
Heavy Chain
Vrc- Pg04
Wu, X., et al., Focused evolution of HIV-1
8356





neutralizing antibodies revealed by structures





and deep sequencing; Science 333 (6049),





1593-1602 (2011)”, NCBI Accession #





3SE9_H (228aa)


HIV738
Heavy chain
VRC01
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 1
8357


HIV739
Heavy chain
VRC01HC/VRCO3LC
WO2013090644 SEQ ID NO: 2
8358


HIV740
Heavy chain
VRC02
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 3
8359


HIV741
Heavy chain
VRC03
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 27
8360


HIV742
Heavy chain
VRC03HC-
WO2013090644 SEQ ID NO: 32
8361




VRC01LC


HIV743
Heavy chain
VRC07
US20140322163 SEQ ID NO: 258
8362




G54H, S58N


HIV744
Heavy chain
VRC07 I37V,
US20140322163 SEQ ID NO: 260
8363




G54H, S58N,




T93A


HIV745
Heavy chain
VRC07 I37V,
US20140322163 SEQ ID NO: 259
8364




G54H, T93A


HIV746
Heavy Chain
Vrc08c
Wu, X., et al., Maturation and Diversity of the
8365





VRC01-Antibody Lineage over 15 Years of





Chronic HIV-1 Infection; Cell 161 (3), 470-485





(2015), NCBI Accession # 4XNY_H (235aa)


HIV747
Heavy Chain
Vrc23
Georgiev, I. S., et al., Delineating antibody
8366





recognition in polyclonal sera from patterns of





HIV-1 isolate neutralization; Science 340





(6133), 751-756 (2013), NCBI Accession #





4J6R_H (224aa)


HIV748
Heavy chain
VRC-CH30
WO2013090644 SEQ ID NO: 22
8367


HIV749
Heavy Chain
Vrc-ch31
Zhou T et al., Immunity 39 (2), 245-258 (2013),
8368





NCBI Accession # 4LSP_H (236aa)


HIV750
Heavy chain
VRC-CH32
Wu X. et al, “Focused evolution of HIV-1
8369





neutralizing antibodies revealed by structures





and deep sequencing” Science 333 (6049),





1593-1602 (2011), NCBI Accession #





AEM62724


HIV751
Heavy chain
VRC-CH33
WO2013090644 SEQ ID NO: 28
8370


HIV752
Heavy chain
VRC-CH34
WO2013090644 SEQ ID NO: 30
8371


HIV753
Heavy chain
VRCO7
US20140322163 SEQ ID NO: 33
8372




G54H


HIV754
Heavy chain
VRC-PG04
Wu X. et al, “Focused evolution of HIV-1
8373





neutralizing antibodies revealed by structures





and deep sequencing” Science 333 (6049),





1593-1602 (2011), NCBI Accession #





AEM62752


HIV755
Heavy chain
VRC-PG04b
WO2013090644 SEQ ID NO: 44
8374


HIV756
Heavy Chain
Vrc-pg20
Zhou T et al., Immunity 39 (2), 245-258 (2013),
8375





NCBI Accession # 4LSU_H (227aa)


HIV757
Heavy chain
X5
U.S. Pat. No. 7,378,093B2 SEQ ID NO: 3
8376


HIV758
Heavy chain
X5
U.S. Pat. No. 8,110,192B2 SEQ ID NO: 5
8377


HIV759
Heavy chain
X5 variant
U.S. Pat. No. 7,378,093B2 SEQ ID NO: 11
8378


HIV760
Heavy Chain
Z13e1
Stanfield, R. L., et al, J. Mol. Biol. 414 (3). 460-
8379





476 (2011), NCBI Accession # 3Q1S_H(230aa)


HIV761
Heavy Chain
Z258-
Zhou. T et al., Structural Repertoire of HIV-1-
8380




vrc27.01
Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession #





4YDI_H(227aa)


HIV762
Heavy Chain

NCBI Accession # 1N0X_K (230aa)
8381


HIV763
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 142
8382


HIV764
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 143
8383


HIV765
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 144
8384


HIV766
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 145
8385


HIV767
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 146
8386


HIV768
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 66
8387


HIV769
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 67
8388


HIV770
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 68
8389


HIV771
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 70
8390


HIV772
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 72
8391


HIV773
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 73
8392


HIV774
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 74
8393


HIV775
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 75
8394


HIV776
Heavy chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 78
8395


HIV777
Heavy chain

WO2014063059 SEQ ID NO: 10
8396


HIV778
Heavy chain

WO2014063059 SEQ ID NO: 12
8397


HIV779
Heavy chain

WO2014063059 SEQ ID NO: 130
8398


HIV780
Heavy chain

WO2014063059 SEQ ID NO: 14
8399


HIV781
Heavy chain

WO2014063059 SEQ ID NO: 16
8400


HIV782
Heavy chain

WO2014063059 SEQ ID NO: 18
8401


HIV783
Heavy chain

WO2014063059 SEQ ID NO: 20
8402


HIV784
Heavy chain

WO2014063059 SEQ ID NO: 22
8403


HIV785
Heavy chain

WO2014063059 SEQ ID NO: 24
8404


HIV786
Heavy chain

WO2014063059 SEQ ID NO: 4
8405


HIV787
Heavy chain

WO2014063059 SEQ ID NO: 6
8406


HIV788
Heavy chain

WO2014063059 SEQ ID NO: 8
8407


HIV789
Heavy chain

WO2014063059 SEQ ID NO: 2
8408



consensus


HIV790
Heavy chain constant
G4D
US20130195881 SEQ ID NO: 6
8409



region


HIV791
Heavy chain constant
G4H
US20130195881 SEQ ID NO: 5
8410



region


HIV792
Heavy chain constant
MV1
US20130195881 SEQ ID NO: 7
8411



region


HIV793
Heavy chain constant
TNX-355,
US20130195881 SEQ ID NO: 4
8412



region
Idalizumab


HIV794
Heavy Chain Fab
Ch04
McLellan, J. S., et al. Nature 480 (7377), 336-
8413





343 (2011), NCBI Accession # 3U46_A





(238aa)


HIV795
Heavy Chain Of
21C
Diskin, R., et al, Nat. Struct. Mol. Biol. 17 (5),
8414



Anti-HIV Fab From

608-613 (2010), NCBI Accession # 3LMJ_H



Human 21c Antibody

(231aa)


HIV796
Heavy Chain Of
830a
Pan et al, J. Virol. 89 (15), 8003-8010 (2015),
8415



Anti-hiv-1 Gp120

NCBI Accession # 4YWG_H (226aa)



V1v2 Antibody 830a


HIV797
Heavy chain partial
412D
Huang C. et al “Structural basis of tyrosine
8416





sulfation and VH-gene usage in antibodies that





recognize the HIV type 1 coreceptor-binding





site on gp120” Proc. Natl. Acad. Sci. U.S.A.





101 (9), 2706-2711 (2004), NCBI Accession #





AAR88379


HIV798
Heavy chain variable
0.5γ(1C10)
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 1
8417



region


HIV799
Heavy chain variable
0.5δ (3D6)
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 5
8418



region


HIV800
Heavy chain variable
10J4 mAb
WO2015103549 SEQ ID NO: 3
8419



region


HIV801
Heavy chain variable
10M6 mAb
WO2015103549 SEQ ID NO: 5
8420



region


HIV802
Heavy chain variable
13110 mAb
WO2015103549 SEQ ID NO: 7
8421



region


HIV803
Heavy chain variable
2N5mAb
WO2015103549 SEQ ID NO: 9
8422



region


HIV804
Heavy chain variable
35022 mAb
WO2015103549 SEQ ID NO: 1
8423



region


HIV805
Heavy chain variable
42F9
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 7
8424



region


HIV806
Heavy chain variable
4835_F12
US20140205612 SEQ ID NO: 404
8425



region
(PGT-124)


HIV807
Heavy chain variable
4838_L06
US20140205612 SEQ ID NO: 66
8426



region
(PGT-121)


HIV808
Heavy chain variable
4858_P08
US20140205612 SEQ ID NO: 167
8427



region
(PGT-123)


HIV809
Heavy chain variable
4869-K15
US20140205612 SEQ ID NO: 419
8428



region
(PGT-133)


HIV810
Heavy chain variable
4873_E03
US20140205612 SEQ ID NO: 62
8429



region
(PGT-121)


HIV811
Heavy chain variable
4876_M06
US20140205612 SEQ ID NO: 434
8430



region
(PGT-134)


HIV812
Heavy chain variable
4877_D15
US20140205612 SEQ ID NO: 155
8431



region
(PGT-122)


HIV813
Heavy chain variable
4964_G22
US20140205612 SEQ ID NO: 275
8432



region
(PGT-141),




4993_K13




(PGT-141)


HIV814
Heavy chain variable
4970_K22
US20140205612 SEQ ID NO: 306
8433



region
(PGT-144)


HIV815
Heavy chain variable
4980_N08
US20140205612 SEQ ID NO: 297
8434



region
(PGT-143)


HIV816
Heavy chain variable
4995_E20
US20140205612 SEQ ID NO: 291
8435



region
(PGT-142)


HIV817
Heavy chain variable
4995_P16
US20140205612 SEQ ID NO: 400
8436



region
(PGT-145)


HIV818
Heavy chain variable
49G2
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 9
8437



region


HIV819
Heavy chain variable
4O20mAb
WO2015103549 SEQ ID NO: 11
8438



region


HIV820
Heavy chain variable
5114_A19
US20140205612 SEQ ID NO: 333
8439



region
(PGT-128)


HIV821
Heavy chain variable
5120_N10
US20140205612 SEQ ID NO: 462
8440



region
(PGT-139)


HIV822
Heavy chain variable
5131_A17
US20140205612 SEQ ID NO: 443
8441



region
(PGT-132)


HIV823
Heavy chain variable
5136_H01
US20140205612 SEQ ID NO: 345
8442



region
(PGT-131)


HIV824
Heavy chain variable
5138_G07
US20140205612 SEQ ID NO: 453
8443



region
(PGT-138)


HIV825
Heavy chain variable
5141_B17
US20140205612 SEQ ID NO: 199
8444



region
(PGT-126)


HIV826
Heavy chain variable
5145_B14
US20140205612 SEQ ID NO: 318
8445



region
(PGT-127)


HIV827
Heavy chain variable
5147_N06
US20140205612 SEQ ID NO: 215
8446



region
(PGT-130)


HIV828
Heavy chain variable
5329_C19
US20140205612 SEQ ID NO: 248
8447



region
(PGT-136),




5366_P21




(PGT-136)


HIV829
Heavy chain variable
5343_B08
US20140205612 SEQ ID NO: 231
8448



region
(PGT-135),




5344_E16




(PGT-135)


HIV830
Heavy chain variable
5345_I01
US20140205612 SEQ ID NO: 362
8449



region
(PGT-137)


HIV831
Heavy chain variable
5G2
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 3
8450



region


HIV832
Heavy chain variable
6808_B09
US20140205612 SEQ ID NO: 546
8451



region
(PGT-156)


HIV833
Heavy chain variable
6831_A21
US20140205612 SEQ ID NO: 473
8452



region
(PGT-151)


HIV834
Heavy chain variable
6843_G20
US20140205612 SEQ ID NO: 516
8453



region
(PGT-154)


HIV835
Heavy chain variable
6881_N05
US20140205612 SEQ ID NO: 572
8454



region
(PGT-158).


HIV836
Heavy chain variable
6889_117
US20140205612 SEQ ID NO: 489
8455



region
(PGT-152)


HIV837
Heavy chain variable
6891_F06
US20140205612 SEQ ID NO: 501
8456



region
(PGT-153)


HIV838
Heavy chain variable
6892_C23
US20140205612 SEQ ID NO: 559
8457



region
(PGT-157)


HIV839
Heavy chain variable
6892_D19
US20140205612 SEQ ID NO: 531
8458



region
(PGT-155)


HIV840
Heavy chain variable
7B9mAb
WO2015103549 SEQ ID NO: 13
8459



region


HIV841
Heavy chain variable
7K3mAb
WO2015103549 SEQ ID NO: 15
8460



region


HIV842
Heavy chain variable
B4
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 2
8461



region


HIV843
Heavy chain variable
B4DIVHv.1
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 5
8462



region


HIV844
Heavy chain variable
B4DIVHv.2
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 6
8463



region


HIV845
Heavy chain variable
B4DTVHv.3
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 7
8464



region


HIV846
Heavy chain variable
B4DIVHv.4
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 8
8465



region


HIV847
Heavy chain variable
bI2 IgA2
WO2014040024 SEQ ID NO: 29
8466



region
antibody


HIV848
Heavy chain variable
CHμ39.1
U.S. Pat. No. 5,773,247 SEQ ID NO: 10
8467



region


HIV849
Heavy chain variable
CHμ5.5
U.S. Pat. No. 5,773,247 SEQ ID NO: 14
8468



region


HIV850
Heavy chain variable
F425-Alg8
WO2014040024 SEQ ID NO: 9
8469



region
antibody


HIV851
Heavy chain variable
Fab 43
US20090191216 SEQ ID NO: 8
8470



region


HIV852
Heavy chain variable
HGN194
US20110212106 SEQ ID NO: 45
8471



region


HIV853
Heavy chain variable
HJ16
US20110212106 SEQ ID NO: 13
8472



region


HIV854
Heavy chain variable
HK20
US20110212106 SEQ ID NO: 29
8473



region


HIV855
Heavy chain variable
IgA antibody
WO2014040024 SEQ ID NO: 11
8474



region


HIV856
Heavy chain variable
L1719A11
US20150158934 SEQ ID NO: 175
8475



region


HIV857
Heavy chain variable
L1719A12
US20150158934 SEQ ID NO: 176
8476



region


HIV858
Heavy chain variable
L1719A9
US20150158934 SEQ ID NO: 174
8477



region


HIV859
Heavy chain variable
L1719B12
US20150158934 SEQ ID NO: 177
8478



region


HIV860
Heavy chain variable
L1719C1
US20150158934 SEQ ID NO: 178
8479



region


HIV861
Heavy chain variable
L1719D10
US20150158934 SEQ ID NO: 179
8480



region


HIV862
Heavy chain variable
L1719E1
US20150158934 SEQ ID NO: 180
8481



region


HIV863
Heavy chain variable
L1719E11
US20150158934 SEQ ID NO: 181
8482



region


HIV864
Heavy chain variable
L1719E12
US20150158934 SEQ ID NO: 182
8483



region


HIV865
Heavy chain variable
L1719F11
US20150158934 SEQ ID NO: 183
8484



region


HIV866
Heavy chain variable
L1719H10
US20150158934 SEQ ID NO: 185
8485



region


HIV867
Heavy chain variable
L1719H9
US20150158934 SEQ ID NO: 184
8486



region


HIV868
Heavy chain variable
L1720C1
US20150158934 SEQ ID NO: 186
8487



region


HIV869
Heavy chain variable
L1720E4
US20150158934 SEQ ID NO: 187
8488



region


HIV870
Heavy chain variable
L1721A3
US20150158934 SEQ ID NO: 188
8489



region


HIV871
Heavy chain variable
L1721A5
US20150158934 SEQ ID NO: 189
8490



region


HIV872
Heavy chain variable
L1721A8
US20150158934 SEQ ID NO: 190
8491



region


HIV873
Heavy chain variable
L1721H4
US20150158934 SEQ ID NO: 191
8492



region


HIV874
Heavy chain variable
L1723A10
US20150158934 SEQ ID NO: 193
8493



region


HIV875
Heavy chain variable
L1723A11
US20150158934 SEQ ID NO: 194
8494



region


HIV876
Heavy chain variable
L1723A9
US20150158934 SEQ ID NO: 192
8495



region


HIV877
Heavy chain variable
L1723E5
US20150158934 SEQ ID NO: 195
8496



region


HIV878
Heavy chain variable
L2319G11
US20150158934 SEQ ID NO: 197
8497



region


HIV879
Heavy chain variable
L2319G7
US20150158934 SEQ ID NO: 196
8498



region


HIV880
Heavy chain variable
L2319H7
US20150158934 SEQ ID NO: 198
8499



region


HIV881
Heavy chain variable
L2320E9
US20150158934 SEQ ID NO: 199
8500



region


HIV882
Heavy chain variable
L2320F9
US20150158934 SEQ ID NO: 200
8501



region


HIV883
Heavy chain variable
L2321B7
US20150158934 SEQ ID NO: 201
8502



region


HIV884
Heavy chain variable
L2321H6
US20150158934 SEQ ID NO: 202
8503



region


HIV885
Heavy chain variable
L81C11
US20150158934 SEQ ID NO: 15
8504



region


HIV886
Heavy chain variable
L81C9
US20150158934 SEQ ID NO: 30
8505



region


HIV887
Heavy chain variable
L81D9
US20150158934 SEQ ID NO: 10
8506



region


HIV888
Heavy chain variable
L81E1
US20150158934 SEQ ID NO: 18
8507



region


HIV889
Heavy chain variable
L81E7
US20150158934 SEQ ID NO: 16
8508



region


HIV890
Heavy chain variable
L81F1
US20150158934 SEQ ID NO: 19
8509



region


HIV891
Heavy chain variable
L81G7
US20150158934 SEQ ID NO: 13
8510



region


HIV892
Heavy chain variable
L81H1
US20150158934 SEQ ID NO: 98
8511



region


HIV893
Heavy chain variable
L81H2
US20150158934 SEQ ID NO: 23
8512



region


HIV894
Heavy chain variable
L81H7
US20150158934 SEQ ID NO: 11
8513



region


HIV895
Heavy chain variable
L81H9
US20150158934 SEQ ID NO: 28
8514



region


HIV896
Heavy chain variable
L82B12A
US20150158934 SEQ ID NO: 105
8515



region


HIV897
Heavy chain variable
L82B1A
US20150158934 SEQ ID NO: 99
8516



region


HIV898
Heavy chain variable
L82B1D
US20150158934 SEQ ID NO: 100
8517



region


HIV899
Heavy chain variable
L82B2A
US20150158934 SEQ ID NO: 101
8518



region


HIV900
Heavy chain variable
L82B3F
US20150158934 SEQ ID NO: 102
8519



region


HIV901
Heavy chain variable
L82B4A
US20150158934 SEQ ID NO: 103
8520



region


HIV902
Heavy chain variable
L82B4E
US20150158934 SEQ ID NO: 104
8521



region


HIV903
Heavy chain variable
L82B4F
US20150158934 SEQ ID NO: 21
8522



region


HIV904
Heavy chain variable
L832G6
US20150158934 SEQ ID NO: 113
8523



region


HIV905
Heavy chain variable
L833E1
US20150158934 SEQ ID NO: 72
8524



region


HIV906
Heavy chain variable
L833F5
US20150158934 SEQ ID NO: 17
8525



region


HIV907
Heavy chain variable
L833H1
US20150158934 SEQ ID NO: 114
8526



region


HIV908
Heavy chain variable
L833H3
US20150158934 SEQ ID NO: 115
8527



region


HIV909
Heavy chain variable
L88B10B
US20150158934 SEQ ID NO: 27
8528



region


HIV910
Heavy chain variable
L88B11B
US20150158934 SEQ ID NO: 12
8529



region


HIV911
Heavy chain variable
L88B12G
US20150158934 SEQ ID NO: 29
8530



region


HIV912
Heavy chain variable
L88B1D
US20150158934 SEQ ID NO: 20
8531



region


HIV913
Heavy chain variable
L88B2A
US20150158934 SEQ ID NO: 106
8532



region


HIV914
Heavy chain variable
L88FA2
US20150158934 SEQ ID NO: 26
8533



region


HIV915
Heavy chain variable
L88FA3
US20150158934 SEQ ID NO: 107
8534



region


HIV916
Heavy chain variable
L88FA5
US20150158934 SEQ ID NO: 108
8535



region


HIV917
Heavy chain variable
L88FB1
US20150158934 SEQ ID NO: 25
8536



region


HIV918
Heavy chain variable
L88FC11
US20150158934 SEQ ID NO: 22
8537



region


HIV919
Heavy chain variable
L88FD12
US20150158934 SEQ ID NO: 24
8538



region


HIV920
Heavy chain variable
L89B12D
US20150158934 SEQ ID NO: 112
8539



region


HIV921
Heavy chain variable
L89B1D
US20150158934 SEQ ID NO: 109
8540



region


HIV922
Heavy chain variable
L89B2C
US20150158934 SEQ ID NO: 110
8541



region


HIV923
Heavy chain variable
L89B3E
US20150158934 SEQ ID NO: 14
8542



region


HIV924
Heavy chain variable
L89B6B
US20150158934 SEQ ID NO: 111
8543



region


HIV925
Heavy chain variable
L8Cb15
US20150158934 SEQ ID NO: 116
8544



region


HIV926
Heavy chain variable
L8Cj3
US20150158934 SEQ ID NO: 73
8545



region


HIV927
Heavy chain variable
L8Fe2
US20150158934 SEQ ID NO: 117
8546



region


HIV928
Heavy chain variable
L8Fg12
US20150158934 SEQ ID NO: 118
8547



region


HIV929
Heavy chain variable
L8Fj19
US20150158934 SEQ ID NO: 119
8548



region


HIV930
Heavy chain variable
L8Fo17
US20150158934 SEQ ID NO: 120
8549



region


HIV931
Heavy chain variable
L8Fp6
US20150158934 SEQ ID NO: 121
8550



region


HIV932
Heavy chain variable
L8Hi20
US20150158934 SEQ ID NO: 122
8551



region


HIV933
Heavy chain variable
L911B11E
US20150158934 SEQ ID NO: 140
8552



region


HIV934
Heavy chain variable
L911B12B
US20150158934 SEQ ID NO: 71
8553



region


HIV935
Heavy chain variable
L911B1E
US20150158934 SEQ ID NO: 137
8554



region


HIV936
Heavy chain variable
L911B1G
US20150158934 SEQ ID NO: 65
8555



region


HIV937
Heavy chain variable
L911B2E
US20150158934 SEQ ID NO: 138
8556



region


HIV938
Heavy chain variable
L911B3D
US20150158934 SEQ ID NO: 75
8557



region


HIV939
Heavy chain variable
L911B9A
US20150158934 SEQ ID NO: 139
8558



region


HIV940
Heavy chain variable
L911F12B
US20150158934 SEQ ID NO: 142
8559



region


HIV941
Heavy chain variable
L911F1B
US20150158934 SEQ ID NO: 141
8560



region


HIV942
Heavy chain variable
L911F1F
US20150158934 SEQ ID NO: 77
8561



region


HIV943
Heavy chain variable
L911F4C
US20150158934 SEQ ID NO: 33
8562



region


HIV944
Heavy chain variable
L91A1
US20150158934 SEQ ID NO: 123
8563



region


HIV945
Heavy chain variable
L91B5
US20150158934 SEQ ID NO: 37
8564



region


HIV946
Heavy chain variable
L91B5, 4A7
US20150158934 SEQ ID NO: 97
8565



region


HIV947
Heavy chain variable
L91B5, A12
US20150158934 SEQ ID NO: 92
8566



region


HIV948
Heavy chain variable
L91B5, A4
US20150158934 SEQ ID NO: 90
8567



region


HIV949
Heavy chain variable
L91B5, A7
US20150158934 SEQ ID NO: 91
8568



region


HIV950
Heavy chain variable
L91B5, B2
US20150158934 SEQ ID NO: 93
8569



region


HIV951
Heavy chain variable
L91B5, D4
US20150158934 SEQ ID NO: 94
8570



region


HIV952
Heavy chain variable
L91B5, F11
US20150158934 SEQ ID NO: 96
8571



region


HIV953
Heavy chain variable
L91B5, F4
US20150158934 SEQ ID NO: 95
8572



region


HIV954
Heavy chain variable
L91C2
US20150158934 SEQ ID NO: 61
8573



region


HIV955
Heavy chain variable
L91E1
US20150158934 SEQ ID NO: 45
8574



region


HIV956
Heavy chain variable
L91E2
US20150158934 SEQ ID NO: 124
8575



region


HIV957
Heavy chain variable
L91F10
US20150158934 SEQ ID NO: 69
8576



region


HIV958
Heavy chain variable
L91G2
US20150158934 SEQ ID NO: 64
8577



region


HIV959
Heavy chain variable
L91H3
US20150158934 SEQ ID NO: 128
8578



region


HIV960
Heavy chain variable
L91H9
US20150158934 SEQ ID NO: 41
8579



region


HIV961
Heavy chain variable
L922B2
US20150158934 SEQ ID NO: 143
8580



region


HIV962
Heavy chain variable
L922B4
US20150158934 SEQ ID NO: 144
8581



region


HIV963
Heavy chain variable
L922E1
US20150158934 SEQ ID NO: 145
8582



region


HIV964
Heavy chain variable
L922E2
US20150158934 SEQ ID NO: 53
8583



region


HIV965
Heavy chain variable
L923A1
US20150158934 SEQ ID NO: 146
8584



region


HIV966
Heavy chain variable
L923A4
US20150158934 SEQ ID NO: 32
8585



region


HIV967
Heavy chain variable
L92A11
US20150158934 SEQ ID NO: 125
8586



region


HIV968
Heavy chain variable
L92C7
US20150158934 SEQ ID NO: 62
8587



region


HIV969
Heavy chain variable
L92D4
US20150158934 SEQ ID NO: 126
8588



region


HIV970
Heavy chain variable
L92E6
US20150158934 SEQ ID NO: 63
8589



region


HIV971
Heavy chain variable
L92E7
US20150158934 SEQ ID NO: 74
8590



region


HIV972
Heavy chain variable
L92E7, A1
US20150158934 SEQ ID NO: 85
8591



region


HIV973
Heavy chain variable
L92E7, A2
US20150158934 SEQ ID NO: 86
8592



region


HIV974
Heavy chain variable
L92E7, A3
US20150158934 SEQ ID NO: 87
8593



region


HIV975
Heavy chain variable
L92E7, A4
US20150158934 SEQ ID NO: 80
8594



region


HIV976
Heavy chain variable
L92E7, A4
US20150158934 SEQ ID NO: 88
8595



region


HIV977
Heavy chain variable
L92E7, A5
US20150158934 SEQ ID NO: 89
8596



region


HIV978
Heavy chain variable
L92E7, B5
US20150158934 SEQ ID NO: 78
8597



region


HIV979
Heavy chain variable
L92E7. C
US20150158934 SEQ ID NO: 79
8598



region


HIV980
Heavy chain variable
L92E7, C3
US20150158934 SEQ ID NO: 82
8599



region


HIV981
Heavy chain variable
L92E7, D3
US20150158934 SEQ ID NO: 83
8600



region


HIV982
Heavy chain variable
L92E7, E1
US20150158934 SEQ ID NO: 84
8601



region


HIV983
Heavy chain variable
L92E7, G4
US20150158934 SEQ ID NO: 81
8602



region


HIV984
Heavy chain variable
L932A9
US20150158934 SEQ ID NO: 58
8603



region


HIV985
Heavy chain variable
L932E10
US20150158934 SEQ ID NO: 35
8604



region


HIV986
Heavy chain variable
L932E8
US20150158934 SEQ ID NO: 147
8605



region


HIV987
Heavy chain variable
L932G9
US20150158934 SEQ ID NO: 34
8606



region


HIV988
Heavy chain variable
L933D10
US20150158934 SEQ ID NO: 50
8607



region


HIV989
Heavy chain variable
L93B3
US20150158934 SEQ ID NO: 70
8608



region


HIV990
Heavy chain variable
L93B4
US20150158934 SEQ ID NO: 127
8609



region


HIV991
Heavy chain variable
L93C3
US20150158934 SEQ ID NO: 51
8610



region


HIV992
Heavy chain variable
L93C6
US20150158934 SEQ ID NO: 67
8611



region


HIV993
Heavy chain variable
L93D3
US20150158934 SEQ ID NO: 129
8612



region


HIV994
Heavy chain variable
L93D4
US20150158934 SEQ ID NO: 43
8613



region


HIV995
Heavy chain variable
L93D9
US20150158934 SEQ ID NO: 130
8614



region


HIV996
Heavy chain variable
L93E3
US20150158934 SEQ ID NO: 55
8615



region


HIV997
Heavy chain variable
L93E6
US20150158934 SEQ ID NO: 131
8616



region


HIV998
Heavy chain variable
L93F12
US20150158934 SEQ ID NO: 133
8617



region


HIV999
Heavy chain variable
L93F2
US20150158934 SEQ ID NO: 132
8618



region


HIV1000
Heavy chain variable
L93F2
US20150158934 SEQ ID NO: 59
8619



region


HIV1001
Heavy chain variable
L93H6
US20150158934 SEQ ID NO: 38
8620



region


HIV1002
Heavy chain variable
L93H9
US20150158934 SEQ ID NO: 134
8621



region


HIV1003
Heavy chain variable
L94A12
US20150158934 SEQ ID NO: 46
8622



region


HIV1004
Heavy chain variable
L94C2
US20150158934 SEQ ID NO: 31
8623



region


HIV1005
Heavy chain variable
L94D12
US20150158934 SEQ ID NO: 42
8624



region


HIV1006
Heavy chain variable
L94D4
US20150158934 SEQ ID NO: 47
8625



region


HIV1007
Heavy chain variable
L94E3
US20150158934 SEQ ID NO: 39
8626



region


HIV1008
Heavy chain variable
L94E4
US20150158934 SEQ ID NO: 54
8627



region


HIV1009
Heavy chain variable
L94E5
US20150158934 SEQ ID NO: 57
8628



region


HIV1010
Heavy chain variable
L94H1
US20150158934 SEQ ID NO: 36
8629



region


HIV1011
Heavy chain variable
L94H2
US20150158934 SEQ ID NO: 40
8630



region


HIV1012
Heavy chain variable
L94H5
US20150158934 SEQ ID NO: 48
8631



region


HIV1013
Heavy chain variable
L94H7
US20150158934 SEQ ID NO: 135
8632



region


HIV1014
Heavy chain variable
L95B10D
US20150158934 SEQ ID NO: 136
8633



region


HIV1015
Heavy chain variable
L95B12A
US20150158934 SEQ ID NO: 68
8634



region


HIV1016
Heavy chain variable
L95B12E
US20150158934 SEQ ID NO: 66
8635



region


HIV1017
Heavy chain variable
L95B8A
US20150158934 SEQ ID NO: 60
8636



region


HIV1018
Heavy chain variable
L98FB10
US20150158934 SEQ ID NO: 76
8637



region


HIV1019
Heavy chain variable
L9Ab16
US20150158934 SEQ ID NO: 148
8638



region


HIV1020
Heavy chain variable
L9Ab19
US20150158934 SEQ ID NO: 149
8639



region


HIV1021
Heavy chain variable
L9Ad13
US20150158934 SEQ ID NO: 151
8640



region


HIV1022
Heavy chain variable
L9Ad14
US20150158934 SEQ ID NO: 152
8641



region


HIV1023
Heavy chain variable
L9Ad3
US20150158934 SEQ ID NO: 150
8642



region


HIV1024
Heavy chain variable
L9Aj2
US20150158934 SEQ ID NO: 153
8643



region


HIV1025
Heavy chain variable
L9An7
US20150158934 SEQ ID NO: 154
8644



region


HIV1026
Heavy chain variable
L9Ao15
US20150158934 SEQ ID NO: 155
8645



region


HIV1027
Heavy chain variable
L9Ap11
US20150158934 SEQ ID NO: 156
8646



region


HIV1028
Heavy chain variable
L9Bb3
US20150158934 SEQ ID NO: 157
8647



region


HIV1029
Heavy chain variable
L9Bc6
US20150158934 SEQ ID NO: 158
8648



region


HIV1030
Heavy chain variable
L9Bd8
US20150158934 SEQ ID NO: 159
8649



region


HIV1031
Heavy chain variable
L9Bd9
US20150158934 SEQ ID NO: 160
8650



region


HIV1032
Heavy chain variable
L9Be11
US20150158934 SEQ ID NO: 161
8651



region


HIV1033
Heavy chain variable
L9Bf11
US20150158934 SEQ ID NO: 49
8652



region


HIV1034
Heavy chain variable
L9Bf19
US20150158934 SEQ ID NO: 162
8653



region


HIV1035
Heavy chain variable
L9Bj13
US20150158934 SEQ ID NO: 163
8654



region


HIV1036
Heavy chain variable
L9Bm10
US20150158934 SEQ ID NO: 164
8655



region


HIV1037
Heavy chain variable
L9Bm16
US20150158934 SEQ ID NO: 56
8656



region


HIV1038
Heavy chain variable
L9Bp16
US20150158934 SEQ ID NO: 165
8657



region


HIV1039
Heavy chain variable
L9Bp5
US20150158934 SEQ ID NO: 44
8658



region


HIV1040
Heavy chain variable
L9Ca12
US20150158934 SEQ ID NO: 166
8659



region


HIV1041
Heavy chain variable
L9Ca13
US20150158934 SEQ ID NO: 167
8660



region


HIV1042
Heavy chain variable
L9Cd12
US20150158934 SEQ ID NO: 168
8661



region


HIV1043
Heavy chain variable
L9Cf15
US20150158934 SEQ ID NO: 169
8662



region


HIV1044
Heavy chain variable
L9Cl22
US20150158934 SEQ ID NO: 52
8663



region


HIV1045
Heavy chain variable
L9Cm18
US20150158934 SEQ ID NO: 170
8664



region


HIV1046
Heavy chain variable
L9Co22
US20150158934 SEQ ID NO: 171
8665



region


HIV1047
Heavy chain variable
L9Cp5
US20150158934 SEQ ID NO: 172
8666



region


HIV1048
Heavy chain variable
L9Cpl3
US20150158934 SEQ ID NO: 173
8667



region


HIV1049
Heavy chain variable
Makandal
US20100111990 SEQ ID NO: 4
8668



region
monoclonal




antibody




(Mmab)


HIV1050
Heavy chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 17
8669



region


HIV1051
Heavy chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 27
8670



region
HuVH


HIV1052
Heavy chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 29
8671



region
HuVK


HIV1053
Heavy chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 31
8672



region
HuVKF


HIV1054
Heavy chain variable
PGT125
Walker L. M. et al “Broad neutralization
8673



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14393


HIV1055
Heavy chain variable
PGT126
Walker L. M. et al “Broad neutralization
8674



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14394


HIV1056
Heavy chain variable
PGT131
Walker L. M. et al “Broad neutralization
8675



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14389


HIV1057
Heavy chain variable
PGT136
Walker L. M. et al “Broad neutralization
8676



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365),466-470





(2011), NCBI Accession # AEN14400


HIV1058
Heavy chain variable
PGT137
Walker L. M. et al “Broad neutralization
8677



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14401


HIV1059
Heavy chain variable
PGT141
Walker L. M. et al “Broad neutralization
8678



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14402


HIV1060
Heavy chain variable
PGT142
Walker L. M. et al “Broad neutralization
8679



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14368


HIV1061
Heavy chain variable
PGT143
Walker L. M. et al “Broad neutralization
8680



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14404


HIV1062
Heavy chain variable
PGT144
Walker L. M. et al “Broad neutralization
8681



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14405


HIV1063
Heavy chain variable
PGT151
Falkowska, E. et al “Broadly Neutralizing HIV
8682



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC3535


HIV1064
Heavy chain variable
PGT152
Falkowska, E. et al “Broadly Neutralizing HIV
8683



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32536


HIV1065
Heavy chain variable
PGT153
Falkowska, E. et al “Broadly Neutralizing HIV
8684



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32537


HIV1066
Heavy chain variable
PGT154
Falkowska, E. et al “Broadly Neutralizing HIV
8685



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32521


HIV1067
Heavy chain variable
PGT155
Falkowska, E. et al “Broadly Neutralizing HIV
8686



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32539


HIV1068
Heavy chain variable
PGT156
Falkowska, E. et al “Broadly Neutralizing HIV
8687



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32540


HIV1069
Heavy chain variable
PGT157
Falkowska, E. et al “Broadly Neutralizing HIV
8688



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32541


HIV1070
Heavy chain variable
PGT158
Falkowska, E. et al “Broadly Neutralizing HIV
8689



region

Antibodies Define a Glycan-Dependent Epitope





on the Perfusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32542


HIV1071
Heavy chain variable
rF105
WO1993012232 SEQ ID NO: 4
8690



region


HIV1072
Heavy chain variable
ScFvX5-
U.S. Pat. No. 7,378,093B2 SEQ ID NO: 14
8691



region
CD4


HIV1073
Heavy chain variable
TNX-355,
US20130195881 SEQ ID NO: 3
8692



region
Idalizumab


HIV1074
Heavy chain variable
VCR14
US20150044137 SEQ ID NO: 13
8693



region


HIV1075
Heavy chain variable
VCR14b
US20150044137 SEQ ID NO: 14
8694



region


HIV1076
Heavy chain variable
VCR14c
US20150044137 SEQ ID NO: 15
8695



region


HIV1077
Heavy chain variable
VCR16
US20150044137 SEQ ID NO: 29
8696



region


HIV1078
Heavy chain variable
VCR16b
US20150044137 SEQ ID NO: 30
8697



region


HIV1079
Heavy chain variable
VCR16c
US20150044137 SEQ ID NO: 31
8698



region


HIV1080
Heavy chain variable
VCR16d
US20150044137 SEQ ID NO: 32
8699



region


HIV1081
Heavy chain variable
VLP_A14
US20150158934 SEQ ID NO: 203
8700



region


HIV1082
Heavy chain variable
VLP_B9
US20150158934 SEQ ID NO: 204
8701



region


HIV1083
Heavy chain variable
VLP3_B21
US20150158934 SEQ ID NO: 205
8702



region


HIV1084
Heavy chain variable
VRC13
US20150044137 SEQ ID NO: 5
8703



region


HIV1085
Heavy chain variable
VRC13b
US20150044137 SEQ ID NO: 6
8704



region


HIV1086
Heavy chain variable
VRC13c
US20150044137 SEQ ID NO: 7
8705



region


HIV1087
Heavy chain variable
VRC13d
US20150044137 SEQ ID NO: 8
8706



region


HIV1088
Heavy chain variable
VRC13e
US20150044137 SEQ ID NO: 9
8707



region


HIV1089
Heavy chain variable
VRC13f
US20150044137 SEQ ID NO: 10
8708



region


HIV1090
Heavy chain variable
VRC13g
US20150044137 SEQ ID NO: 11
8709



region


HIV1091
Heavy chain variable
VRC13h
US20150044137 SEQ ID NO: 12
8710



region


HIV1092
Heavy chain variable
VRC15
US20150044137 SEQ ID NO: 16
8711



region


HIV1093
Heavy chain variable

US20150004190 SEQ ID NO: 56
8712



region


HIV1094
Heavy chain variable
P7
NCBI Accession # AAB41043.1 (136aa)
8713



region, partial


HIV1095
Heavy Chain, Fab
Ch04
McLellan, J. S. et al., Structure of HIV-1 gp120
8714





V1 V2 domain with broadly neutralizing





antibody PG9; Nature 480 (7377), 336-343





(2011), NCBI Accession # 3TCL_A (237aa)


HIV1096
Heavy Chain, Fab
N5-i5
Acharya, P., et al., Structural Definition of an
8715





Antibody-Dependent Cellular Cytotoxicity





Response Implicated in Reduced Risk for HIV-





1 infection; J. Virol. 88 (21), 12895-12906





(2014), NCBI Accession # 4H8W_H (226aa)


HIV1097
Heavy Chain, Fab
N60-i3
Gohain, N., et al., Cocrystal Structures of
8716





Antibody N60-i3 and Antibody JR4 in





Complex with gp120 Define More Cluster A





Epitopes Involved in Effective Antibody-





Dependent Effector Function against HIV-1; J.





Virol. 89 (17), 8840-8854 (2015), NCBI





Accession # 4RFO_H (229aa)


HIV1098
Heavy Chain, Ig
Nih45-46 Fab
Diskin, R., et al., Science 334 (6060), 1289-
8717



Gamma-1 Chain C

1293 (2011), NCBI Accession # 3U7Y_H



Region

(229aa)


HIV1099
Heavy Chain, Ig
Pgt127
Pejchal, R., et al., Science 334 (6059), 1097-
8718



Gamma-1 Chain C

1103 (2011), NCBI Accession #



Region

3TWC_H(239aa)


HIV1100
Heavy Chain, Ig
Pgt128
Pejchal, R., et al., Science 334 (6059), 1097-
8719



Gamma-1 Chain C

1103 (2011), NCBI Accession #



Region

3TV3_H(239aa)


HIV1101
HIV, heavy chain
Suvizumab

8720


HIV1102
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 43
8721



antibody, heavy chain
antibody


HIV1103
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 44
8722



antibody, heavy chain
antibody


HIV1104
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 45
8723



antibody, heavy chain
antibody


HIV1105
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 46
8724



antibody, heavy chain
antibody


HIV1106
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 47
8725



antibody, heavy chain
antibody


HIV1107
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 48
8726



antibody, heavy chain
antibody


HIV1108
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 49
8727



antibody, heavy chain
antibody


HIV1109
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 57
8728



antibody, heavy chain
antibody


HIV1110
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 58
8729



antibody, heavy chain
antibody


HIV1111
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 59
8730



antibody, heavy chain
antibody


HIV1112
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 60
8731



antibody, heavy chain
antibody


HIV1113
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 61
8732



antibody, heavy chain
antibody


HIV1114
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 62
8733



antibody, heavy chain
antibody


HIV1115
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 63
8734



antibody, heavy chain
antibody


HIV1116
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 64
8735



antibody, heavy chain
antibody


HIV1117
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 73
8736



antibody, heavy chain
antibody


HIV1118
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 74
8737



antibody, heavy chain
antibody


HIV1119
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 75
8738



antibody, heavy chain
antibody


HIV1120
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 76
8739



antibody, heavy chain
antibody


HIV1121
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 77
8740



antibody, heavy chain
antibody


HIV1122
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 78
8741



antibody, heavy chain
antibody


HIV1123
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 50
8742



antibody, light chain
antibody


HIV1124
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 51
8743



antibody, light chain
antibody


HIV1125
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 52
8744



antibody, light chain
antibody


HIV1126
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 53
8745



antibody, light chain
antibody


HIV1127
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 54
8746



antibody, light chain
antibody


HIV1128
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 55
8747



antibody, light chain
antibody


HIV1129
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 56
8748



antibody, light chain
antibody


HIV1130
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 65
8749



antibody, light chain
antibody


HIV1131
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 66
8750



antibody, light chain
antibody


HIV1132
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 67
8751



antibody, light chain
antibody


HIV1133
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 68
8752



antibody, light chain
antibody


HIV1134
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 69
8753



antibody, light chain
antibody


HIV1135
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 70
8754



antibody, light chain
antibody


HIV1136
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 71
8755



antibody, light chain
antibody


HIV1137
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 72
8756



antibody, light chain
antibody


HIV1138
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 79
8757



antibody, light chain
antibody


HIV1139
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 80
8758



antibody, light chain
antibody


HIV1140
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 81
8759



antibody, light chain
antibody


HIV1141
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 82
8760



antibody, light chain
antibody


HIV1142
HIV1 gp120
HIV1 gp120
WO2001000678 SEQ ID NO: 83
8761



antibody, light chain
antibody


HIV1143
Kappa light chain
1460_G14
U.S. Pat. No. 9,051,362 SEQ ID NO: 22
8762


HIV1144
Kappa light chain
1456_P20
U.S. Pat. No. 9,051,362 SEQ ID NO: 34
8763



variable region


HIV1145
Kappa light chain
1460_G14
U.S. Pat. No. 9,051,362 SEQ ID NO: 36
8764



variable region


HIV1146
Kappa light chain
1456_P20
U.S. Pat. No. 9,051,362 SEQ ID NO: 18
8765


HIV1147
Lambda light chain
1456_A12
U.S. Pat. No. 9,051,362 SEQ ID NO: 50
8766


HIV1148
Lambda light chain
1469 M23
U.S. Pat. No. 9,051,362 SEQ ID NO: 142
8767


HIV1149
Lambda light chain
1489_I13
U.S. Pat. No. 9,051,362 SEQ ID NO: 14
8768


HIV1150
Lambda light chain
1495_C14
U.S. Pat. No. 9,051,362 SEQ ID NO: 26
8769


HIV1151
Lambda light chain
1489_I13
U.S. Pat. No. 9,051,362 SEQ ID NO: 32
8770



variable region


HIV1152
Lambda light chain
1495_C14
U.S. Pat. No. 9,051,362 SEQ ID NO: 38
8771



variable region


HIV1153
Lambda light chain
1496_C09
U.S. Pat. No. 9,051,362 SEQ ID NO: 40
8772



variable region


HIV1154
Lambda light chain
1456_A12
U.S. Pat. No. 9,051,362 SEQ ID NO: 51
8773



variable region


HIV1155
Lambda light chain
1503_H05
U.S. Pat. No. 9,051,362 SEQ ID NO: 56
8774



variable region


HIV1156
Lambda light chain
1496_C09
U.S. Pat. No. 9,051,362 SEQ ID NO: 30
8775


HIV1157
Light chain
2424
Kumar, R., et al., Functional and Structural
8776





Characterization of Human V3-Specific





Monoclonal Antibody 2424 with Neutralizing





Activity against HIV-1 JRFL; J. Virol. 89 (17),





9090-9102 (2015), NCBI Accession #





4XML_L(215aa)


HIV1158
Light chain
8062
Gustchina, E., PLoS ONE 8 (11), E78187
8777





(2013), NCBI Accession # 4KHX_L(213aa)


HIV1159
Light chain
1.00E+09
US20140348785 SEQ ID NO: 2
8778


HIV1160
Light Chain
10e8
Huang J et al., Nature 491 (7424), 406-412
8779




(monoclonal)
(2012), NCBI Accession # 4G6F_D (215aa)


HIV1161
Light chain
12a12kc
US20140328862 SEQ ID NO: 453
8780


HIV1162
Light chain
12a13kc
US20140328862 SEQ ID NO: 454
8781


HIV1163
Light chain
12a16kc
US20140328862 SEQ ID NO: 455
8782


HIV1164
Light chain
12a1kc
US20140328862 SEQ ID NO: 456
8783


HIV1165
Light chain
12a20kc
US20140328862 SEQ ID NO: 457
8784


HIV1166
Light chain
12a21
NCBI Accession # 4JPW_L (210aa)
8785


HIV1167
Light chain
12a21kc
US20140328862 SEQ ID NO: 458
8786


HIV1168
Light chain
12a22kc
US20140328862 SEQ ID NO: 459
8787


HIV1169
Light chain
12a23kc
US20140328862 SEQ ID NO: 460
8788


HIV1170
Light chain
12a27kc
US20140328862 SEQ ID NO: 461
8789


HIV1171
Light chain
12a46kc
US20140328862 SEQ ID NO: 462
8790


HIV1172
Light chain
12a55kc
US20140328862 SEQ ID NO: 463
8791


HIV1173
Light chain
12a56kc
US20140328862 SEQ ID NO: 464
8792


HIV1174
Light chain
12a6kc
US20140328862 SEQ ID NO: 465
8793


HIV1175
Light chain
12a7kc
US20140328862 SEQ ID NO: 466
8794


HIV1176
Light chain
17b
Kwong, P. D., et al., structure of an HIV gp120
8795





envelope glycoprotein in complex with the CD4





receptor and a neutralizing human antibody;





Nature 393 (6686). 648-659 (1998), NCBI





Accession # 1G9M_L(214aa)


HIV1177
Light chain
1b2530
Zhou T et al., Structural Repertoire of HIV-1-
8796





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YFL_L





(215aa)


HIV1178
Light chain
1F7
U.S. Pat. No. 6,057,421A FIG. 8
8797


HIV1179
Light chain
1NC9
WO2012154312 SEQ ID NO: 2472
8798


HIV1180
Light chain
2.2C
Acharya, P., et al., Structural Definition of an
8799





Antibody-Dependent Cellular Cytotoxicity





Response Implicated in Reduced Risk for HIV-





1 Infection; J. Virol. 88 (21), 12895-12906





(2014), NCBI Accession # 4R4N_L (210aa)


HIV1181
Light chain
2F5
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 10
8800


HIV1182
Light chain
3040LC
WO2015117008 SEQ ID NO: 29
8801


HIV1183
Light chain
3044LC
WO2015117008 SEQ ID NO: 32
8802


HIV1184
Light chain
3430LC
WO2015117008 SEQ ID NO: 30
8803


HIV1185
Light chain
3484LC
WO2015117008 SEQ ID NO: 31
8804


HIV1186
Light chain
3630LC
WO2015117008 SEQ ID NO: 33
8805


HIV1187
Light chain
3A124KC
US20140328862 SEQ ID NO: 506
8806


HIV1188
Light chain
3A125KC
US20140328862 SEQ ID NO: 507
8807


HIV1189
Light chain
3A140LC
US20140328862 SEQ ID NO: 508
8808


HIV1190
Light chain
3A144KC
US20140328862 SEQ ID NO: 509
8809


HIV1191
Light chain
3A160KC
US20140328862 SEQ ID NO: 510
8810


HIV1192
Light chain
3A18KC
US20140328862 SEQ ID NO: 511
8811


HIV1193
Light chain
3A204KC
US20140328862 SEQ ID NO: 512
8812


HIV1194
Light chain
3A228KC
US20140328862 SEQ ID NO: 513
8813


HIV1195
Light chain
3A233LC
US20140328862 SEQ ID NO: 514
8814


HIV1196
Light chain
3A244LC
US20140328862 SEQ ID NO: 515
8815


HIV1197
Light chain
3A255LC
US20140328862 SEQ ID NO: 516
8816


HIV1198
Light chain
3A296KC
US20140328862 SEQ ID NO: 517
8817


HIV1199
Light chain
3A334LC
US20140328862 SEQ ID NO: 518
8818


HIV1200
Light chain
3A366KC
US20140328862 SEQ ID NO: 519
8819


HIV1201
Light chain
3A384KC
US20140328862 SEQ ID NO: 520
8820


HIV1202
Light chain
3A419KC
US20140328862 SEQ ID NO: 521
8821


HIV1203
Light chain
3a426kc
US20140328862 SEQ ID NO: 535
8822


HIV1204
Light chain
3A461KC
US20140328862 SEQ ID NO: 522
8823


HIV1205
Light chain
3A474KC
US20140328862 SEQ ID NO: 523
8824


HIV1206
Light chain
3a515kc
US20140328862 SEQ ID NO: 536
8825


HIV1207
Light chain
3A518KC
US20140328862 SEQ ID NO: 524
8826


HIV1208
Light chain
3A539LC
US20140328862 SEQ ID NO: 525
8827


HIV1209
Light chain
3A576LC
US20140328862 SEQ ID NO: 526
8828


HIV1210
Light chain
3A613LC
US20140328862 SEQ ID NO: 527
8829


HIV1211
Light chain
3A64KC
US20140328862 SEQ ID NO: 528
8830


HIV1212
Light chain
3A650KC
US20140328862 SEQ ID NO: 529
8831


HIV1213
Light chain
3A67KC
US20140328862 SEQ ID NO: 530
8832


HIV1214
Light chain
3A779KC
US20140328862 SEQ ID NO: 531
8833


HIV1215
Light chain
3A816KC
US20140328862 SEQ ID NO: 532
8834


HIV1216
Light chain
3A869KC
US20140328862 SEQ ID NO: 533
8835


HIV1217
Light chain
3A93LC
US20140328862 SEQ ID NO: 534
8836


HIV1218
Light chain
3anc3kc
US20140328862 SEQ ID NO: 547
8837


HIV1219
Light chain
3b106kc
US20140328862 SEQ ID NO: 548
8838


HIV1220
Light chain
3b129kc
US20140328862 SEQ ID NO: 537
8839


HIV1221
Light chain
3b16kc
US20140328862 SEQ ID NO: 549
8840


HIV1222
Light chain
3b171lc
US20140328862 SEQ ID NO: 538
8841


HIV1223
Light chain
3b180kc
US20140328862 SEQ ID NO: 550
8842


HIV1224
Light chain
3b183kc
US20140328862 SEQ ID NO: 551
8843


HIV1225
Light chain
3b191kc
US20140328862 SEQ ID NO: 552
8844


HIV1226
Light chain
3b21kc
US20140328862 SEQ ID NO: 553
8845


HIV1227
Light chain
3b27kc
US20140328862 SEQ ID NO: 539
8846


HIV1228
Light chain
3b41kc
US20140328862 SEQ ID NO: 540
8847


HIV1229
Light chain
3b46kc
US20140328862 SEQ ID NO: 542
8848


HIV1230
Light chain
3b57lc
US20140328862 SEQ ID NO: 543
8849


HIV1231
Light chain
3b5kc
US20140328862 SEQ ID NO: 541
8850


HIV1232
Light chain
3b8kc
US20140328862 SEQ ID NO: 544
8851


HIV1233
Light chain
3bnc102kc
US20140328862 SEQ ID NO: 554
8852


HIV1234
Light chain
3bnc104kc
US20140328862 SEQ ID NO: 555
8853


HIV1235
Light chain
3bnc105kc
US20140328862 SEQ ID NO: 556
8854


HIV1236
Light chain
3bnc107kc
US20140328862 SEQ ID NO: 557
8855


HIV1237
Light chain
3bnc108kc
US20140328862 SEQ ID NO: 558
8856


HIV1238
Light chain
3bnc117
Zhou T et al., Immunity 39 (2), 245-258 (2013),
8857





NCBI Accession # 4LSV_L(206aa)


HIV1239
Light chain
3bnc117kc
US20140328862 SEQ ID NO: 559
8858


HIV1240
Light chain
3bnc134kc
US20140328862 SEQ ID NO: 560
8859


HIV1241
Light chain
3bnc142kc
US20140328862 SEQ ID NO: 561
8860


HIV1242
Light chain
3bnc151kc
US20140328862 SEQ ID NO: 562
8861


HIV1243
Light chain
3bnc153kc
US20140328862 SEQ ID NO: 563
8862


HIV1244
Light chain
3bnc156kc
US20140328862 SEQ ID NO: 564
8863


HIV1245
Light chain
3bnc158kc
US20140328862 SEQ ID NO: 565
8864


HIV1246
Light chain
3bnc159kc
US20140328862 SEQ ID NO: 566
8865


HIV1247
Light chain
3bnc15kc
US20140328862 SEQ ID NO: 567
8866


HIV1248
Light chain
3bnc176kc
US20140328862 SEQ ID NO: 568
8867


HIV1249
Light chain
3bnc193kc
US20140328862 SEQ ID NO: 569
8868


HIV1250
Light chain
3bnc196kc
US20140328862 SEQ ID NO: 570
8869


HIV1251
Light chain
3bnc31kc
US20140328862 SEQ ID NO: 571
8870


HIV1252
Light chain
3bnc42kc
US20140328862 SEQ ID NO: 572
8871


HIV1253
Light chain
3bnc53kc
US20140328862 SEQ ID NO: 573
8872


HIV1254
Light chain
3BNC55KC
US20140328862 SEQ ID NO: 545
8873


HIV1255
Light chain
3BNC60KC
US20140328862 SEQ ID NO: 546
8874


HIV1256
Light chain
3bnc62kc
US20140328862 SEQ ID NO: 574
8875


HIV1257
Light chain
3bnc65kc
US20140328862 SEQ ID NO: 575
8876


HIV1258
Light chain
3bnc66kc
US20140328862 SEQ ID NO: 576
8877


HIV1259
Light chain
3bnc75kc
US20140328862 SEQ ID NO: 577
8878


HIV1260
Light chain
3bnc79kc
US20140328862 SEQ ID NO: 578
8879


HIV1261
Light chain
3bnc81kc
US20140328862 SEQ ID NO: 579
8880


HIV1262
Light chain
3bnc84kc
US20140328862 SEQ ID NO: 580
8881


HIV1263
Light chain
3bnc87kc
US20140328862 SEQ ID NO: 581
8882


HIV1264
Light chain
3bnc89kc
US20140328862 SEQ ID NO: 582
8883


HIV1265
Light chain
3bnc91kc
US20140328862 SEQ ID NO: 583
8884


HIV1266
Light chain
3bnc95kc
US20140328862 SEQ ID NO: 584
8885


HIV1267
Light chain
412d
Huang et al., Science 317 (5846), 1930-1934
8886





(2007), NCBI Accession # 2QAD_G (214aa)


HIV1268
Light Chain
44-vrc13.01
Zhon T et al., Structural Repertoire of HIV-1-
8887





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YDJ_B





(206aa)


HIV1269
Light chain
45-46m2
Diskin, R., et al., Restricting HIV-1 pathways
8888





for escape using rationally designed anti-HIV-1





antibodies; J. Exp. Med. 210 (6), 1235-1249





(2013), NCBI Accession # 4JKP_L (210aa)


HIV1270
Light chain
4835_F12
US20140205612 SEQ ID NO: 413
8889




(PGT-124)


HIV1271
Light chain
4838_L06
US20140205612 SEQ ID NO: 148
8890




(PGT-121)


HIV1272
Light chain
4858_P08
US20140205612 SEQ ID NO: 176
8891




(PGT-123)


HIV1273
Light chain
4869-K15
US20140205612 SEQ ID NO: 428
8892




(PGT-133)


HIV1274
Light chain
4873_E03
US20140205612 SEQ ID NO: 147
8893




(PGT-121)


HIV1275
Light chain
4876_M06
US20140205612 SEQ ID NO: 439
8894




(PGT-134)


HIV1276
Light chain
4877_D15
US20140205612 SEQ ID NO: 160
8895




(PGT-122)


HIV1277
Light chain
4964_G22
US20140205612 SEQ ID NO: 284
8896




(PGT-141),




4993_K13




(PGT-141),




4995_E20




(PGT-142)


HIV1278
Light chain
4970_K22
US20140205612 SEQ ID NO: 312
8897




(PGT-144)


HIV1279
Light chain
4980_N08
US20140205612 SEQ ID NO: 301
8898




(PGT-143)


HIV1280
Light chain
4995_P16
US20140205612 SEQ ID NO: 385
8899




(PGT-145)


HIV1281
Light chain
4e10 Fv
Finton, K. A., et al., PLoS Pathol. 9 (9),
8900





E1003639 (2013), NCBI Accession # 4LLV_B





(112aa)


HIV1282
Light chain
5114_A19
US20140205612 SEQ ID NO: 392
8901




(PGT-128)


HIV1283
Light chain
5120_N10
US20140205612 SEQ ID NO: 469
8902




(PGT-139)


HIV1284
Light chain
5131_A17
US20140205612 SEQ ID NO: 488
8903




(PGT-132)


HIV1285
Light chain
5136_H01
US20140205612 SEQ ID NO: 355
8904




(PGT-131)


HIV1286
Light chain
5138_G07
US20140205612 SEQ ID NO: 483
8905




(PGT-138)


HIV1287
Light chain
5141_B17
US20140205612 SEQ ID NO: 208
8906




(PGT-126)


HIV1288
Light chain
5145_B14
US20140205612 SEQ ID NO: 329
8907




(PGT-127)


HIV1289
Light chain
5147_N06
US20140205612 SEQ ID NO: 244
8908




(PGT-130)


HIV1290
Light chain
5329_C19
US20140205612 SEQ ID NO: 257
8909




(PGT-136),




5366_P21




(PGT-136)


HIV1291
Light chain
5343_B08
US20140205612 SEQ ID NO: 240
8910




(PGT-135),




5344_E16




(PGT-135)


HIV1292
Light chain
5345_I01
US20140205612 SEQ ID NO: 396
8911




(PGT-137)


HIV1293
Light chain
6808_B09
US20140205612 SEQ ID NO: 553
8912




(PGT-156)


HIV1294
Light chain
6831_A21
US20140205612 SEQ ID NO: 482
8913




(PGT-151)


HIV1295
Light chain
6843_G20
US20140205612 SEQ ID NO: 524
8914




(PGT-154)


HIV1296
Light chain
6881_N05
US20140205612 SEQ ID NO: 578
8915




(PGT-158).


HIV1297
Light chain
6889_I17
US20140205612 SEQ ID NO: 496
8916




(PGT-152)


HIV1298
Light chain
6891_F06
US20140205612 SEQ ID NO: 510
8917




(PGT-153)


HIV1299
Light chain
6892_C23
US20140205612 SEQ ID NO: 565
8918




(PGT-157)


HIV1300
Light chain
6892_D19
US20140205612 SEQ ID NO: 539
8919




(PGT-155)


HIV1301
Light chain
7H6
US20140348785 SEQ ID NO: 4
8920


HIV1302
Light chain
7N16
US20140348785 SEQ ID NO: 6
8921


HIV1303
Light chain
8anc131
Zhou T et al. Structural Repertoire of HIV-1-
8922





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4RWY_L





(213aa)


HIV1304
Light chain
8ANC131KC
US20140328862 SEQ ID NO: 440
8923


HIV1305
Light chain
8anc134
Zhou T et al, Structural Repertoire of HIV-1-
8924





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4RX4_L





(213aa)


HIV1306
Light chain
8ANC134KC
US20140328862 SEQ ID NO: 441
8925


HIV1307
Light chain
8ANC13KC
US20140328862 SEQ ID NO: 442
8926


HIV1308
Light chain
8ANC14KC
US20140328862 SEQ ID NO: 448
8927


HIV1309
Light chain
8ANC16KC
US20140328862 SEQ ID NO: 449
8928


HIV1310
Light chain
8anc182kc
US20140328862 SEQ ID NO: 446
8929


HIV1311
Light chain
8anc192kc
US20140328862 SEQ ID NO: 447
8930


HIV1312
Light chain
8ANC195KC
US20140328862 SEQ ID NO: 450
8931


HIV1313
Light chain
8ANC24KC
US20140328862 SEQ ID NO: 451
8932


HIV1314
Light chain
8ANC45KC
US20140328862 SEQ ID NO: 443
8933


HIV1315
Light chain
8ANC50KC
US20140328862 SEQ ID NO: 444
8934


HIV1316
Light chain
8ANC5KC
US20140328862 SEQ ID NO: 452
8935


HIV1317
Light chain
8ANC88KC
US20140328862 SEQ ID NO: 445
8936


HIV1318
Light chain
Anti-HcG
Fotinou C. et al “Structure of an Fab fragment
8937





against a C-terminal peptide of hCG at 2.0 A





resolution” J. Biol. Chem. 273 (35), 22515-





22518 (1998); NCBI Accession # 1SBS_L


HIV1319
Light chain
B12
Zhou T et al., Structural definition of a
8938





conserved neutralization epitope on HIV-1





gp120; Nature 445 (7129), 732-737 (2007),





NCBI Accession # 2NY7_L (215aa)


HIV1320
Light Chain
C38-vrc16.01
Zhou T et al., Structural Repertoire of HIV-1-
8939





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YDK_L





(214aa)


HIV1321
Light chain
C38-vrc18.02
Zhou T et al., Structural Repertoire of HIV-1-
8940





Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YDL_L





(211aa)


HIV1322
Light chain
CAP256-
WO2015128846 SEQ ID NO: 14
8941




VRC26.01


HIV1323
Light chain
CAP256-
WO2015128846 SEQ ID NO: 18
8942




VRC26.02


HIV1324
Light chain
CAP256-
WO2015128846 SEQ ID NO: 22
8943




VRC26.03


HIV1325
Light chain
CAP256-
WO2015128846 SEQ ID NO: 26
8944




VRC26.04


HIV1326
Light chain
CAP256-
WO2015128846 SEQ ID NO: 30
8945




VRC26.05


HIV1327
Light chain
CAP256-
WO2015128846 SEQ ID NO: 34
8946




VRC26.06


HIV1328
Light chain
CAP256-
WO2015128846 SEQ ID NO: 38
8947




VRC26.07


HIV1329
Light chain
CAP256-
WO2015128846 SEQ ID NO: 42
8948




VRC26.08


HIV1330
Light chain
CAP256-
WO2015128846 SEQ ID NO: 46
8949




VRC26.09


HIV1331
Light chain
CAP256-
WO2015128846 SEQ ID NO: 50
8950




VRC26.10


HIV1332
Light chain
CAP256-
WO2015128846 SEQ ID NO: 54
8951




VRC26.11


HIV1333
Light chain
CAP256-
WO2015128846 SEQ ID NO: 58
8952




VRC26.12


HIV1334
Light chain
CAP256-
WO2015128846 SEQ ID NO: 171
8953




VRC26.25


HIV1335
Light chain
CAP256-
WO2015128846 SEQ ID NO: 179
8954




VRC26.26


HIV1336
Light chain
CAP256-
WO2015128846 SEQ ID NO: 187
8955




VRC26.27


HIV1337
Light chain
CAP256-
WO2015128846 SEQ ID NO: 6
8956




VRC26-I1


HIV1338
Light chain
CAP256-
WO2015128846 SEQ ID NO: 10
8957




VRC26-I2


HIV1339
Light chain
CAP256-
WO2015128846 SEQ ID NO: 2
8958




VRC26-




UCA.


HIV1340
Light chain
construct
WO2015013390 SEQ ID NO: 5
8959




#2816, #2861


HIV1341
Light chain
construct
WO2015013390 SEQ ID NO: 6
8960




#2817, #2860


HIV1342
Light chain
construct
WO2015013390 SEQ ID NO: 7
8961




#2858,




#2859, #2861


HIV1343
Light chain
Fab 2219
Stanfield, R. L., et al., J. Virol. 80 (12), 6093-
8962





6105 (2006), NCBI Accession # 2B0S_L





(215aa)


HIV1344
Light chain
Fab 2g12
Doores, K. J., et al., J. Virol. 84 (20), 10690-
8963





10699 (2010), NCBI Accession #





3OAU_L(212a)


HIV1345
Light chain
Fab 2g12
Stanfield, R. L. et al., Crystal structure of the
8964





HIV neutralizing antibody 2G12, in complex





with a bacterial oligosaccharide analog of





mammalian oligomannose; Glycobiology 25





(4), 412-419 (2015), NCBI Accession #





4RBP_L (213aa)


HIV1346
Light chain
Fab F425-
Bell et al., J. Mol. Biol. 375 (4), 969-978
8965




b4e8
(2008), NCBI Accession # 2QSC_L (215aa)


HIV1347
Light chain
G4D
US20130195881 SEQ ID NO: 39
8966


HIV1348
Light chain
G4H
US20130195881 SEQ ID NO: 38
8967


HIV1349
Light chain
gVRC-H5(d74)/
WO2013090644 SEQ ID NO: 19
8968




VRC-PG04LC,




gVRCOH12(D74)/




VRC-PG04LC


HIV1350
Light chain
12 (unbound)
Fera, D. et al., Affinity maturation in an HIV
8969




From Ch103
broadly neutralizing B-cell lineage through




Lineage
reorientation of variable domains; Proc. Natl.





Acad. Sci. U.S.A. 111 (28), 10275-10280





(2014), NCBI Accession # 4QHN_B (213aa)


HIV1351
Light chain
IGLV3-
US20140348785 SEQ ID NO: 8
8970




19*01


HIV1352
Light chain
k3
WO2015117008 SEQ ID NO: 19
8971


HIV1353
Light chain
k5
WO2015117008 SEQ ID NO: 20
8972


HIV1354
Light chain
k53
WO2015117008 SEQ ID NO: 24
8973


HIV1355
Light chain
k59
WO2015117008 SEQ ID NO: 21
8974


HIV1356
Light chain
k61
WO2015117008 SEQ ID NO: 25
8975


HIV1357
Light chain
k62
WO2015117008 SEQ ID NO: 22
8976


HIV1358
Light chain
k81
WO2015117008 SEQ ID NO: 28
8977


HIV1359
Light chain
kl 1
WO2015117008 SEQ ID NO: 26
8978


HIV1360
Light chain
kl8
WO2015117008 SEQ ID NO: 23
8979


HIV1361
Light chain
kl9
WO2015117008 SEQ ID NO: 27
8980


HIV1362
Light chain
LSSB2066KC
US20140328862 SEQ ID NO: 501
8981


HIV1363
Light chain
LSSB2080KC
US20140328862 SEQ ID NO: 502
8982


HIV1364
Light chain
LSSB2133KC
US20140328862 SEQ ID NO: 503
8983


HIV1365
Light chain
LSSB2182KC
US20140328862 SEQ ID NO: 504
8984


HIV1366
Light chain
LSSB2339LC
US20140328862 SEQ ID NO: 467
8985


HIV1367
Light chain
LSSB2351LC
US20140328862 SEQ ID NO: 468
8986


HIV1368
Light chain
LSSB2364LC
US20140328862 SEQ ID NO: 469
8987


HIV1369
Light chain
LSSB2367LC
US20140328862 SEQ ID NO: 470
8988


HIV1370
Light chain
LSSB2490LC
US20140328862 SEQ ID NO: 471
8989


HIV1371
Light chain
LSSB2530LC
US20140328862 SEQ ID NO: 472
8990


HIV1372
Light chain
LSSB2554LC
US20140328862 SEQ ID NO: 473
8991


HIV1373
Light chain
LSSB2586LC
US20140328862 SEQ ID NO: 474
8992


HIV1374
Light chain
LSSB2612LC
US20140328862 SEQ ID NO: 475
8993


HIV1375
Light chain
LSSB2640LC
US20140328862 SEQ ID NO: 476
8994


HIV1376
Light chain
LSSB2644LC
US20140328862 SEQ ID NO: 477
8995


HIV1377
Light chain
LSSB2666LC
US20140328862 SEQ ID NO: 478
8996


HIV1378
Light chain
LSSB2680LC
US20140328862 SEQ ID NO: 479
8997


HIV1379
Light chain
LSSB2683LC
US20140328862 SEQ ID NO: 480
8998


HIV1380
Light chain
LSSB331KC
US20140328862 SEQ ID NO: 505
8999


HIV1381
Light chain
LSSB344LC
US20140328862 SEQ ID NO: 481
9000


HIV1382
Light chain
LSSNEC107LC
US20140328862 SEQ ID NO: 482
9001


HIV1383
Light chain
LSSNEC108LC
US20140328862 SEQ ID NO: 483
9002


HIV1384
Light chain
LSSNEC117LC
US20140328862 SEQ ID NO: 484
9003


HIV1385
Light chain
LSSNEC118LC
US20140328862 SEQ ID NO: 485
9004


HIV1386
Light chain
LSSNEC122LC
US20140328862 SEQ ID NO: 486
9005


HIV1387
Light chain
LSSNEC24LC
US20140328862 SEQ ID NO: 487
9006


HIV1388
Light chain
LSSNEC2LC
US20140328862 SEQ ID NO: 488
9007


HIV1389
Light chain
LSSNEC33LC
US20140328862 SEQ ID NO: 489
9008


HIV1390
Light chain
LSSNEC46LC
US20140328862 SEQ ID NO: 490
9009


HIV1391
Light chain
LSSNEC48LC
US20140328862 SEQ ID NO: 491
9010


HIV1392
Light chain
LSSNEC52LC
US20140328862 SEQ ID NO: 492
9011


HIV1393
Light chain
LSSNEC56LC
US20140328862 SEQ ID NO: 493
9012


HIV1394
Light chain
LSSNEC60LC
US20140328862 SEQ ID NO: 494
9013


HIV1395
Light chain
LSSNEC70LC
US20140328862 SEQ ID NO: 495
9014


HIV1396
Light chain
LSSNEC72LC
US20140328862 SEQ ID NO: 496
9015


HIV1397
Light chain
LSSNEC7LC
US20140328862 SEQ ID NO: 497
9016


HIV1398
Light chain
LSSNEC89LC
US20140328862 SEQ ID NO: 498
9017


HIV1399
Light chain
LSSNEC94LC
US20140328862 SEQ ID NO: 499
9018


HIV1400
Light chain
LSSNEC9LC
US20140328862 SEQ ID NO: 500
9019


HIV1401
Light chain
m12-Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 7
9020


HIV1402
Light chain
m14-Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 5
9021


HIV1403
Light chain
m16-Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 8
9022


HIV1404
Light chain
m18 Fd-aa
U.S. Pat. No. 7,803,913B2 SEQ ID NO: 6
9023


HIV1405
Light chain
M66
Ofek, G., et al., Structural Basis for HIV-1
9024





Neutralization by 2F5-Like Antibodies m66





and m66.6; J. Virol. 88 (5), 2426-2441 (2014),





NCBI Accession # 4NRY_H (235aa)


HIV1406
Light chain
M66.6
Ofek, G., et al., Structural Basis for HIV-1
9025





Neutralization by 2F5-Like Antibodies m66





and m66.6; J. Virol. 88 (5), 2426-2441 (2014),





NCBI Accession # 4NRZ_L (213aa)


HIV1407
Light Chain
Mab 2158
Spurrier, B., et al., Functional Implications of
9026





the Binding Mode of a Human Conformation-





Dependent V2 Monoclonal Antibody against





HIV; J. Virol, 88 (8), 4100-4112 (2014), NCBI





Accession # 4OAW_C (214aa)


HIV1408
Light chain
MV1
US20130195881 SEQ ID NO: 40
9027


HIV1409
Light chain
Pg16 Fab
Pancera, M., et al., Nat. Struct. Mol. Biol. 20
9028





(7), 804-813 (2013), NCBI Accession #





4DQO_L (216aa)


HIV1410
Light chain
Pg9
Willis, J. R., et al., J. Clin. Invest. 125 (6), 2523-
9029





2531 (2015), NCBI Accession # 4YAQ_L





(216aa)


HIV1411
Light chain
Pgt121-Gl
Mouquet H et al., Complex-type N-glycan
9030




Fab
recognition by potent broadly neutralizing HIV





antibodies; Proc Natl Acad Sci USA. 2012





Nov. 20; 109(47): E3268-77, NCBI Accession #





4FQQ_A (215aa)


HIV1412
Light chain
Pgt122
Julien, J. P., et al., PLoS Pathol. 9 (5),
9031





E1003342 (2013)”, NCBI Accession # 4JY5_L





(211aa)


HIV1413
Light chain
Pgt123
Julien, J. P., et al., PLoS Pathol. 9 (5),
9032





E1003342 (2013)”, NCBI Accession # 4JY6_A





(211aa)


HIV1414
Light chain
Pgt124
Garces, F., et al., Structural Evolution of
9033





Glycan Recognition by a Family of Potent HIV





Antibodies; Cell 159 (1), 69-79 (2014), NCBI





Accession # 4R26_L (214aa)


HIV1415
Light chain
Pgt130
Doores, K. J., et al., J. Virol. 89 (2), 1105-1118
9034





(2015), NCBI Accession # 4RNR_B (216aa)


HIV1416
Light chain
Pgt135
Grover et al., Science 343 (6171), 656-661
9035





(2014), NCBI Accession # 4NZR_L (214aa)


HIV1417
Light chain
S8, S19, S20
US20110059015 SEQ ID NO: 2
9036


HIV1418
light chain
Suvizumab

9037


HIV1419
Light Chain
Vrc- Pg04
Wu, X., et al., Focused evolution of HIV-1
9038





neutralizing antibodies revealed by structures





and deep sequencing; Science 333 (6049),





1593-1602 (2011)”, NCBI Accession # 3SE9_L





(208aa)


HIV1420
Light chain
VRC01
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 2
9039


HIV1421
Light chain
VRC01
US2014 0322163 SEQ ID NO: 53
9040




E1/12




deletion


HIV1422
Light chain
VRC01
US2014 0322163 SEQ ID NO: 222
9041




E1/I2del




F97D


HIV1423
Light chain
VRC01
US2014 0322163 SEQ ID NO: 225
9042




E1/I2del




F97H


HIV1424
Light chain
VRC01
US2014 0322163 SEQ ID NO: 223
9043




E1/I2del




F97K


HIV1425
Light chain
VRC01
US2014 0322163 SEQ ID NO: 224
9044




E1/I2del




F97S


HIV1426
Light chain
VRC01
US2014 0322163 SEQ ID NO: 219
9045




E1/I2del V3E


HIV1427
Light chain
VRC01
US2014 0322163 SEQ ID NO: 227
9046




E1/I2del




V3E, F97H


HIV1428
Light chain
VRC01
US2014 0322163 SEQ ID NO: 226
9047




E1/I2del




V3E, F97S


HIV1429
Light chain
VRC01
US2014 0322163 SEQ ID NO: 220
9048




E1/I2del V3K


HIV1430
Light chain
VRC01
US2014 0322163 SEQ ID NO: 221
9049




E1/I2del V3S


HIV1431
Light chain
VRC01HC/
WO2013090644 SEQ ID NO: 31
9050




VRC03LC


HIV1432
Light chain
VRC01hpL02
US2014 0322163 SEQ ID NO: 50
9051


HIV1433
Light chain
VRC01hpL02
US2014 0322163 SEQ ID NO: 232
9052




E1/I2-




deletion, V3S


HIV1434
Light chain
VRC01hpL03
US2014 0322163 SEQ ID NO: 228
9053


HIV1435
Light chain
VRC01hpL04
US2014 0322163 SEQ ID NO: 229
9054


HIV1436
Light chain
VRC01hpL05
US2014 0322163 SEQ ID NO: 230
9055


HIV1437
Light chain
VRC01hpL06
US2014 0322163 SEQ ID NO: 231
9056


HIV1438
Light chain
VRC01LhpL
US2014 0322163 SEQ ID NO: 233
9057




03 E1/I2-




deletion, V3S


HIV1439
Light chain
VRC01LhpL
US2014 0322163 SEQ ID NO: 237
9058




04 E1/I2-




deletion, V3E


HIV1440
Light chain
VRC01LhpL
US2014 0322163 SEQ ID NO: 234
9059




04 E1/I2-




deletion, V3S


HIV1441
Light chain
VRC01LhpL
US2014 0322163 SEQ ID NO: 235
9060




05 E1/12




deletion, V3S


HIV1442
Light chain
VRC01LhpL
US2014 0322163 SEQ ID NO: 236
9061




06 E1/I2-




deletion, V3S


HIV1443
Light chain
VRC02
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 4
9062


HIV1444
Light chain
VRC03
U.S. Pat. No. 8,637,036B2 SEQ ID NO: 28
9063


HIV1445
Light chain
VRC03HC-
WO2013090644 SEQ ID NO: 1
9064




VRC01LC


HIV1446
Light chain
Vrc06b
Wu, X., et al., Maturation and Diversity of the
9065





VRC01-Antibody Lineage over 15 Years of





Chronic HIV-1 Infection; Cell 161 (3), 470-485





(2015), NCBI Accession # 4XNZ_F (209aa)


HIV1447
Light chain
Vrc08c
Wu, X., et al., Maturation and Diversity of the
9066





VRC01-Antibody Lineage over 15 Years of





Chronic HIV-1 Infection; Cell 161 (3), 470-485





(2015), NCBI Accession # 4XNY_L (211aa)


HIV1448
Light chain
Vrc23
Georgiev, I. S., et al., Delineating antibody
9067





recognition in polyclonal sera from patterns of





HIV-1 isolate neutralization; Science 340





(6133), 751-756 (2013), NCBI Accession #





4J6R_L (210aa)


HIV1449
Light chain
VRC-CH30
WO2013090644 SEQ ID NO: 21
9068


HIV1450
Light chain
Vrc-ch31
Zhou T et al., Immunity 39 (2), 245-258 (2013),
9069





NCBI Accession # 4LSP_L (210aa)


HIV1451
Light chain
VRC-CH32
Wu X. et al., “Focused evolution of HIV-1
9070





neutralizing antibodies revealed by structures





and deep sequencing” Science 333 (6049),





1593-1602 (2011), NCBI Accession #





AEM62727


HIV1452
Light chain
VRC-CH33
WO2013090644 SEQ ID NO: 27
9071


HIV1453
Light chain
VRC-CH34
WO2013090644 SEQ ID NO: 29
9072


HIV1454
Light chain
VRC-PG04
Wu X. et al,“Focused evolution of HIV-1
9073





neutralizing antibodies revealed by structures





and deep sequencing” Science 333 (6049),





1593-1602 (2011), NCBI Accession #





AEM62754


HIV1455
Light chain
VRC-PG04b
WO2013090644 SEQ ID NO: 43
9074


HIV1456
Light chain
Vrc-pg20
Zhou T et al., immunity 39 (2), 245-258 (2013),
9075





NCBI Accession # 4LSU_L (204aa)


HIV1457
Light chain
X5
U.S. Pat. No. 7,378,093B2 SEQ ID NO: 2
9076


HIV1458
Light chain
X5
U.S. Pat. No. 8,110,192B2 SEQ ID NO: 4
9077


HIV1459
Light chain
Z13e1
Stanfield. R. L., et al, J. Mol. Biol. 414 (3), 460-
9078





476 (2011), NCBI Accession # 3Q1S_L





(212aa)


HIV1460
Light Chain
Z258-
Zhon T et al., Structural Repertoire of HIV-1-
9079




vrc27.01
Neutralizing Antibodies Targeting the CD4





Supersite in 14 Donors; Cell 161 (6), 1280-





1292 (2015), NCBI Accession # 4YDI_L





(210aa)


HIV1461
Light chain

NCBI Accession # 1N0X_M (215aa)
9080


HIV1462
Light chain

Okada, N., et al., Human IgM Monoclonal
9081





Antibodies Reactive with HIV-1-Infected Cells





Generated Using a Trans-Chromosome Mouse;





Microbiol. Immunol. 49 (5), 447-459 (2005),





NCBI Accession # AAS01772.1(236aa)


HIV1463
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 101
9082


HIV1464
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 102
9083


HIV1465
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 103
9084


HIV1466
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 104
9085


HIV1467
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 105
9086


HIV1468
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 107
9087


HIV1469
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 110
9088


HIV1470
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 115
9089


HIV1471
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 118
9090


HIV1472
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 121
9091


HIV1473
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 122
9092


HIV1474
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 124
9093


HIV1475
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 132
9094


HIV1476
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 147
9095


HIV1477
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 148
9096


HIV1478
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 149
9097


HIV1479
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 150
9098


HIV1480
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 151
9099


HIV1481
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 95
9100


HIV1482
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 96
9101


HIV1483
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 97
9102


HIV1484
Light chain

U.S. Pat. No. 5,804,440A SEQ ID NO: 98
9103


HIV1485
Light chain

WO2014063059 SEQ ID NO: 11
9104


HIV1486
Light chain

WO2014063059 SEQ ID NO: 129
9105


HIV1487
Light chain

WO2014063059 SEQ ID NO: 13
9106


HIV1488
Light chain

WO2014063059 SEQ ID NO: 15
9107


HIV1489
Light chain

WO2014063059 SEQ ID NO: 17
9108


HIV1490
Light chain

WO2014063059 SEQ ID NO: 19
9109


HIV1491
Light chain

WO2014063059 SEQ ID NO: 21
9110


HIV1492
Light chain

WO2014063059 SEQ ID NO: 23
9111


HIV1493
Light chain

WO2014063059 SEQ ID NO: 3
9112


HIV1494
Light chain

WO2014063059 SEQ ID NO: 5
9113


HIV1495
Light chain

WO2014063059 SEQ ID NO: 7
9114


HIV1496
Light chain

WO2014063059 SEQ ID NO: 9
9115


HIV1497
Light chain

WO2014063059 SEQ ID NO: 1
9116



consensus


HIV1498
Light chain constant
TNX-355,
US20130195881 SEQ ID NO: 2
9117



region
Idalizumab


HIV1499
Light Chain Fab
Ch02
McLellan, J. S., et al., Nature 480 (7377), 336-
9118





343 (2011), NCBI Accession # 3U46_B





(215aa)


HIV1500
Light Chain Of Anti-
21C
Diskin, R., et al., Nat. Struct. Mol. Biol. 17 (5),
9119



HIV Fab From

608-613 (2010), NCBI Accession # 3LMJ_L



Human 21c Antibody

(217aa)


HIV1501
Light Chain Of Anti-
830a
Pan et al., J. Virol. 89 (15), 8003-8010 (2015),
9120



hiv-1 Gp120 V1v2

NCBI Accession # 4YWG_L (216aa)



Antibody 830a


HIV1502
Light Chain Of Anti-
Fab 2558
Gorny et al., PLoS ONE 6 (12), E27780 (2011),
9121



hiv-1 V3 Monoclonal

NCBI Accession # 3UJI_L (209aa)



Antibody


HIV1503
Light Chain Of Anti-
Fab 4025
Gorny et al., PLoS ONE 6 (12), E27780 (2011),
9122



hiv-1 V3 Monoclonal

NCBI Accession # 3UJJ_L (213aa)



Antibody


HIV1504
Light chain partial
412D
Huang C. et al “Structural basis of tyrosine
9123





sulfation and VH-gene usage in antibodies that





recognize the HIV type 1 coreceptor-binding





site on gp120” Proc. Natl. Acad. Sci. U.S.A.





101 (9), 2706-2711 (2004), NCBI Accession #





AAR88380


HIV1505
Light chain partial
694/98D
Li L. et al, “A broad range of mutations in HIV-
9124





1 neutralizing human monoclonal antibodies





specific for V2, V3, and the CD4 binding site”,





Mol. Immunol. 66 (2), 364-374 (2015); NCBI





Accession # AKH36512


HIV1506
Light chain variable
0.5γ (1C10)
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 2
9125



region


HIV1507
Light chain variable
0.5γ (3D6)
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 6
9126



region


HIV1508
Light chain variable
10J4 mAb
WO2015103549 SEQ ID NO: 4
9127



region


HIV1509
Light chain variable
10M6 mAb
WO2015103549 SEQ ID NO: 6
9128



region


HIV1510
Light chain variable
13110 mAb
WO2015103549 SEQ ID NO: 8
9129



region


HIV1511
Light chain variable
2N5mAb
WO2015103549 SEQ ID NO: 10
9130



region


HIV1512
Light chain variable
35022 mAb
WO2015103549 SEQ ID NO: 2
9131



region


HIV1513
Light chain variable
42F9
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 8
9132



region


HIV1514
Light chain variable
49G2
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 10
9133



region


HIV1515
Light chain variable
4O20mAb
WO2015103549 SEQ ID NO: 12
9134



region


HIV1516
Light chain variable
5G2
U.S. Pat. No. 8,722,861B2 SEQ ID NO: 4
9135



region


HIV1517
Light chain variable
7B9mAb
WO2015103549 SEQ ID NO: 14
9136



region


HIV1518
Light chain variable
7K3mAb
WO2015103549 SEQ ID NO: 16
9137



region


HIV1519
Light chain variable
B4
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 4
9138



region


HIV1520
Light chain variable
B4DIVKv.1
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 9
9139



region


HIV1521
Light chain variable
B4DIVKv.2
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 10
9140



region


HIV1522
Light chain variable
B4DIVKv.3
U.S. Pat. No. 7,872,110B2 SEQ ID NO: 11
9141



region


HIV1523
Light chain variable
bl2 IgA2
WO2014040024 SEQ ID NO: 30
9142



region
antibody


HIV1524
Light chain variable
CHμ39.1
U.S. Pat. No. 5,773,247 SEQ ID NO: 12
9143



region


HIV1525
Light chain variable
CHμ5.5
U.S. Pat. No. 5,773,247 SEQ ID NO: 16
9144



region


HIV1526
Light chain variable
F425-Alg8
WO2014040024 SEQ ID NO: 13
9145



region
antibody


HIV1527
Light chain variable
Fab 43
US20090191216 SEQ ID NO: 9
9146



region


HIV1528
Light chain variable
HGN194
US20110212106 SEQ ID NO: 46
9147



region


HIV1529
Light chain variable
HJ16
US20110212106 SEQ ID NO: 14
9148



region


HIV1530
Light chain variable
HK20
US20110212106 SEQ ID NO: 30
9149



region


HIV1531
Light chain variable
IgA antibody
WO2014040024 SEQ ID NO: 15
9150



region


HIV1532
Light chain variable
Makandal
US20100111990 SEQ ID NO: 3
9151



region
monoclonal




antibody




(Mmab)


HIV1533
Light chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 18
9152



region


HIV1534
Light chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 28
9153



region
HuVH


HIV1535
Light chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 30
9154



region
HuVK


HIV1536
Light chain variable
NM-01
U.S. Pat. No. 5,665,569 SEQ ID NO: 32
9155



region
HuVKF


HIV1537
Light chain variable
PGT125
Walker L. M. et al “Broad neutralization
9156



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14410


HIV1538
Light chain variable
PGT126
Walker L. M. et al “Broad neutralization
9157



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14411


HIV1539
Light chain variable
PGT131
Walker L. M. et al “Broad neutralization
9158



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AENT4415


HIV1540
Light chain variable
PGT136
Walker L. M. et al “Broad neutralization
9159



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14417


HIV1541
Light chain variable
PGT137
Walker L. M. et al “Broad neutralization
9160



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14418


HIV1542
Light chain variable
PGT141
Walker L. M. et al “Broad neutralization
9161



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession# AEN14419


HIV1543
Light chain variable
PGT142
Walker L.M. et al “Broad neutralization
9162



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(20 1 I), NCBI Accessiots # AEN14385


HIV1544
Light chain variable
PGT143
Walker L.M. et al “Broad neutralization
9163



region

coverage of HIV by multiple liighly potent





antibodies”. Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14421


HIV1545
Light chain variable
PGT144
Walker L.M. et al “Broad neutralization
9164



region

coverage of HIV by multiple highly potent





antibodies”, Nature 477 (7365), 466-470





(2011), NCBI Accession # AEN14422


HIV1546
Light chain variable
PGT151
Falkowska, E. et al “Broadly Neutralizing HIV
9165



region

Antibodies Define a Gly can-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32543


HIV1547
Light chain variable
PGT152
Falkowska, E. et al “Broadly Neutralizing HIV
9166



region

Antibodies Define a Glycan-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32544


HIV1548
Light chain variable
PGT153
Falkowska, E. et al “Broadly Neutralizing HIV
9167



region

Antibodies Define a Glycan-Dependent Epitope





on the Profusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (>).





657-668 (2014), NCBI Accession # AIC32545


HIV1549
Light chain variable
PGT154
Falkowska, E. et al “Broadly Neutralizing HIV
9168



region

Antibodies Define a Glycan-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32529


HIV1550
Light chain variable
PGT155
Falkowska, E. et al “Broadly Neutralizing HIV
9169



region

Antibodies Define a Glycan-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32547


HIV1551
Light chain variable
PGT156
Falkowska, E. et al “Broadly Neutralizing HIV
9170



region

Antibodies Define a Glycan-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32548


HIV1552
Light chain variable
PGT157
Falkowska, E. et al “Broadly Neutralizing HIV
9171



region

Antibodies Define a Glycan-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32549


HIV1553
Light chain variable
PGTI58
Falkowska, E. et al “Broadly Neutralizing HIV
9172



region

Antibodies Define a Glycan-Dependent Epitope





on the Prefusion Conformation of gp41 on





Cleaved Envelope Trimers” Immunity 40 (5),





657-668 (2014), NCBI Accession # AIC32550


HIV1554
Light chain variable
rF105
WO1993012232 SEQ ID NO: 3
9173



region


HIV1555
Light chain variable
ScFvX5-CD4
U.S. Pat. No. 7,378,093B2 SEQ ID NO: 15
9174



region


HIV1556
Light chain variable
TNX-355,
US20130195881 SEQ ID NO: 1
9175



region
Idalizumab


HIV1557
Light chain variable
VCR14
US20150044137 SEQ ID NO: 25
9176



region


HIV1558
Light chain variable
VCR14b
US20150044137 SEQ ID NO: 26
9177



region


HIV1559
Light chain variable
VCR14c
US20150044137 SEQ ID NO: 27
9178



region


HIV1560
Light chain variable
VCR16
US20150044137 SEQ ID NO: 33
9179



region


HIV1561
Light chain variable
VCR16b
US20150044137 SEQ ID NO: 34
9180



region


HIV1562
Light chain variable
VCR16c
US20150044137 SEQ ID NO: 35
9181



region


HIV1563
Light chain variable
VCR16d
US20150044137 SEQ ID NO: 36
9182



region


HIV1564
Light chain variable
VRC13
US20150044137 SEQ ID NO: 17
9183



region


HIV1565
Light chain variable
VRC13b
US20150044137 SEQ ID NO: 18
9184



region


HIV1566
Light chain variable
VRC13c
US20150044137 SEQ ID NO: 19
9185



region


HIV1567
Light chain variable
VRC13d
US20150044137 SEQ ID NO: 20
9186



region


HIV1568
Light chain variable
VRC13e
US20150044137 SEQ ID NO: 21
9187



region


HIV1569
Light chain variable
VRC13f
US20150044137 SEQ ID NO: 22
9188



region


HIV1570
Light chain variable
VRC13g
US20150044137 SEQ ID NO: 23
9189



region


HIV1571
Light chain variable
VRC13h
US20150044137 SEQ ID NO: 24
9190



region


HIV1572
Light chain variable
VRC15
US20150044137 SEQ ID NO: 28
9191



region


HIV1573
Light chain variable

US20150004190 SEQ ID NO: 57
9192



region


HIV1574
Light Chain, Fab
Ch04
McLellan, J. S. et al., Structure of HIV-1 gp120
9193





V1 V2 domain with broadly neutralizing





antibody PC9; Nature 480 (7377), 336-343





(2011), NCBI Accession # 3TCL_B (215aa)


HIV1575
Light Chain, Fab
N5-i5
Acharya, P., et al., Structural Definition of an
9194





Antibody-Dependent Cellular Cytotoxicity





Response Implicated in Reduced Risk for HIV-





1 Infection; J. Virol. 88 (21), 12895-12906





(2014), NCBI Accession # 4H8W_L (217aa)


HIV1576
Light Chain, Ig
Nih45-46 Fab
Diskin, R., et al., Science 334 (6060), 1289-
9195



Kappa Chain C

1293 (2011), NCBI Accession # 3U7Y_L



Region

(210aa)


HIV1577
Light Chain, Ig
Pgt127
Pejchal, R., et al., Science 334 (6059), 1097-
9196



Lambda-2 Chain C

1103 (2011), NCBI Accession #



region

3TWC_L(211aa)


HIV1578
Light Chain, Ig
7b2
Santra, S., et al., PLoS Pathol. 11 (8),
9197



Kappa Chain C

E1005042 (2015), NCBI Accession # 4YDV_L



Region

(265aa)


HIV1579
Light Chain; Fab
N60-i3
Gohain, N., et al., Cocrystal Structures of
9198





Antibody N60-i3 and Antibody JR4 in





Complex with gp120 Define More Cluster A





Epitopes Invoked in Effective Antibody-





Dependent Effector Function against HIV-1; J.





Virol. 89 (17), 8840-8854 (2015), NCBI





Accession # 4RFO_L (221aa)


HIV1580
Light Chain; Ig
Pgt128
Pejchal, R., et al., Science 334 (6059), 1097-
9199



Lambda-2 Chain C

1103 (2011), NCBI Accession # 3TV3_L



region

(211aa)


HIV1581
Scfv
B11
U.S. Pat. No. 7,744,887B2 SEQ ID NO: 8
9200


HIV1582
Scfv

U.S. Pat. No. 8,110,192B2 SEQ ID NO: 1
9201


HIV1583
Scfv

U.S. Pat. No. 8,110,192B2 SEQ ID NO: 2
9202


HIV1584
Scfv

U.S. Pat. No. 8,110,192B2 SEQ ID NO: 3
9203


HIV1585
Scfv (SEQRES)
3b3 variant
Clark et al., Protein Sci. 18 (12), 2429-2441
9204





(2009), NCBI Accession # 3JUY_A (256aa)


HIV1586
Scfv
D5
U.S. Pat. No. 7,744,887B2 SEQ ID NO: 2
9205


HIV1587
Scfv-cd4 fusion

U.S. Pat. No. 8,110,192B2 SEQ ID NO: 8
9206



protein


HIV1588

447-52d
Dhillon, A. K., et al., Acta Crystallogr. D Biol.
9207





Crystallogr. D64 (PT 7), 792-802 (2008), NCBI





Accession # 3C2A_1(231aa)


HIV1589

447-52d
Dhillon, A. K., et al., Acta Crystallogr, D Biol.
9208





Crystallogr. D64 (PT 7), 792-802 (2008), NCBI





Accession # 3C2A_M (216aa)


HIV1590

F105
Wilkinson, R. A., et al., J. Virol. 79 (20), 13060-
9209





13069 (2005), NCBI Accession # 1U6A_H





(224aa)


HIV1591

F105
Wilkinson, R. A., et al., J. Virol. 79 (20), 13060-
9210





13069 (2005), NCBI Accession # 1U6A_L





(215aa)


HIV1592

Fab 8062
Frisch, C., et al., PLoS Pathol. 6 (11),
9211





E1001182 (2010), NCBI Accession # 3MAC_H





(245aa)


HIV1593

Fab 8062
Frisch, C., et al., PLoS Pathol. 6 (11),
9212





E1001182 (2010), NCBI Accession # 3MAC_L





(213aa)


HIV1594

Fab 8066
Frisch, C., et al., PLoS Pathol. 6 (11),
9213





E1001182 (2010), NCBI Accession # 3MA9_H





(245aa)


HIV1595

Fab 8066
Frisch, C., et al., PLoS Pathol. 6 (11),
9214





E1001182 (2010), NCBI Accession # 3MA9_L





(213aa)


HIV1596

Fab′2F5
U.S. Pat. No. 6,482,928 SEQ ID NO: 6
9215




fragment


HIV1597

Fab′2F5
U.S. Pat. No. 6,482,928 SEQ ID NO: 7
9216




fragment


HIV1598

M18 Fab
Prabakaran, P., et al., J. Mol. Biol. 357 (1), 82-
9217





99 (2006), NCBI Accession # 2AJ3_D (228aa)


HIV1599

M18 Fab
Prabakaran, P., et al., J. Mol. Biol. 357 (1), 82-
9218





99 (2006), NCBI Accession # 2AJ3_E (213aa)


HIV1600

Pg16
Pancera, M. et al., J. Virol. 84 (16), 8098-8110
9219





(2010), NCBI Accession # 3MME_A (238aa)


HIV1601

Pg16
Paneera, M, et al., J. Virol. 84 (16), 8098-8110
9220





(2010), NCBI Accession # 3MME_B (216aa)









In one embodiment, the payload region of the AAV particle comprises one or more nucleic acid sequences, fragment or variants thereof or encodes one or more polypeptides, fragments or variants thereof described in European Patent Publication No. EP327000, EP478689, EP554401, EP581353 and EP711439, US Publication No US20110104163, US20110212106, US20130215726 and US20130251726, U.S. Pat. Nos. 5,266,479, 5,804,440, 6,657,050, 8,637,036, and 9,090,675, and International Publication No. WO2012154312, WO2013163427, WO2014043386, WO2015048462, WO2015048610, WO2015048770 the contents of each of which are herein incorporated by reference in their entirety, against HIV.


Disease Specific Epitopes, Innate Defense Regulator Peptides, Cyclic Peptides

In one embodiment, the viral genomes of the AAV particles may comprise nucleic acids which have been engineered to enable expression of antibodies binding to disease-specific epitopes of proteins. Such antibodies may be used to diagnose, prevent, and/or treat the corresponding medical conditions by targeting epitopes of the protein presented by or accessible on native or non-native forms (e.g., misfolded forms of native proteins) of the target Such epitopes may be specific to diseases involved with misfolding of a protein due to pathologic condition and resulting in misfolded aggregates. The disease-specific proteins are considered to be toxic to neurons and to have a role in neuronal cell death and dysfunction in neurodegenerative diseases including, but not limited to. Alzheimer's disease (AD), armyotrophic lateral sclerosis (ALS), Parkinson's disease, dementia by Lew body (DLB), and prion diseases. e.g. Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), kuru, and fatal farnilial insomnia (FFI).


In one embodiment, the encoded disease-specific epitopes may include epitopes on SOD1 that are revealed as SOD1 (Superoxide dismutase [Cu—Zn]) dissociates from its homodimeric, normal state. The SOD epitopes may be selectively presented or accessible in non-native SOD1 forms including misfolded SOD1 monomer, misfolded SOD1 dimer, and the epitopes selectively presented or accessible in SOD1 aggregates. Such epitopes may be specific to neurodegenerative diseases including, but not limited to, armyotrophic lateral sclerosis (ALS), Alzheimer's (AD). Parkinson's (PD), and Lewr body diseases (LBD).


In one embodiment, the expressed antibodies may bind to epitopes presented by or accessible on non-native forms of SOD1, such as those presented by SEQ ID NO: 2, 3, 5, 6, and 7 of U.S. Pat. No. 7,977,314 (the contents of which are herein incorporated by reference in its entirety), or presented by or accessible on monomeric forms of SOD1, such as those presented by SEQ ID NOs: 1 and 4 of U.S. Pat. No. 7,977,314, the contents of which are herein incorporated by reference in their entirety. In one embodiment, the expressed antibodies may comprise isolated peptides corresponding to such epitopes, such as those presented in SEQ ID NOs: 1-8 or SEQ ID NOs-8-16, or epitopes presented by SEQ ID NOs: 34-63, 65-79 of U.S. Pat. No. 7,977,314, the contents of which are herein incorporated by reference in their entirety.


In one embodiment, the encoded disease-specific epitopes may be specific to diseases associated with prion protein (PrP), familial amyloid polyneuropathy or senile systemic amyloidosis or a disease related by the presence of misfolded transthyretine (TTR); renal accumulation of 1(2 microglobulin amyloid deposits or a disease related by the presence of misfolded D12 microglobulin, amyotrophic lateral sclerosis (ALS) or a disease related by the presence of misfolded SOD1; leukemias or myelomas or a disease related by the presence of misfolded cluster of differentiation 38 (CD38); colon cancer metastasis and or a disease related by the presence of misfolded cluster of differentiation (CD44); tumors associated with tumor necrosis factor receptor (TNFR); cancers including cervical, head and neck, endometrial, lung and breast carcinomas, pleural mesotheliomas, malignant melanomas, Hodgkin lymphomas, anaplastic large cell non-Hodgkin lymphomas, or a disease related by the presence of misfolded Notch homolog 1 (NOTCH1) e.g. acute myeloid leukemias and B-cell chronic lymphoid leukemias; cancer in which Fas receptor (FasR) is implicated, cancers and related disorders in which misfolded epidermal growth factor (EGFR) is implicated; and/or other related diseases, disorders and conditions.


In one embodiment, the encoded disease specific epitopes may include epitopes that are revealed as the proteins misfold. In one embodiment, the expressed antibodies may bind to predicted epitopes of human PrP, such as those presented by SEQ ID NOs: 1-10 of US Patent Publication No. US20100233176; bovine PrP, such as those presented by SEQ ID NOs: 11-15 of US Patent Publication No. US20100233176. TTR, such as those presented by SEQ ID NOs: 16-22 of US Patent Publication No US20100233176; beta-2 microglobulin, such as those presented by SEQ ID NOs: 23-26 of US Patent Publication No. US20100233176; SOD1, such as those presented by SEQ ID NOs: 27-40 of US Patent Publication No. US201100233176; CD38, such as those presented by SEQ ID NOs: 41-45 of US Patent Publication No. US20100233176; CD44, such as those presented by 46-50 of US Patent Publication No. US20100233176; TNFR, such as those presented by 51-55 of US Patent Publication No. US20100233176; notch protein, such as those presented in SEQ ID NOs: 56-60 of US Patent Publication No US201100233176; FasR, such as those presented by SEQ ID NOs: 61-65 of US Patent Publication No. US20100233176 and EGFR, such as those presented by SEQ ID NOs: 66-80 of US Patent Publication No. US20100233176; the contents of which are herein incorporated by reference in their entirety.


In one embodiment, the expressed antibodies may comprise peptides corresponding to such epitopes. In one embodiment, the expressed antibodies may comprise prion-specific peptides, such as those presented by SEQ ID NOs: 81-88 of US Patent Publication No. US20100233176, the contents of which are herein incorporated by reference in their entirety, and variations thereof.


In one embodiment, the encoded disease-specific epitopes may be specific to prion diseases, including transmissible spongiform encephalopathies (TSEs) or other prion diseases. In one embodiment, the expressed antibodies may bind to predicted epitopes of PrP, such as those presented by SEQ ID NOs: 24, 26, 28, 30, 32, 34, 36, 39-43, of US Patent Publication No. US20150004185, the contents of which are herein incorporated by reference in their entirety. In one embodiment, the expressed antibodies may comprise prion-specific peptides or peptide fusions, such as those presented by SEQ ID NOs: 12-23, 25, 27, 29, 31, 33, 35, 37, 38, 43, and 44-48 of US Patent Publication No. US20150004185, the contents of which are herein incorporated by reference in their entirety.


In one embodiment, the expressed antibodies may comprise prion peptides binding to prion specific abnormal isoform of the prion protein, such as those presented by SEQ ID NOs: 2-10 of US Patent Publication No. US20040072236, the contents of which are herein incorporated by reference in their entirety.


In one embodiment, the viral genomes of the AAV particles may comprise nucleic acids which have been engineered to express innate defense regulator (IDR) peptides. IDRs are immunomodulatory peptides that act directly on cells to effect an innate immune response. Such IDRs may be used to treat neurodegenerative diseases associated with neuroinflammation, e.g. amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Friedreich's ataxia. Huntington's disease, Lewr body disease, Parkinson's disease, spinal muscular atrophy, and multiple sclerosis (MS) and other neurodegenerative diseases. In one embodiment. IDRs may be those presented by SEQ ID NOS: 1-969, and 973-1264 of International Publication No. WO2013034982, the contents of which are herein incorporated by reference in their entirety, or analogs, derivatives, amidated variations and conservative variations thereof.


In one embodiment, the viral genomes of the AAV particles may comprise nucleic acids which have been engineered to express antibodies binding to an epitope of the Tropomyosin receptor kinase (TrkC) receptor. Such antibodies may comprise a peptide, such as one presented by SEQ ID NO: 1 of U.S. Pat. No. 9,200,080, the contents of which are herein incorporated by reference in their entirety.


In some embodiments, the viral genomes of the AAV particles may comprise nucleic acids which have been engineered to express cyclic peptides with an amino acid sequence SNK, Non-limiting examples of other cyclic peptides include SEQ ID NO: 1-7 of U.S. Pat. No. 9,216,217, the contents of which are herein incorporated by reference in their entirety. The method of preparing the antibodies may include hyperimmune preparation method, as described in U.S. Pat. No. 9,216,217, the contents of which are herein incorporated by reference in their entirety.


Prions

In one embodiment, the viral genomes of the AAV particles may comprise a nucleic acid sequence encoding antibodies comprising prion peptides comprising prion epitopes, and fusions and repeats thereof, such as those presented by SEQ ID NOs: 8-32, 35, and 36 of U.S. Pat. No. 9,056,918, the contents of which are herein incorporated by reference in their entirety.


In one embodiment, the viral genomes of the AAV particles may comprise a nucleic acid sequence encoding prion binding proteins (PrPBP). In one embodiment, the PrPBPs are cadherins, such as those presented by SEQ ID NOs: 1 and 2 of International Publication WO 1997/045746, the contents of which are herein incorporated by reference in their entirety. In one embodiment, the PrPBPs are cadherins, such as those presented by SEQ ID NOs: 2 and 7-9 of International Publication No. WO2001000235, the contents of which are herein incorporated by reference in their entirety.


The Nature of the Polypeptides and Variants

Antibodies encoded by payload regions of the viral genomes of the invention may be translated as a whole polypeptide, a plurality of polypeptides or fragments of polypeptides, which independently may be encoded by one or more nucleic acids, fragments of nucleic acids or variants of any of the aforementioned. As used herein, “polypeptide” means a polymer of amino acid residues (natural or unnatural) linked together most often by peptide bonds. The term, as used herein, refers to proteins, polypeptides, and peptides of any size, structure, or function. In some instances, the polypeptide encoded is smaller than about 50 amino acids and the polypeptide is then termed a peptide. If the polypeptide is a peptide, it will be at least about 2, 3, 4, or at least 5 amino acid residues long. Thus, polypeptides include gene products, naturally occurring polypeptides, synthetic polypeptides, homologs, orthologs, paralogs, fragments and other equivalents, variants, and analogs of the foregoing. A polypeptide may be a single molecule or may be a multi-molecular complex such as a dimer, trimer or tetramer. They may also comprise single chain or multichain polypeptides and may be associated or linked. The term polypeptide may also apply to amino acid polymers in which one or more amino acid residues are an artificial chemical analogue of a corresponding naturally occurring amino acid.


The term “polypeptide variant” refers to molecules which differ in their amino acid sequence from a native or reference sequence. The amino acid sequence variants may possess substitutions, deletions, and/or insertions at certain positions within the amino acid sequence, as compared to a native or reference sequence Ordinarily, variants will possess at least about 50% identity (homology) to a native or reference sequence, and preferably, they will be at least about 80%, more preferably at least about 90% identical (homologous) to a native or reference sequence.


In some embodiments “variant mimics” are provided. As used herein, the term “variant mimic” is one which contains one or more amino acids which would mimic an activated sequence. For example, glutamate may serve as a mimic for phosphoro-threonine and/or phosphoro-serine. Alternatively, variant mimics may result in deactivation or in an inactivated product containing the mimic, e.g., phenylalanine may act as an inactivating substitution for tyrosine; or alanine may act as an inactivating substitution for serine.


The term “amino acid sequence variant” refers to molecules with some differences in their amino acid sequences as compared to a native or starting sequence. The amino acid sequence variants may possess substitutions, deletions, and/or insertions at certain positions within the amino acid sequence. “Native” or “starting” sequence should not be confused with a wild type sequence. As used herein, a native or starting sequence is a relative term referring to an original molecule against which a comparison may be made. “Native” or “starting” sequences or molecules may represent the wild-type (that sequence found in nature) but do not have to be the wild-type sequence.


Ordinarily, variants will possess at least about 70% homology to a native sequence, and preferably, they will be at least about 80%, more preferably at least about 90% homologous to a native sequence. “Homology” as it applies to amino acid sequences is defined as the percentage of residues in the candidate amino acid sequence that are identical with the residues in the amino acid sequence of a second sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent homology. Methods and computer programs for the alignment are well known in the art. It is understood that homology depends on a calculation of percent identity but may differ in value due to gaps and penalties introduced in the calculation.


By “homologs” as it applies to amino acid sequences is meant the corresponding sequence of other species having substantial identity to a second sequence of a second species.


“Analogs” is meant to include polypeptide variants which differ by one or more amino acid alterations, e.g., substitutions, additions or deletions of amino acid residues that still maintain the properties of the parent polypeptide.


Sequence tags or amino acids, such as one or more lysines, can be added to the peptide sequences of the invention (e.g., at the N-terminal or C-terminal ends). Sequence tags can be used for peptide purification or localization. Lysines can be used to increase peptide solubility or to allow for biotinylation. Alternatively, amino acid residues located at the carboxy and amino terminal regions of the amino acid sequence of a peptide or protein may optionally be deleted providing for truncated sequences. Certain amino acids (e.g., C-terminal or N-terminal residues) may alternatively be deleted depending on the use of the sequence, as for example, expression of the sequence as part of a larger sequence which is soluble, or linked to a solid support.


“Substitutional variants” when referring to proteins are those that have at least one amino acid residue in a native or starting sequence removed and a different amino acid inserted in its place at the same position. The substitutions may be single, where only one amino acid in the molecule has been substituted, or they may be multiple, where two or more amino acids have been substituted in the same molecule.


As used herein the term “conservative amino acid substitution” refers to the substitution of an amino acid that is normally present in the sequence with a different amino acid of similar size, charge, or polarity. Examples of conservative substitutions include the substitution of a non-polar (hydrophobic) residue such as isoleucine, valine and leucine for another non-polar residue. Likewise, examples of conservative substitutions include the substitution of one polar (hydrophilic) residue for another such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine. Additionally, the substitution of a basic residue such as lysine, arginine or histidine for another, or the substitution of one acidic residue such as aspartic acid or glutamic acid for another acidic residue are additional examples of conservative substitutions. Examples of non-conservative substitutions include the substitution of a non-polar (hydrophobic) amino acid residue such as isoleucine, valine, leucine, alanine, methionine for a polar (hydrophilic) residue such as cysteine, glutanane, glutamic acid or lysine and/or a polar residue for a non-polar residue.


“Insertional variants” when referring to proteins are those with one or more amino acids inserted immediately adjacent to an amino acid at a particular position in a native or starting sequence. “Immediately adjacent” to an amino acid means connected to either the alpha-carboxy or alpha-amino functional group of the amino acid.


“Deletional variants” when referring to proteins, are those with one or more amino acids in the native or starting amino acid sequence removed. Ordinarily, deletional variants will have one or more amino acids deleted in a particular region of the molecule.


As used herein, the term “derivative” is used synonymously with the term “variant” and refers to a molecule that has been modified or changed in any way relative to a reference molecule or starting molecule. In some embodiments, derivatives include native or starting proteins that have been modified with an organic proteinaceous or non-proteinaceous derivatizing agent, and post-translational modifications. Covalent modifications are traditionally introduced by reacting targeted amino acid residues of the protein with an organic derivatizing agent that is capable of reacting with selected side-chains or terminal residues, or by harnessing mechanisms of post-translational modifications that function in selected recombinant host cells. The resultant covalent derivatives are useful in programs directed at identifying residues important for biological activity, for immunoassays, or for the preparation of anti-protein antibodies for immunoaffinity purification of the recombinant glycoprotein. Such modifications are within the ordinary skill in the art and are performed without undue experimentation.


Certain post-translational modifications are the result of the action of recombinant host cells on the expressed polypeptide. Glutaminyl and asparaginyl residues are frequently post-translationally deaminated to the corresponding glutamyl and aspartyl residues. Alternatively, these residues are deaminated under mildly acidic conditions. Either form of these residues may be present in the proteins used in accordance with the present invention.


Other post-translational modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecular Properties, W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)).


“Features” when referring to proteins are defined as distinct amino acid sequence-based components of a molecule. Features of the proteins of the present invention include surface manifestations, local conformational shape, folds, loops, half-loops, domains, half-domains, sites, termini or any combination thereof.


As used herein when referring to proteins the term “surface manifestation” refers to a polypeptide based component of a protein appearing on an outermost surface.


As used herein when referring to proteins the term “local conformational shape” means a polypeptide based structural manifestation of a protein which is located within a definable space of the protein.


As used herein when referring to proteins the term “fold” means the resultant conformation of an amino acid sequence upon energy minimization. A fold may occur at the secondary or tertiary level of the folding process. Examples of secondary level folds include beta sheets and alpha helices Examples of tertiary folds include domains and regions formed due to aggregation or separation of energetic forces. Regions formed in this way include hydrophobic and hydrophilic pockets, and the like.


As used herein the term “turn” as it relates to protein conformation means a bend which alters the direction of the backbone of a peptide or polypeptide and may involve one, two, three or more amino acid residues.


As used herein when referring to proteins the term “loop” refers to a structural feature of a peptide or polypeptide which reverses the direction of the backbone of a peptide or polypeptide and comprises four or more amino acid residues. Oliva et al. have identified at least 5 classes of protein loops (J. Mol Biol 266 (4): 814-830: 1997).


As used herein when referring to proteins the term “half-loop” refers to a portion of an identified loop having at least half the number of amino acid residues as the loop from which it is derived. It is understood that loops may not always contain an even number of amino acid residues. Therefore, in those cases where a loop contains or is identified to comprise an odd number of amino acids, a half-loop of the odd-numbered loop will comprise the whole number portion or next whole number portion of the loop (number of amino acids of the loop/2+/−0.5 amino acids). For example, a loop identified as a 7 amino acid loop could produce half-loops of 3 amino acids or 4 amino acids (7/2=3.5+/−0.5 being 3 or 4).


As used herein when referring to proteins the term “domain” refers to a motif of a polypeptide having one or more identifiable structural or functional characteristics or properties (e.g., binding capacity, serving as a site for protein-protein interactions).


As used herein when referring to proteins the term “half-domain” means portion of an identified domain having at least half the number of amino acid residues as the domain from which it is derived. It is understood that domains may not always contain an even number of amino acid residues. Therefore, in those cases where a domain contains or is identified to comprise an odd number of amino acids, a half-domain of the odd-numbered domain will comprise the whole number portion or next whole number portion of the domain (number of amino acids of the domain/2+/−0.5 amino acids). For example, a domain identified as a 7 amino acid domain could produce half-domains of 3 amino acids or 4 amino acids (7/2=3.5+/−0.5 being 3 or 4). It is also understood that sub-domains may be identified within domains or half-domains, these subdomains possessing less than all of the structural or functional properties identified in the domains or half domains from which they were derived. It is also understood that the amino acids that comprise any of the domain types herein need not be contiguous along the backbone of the poly peptide (i.e., nonadjacent amino acids may fold structurally to produce a domain, half-domain or subdomain).


As used herein when referring to proteins the terms “site” as it pertains to amino acid based embodiments is used synonymous with “amino acid residue” and “amino acid side chain”. A site represents a position within a peptide or polypeptide that may be modified, manipulated, altered, derivatized or varied within the polypeptide based molecules of the present invention.


As used herein the terms “termini or terminus” when referring to proteins refers to an extremity of a peptide or polypeptide. Such extremity is not limited only to the first or final site of the peptide or polypeptide but may include additional amino acids in the terminal regions. The polypeptide based molecules of the present invention may be characterized as having both an N-terminus (terminated by an amino acid with a free amino group (NH2)) and a C-terminus (terminated by an amino acid with a free carboxyl group (COOH)). Proteins of the invention are in some cases made up of multiple polypeptide chains brought together by disulfide bonds or by non-covalent forces (multimers, oligomers). These sorts of proteins will have multiple N- and C-termini. Alternatively, the termini of the polypeptides may be modified such that they begin or end, as the case may be, with a non-polypeptide based moiety such as an organic conjugate.


Once any of the features have been identified or defined as a component of a molecule of the invention, any of several manipulations and/or modifications of these features may be performed by moving, swapping, inverting, deleting, randomizing or duplicating. Furthermore, it is understood that manipulation of features may result in the same outcome as a modification to the molecules of the invention. For example, a manipulation which involves deleting a domain would result in the alteration of the length of a molecule just as modification of a nucleic acid to encode less than a full-length molecule would.


Modifications and manipulations can be accomplished by methods known in the art such as site directed mutagenesis. The resulting modified molecules may then be tested for activity using in vitro or in vivo assays such as those described herein or any other suitable screening assay known in the art.


AAV Production

The present invention provides methods for the generation of parvoviral particles, e.g. AAV particles, by viral genome replication in a viral replication cell.


In accordance with the invention, the viral genome comprising a payload region encoding an antibody, an antibody-based composition or fragment thereof, will be incorporated into the AAV particle produced in the viral replication cell. Methods of making AAV particles are well known in the art and are described in e.g., U.S. Pat. Nos. 6,204,059, 5,756,283, 6,258,595, 6,261,551, 6,270,996, 6,281,10, 6,365,394, 6,475,769, 6,482,634, 6,4859,669, 6,943,01, 6,953,690, 7,022,519, 7,238,526, 7,291,498 and 7,491,508, 5,064,764, 6,194,191, 6,566,118, 8,137,948, or International Publication Nos. WO1996039530, WO1998010088, WO999014354, WO1999015685, WO1999047691, WO2000055342, WO2000075353 and WO2001023597; Methods In Molecular Biology, ed. Richard, Humana Press, N J (1995); O'Reilly et al., Baculovirus Expression Vectors, A Laboratory Manual. Oxford Univ. Press (1994); Samulski et al., J. Vir. 63:3822-8 (1989); Kajigaya et al., Proc. Nat'l. Acad. Sci. USA 88: 4646-50 (1991); Ruffing et al., J. Vir. 66:6922-30 (1992); Kimbauer et al., Vir. 219:37-44 (1996); Zhao et al., Vir. 272:382-93 (2000); the contents of each of which are herein incorporated by reference in their entirety. In one embodiment, the AAV particles are made using the methods described in WO2015191508, the contents of which are herein incorporated by reference in their entirety.


Viral replication cells commonly used for production of recombinant AAV viral vectors include but are not limited to 293 cells, COS cells. HeLa cells, KB cells, and other mammalian cell lines as described in U.S. Pat. Nos. 6,156,303, 5,387,484, 5,741,683, 5,691,176, and 5,688,676; U.S. patent publication No. 2002/0081721, and International Patent Publication Nos. WO 00/47757, WO 00/24916, and WO 96/17947, the contents of each of which are herein incorporated by reference in their entireties.


In some embodiments, the present invention provides a method for producing an AAV particle having enhanced (increased, improved) transduction efficiency comprising the steps of: 1) co-transfecting competent bacterial cells with a bacmid vector and either a viral construct vector and/or AAV payload construct vector, 2) isolating the resultant viral construct expression vector and AAV payload construct expression vector and separately transfecting viral replication cells, 3) isolating and purifying resultant payload and viral construct particles comprising viral construct expression vector or AAV payload construct expression vector, 4) co-infecting a viral replication cell with both the AAV payload and viral construct particles comprising viral construct expression vector or AAV payload construct expression vector, and 5) harvesting and purifying the AAV particle comprising a viral genome.


In some embodiments, the present invention provides a method for producing an AAV particle comprising the steps of 1) simultaneously co-transfecting mammalian cells, such as, but not limited to HEK293 cells, with a pay load region, a construct expressing rep and cap genes and a helper construct, 2) harvesting and purifying the AAV particle comprising a viral genome.


In some embodiments, the viral genome of the AAV particle of the invention optionally encodes a selectable marker. The selectable marker may comprise a cell-surface marker, such as any protein expressed on the surface of the cell including, but not limited to receptors. CD markers, lectins, integrins, or truncated versions thereof.


In some embodiments, selectable marker reporter genes as described in International application No WO 96/23810, Heirn et al, Current Biology 2:178-182 (1996); Heim et al., Proc. Natl. Acad. Sci. USA (1995); or Heim et al., Science 373:663-664 (1995); WO 96/30540, the contents of each of which are incorporated herein by reference in their entireties).


II. Formulation and Delivery
Pharmaceutical Compositions

According to the present invention the AAV particles may be prepared as pharmaceutical compositions. It will be understood that such compositions necessarily comprise one or more active ingredients and, most often, a pharmaceutically acceptable excipient.


Relative amounts of the active ingredient (e.g. AAV particle), a pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition in accordance with the present disclosure may vary, depending upon the identity, size, and/or condition of the subject being treated and further depending upon the route by which the composition is to be administered. For example, the composition may comprise between 0.1% and 99% (w/w) of the active ingredient. By way of example, the composition may comprise between 0.1% and 100%, e.g., between 5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient.


In some embodiments, the AAV particle pharmaceutical compositions described herein may comprise at least one pa load. As a non-limiting example, the pharmaceutical compositions may contain an AAV particle with 1, 2, 3, 4 or 5 payloads. In one embodiment, the pharmaceutical composition may contain a nucleic acid encoding a payload construct encoding proteins selected from antibodies and/or antibody-based compositions.


Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to any other animal, e.g., to non-human animals, e.g. non-human mammals. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with merely ordinary, if any, experimentation. Subjects to which administration of the pharmaceutical compositions is contemplated include, but are not limited to, humans and/or other primates; mammals, including commercially relevant mammals such as cattle, pigs, horses, sheep, cats, dogs, mice, rats, birds, including commercially relevant birds such as poultry, chickens, ducks, geese, and/or turkeys.


In some embodiments, compositions are administered to humans, human patients or subjects.


Formulations

The AAV particles of the invention can be formulated using one or more excipients to: (1) increase stability; (2) increase cell transfection or transduction; (3) permit the sustained or delayed expression of the payload; (4) alter the biodistribution (e.g., target the viral particle to specific tissues or cell types); (5) increase the translation of encoded protein; (6) alter the release profile of encoded protein and/or (7) allow for regulatable expression of the payload.


Formulations of the present invention can include, without limitation, saline, liposomes, lipid nanoparticles, polymers, peptides, proteins, cells transfected with viral vectors (e.g., for transfer or transplantation into a subject) and combinations thereof.


Formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. As used herein the term “pharmaceutical composition” refers to compositions comprising at least one active ingredient and optionally one or more pharmaceutically acceptable excipients.


In general, such preparatory methods include the step of associating the active ingredient with an excipient and/or one or more other accessory ingredients. As used herein, the phrase “active ingredient” generally refers either to an AAV particle carrying a payload region encoding the polypeptides of the invention or to the antibody or antibody-based composition encoded by a viral genome of by an AAV particle as described herein.


Formulations of the AAV particles and pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient into association with an excipient and/or one or more other accessor ingredients, and then, if necessary and/or desirable, dividing, shaping and/or packaging the product into a desired single- or multi-dose unit.


A pharmaceutical composition in accordance with the present disclosure may be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. As used herein, a “unit dose” refers to a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage.


In one embodiment, the AAV particles of the invention may be formulated in PBS with 0.001% of pluronic acid (F-68) at a pH of about 7.0.


Relative amounts of the active ingredient (e.g. AAV particle), the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition in accordance with the present disclosure may vary, depending upon the identity, size, and/or condition of the subject being treated and further depending upon the route by which the composition is to be administered. For example, the composition may comprise between 0.1% and 99% (w/w) of the active ingredient. By way of example, the composition may comprise between 0.1% and 100%, e.g., between 0.5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient.


In some embodiments, the AAV formulations described herein may contain sufficient AAV particles for expression of at least one expressed functional antibody or antibody-based composition. As a non-limiting example, the AAV particles may contain viral genomes encoding 1, 2, 3, 4 or 5 functional antibodies.


According to the present invention AAV particles may be formulated for CNS delivery. Agents that cross the brain blood barrier may be used. For example, some cell penetrating peptides that can target molecules to the brain blood barrier endothelium may be used for formulation (e.g., Mathupala, Expert Opin Ther Pat., 2009, 19, 137-140; the content of which is incorporated herein by reference in its entirety).


Excipients and Diluents

The AAV particles of the invention can be formulated using one or more excipients or diluents to (1) increase stability; (2) increase cell transfection or transduction; (3) permit the sustained or delayed release; (4) alter the biodistribution (e.g. target the viral particle to specific tissues or cell types); (5) increase the translation of encoded protein in vivo; (6) alter the release profile of encoded protein in vivo and/or (7) allow for regulatable expression of the polypeptides of the invention.


In some embodiments, a pharmaceutically acceptable excipient may be at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% pure. In some embodiments, an excipient is approved for use for humans and for veterinary use. In some embodiments, an excipient may be approved by United States Food and Drug Administration. In some embodiments, an excipient may be of pharmaceutical grade. In some embodiments, an excipient may meet the standards of the United States Pharmacopoeia (USP), the European Pharmacopoeia (EP), the British Pharmacopoeia, and/or the International Pharmacopoeia.


Excipients, as used herein, include, but are not limited to, any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, and the like, as suited to the particular dosage form desired. Various excipients for formulating pharmaceutical compositions and techniques for preparing the composition are known in the art (see Remington: The Science and Practice of Pharmacy, 21st Edition, A R Gennaro. Lippincott, Williams & Wilkins, Baltimore, Md., 2006; incorporated herein by reference in its entirety). The use of a conventional excipient medium may be contemplated within the scope of the present disclosure, except insofar as any conventional excipient medium may be incompatible with a substance or its derivatives, such as by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutical composition.


Exemplary diluents include, but are not limited to, calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, etc., and/or combinations thereof.


Inactive Ingredients

In some embodiments, AAV particle formulations may comprise at least one inactive ingredient. As used herein, the term “inactive ingredient” refers to one or more agents that do not contribute to the activity of the active ingredient of the pharmaceutical composition included in formulations. In some embodiments, all, none or some of the inactive ingredients which may be used in the formulations of the present invention may be approved by the US Food and Drug Administration (FDA).


In one embodiment, the AAV particle pharmaceutical compositions comprise at least one inactive ingredient such as, but not limited to, 1,2,6-Hexanetriol; 1,2-Dimyristoyl-Sn-Glycero-3-(Phospho-S-(1-Glycerol)); 1,2-Dilmyristoyl-Sn-Glycero-3-Phospho choline; 1,2-Dioleoyl-Sn-Glycero-3-Phosphocholine; 1,2-Dialmitoyl-Sn-Glycero-3-(Phospho-Rac-(1-Glycerol)); 1,2-Distearyl-Sn-Glycero-3-(Phospho-Rac-(1-Glycerol)); 1,2-Distearoyl-Sn-Glycero-3-Phosphocholine; 1-O-Tolylbiguanide; 2-Ethyl-1,6-Hexanediol; Acetic Acid; Acetic Acid, Glacial; Acetic Anhydride; Acetone, Acetone Sodium Bisulfite; Acetylated Lanolin Alcohols; Acetylated Monoglycerides; Acetylcysteine; Acetyltryptophan. DL-; Acrylates Copolymer; Acrylic Acid-Isooctyl Acrylate Copolymer; Acrylic Adhesive 788; Activated Charcoal; Adcote 72A103; Adhesive Tape; Adipic Acid; Aerotex Resin 3730; Alanine; Albumin Aggregated; Albumin Colloidal, Albumin Human, Alcohol, Alcohol, Dehydrated; Alcohol, Denatured; Alcohol; Diluted; Alfadex; Alginic Acid; Alkyl Ammonium Sulfonic Acid Betaine; Alkyl Aryl Sodium Sulfonate; Allantoin; Allyl .Alpha-Ionone; Almond Oil; Alpha-Terpineol; Alpha-Tocopherol; Alpha-Tocopherol Acetate; Dl-; Alpha-Tocopherol; Dl-; Aluminum Acetate; Aluminum Chlorhydroxy Allantoinate; Aluminum Hydroxide; Aluminum Hydroxide-Sucrose; Hydrated; Aluminum Hydroxide Gel; Aluminum Hydroxide Gel F 500; Aluminum Hydroxide Gel F 5000; Aluminum Monostearate; Aluminum Oxide; Aluminum Polyester; Aluminum Silicate; Aluminum Starch Octenylsuccinate; Aluminum Stearate; Aluminum Subacetate; Aluminum Sulfate Anhydrous; Amerchol C; Amerchol-Cab; Aminomethylpropanol; Ammonia; Ammonia Solution; Ammonia Solution; Strong; Ammonium Acetate; Ammonium Hydroxide; Ammonium Lauryl Sulfate; Ammonium Nonoxynol-4 Sulfate; Ammonium Salt Of C-12-C-15 Linear Primary Alcohol Ethoxylate; Ammonium Sulfate; Ammonyx; Amphoteric-2; Amphoteric-9; Anethole; Anhydrous Citric Acid; Anhydrous Dextrose; Anhydrous Lactose; Anhydrous Trisodium Citrate; Aniseed Oil; Anoxid Sbn; Antifoam; Antipyrine; Apaflurane; Apricot Kernel Oil Peg-6 Esters; Aquaphor; Arginine; Arlacel; Ascorbic Acid; Ascorbyl Palmitate; Aspartic Acid; Balsam Peru; Barium Sulfate; Beeswax; Beeswax; Synthetic; Beheneth-10; Bentonite; Benzalkonium Chloride; Benzenesulfonic Acid; Benzethonium Chloride; Benzododecinium Bromide; Benzoic Acid; Benzyl Alcohol; Benzyl Benzoate; Benzyl Chloride; Betadex; Bibapcitide; Bismuth Subgallate; Boric Acid; Brocrinat; Butane; Butyl Alcohol; Butyl Ester Of Vinyl Methyl Ether/Maleic Anhydride Copolymer (125000) Mw); Butyl Stearate; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Butylene Glycol; Butylparaben; Butyric Acid; C20-40 Pareth-24; Caffeine; Calcium; Calcium Carbonate; Calcium Chloride; Calcium Gluceptate; Calcium Hydroxide; Calcium Lactate; Calcobutrol; Caldiamide Sodium; Caloxetate Trisodium; Calteridol Calcium; Canada Balsam; Caprylic/Capric Triglyceride; Caprylic/Capric/Stearic Triglyceride; Captan; Captisol; Caramel; Carbomer 1342; Carbomer 1382; Carbomer 934; Carbomer 934p; Carbomer 940; Carbomer 941; Carbomer 980; Carbomer 981; Carbomer Homopolymer Type B (Allyl Pentaerythrtol Crosslinked); Carbomer Homopolymer Type C (Allyl Pentaerythritol Crosslinked); Carbon Dioxide; Carboxy Vinyl Copolymer; Carboxymethylcellulose; Carboxymethylcellulose Sodium; Carboxypolymethylene; Carrageenan; Carrageenan Salt; Castor Oil; Cedar Leaf Oil; Cellulose; Cellulose; Microcrystalline; Cerasynt-Se; Ceresin; Ceteareth-12; Ceteareth-15; Ceteareth-30; Cetearyl Alcohol/Ceteareth-20; Cetearyl Ethylhexanoate; Ceteth-10; Ceteth-2; Ceteth-20; Ceteth-23; Cetostearyl Alcohol; Cetrimonium Chloride; Cetyl Alcohol; Cetyl Esters Wax; Cetyl Palmitate; Cetylpyridinium Chloride; Chlorobutanol; Chlorobutanol H-Hhemihydrate; Chlorobutanol; Anhydrous; Chlorocresol; Chloroxylenol; Cholesterol; Choleth; Choleth-24; Citrate; Citric Acid; Citric Acid Monohydrate; Citric Acid, Hydrous. Cocamide Ether Sulfate; Cocamine Oxide; Coco Betaine; Coco Diethanolamide; Coco Monoethanolamide, Cocoa Butter; Coco-Glycerides; Coconut Oil; Coconut Oil; Hydrogenated; Coconut Oil/Palm Kernel Oil Glycerides, Hydrogenated; Cocoyl Caprylocaprate; Cola Nitida Seed Extract; Collagen; Coloring Suspension, Corn Oil. Cottonseed Oil; Cream Base; Creatine; Creatinine; Cresol; Croscarmellose Sodium; Crospovidone; Cupric Sulfate, Cupric Sulfate Anhydrous; Cyclomethicone; Cyclomethicone/Dimethicone Copolyol; Cysteine; Cysteine Hydrochloride; Cysteine Hydrochloride Anhydrous; Cysteine, D1-; D&C Red No. 28; D&C Red No. 33; D&C Red No. 36; D&C Red No. 39, D&C Yellow No. 10; Dalfampridine; Daubert 1-5 Pestr (Matte) 164z; Decyl Methyl Sulfoxide; Dehydag Wax Sx; Dehydroacetic Acid; Dehymuls E; Denatonium Benzoate; Deoxycholic Acid; Dextran; Dextran 40; Dextrin; Dextrose; Dextrose Monohydrate, Dextrose Solution; Diatrizoic Acid; Diazolidinyl Urea; Dichlorobenzl Alcohol; Dichlorodifluoromethane; Dichlorotetrafluoroethane; Diethanolamine, Diethyl Pyrocarbonate; Diethyl Sebacate; Diethylene Glycol Monoethyl Ether; Diethylhexyl Phthalate; Dihydroxyaluminum Aminoacetate; Diisopropanolamine; Diisopropyl Adipate; Diisopropyl Dilinoleate, Dimethicone 350; Dimethicone Copolyol; Dimethicone Mdx4-4210; Dimethicone Medical Fluid 360; Dimethyl Isosorbide; Dimethyl Sulfoxide; Dimethylaminoethyl Methacrylate-Butyl Methacrylate—Methyl Methacrylate Copolymer; Dimethyldioctadecylammonium Bentonite; Dimethylsiloxane/Methylvinylsiloxane Copolymer; Dinoseb Ammonium Salt; Dipalmitoylphosphatidylglycerol, Dl-; Dipropylene Glycol; Disodium Cocoamphodiacetate; Disodium Laureth Sulfosuccinate; Disodium Lauryl Sulfosuccinate; Disodium Sulfosalicylate; Disofenin; Divinylbenzene Styrene Copolymer; Dmdm Hydantoin; Docosanol; Docusate Sodium, Duro-Tak 280-2516; Duro-Tak 387-2516; Duro-Tak 80-1196, Duro-Tak 87-2070; Duro-Tak 87-2194; Duro-Tak 87-2287; Duro-Tak 87-2296; Duro-Tak 87-2888; Duro-Tak 87-2979; Edetate Calcium Disodium; Edetate Disodium; Edetate Disodium Anhydrous; Edetate Sodium; Edetic Acid; Egg Phospholipids, Entsufon; Entsufon Sodium; Epilactose; Epitetracycline Hydrochloride; Essence Bouquet 9200; Ethanolamine Hydrochloride, Ethyl Acetate; Ethyl Oleate; Ethylcelluloses; Ethylene Glycol; Ethylene Vinyl Acetate Copolymer; Ethylenediamrne; Ethylenediamrne Dihydrochloride. Ethylene-Propylene Copolymer; Ethylene-Vinyl Acetate Copolymer (28% Vinyl Acetate), Ethylene-Vinyl Acetate Copolymer (9% Vinylacetate); Ethylhexyl Hydroxystearate; Ethylparaben; Eucalyptol; Exametazime; Fat, Edible; Fat, Hard; Fatty Acid Esters; Fatty Acid Pentaerythriol Ester; Fatty Acids; Fatty Alcohol Citrate; Fatty Alcohols; Fd&C Blue No. 1; Fd&C Green No. 3; Fd&C Red No. 4; Fd&C Red No. 40; Fd&C Yellow No. 10 (Delisted); Fd&C Yellow No 5; Fd&C Yellow No 6; Ferric Chloride; Ferric Oxide; Flavor 89-186; Flavor 89-259. Flavor Df-119; Flavor Df-1530; Flavor Enhancer; Flavor Fig 827118; Flavor Raspberry Pfc-8407; Flavor Rhodia Pharmaceutical No. Rf 451; Fluorochlorohydrocarbons; Formaldehyde; Formaldehyde Solution; Fractionated Coconut Oil; Fragrance 3949-5; Fragrance 520a; Fragrance 6.007; Fragrance 91-122; Fragrance 9128-Y; Fragrance 93498g; Fragrance Balsam Pine No. 5124. Fragrance Bouquet 10328; Fragrance Chemoderm 6401-B; Fragrance Chemoderm 6411, Fragrance Cream No. 73457, Fragrance Cs-28197; Fragrance Felton 066m; Fragrance Firmenich 47373; Fragrance Givaudan Ess 9090/1c; Fragrance H-6540; Fragrance Herbal 10396, Fragrance Nj-1085; Fragrance PO Fl-147. Fragrance Pa 52805; Fragrance Pera Derm D, Fragrance Rbd-9819; Fragrance Shaw Mudge U-7776; Fragrance Tf 044078; Fragrance Ungerer Honeysuckle K 2771; Fragrance Ungerer N5195; Fructose; Gadolinium Oxide; Galactose; Gamma Cyclodextrin; Gelatin; Gelatin, Crosslinked; Gelfoam Sponge; Gellan Gum (Low Acyl); Gelva 737; Gentisic Acid; Gentisic Acid Ethanolamide, Gluceptate Sodium; Gluceptate Sodium Dihydrate; Gluconolactone, Glucuronic Acid; Glutamic Acid; D1-; Glutathione; Glycerin; Glycerol Ester Of Hydrogenated Rosin; Glyceryl Citrate; Glyceryl Isostearate, Glyceryl Laurate; Glyceryl Monostearate; Glyceryl Oleate; Glyceryl Oleate/Propylene Glycol; Glyceryl Palmitate; Glyceryl Ricinoleate; Glyceryl Stearate; Glyceryl Stearate-Laureth-23; Glyceryl Stearate/Peg Stearate; Glyceryl Stearate/Peg-100 Stearate; Glyceryl Stearate/Peg-40 Stearate; Glyceryl Stearate-Stearamidoethyl Diethylamine; Glyceryl Trioleate; Glycine; Glycine Hydrochloride; Glycol Distearate; Glycol Stearate; Guanidine Hydrochloride; Guar Gum; Hair Conditioner (18n195-1m); Heptane, Hetastarch; Hexylene Glycol; High Density Polyethylene; Histidine; Human Albumin Microspheres; Hyaluronate Sodium; Hydrocarbon; Hydrocarbon Gel, Plasticized; Hydrochloric Acid; Hydrochloric Acid, Diluted; Hydrocortisone; Hydrogel Polymer; Hydrogen Peroxide; Hydrogenated Castor Oil; Hydrogenated Palm Oil; Hydrogenated Palm/Palm Kernel Oil Peg-6 Esters; Hydrogenated Polybutene 635-690; Hydroxide Ion; Hydroxyethyl Cellulose; Hydroxyethylpiperazine Ethane Sulfonic Acid; Hydroxymethyl Cellulose; Hydroxyoctacosanyl Hydroxystearate; Hydroxypropyl Cellulose; Hydroxypropyl Methylcellulose 2906; Hydroxypropyl-Beta-cyclodextrn; Hypromellose 2208 (15000 Mpa S); Hypromellose 2910 (1500 Mpa·S); Hypromellose; Imidurea; Iodine; Iodoxamic Acid; Iofetamine Hydrochloride; Irish Moss Extract; Isobutane; Isoceteth-20; Isoleucine; Isooctyl Acrylate; Isopropyl Alcohol; Isopropyl Isostearate; Isopropyl Myristate; Isopropyl Myristate-Myristyl Alcohol; Isopropyl Palmatate; Isopropyl Stearate; Isostearic Acid; Isostearyl Alcohol; Isotonic Sodium Chloride Solution; Jelene, Kaolin; Kathon Cg; Kathon Cg II, Lactate; Lactic Acid; Lactic Acid. Dl-; Lactic Acid. L-; Lactobionic Acid; Lactose; Lactose Monohydrate; Lactose, Hydrous, Laneth; Lanolin, Lanolin Alcohol-Mineral Oil; Lanolin Alcohols; Lanolin Anhydrous; Lanolin Cholesterols; Lanolin Nonionic Derivatives; Lanolin, Ethoxylated; Lanolin, Hydrogenated, Lauralkonium Chloride; Lauramine Oxide; Laurdimonium Hydrolyzed Animal Collagen; Laureth Sulfate; Laureth-2; Laureth-23; Laureth-4; Lauric Diethanolamide; Lauric Myristic Diethanolamide; Lauroyl Sarcosine; Lauryl Lactate; Lauryl Sulfate; Lavandula Angustifolia Flowering Top; Lecithin; Lecithin Unbleached; Lecithin, Egg; Lecithin, Hydrogenated; Lecithin, Hydrogenated Soy; Lecithin, Soybean; Lemon Oil; Leucine; Levulinic Acid; Lidofenin; Light Mineral Oil; Light Mineral Oil (85 Ssu); Limonene, (+/−)-; Lipocol Sc-15; Lysine. Lysine Acetate; Lysine Monohydrate, Magnesium Aluminum Silicate, Magnesium Aluminum Silicate Hydrate; Magnesium Chloride; Magnesium Nitrate; Magnesium Stearate; Maleic Acid; Mannitol; Maprofix; Mebrofenin; Medical Adhesive Modified S-15; Medical Antiform A-F Emulsion. Medronate Disodium; Medronic Acid. Meglumine; Menthol; Metacresol; Metaphosphoric Acid; Methanesulfonic Acid, Methionine; Methyl Alcohol; Methyl Gluceth-10; Methyl Gluceth-20; Methyl Gluceth-20 Sesquistearate; Methyl Glucose Sesquistearate; Methyl Laurate; Methyl Pyrrolidone; Methyl Salicylate; Methyl Stearate; Methylboronic Acid; Methylcellulose (4000 Mpa·S); Methylcelluloses; Methylchloroisothiazolinone; Methylene Blue, Methylisothiazolinone; Methylparaben; Microcrystalline Wax; Mineral Oil; Mono and Diglyceride; Monostearyl Citrate; Monothioglycerol; Multisterol Extract; Myristyl Alcohol; Myristyl Lactate; Myristyl-.Gamma.-Picolinium Chloride, N-(Carbamoyl-Methoxy Peg-40)-1,2-Distearoyl-Cephalin Sodium; N,N-Dimethylacetamide; Niacinamide, Nioxime; Nitric Acid; Nitrogen; Nonoxynol Iodine; Nonoxynol-15; Nonoxynol-9; Norflurane; Oatmeal; Octadecene-1/Maleic Acid Copolymer; Octanoic Acid; Octisalate; Octoxynol-1; Octoxynol-40, Octoxynol-9. Octyldodecanol, Octylphenol Polymethylene, Oleic Acid; Oleth-10/Oleth-5; Oleth-2; Oleth-20; Oleyl Alcohol; Oleyl Oleate; Olive Oil; Oxidronate Disodium; Oxyquinoline; Palm Kernel Oil; Palmitamine Oxide; Parabens; Paraffin; Paraffin, White Soft; Parfum Creme 45/3; Peanut Oil; Peanut Oil, Refined. Pectin; Peg 6-32 Stearate/Glycol Stearate; Peg Vegetable Oil; Peg-100 Stearate; Peg-12 Glyceryl Laurate; Peg-120 Glyceryl Stearate; Peg-120 Methyl Glucose Dioleate; Peg-15 Cocanmine; Peg-150 Distearate; Peg-2 Stearate; Peg-20 Sorbitan Isostearate; Peg-22 Methyl Ether/Dodecyl Glycol Copolymer; Peg-25 Propylene Glycol Stearate; Peg-4 Dilaurate; Peg-4 Laurate, Peg-40 Castor Oil; Peg-40 Sorbitan Diisostearate; Peg-45/Dodecyl Glycol Copolymer; Peg-5 Oleate; Peg-50 Stearate; Peg-54 Hydrogenated Castor Oil; Peg-6 Isostearate; Peg-60 Castor Oil; Peg-60 Hydrogenated Castor Oil; Peg-7 Methyl Ether; Peg-75 Lanolin; Peg-8 Laurate; Peg-8 Stearate, Pegoxol 7 Stearate; Pentadecalactone; Pentaerythrtol Cocoate; Pentasodium Pentetate, Pentetate Calcium Trisodium, Pentetic Acid, Peppermint Oil; Perflutren; Perfume 25677; Perfume Bouquet, Perfume E-1991; Perfume Gd 5604; Perfume Tana 90/42 Scba; Perfume W-1952-1, Petrolatum, Petrolatum; White; Petroleum Distillates; Phenol; Phenol; Liquefied; Phenonip; Phenoxyethanol; Phenylalanine; Phenylethyl Alcohol; Phenylmercuric Acetate; Phenylmercuric Nitrate; Phosphatidyl Glycerol; Egg; Phospholipid; Phospholipid, Egg; Phospholipon 90g; Phosphoric Acid, Pine Needle Oil (Pinus Sylvestris); Piperazine Hexahydrate; Plastibase-50w; Polacrilin; Polidronium Chloride, Poloxamer 124; Poloxamer 181; Poloxamer 182; Poloxamer 188; Poloxamer 237; Poloxamer 407; Poly(Bis(P-Carboxyphenoxy)Propane Anhydride); Sebacic Acid;


Poly(Dimethylsiloxane/Methylvinylsiloxane/Methylhydrogensiloxane) Dimethylvinyl Or Dimethylhydroxy Or Trimethyl Endblocked; Poly(Dl-Lactic-Co-Glycolic Acid), (50:50; Poly(Dl-Lactic-Co-Glycolic Acid), Ethyl Ester Terminated; (50:50; Polyacrylic Acid (250000 Mw); Polybutene (1400 Mw); Polycarbophil; Polyester; Polyester Pol amine Copolymer; Polyester Rayon, Polyethylene Glycol 1000; Polyethylene Glycol 1450; Polyethylene Glycol 1500); Polyethylene Glycol 1540; Polyethylene Glycol 200; Polyethylene Glycol 300; Polyethylene Glycol 300-1600, Polyethylene Glycol 3350; Polyethylene Glycol 400; Polyethylene Glycol 4000; Polyethylene Glycol 540; Polyethylene Glycol 600; Polyethylene Glycol 6000; Polyethylene Glycol 8000; Polyethylene Glycol 900; Polyethylene High Density Containing Ferric Oxide Black (<1%); Polyethylene Low Density Containing Barium Sulfate (20-24%); Polyethylene T; Polyethylene Terephthalates; Polyglactin; Polyglyceryl-3 Oleate; Polyglyceryl-4 Oleate, Ppolyhydroxyethyl Methacrylate, Polyisobutylene, Polyisobutylene (1100000 Mw); Polyisobutylene (35000 Mw); Polyisobutylene 178-236; Polyisobutylene 241-294; Polyisobutylene 35-39; Polyisobutylene Low Molecular Weight; Polyisobutylene Medium Molecular Weight; Polyisobutylene/Polybutene Adhesive; Polylactide; Polyols, Polyoxyethylene Polyoxypropylene 1800; Polyoxyethylene Alcohols; Polyoxyethylene Fatty Acid Esters; Polyoxyethylene Propylene; Polyoxyl 20 Cetostearyl Ether; Polyoxyl 35 Castor Oil; Polyoxyl 40 Hydrogenated Castor Oil; Polyoxyl 40 Stearate; Polyoxyl 400 Stearate; Polyoxyl 6 And Polyoxyl 32 Palmitostearate; Polyoxyl Distearate; Polyoxyl Glyceryl Stearate, Polyoxyl Lanolin; Polyoxyl Palmitate; Polyoxyl Stearate; Polypropylene; Polypropylene Glycol; Polyquarternium-10; Polyquarternium-7 (70/30 Acrylamide/Dadmac; Polysiloxane; Polysorbate 20; Polysorbate 40; Polysorbate 60, Polysorbate 65, Polysorbate 80; Polyurethane; Polyvinyl Acetate, Polyvinyl Alcohol; Polyvinyl Chloride; Polyvinyl Chloride-Polyvinyl Acetate Copolymer; Polyvinylpyridine; Poppy Seed Oil; Potash; Potassium Acetate; Potassium Alum; Potassium Bicarbonate; Potassium Bisulfate; Potassium Chloride; Potassium Citrate; Potassium Hydroxide; Potassium Metabisulfite; Potassium Phosphate, Dibasic; Potassium Phosphate, Monobasic; Potassium Soap; Potassium Sorbate; Povidone Acrylate Copolymer; Povidone Hydrogel; Povidone K17; Povidone K25; Povidone K29/32, Povidone K30, Povidone K90; Povidone K90f; Povidone/Eicosene Copolymer; Povidones; Ppg-12/Smdi Copolymer; Ppg-15 Stearyl Ether; Ppg-20 Methyl Glucose Ether Distearate; Ppg-26 Oleate; Product Wat; Proline; Promulgen D; Promulgen G; Propane; Propellant A-46; Propyl Gallate; Propylene Carbonate; Propylene Glycol; Propylene Glycol Diacetate; Propylene Glycol Dicaprylate, Propylene Glycol Monolaurate; Propylene Glycol Monopalmitostearate; Propylene Glycol Palmitostearate; Propylene Glycol Ricinoleate; Propylene Glycol/Diazolidinyl Urea/Methylparaben/Propylparben; Propylparaben; Protamine Sulfate; Protein Hydrolysate, Pvm/Ma Copolymer; Quaternium-15; Quaternium-15 Cis-Form; Quaternium-52; Ra-2397; Ra-3011; Saccharin; Saccharin Sodium; Saccharin Sodium Anhydrous; Safflower Oil; Sd Alcohol 3a; Sd Alcohol 40; Sd Alcohol 40-2; Sd Alcohol 40b, Sepineo P600; Serine; Sesame Oil; Shea Butter, Silastic Brand Medical Grade Tubing; Silastic Medical Adhesive, Silicone Type A; Silica, Dental; Silicon; Silicon Dioxide; Silicon Dioxide, Colloidal; Silicone; Silicone Adhesive 4102; Silicone Adhesive 4502, Silicone Adhesive Bio-Psa Q7-4201; Silicone Adhesive Bio-Psa Q7-4301; Silicone Emulsion, Silicone/Polyester Film Strip; Simethicone; Simethicone Emulsion; Sipon Ls 20np; Soda Ash; Sodium Acetate; Sodium Acetate Anhydrous; Sodium Alkyl Sulfate; Sodium Ascorbate; Sodium Benzoate; Sodium Bicarbonate; Sodium Bisulfate; Sodium Bisulfite; Sodium Borate; Sodium Borate Decahydrate; Sodium Carbonate; Sodium Carbonate Decahydrate, Sodium Carbonate Monohydrate; Sodium Cetostearyl Sulfate, Sodium Chlorate, Sodium Chloride; Sodium Chloride Injection; Sodium Chloride Injection, Bacteriostatic; Sodium Cholesteryl Sulfate, Sodium Citrate; Sodium Cocoyl Sarcosinate; Sodium Desoxycholate; Sodium Dithionite; Sodium Dodecylbenzenesulfonate; Sodium Formaldehyde Sulfoxylate; Sodium Gluconate; Sodium Hydroxide; Sodium Hypochlorite; Sodium Iodide; Sodium Lactate; Sodium Lactate, L-; Sodium Laureth-2 Sulfate; Sodium Laureth-3 Sulfate; Sodium Laureth-5 Sulfate; Sodium Lauroyl Sarcosinate, Sodium Lauryl Sulfate; Sodium Lauryl Sulfoacetate; Sodium Metabisulfite; Sodium Nitrate; Sodium Phosphate; Sodium Phosphate Dihydrate; Sodium Phosphate, Dibasic; Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic; Dihydrate; Sodium Phosphate, Dibasic, Dodecahydrate; Sodium Phosphate, Dibasic, Heptahydrate; Sodium Phosphate, Monobasic; Sodium Phosphate; Monobasic; Anhydrous, Sodium Phosphate, Monobasic; Dihydrate; Sodium Phosphate, Monobasic; Monohydrate; Sodium Polyacrylate (2500000 Mw); Sodium Pyrophosphate; Sodium Pyrrolidone Carboxylate; Sodium Starch Glycolate; Sodium Succinate Hexahydrate; Sodium Sulfate; Sodium Sulfate Anhydrous; Sodium Sulfate Decahydrate; Sodium Sulfite; Sodium Sulfosuccinated Undecyclenic Monoalkylolamide; Sodium Tartrate; Sodium Thioglycolate; Sodium Thiomalate, Sodium Thiosulfate; Sodium Thiosulfate Anhydrous; Sodium Trimetaphosphate, Sodium Xylenesulfonate; Somay 44; Sorbic Acid; Sorbitan; Sorbitan Isostearate; Sorbitan Monolaurate; Sorbitan Monooleate; Sorbitan Monopalmitate; Sorbitan Monostearate; Sorbitan Sesquioleate; Sorbitan Trioleate; Sorbitan Tristearate; Sorbitol; Sorbitol Solution, Soybean Flour; Soybean Oil; Spearmint Oil, Spermaceti; Squalane; Stabilized Oxychloro Complex; Stannous 2-Ethylhexanoate; Stannous Chloride; Stannous Chloride Anhydrous; Stannous Fluoride; Stannous Tartrate; Starch; Starch 1500; Pregelatinized; Starch, Corn; Stearalkoniun Chloride; Stearalkonium Hectorite/Propylene Carbonate; Stearamidoethyl Diethylamine; Steareth-10, Steareth-100; Steareth-2; Steareth-20; Steareth-21; Steareth-40; Stearic Acid; Stearic Diethanolamide; Stearoxytrimethylsilane; Steartrimonium Hydrolyzed Animal Collagen; Stearyl Alcohol; Sterile Water For Inhalation; Styrene/Isoprene/Styrene Block Copolymer; Succimer; Succinic Acid; Sucralose; Sucrose; Sucrose Distearate; Sucrose Polyesters; Sulfacetamide Sodium; Sulfobutylether .Beta.-Cyclodextrin; Sulfur Dioxide; Sulfuric Acid; Sulfurous Acid; Surfactol Qs; Tagatose, D-; Talc; Tall Oil; Tallow Glycerides; Tartaric Acid; Tartaric Acid; Dl-; Tenox; Tenox-2, Tert-Butyl Alcohol; Tert-Butyl Hydroperoxide; Tert-Butvlhydroquinone; Tetrakis(2-Methoxyisobutylisocyanide)Copper(I) Tetrafluoroborate; Tetrapropyl Orthosilicate; Tetrofosmin; Theophylline; Thimerosal; Threonine; Thymol; Tin; Titanium Dioxide; Tocopherol; Tocophersolan; Total parenteral nutrition, lipid emulsion; Triacetin; Tricaprylin; Trichloromonofluoromethane; Trideceth-10; Triethanolamine Lauryl Sulfate, Trifluoroacetic Acid; Triglycerides, Medium Chain; Trihydroxystearin; Trilaneth-4 Phosphate; Trilaureth-4 Phosphate, Trisodium Citrate Dihydrate; Trisodium Hedta; Triton 720; Triton X-200; Trolamine; Tromantadine; Tromethamine (TRIS); Typtophan; Tyloxapol; Tyrosine; Undecylenic Acid; Union 76 Amsco-Res 6038; Urea; Valine; Vegetable Oil; Vegetable Oil Glyceride, Hydrogenated; Vegetable Oil, Hydrogenated; Versetamide; Viscarin; Viscose/Cotton; Vitamin E; Wax, Emulsifying; Wecobee Fs; White Ceresin Wax; White Wax; Xanthan Gum; Zinc; Zinc Acetate; Zinc Carbonate; Zinc Chloride; and Zinc Oxide.


Pharmaceutical composition formulations of AAV particles disclosed herein may include cations or anions. In one embodiment, the formulations include metal cations such as, but not limited to, Zn2+, Ca2+, Cu2+, Mn2+, Mg+ and combinations thereof. As a non-limiting example, formulations may include polymers and complexes with a metal cation (See e.g., U.S. Pat. Nos. 6,265,389 and 6,555,525, each of which is herein incorporated by reference in its entirety).


Formulations of the invention may also include one or more pharmaceutically acceptable salts. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form (e.g., by reacting the free base group with a suitable organic acid). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Representative acid addition salts include acetate, acetic acid, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzene sulfonic acid, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids.


Solvates may be prepared by crystallization, recrystallization, or precipitation from a solution that includes organic solvents, water, or a mixture thereof. Examples of suitable solvents are ethanol, water (for example, mono-, di-, and tri-hydrates), N-methylpyrrolidinone (NMP), dimethyl sulfoxide (DMSO), N,N′-dimethylformamide (DMF), N,N′-dimethylacetamide (DMAC), 1,3-dimethyl-2-imidazolidinone (DMEU), 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPU), acetonitrile (ACN), propylene glycol, ethyl acetate, benzyl alcohol, 2-pyrrolidone, benzyl benzoate, and the like. When water is the solvent, the solvate is referred to as a “hydrate”


III. Administration and Dosing
Administration

The AAV particles of the present invention may be administered by any delivery route which results in a therapeutically effective outcome. These include, but are not limited to, enteral (into the intestine), gastroenteral, epidural (into the dura mater), oral (by way of the mouth), transdermal, intracerebral (into the cerebrum), intracerebroventricular (into the cerebral ventricles), epicutaneous (application onto the skin), intradermal. (into the skin itself), subcutaneous (under the skin), nasal administration (through the nose), intravenous (into a vein), intravenous bolus, intravenous drip, intra-arterial (into an artery), intramuscular (into a muscle), intracardiac (into the heart), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intraparenchymal (into brain tissue), Intraperitoneal. (infusion or injection into the peritoneum), Intravesical infusion, intravitreal, (through the eye), intracavernous injection (into a pathologic cavity) intracavitary (into the base of the penis), intravaginal administration, intrauterine, extra-amniotic administration, transdermal (diffusion through the intact skin for systemic distribution), transmucosal (diffusion through a mucous membrane), transvaginal, insufflation (snorting), sublingual, sublabial, enema, eye drops (onto the conjunctiva), or in ear drops, auricular (in or by way of the ear), buccal (directed toward the cheek), conjunctival, cutaneous, dental (to a tooth or teeth), electro-osmosis, endocervical, endosinusial, endotracheal, extracorporeal, hemodialysis, infiltration, interstitial, intra-abdominal, intra-amniotic, intra-articular, intrabiliary, intrabronchial, intrabursal, intracartilaginous (within a cartilage), intracaudal (within the cauda equine), intracisternal (within the cisterna magna cerebellomedularis), intracorneal (within the cornea), dental intracornal, intracoronary (within the coronary arteries), intracorporus cavernosum (within the dilatable spaces of the corporus cavernosa of the penis), intradiscal (within a disc), intraductal (within a duct of a gland), intraduodenal (within the duodenum), intradural (within or beneath the dura), intraepidermal (to the epidermis), intraesophageal (to the esophagus), intragastric (within the stomach), intragingival (within the gingivae), intraileal (within the distal portion of the small intestine), intralesional (within or introduced directly to a localized lesion), intraluminal (within a lumen of a tube), intralymphatic (within the lymph), intramedullary (within the marrow cavity of a bone), intrameningeal (within the meninges), intramyocardial (within the myocardium), intraocular (within the eye), intraovarian (within the ovary), intrapericardial (within the pericardium), intrapleural (within the pleura), intraprostatic (within the prostate gland), intrapulmonary (within the lungs or its bronchi), intrasinal (within the nasal or periorbital sinuses), intraspinal (within the vertebral column), intrasynovial (within the synovial cavity of a joint), intratendinous (within a tendon), intratesticular (within the testicle), intrathecal (within the cerebrospinal fluid at any level of the cerebrospinal axis), intrathoracic (within the thorax), intratubular (within the tubules of an organ), intratumor (within a tumor), intratympanic (within the aurus media), intravascular (within a vessel or vessels), intraventricular (within a ventricle), iontophoresis (by means of electric current where ions of soluble salts migrate into the tissues of the body), irrigation (to bathe or flush open wounds or body cavities), laryngeal (directly upon the larynx), nasogastric (through the nose and into the stomach), occlusive dressing technique (topical route administration which is then covered by a dressing which occludes the area), ophthalmic (to the external eye), oropharyngeal (directly to the mouth and pharynx), parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, respiratory (within the respiratory tract by inhaling orally or nasally for local or systemic effect), retrobulbar (behind the pons or behind the eyeball), soft tissue, subarachnoid, subconjunctival, submucosal, topical, transplacental (through or across the placenta), transtracheal (through the wall of the trachea), transtympanic (across or through the tympanic cavity), ureteral (to the ureter), urethral (to the urethra), vaginal, caudal block, diagnostic, nerve block, biliary perfusion, cardiac perfusion, photopheresis and spinal.


In some embodiments, compositions may be administered in a way which allows them to cross the blood-brain barrier, vascular barrier, or other epithelial barrier. The AAV particles of the present invention may be administered in any suitable form, either as a liquid solution or suspension, as a solid form suitable for liquid solution or suspension in a liquid solution. The AAV particles may be formulated with any appropriate and pharmaceutically acceptable excipient.


In one embodiment, the AAV particles of the present invention may be delivered to a subject, in a single route administration.


In one embodiment, the AAV particles of the present invention may be delivered to a subject via a multi-site route of administration. A subject may be administered at 2, 3, 4, 5 or more than 5 sites.


In one embodiment, a subject may be administered the AAV particles of the present invention using a bolus infusion.


In one embodiment, a subject may be administered the AAV particles of the present invention using sustained delivery over a period of minutes, hours or days. The infusion rate may be changed depending on the subject, distribution, formulation or another delivery parameter.


In one embodiment, the AAV particles of the present invention may be delivered by intramuscular delivery route. (See, e.g., U.S. Pat. No. 6,506,379, the content of which is incorporated herein by reference in its entirety). Non-limiting examples of intramuscular administration include an intravenous injection or a subcutaneous injection.


In one embodiment, the AAV particles of the present invention may be delivered by oral administration. Non-limiting examples of oral administration include a digestive tract administration and a buccal administration.


In one embodiment, the AAV particles of the present invention may be delivered by intraocular delivery route A non-limiting example of intraocular administration include an intravitreal injection.


In one embodiment, the AAV particles of the present invention may be delivered by intranasal delivery route. Non-limiting examples of intranasal delivery include administration of nasal drops or nasal sprays.


In some embodiments, the AAV particles that may be administered to a subject by peripheral injections. Non-limiting examples of peripheral injections include intraperitoneal, intramuscular, intravenous, conjunctival or joint injection. It was disclosed in the art that the peripheral administration of AAV vectors can be transported to the central nervous system, for example, to the motor neurons (e.g., U.S. Patent Publication Nos. 20100240739; and 20100130594; the content of each of which is incorporated herein by reference in their entirety).


In one embodiment, the AAV particles may be delivered by injection into the CSF pathway. Non-limiting examples of delivery to the CSF pathway include intrathecal and intracerebroventricular administration.


In one embodiment, the AAV particles may be delivered by systemic delivery. As a non-limiting example, the systemic delivery may be by intravascular administration.


In one embodiment, the AAV particles of the present invention may be administered to a subject by intracranial delivers' (See, e.g., U.S. Pat. No. 8,119,611; the content of which is incorporated herein by reference in its entirety).


In one embodiment, the AAV particles of the present invention may be administered to a subject by intraparenchymal administration.


In one embodiment, the AAV particles of the present invention may be administered to a subject by intramuscular administration.


In one embodiment, the AAV particles of the present invention are administered to a subject and transduce muscle of a subject. As a non-limiting example, the AAV particles are administered by intramuscular administration.


In one embodiment, the AAV particles of the present invention may be administered to a subject by intravenous administration.


In one embodiment, the AAV particles of the present invention may be administered to a subject by subcutaneous administration.


In one embodiment, the AAV particles of the present invention may be administered to a subject by topical administration.


In one embodiment, the AAV particles may be delivered by direct injection into the brain. As a non-limiting example, the brain delivery may be by intrastriatal administration.


In one embodiment, the AAV particles may be delivered by more than one route of administration. As non-limiting examples of combination administrations, AAV particles may be delivered by intrathecal and intracerebroventricular, or by intravenous and intraparenchymal administration.


Parenteral and Injectable Administration

In some embodiments, pharmaceutical compositions, AAV particles of the present invention may be administered parenterally. Liquid dosage forms for oral and parenteral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and/or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and/or perfuming agents. In certain embodiments for parenteral administration, compositions are mixed with solubilizing agents such as CREMOPHOR®, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and/or combinations thereof. In other embodiments, surfactants are included such as hydroxypropylcellulose.


Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing agents, wetting agents, and/or suspending agents. Sterile injectable preparations may be sterile injectable solutions, suspensions, and/or emulsions in nontoxic parenterally acceptable diluents and/or solvents, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P, and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono- or diglycerides Fatty acids such as oleic acid can be used in the preparation of injectables.


Injectable formulations may be sterilized, for example, by filtration through a bacterial-retaining filter, and/or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.


In order to prolong the effect of active ingredients, it is often desirable to slow the absorption of active ingredients from subcutaneous or intramuscular injections. This may be accomplished by the use of liquid suspensions of crystalline or amorphous material with poor water solubility. The rate of absorption of active ingredients depends upon the rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues.


Rectal and Vaginal Administration

In some embodiments, pharmaceutical compositions, AAV particles of the present invention may be administered rectally and/or vaginally Compositions for rectal or vaginal administration are typically suppositories which can be prepared by mixing compositions with suitable non-irritating excipients such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient.


Oral Administration

In some embodiments, pharmaceutical compositions, AAV particles of the present invention may be administered orally. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, an active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient such as sodium citrate or dicalcium phosphate and/or fillers or extenders (e.g. starches, lactose, sucrose, glucose, mannitol, and silicic acid), binders (e.g. carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia), humectants (e.g. glycerol), disintegrating agents (e.g. agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate), solution retarding agents (e.g. paraffin), absorption accelerators (e.g. quaternary ammonium compounds), wetting agents (e.g. cetyl alcohol and glycerol monostearate), absorbents (e.g. kaolin and bentonite clay), and lubricants (e.g. talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate), and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may comprise buffering agents.


Topical or Transdermal Administration

As described herein, pharmaceutical compositions, AAV particles of the present invention may be formulated for administration topically. The skin may be an ideal target site for delivery as it is readily accessible. Three routes are commonly considered to deliver pharmaceutical compositions, AAV particles of the present invention to the skin: (i) topical application (e.g. for local/regional treatment and/or cosmetic applications); (ii) intradermal injection (e.g. for local/regional treatment and/or cosmetic applications), and (iii) systemic delivery (e.g. for treatment of dermatologic diseases that affect both cutaneous and extracutaneous regions). Pharmaceutical compositions, AAV particles of the present invention can be delivered to the skin by several different approaches known in the art.


In some embodiments, the invention provides for a variety of dressings (e.g., wound dressings) or bandages (e.g., adhesive bandages) for conveniently and/or effectively carrying out methods of the present invention. Typically dressing or bandages may comprise sufficient amounts of pharmaceutical compositions, AAV particles of the present invention described herein to allow users to perform multiple treatments.


Dosage forms for topical and/or transdermal administration may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants and/or patches. Generally, active ingredients are admixed under sterile conditions with pharmaceutically acceptable excipients and/or any needed preservatives and/or buffers. Additionally, the present invention contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of pharmaceutical compositions, AAV particles of the present invention to the body. Such dosage forms may be prepared, for example, by dissolving and/or dispensing pharmaceutical compositions, AAV particles in the proper medium. Alternatively, or additionally, rates may be controlled by either providing rate controlling membranes and/or by dispersing pharmaceutical compositions, AAV particles in a polymer matrix and/or gel.


Formulations suitable for topical administration include, but are not limited to, liquid and/or semi liquid preparations such as liniments, lotions, oil in water and/or water in oil emulsions such as creams, ointments and/or pastes, and/or solutions and/or suspensions.


Topically-administrable formulations may, for example, comprise from about 1% to about 10% (w/w) active ingredient, although the concentration of active ingredient may be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further comprise one or more of the additional ingredients described herein.


Depot Administration

As described herein, in some embodiments, pharmaceutical compositions, AAV particles of the present invention are formulated in depots for extended release. Generally, specific organs or tissues (“target tissues”) are targeted for administration.


In some aspects of the invention, pharmaceutical compositions, AAV particles of the present invention are spatially retained within or proximal to target tissues. Provided are methods of providing pharmaceutical compositions, AAV particles, to target tissues of mammalian subjects by contacting target tissues (which comprise one or more target cells) with pharmaceutical compositions, AAV particles, under conditions such that they are substantially retained in target tissues, meaning that at least 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the composition is retained in the target tissues. Advantageously, retention is determined by measuring the amount of pharmaceutical compositions, AAV particles, that enter one or more target cells. For example, at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9%, 99.99% or greater than 99.99% of pharmaceutical compositions, AAV particles, administered to subjects are present intracellularly at a period of time following administration. For example, intramuscular injection to mammalian subjects may be performed using aqueous compositions comprising pharmaceutical compositions, AAV particles of the present invention and one or more transfection reagents, and retention is determined by measuring the amount of pharmaceutical compositions, AAV particles, present in muscle cells.


Certain aspects of the invention are directed to methods of providing pharmaceutical compositions, AAV particles of the present invention to a target tissues of mammalian subjects, by contacting target tissues (comprising one or more target cells) with pharmaceutical compositions, AAV particles under conditions such that they are substantially retained in such target tissues. Pharmaceutical compositions, AAV particles comprise enough active ingredient such that the effect of interest is produced in at least one target cell. In some embodiments, pharmaceutical compositions, AAV particles generally comprise one or more cell penetration agents, although “naked” formulations (such as without cell penetration agents or other agents) are also contemplated, with or without pharmaceutically acceptable carriers.


Pulmonary Administration

In some embodiments, pharmaceutical compositions, AAV particles of the present invention may be prepared, packaged, and/or sold in formulations suitable for pulmonary administration. In some embodiments, such administration is via the buccal cavity. In some embodiments, formulations may comprise dry particles comprising active ingredients. In such embodiments, dry particles may have a diameter in the range from about 0.5 nm to about 7 nm or from about 1 nm to about 6 nm. In some embodiments, formulations may be in the form of dry powders for administration using devices comprising dry powder reservoirs to which streams of propellant may be directed to disperse such powder. In some embodiments, self-propelling solvent/powder dispensing containers may be used. In such embodiments, active ingredients may be dissolved and/or suspended in low-boiling propellant in sealed containers. Such powders may comprise particles wherein at least 98% of the particles by weight have diameters greater than 0.5 nm and at least 95% of the particles by number have diameters less than 7 nm. Alternatively, at least 95% of the particles by weight have a diameter greater than 1 nm and at least 90% of the particles by number have a diameter less than 6 nm. Dry powder compositions may include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form.


Low boiling propellants generally include liquid propellants having a boiling point of below 65° F. at atmospheric pressure. Generally, propellants may constitute 50% to 99.9% (w/w) of the composition, and active ingredient may constitute 0.1% to 20% (w/w) of the composition. Propellants may further comprise additional ingredients such as liquid non-ionic and/or solid anionic surfactant and/or solid diluent (which may have particle sizes of the same order as particles comprising active ingredients).


Pharmaceutical compositions formulated for pulmonary delivery may provide active ingredients in the form of droplets of solution and/or suspension. Such formulations may be prepared, packaged, and/or sold as aqueous and/or dilute alcoholic solutions and/or suspensions, optionally sterile, comprising active ingredients, and may conveniently be administered using any nebulization and/or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and/or a preservative such as methylhydroxybenzoate. Droplets provided by this route of administration may have an average diameter in the range from about 0.1 nm to about 200 nm.


Intranasal, Nasal and Buccal Administration

In some embodiments, pharmaceutical compositions, AAV particles of the present invention may be administered nasally and/or intranasal. In some embodiments, formulations described herein useful for pulmonary delivery may also be useful for intranasal deliver. In some embodiments, formulations for intranasal administration comprise a coarse powder comprising the active ingredient and having an average particle from about 0.2 μm to 500 μm. Such formulations are administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nose.


Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w/w) and as much as 100% (w/w) of active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition may be prepared, packaged, and/or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods, and may, for example, 0.1% to 20% (w/w) active ingredient, the balance comprising an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise powders and/or an aerosolized and/or atomized solutions and/or suspensions comprising active ingredients. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may comprise average particle and/or droplet sizes in the range of from about 0.1 nm to about 200 nm, and may further comprise one or more of any additional ingredients described herein


Ophthalmic or Otic Administration

In some embodiments, pharmaceutical compositions, AAV particles of the present invention may be prepared, packaged, and/or sold in formulations suitable for ophthalmic and/or otic administration. Such formulations may, for example, be in the form of eye and/or ear drops including, for example, a 0.1/1.0% (w/w) solution and/or suspension of the active ingredient in aqueous and/or oily liquid excipients. Such drops may further comprise buffering agents, salts, and/or one or more other of any additional ingredients described herein. Other ophthalmically-administrable formulations which are useful include those which comprise active ingredients in microcrystalline form and/or in liposomal preparations. Subretinal inserts may also be used as forms of administration.


Delivery to Cells

The present disclosure provides a method of delivering to a cell or tissue any of the above-described AAV particles, comprising contacting the cell or tissue with said AAV particle or contacting the cell or tissue with a formulation comprising said AAV particle, or contacting the cell or tissue with any of the described compositions, including pharmaceutical compositions. The method of delivering the AAV particle to a cell or tissue can be accomplished in vitro, ex vivo, or in vivo.


Delivery to Subjects

The present disclosure additionally provides a method of delivering to a subject, including a mammalian subject, any of the above-described AAV particles comprising administering to the subject said AAV particle, or administering to the subject a formulation comprising said AAV particle, or administering to the subject any of the described compositions, including pharmaceutical compositions.


Dose and Regimen

The present invention provides methods of administering AAV particles in accordance with the invention to a subject in need thereof. The pharmaceutical, diagnostic, or prophylactic AAV particles and compositions of the present invention may be administered to a subject using any amount and any route of administration effective for preventing, treating, managing, or diagnosing diseases, disorders and/or conditions. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the disease, the particular composition, its mode of administration, its mode of activity, and the like. The subject may be a human, a mammal, or an animal. Compositions in accordance with the invention are typically formulated in unit dosage form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions of the present invention may be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective, prophylactically effective, or appropriate diagnostic dose level for any particular individual will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific payload employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific AAV particle employed; the duration of the treatment; drugs used in combination or coincidental with the specific AAV particle employed; and like factors well known in the medical arts.


In certain embodiments, AAV particle pharmaceutical compositions in accordance with the present invention may be administered at dosage levels sufficient to deliver from about 0.0001 mg/kg to about 100 mg/kg, from about 0.001 mg/kg to about 0.05 mg/kg, from about 0.005 mg/kg to about 0.05 mg/kg, from about 0.001 mg/kg to about 0.005 mg/kg, from about 0.05 mg/kg to about 0.5 mg/kg, from about 0.01 mg/kg to about 50 mg/kg, from about 0.1 mg/kg to about 40 mg/kg, from about 0.5 mg/kg to about 30 mg/kg, from about 0.01 mg/kg to about 10 mg/kg, from about 0.1 mg/kg to about 10 mg/kg, or from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic, diagnostic, or prophylactic, effect. It will be understood that the above dosing concentrations may be converted to vg or viral genomes per kg or into total viral genomes administered by one of skill in the art.


In certain embodiments, AAV particle pharmaceutical compositions in accordance with the present disclosure may be administered at about 10 to about 600 μl/site, 50 to about 500 μl/site, 100 to about 400 μl/site, 120 to about 300 μl/site, 140 to about 200 μl/site, about 160 μl/site. As non-limiting examples, AAV particles may be administered at 50 μl/site and/or 150 μl/site.


The desired dosage of the AAV particles of the present invention may be delivered only once, three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage may be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). When multiple administrations are employed, split dosing regimens such as those described herein may be used. As used herein, a “split dose” is the division of “single unit dose” or total daily dose into two or more doses, e.g., two or more administrations of the “single unit dose”. As used herein, a “single unit dose” is a dose of any therapeutic administered in one dose/at one time/single route/single point of contact, i.e., single administration event.


The desired dosage of the AAV particles of the present invention may be administered as a “pulse dose” or as a “continuous flow” As used herein, a “pulse dose” is a series of single unit doses of any therapeutic administered with a set frequency over a period of time. As used herein, a “continuous flow” is a dose of therapeutic administered continuously for a period of time in a single route/single point of contact, i.e., continuous administration event. A total daily dose, an amount given or prescribed in 24 hour period, may be administered by any of these methods, or as a combination of these methods, or by any other methods suitable for a pharmaceutical administration.


In one embodiment, delivery of the AAV particles of the present invention to a subject provides neutralizing activity to a subject. The neutralizing activity can be for at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 20 months, 21 months, 22 months, 23 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years or more than 10 years.


In one embodiment, delivery, of the AAV particles of the present invention results in minimal serious adverse events (SAEs) as a result of the delivery of the AAV particles.


In one embodiment, delivery of AAV particles to cells of the central nervous system (e.g., parenchyma) may comprise a total dose between about 1×106 VG and about 1×1016 VG, In some embodiments, delivery may comprise a total dose of about 1×106, 2×106, 3×106, 4×106, 5×106, 6×106, 7×106, 8×106, 9×106, 1×107, 2×107, 3×107, 4×107, 5×107, 6×107, 7×107, 8×107, 9×107, 1×108, 2×108, 3×108, 4×108, 5×108, 6×108, 7×108, 8×108, 9×108, 1×109, 2×109, 3×109, 4×109, 5×109, 6×109, 7×109, 8×109, 9×109, 1×1010, 1.9×1010, 2×1010, 3×1010, 3.73×1010, 4×1010, 5×1010, 6×1010, 7×1010, 8×1010, 9×1010, 1×1011, 2×1011, 2.5×1011, 3×1011, 4×1011, 5×1011, 6×1011, 7×1011, 8×1011, 9×1011, 1×1012, 2×1012, 3×1012, 4×1012, 5×1012, 6×1012, 7×1012, 8×1012, 9×1012, 1×1013, 2×1013, 3×1013, 4×1013, 4×1013, 6×1013, 7×1013, 8×1013, 9×1013, 1×1014, 2×1014, 3×1014, 4×1014, 5×1014, 6×1014, 7×1014, 8×1014, 9×1014, 1×1015, 2×1015, 3×1015, 4×1015, 5×1015, 6×1015, 7×1015, 8×1015, 9×1015, or 1×1016 VG. As a non-limiting example, the total dose is 1×1013 VG. As another non-limiting example, the total dose is 2.1×1012 VG.


In one embodiment, delivery of AAV particles to cells of the central nervous system (e.g., parenchyma) may comprise a composition concentration between about 1×106 VG/mL and about 1×1016 VG/mL. In some embodiments, delivery may comprise a composition concentration of about 1×106, 2×106, 3×106, 4×106, 5×106, 6×106, 7×106, 8×106, 9×106, 1×107, 2×107, 3×107, 4×107, 5×107, 6×107, 7×107, 8×107, 9×107, 1×108, 2×108, 3×108, 4×108, 5×108, 6×108, 7×108, 8×108, 9×108, 1×109, 2×109, 3×109, 4×109, 5×109, 6×109, 7×109, 8×109, 9×109, 1×1010, 2×1010, 3×1010, 4×1010, 5×1010, 6×1010, 7×1010, 8×1010, 9×1010, 1×1011, 2×1011, 3×1011, 4×1011, 5×1011, 6×1011, 7×1011, 8×1011, 9×1011, 1×1012, 2×1012, 3×1012, 4×1012, 5×1012, 6×1012, 7×1012, 8×1012, 9×1012, 1×1013, 2×1013, 3×1013, 4×1013, 5×1013, 6×1013, 7×1013, 8×1013, 9×1013, 1×1014, 2×1014, 3×1014, 4×1014, 5×1014, 6×1014, 7×1014, 8×1014, 9×1014, 1×1015, 2×1015, 3×1015, 4×1015, 5×1015, 6×1015, 7×1015, 8×1015, 9×1015, or 1×1016 VG/mL. In one embodiment, the delivery comprises a composition concentration of 1×1013 VG/mL. In one embodiment, the delivery comprises a composition concentration of 2.1×1012 VG/mL.


Combinations

The AAV particles may be used in combination with one or more other therapeutic, prophylactic, research or diagnostic agents. By “in combination with,” it is not intended to imply that the agents must be administered at the same time and/or formulated for delivery together, although these methods of delivery are within the scope of the present invention. Compositions can be administered concurrently with, prior to, or subsequent to, one or more other desired therapeutics or medical procedures. In general, each agent will be administered at a dose and/or on a time schedule determined for that agent. In some embodiments, the present disclosure encompasses the delivery of pharmaceutical, prophylactic, research, or diagnostic compositions in combination with agents that may improve their bioavailability, reduce and/or modify their metabolism, inhibit their excretion, and/or modify their distribution within the body.


Measurement of Expression

Expression of payloads from viral genomes may be determined using various methods known in the art such as, but not limited to immunochemistry (e.g., IHC), in situ hybridization (ISH), enzyme-linked immunosorbant assay (ELISA), affinity ELISA, ELISPOT, flow cytometry, immunocytology, surface plasmon resonance analysis, kinetic exclusion assay, liquid chromatography-mass spectrometry (LCMS), high-performance liquid chromatography (HPLC). BCA assay, immunoelectrophoresis. Western blot, SDS-PAGE, protein immunoprecipitation, and/or PCR,


Bioavalability

The AAV particles, when formulated into a composition with a delivery agent as described herein, can exhibit an increase in bioavailability as compared to a composition lacking a delivery agent as described herein. As used herein, the term “bioavailability” refers to the systemic availability of a given amount of AAV particle or expressed payload administered to a mammal. Bioavailability can be assessed by measuring the area under the curve (AUC) or the maximum serum or plasma concentration (Cmax) of the composition following. AUC is a determination of the area under the curve plotting the serum or plasma concentration of a compound (e.g., AAV particles or expressed payloads) along the ordinate (Y-axis) against time along the abscissa (X-axis). Generally, the AUC for a particular compound can be calculated using methods known to those of ordinary skill in the art and as described in G. S. Banker, Modern Pharmaceutics, Drugs and the Pharmaceutical Sciences, v. 72, Marcel Dekker, New York, Inc., 1996, the contents of which are herein incorporated by reference in its entirety.


The Cmax value is the maximum concentration of the AAV particle or expressed payload achieved in the serum or plasma of a mammal following administration of the AAV particle to the mammal. The Cmax value of can be measured using methods known to those of ordinary skill in the art. The phrases “increasing bioavailability” or “improving the pharmacokinetics,” as used herein mean that the systemic availability of a first AAV particle or expressed payload, measured as AUC, Cmax, or Cmin in a mammal is greater, when co-administered with a delivery agent as described herein, than when such co-administration does not take place. In some embodiments, the bioavailability can increase by at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.


Therapeutic Window

As used herein “therapeutic window” refers to the range of plasma concentrations, or the range of levels of therapeutically active substance at the site of action, with a high probability of eliciting a therapeutic effect. In some embodiments, the therapeutic window of the AAV particle as described herein can increase by at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.


Volume of Distribution

As used herein, the term “volume of distribution” refers to the fluid volume that would be required to contain the total amount of the drug in the body at the same concentration as in the blood or plasma: Vdist equals the amount of drug in the body/concentration of drug in blood or plasma. For example, for a 10 mg dose and a plasma concentration of 10 mg/L, the volume of distribution would be 1 liter. The volume of distribution reflects the extent to which the drug is present in the extravascular tissue. A large volume of distribution reflects the tendency of a compound to bind to the tissue components compared with plasma protein binding. In a clinical setting, Vdist can be used to determine a loading dose to achieve a steady state concentration. In some embodiments, the volume of distribution of the AAV particles as described herein can decrease at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%.


Biological Effect

In one embodiment, the biological effect of the AAV particles delivered to the animals may be categorized by analyzing the payload expression in the animals. The payload expression may be determined from analyzing a biological sample collected from a mammal administered the AAV particles of the present invention. For example, a protein expression of 50-200 pg/ml for the protein encoded by the AAV particles delivered to the mammal may be seen as a therapeutically effective amount of protein in the mammal.


IV. Methods and Uses of the Compositions of the Invention

The present disclosure provides a method for treating a disease, disorder and/or condition in a mammalian subject, including a human subject, comprising administering to the subject any of the AAV particles described herein or administering to the subject any of the described compositions, including pharmaceutical compositions, described herein.


In one embodiment, the AAV particles of the present invention are administered to a subject prophylactically.


In one embodiment, the AAV particles of the present invention are administered to a subject having at least one of the diseases described herein.


In one embodiment, the AAV particles of the present invention are administered to a subject to treat a disease or disorder described herein. The subject may have the disease or disorder or may be at-risk to developing the disease or disorder.


In one embodiment, the AAV particles of the present invention are part of an active immunization strategy to protect against diseases and disorders. In an active immunization strategy, a vaccine or AAV particles are administered to a subject to prevent an infectious disease by activating the subject's production of antibodies that can fight off invading bacteria or viruses.


In one embodiment, the AAV particles of the present invention are part of a passive immunization strategy. In a passive immunization strategy, antibodies against a particular infectious agent are given directly to the subject.


Diseases and Toxins

Various infectious diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As used herein, the term “infectious disease” refers to any disorders caused by organisms such as bacteria, viruses, fungi or parasites. As a non-limiting example, the infectious disease may be Acute bacterial rhinosinusitis, 14-day measles. Acne, Acrodermatitis chronica atrophicans (ACA)-(late skin manifestation of latent Lyme disease), Acute hemorrhagic conjunctivitis, Acute hemorrhagic cystitis, Acute rhinosinusitis, Adult T-cell Leukemia-Lymphoma (ATLL), African Sleeping Sickness, AIDS (Acquired Immunodeficiency Syndrome), Alveolar hydatid, Amebiasis, Amebic meningoencephalitis, Anaplasmosis, Anthrax, Arboviral or parainfectious, Ascariasis—(Roundworm infections), Aseptic meningitis, Athlete's foot (Tinea pedis), Australian tick typhus, Avian Influenza, Babesiosis, Bacillary angiomatosis, Bacterial meningitis, Bacterial vaginosis, Balanitis, Balantidiasis, Bang's disease, Barmah Forest virus infection, Bartonellosis (Verruga peruana; Carrion's disease; Oroya fever), Bat Lyssavirus Infection, Bay sore (Chiclero's ulcer), Baylisascaris infection (Racoon roundworm infection), Beaver fever, Beef tapeworm, Bejel (endemic syphilis), Biphasic meningoencephalitis, Black Bane, Black death, Black piedra, Blackwater Fever, Blastomycosis, Blennorrhea of the newborn, Blepharitis, Boils, Bomholm disease (pleurodynia), Borrelia miyamotoi Disease, Botulism, Boutonneuse fever, Brazilian purpuric fever, Break Bone fever, Brill, Bronchiolitis, Bronchitis, Brucellosis (Bang's disease), Bubonic plague, Bullous impetigo, Burkholderia mallei (Glanders), Burkholderia pseudomallei (Melioidosis), Buruli ulcers (also Mycoburuli ulcers), Busse Busse-Buschke disease (Cryptococcosis), California group encephalitis, Campylobacteriosis, Candidiasis, Canefield fever (Canicola fever; 7-day fever; Weil's disease; leptospirosis; canefield fever), Canicola fever, Capillanasis, Carate, Carbapenem-resistant Enterobacteriaceae (CRE), Carbuncle, Carrion's disease, Cat Scratch fever, Cave disease, Central Asian hemorrhagic fever, Central European tick, Cervical cancer, Chagas disease, Chancroid (Soft chancre), Chicago disease, Chickenpox (Varicella), Chiclero's ulcer, Chikungunya fever, Chlarmydial infection, Cholera, Chromoblastomycosis, Ciguatera, Clap, Clonorchiasis (Liver fluke infection), Clostridium difficile Infection, Clostridium perfringens (Epsilon Toxin), Coccidioidonycosis fungal infection (Valley fever; desert rheumatism), Coenurosis, Colorado tick fever, Condyloma accuminata, Condyloma accununata (Warts), Condyloma lata, Congo fever, Congo hemorrhagic fever virus, Conjunctivitis, cowpox, Crabs, Crimean, Croup, Cryptococcosis, Cryptosporidiosis (Crypto), Cutaneous Larval Migrans, Cyclosporiasis, Cystic hydatid, Cysticercosis, Cystatis, Czechoslovak tick, D68 (EV-D68), Dacryocytitis, Dandy fever, Darling's Disease, Deer fly fever, Dengue fever (1, 2, 3 and 4), Desert rheumatism, Devil's grip, Diphasic milk fever, Diphtheria, Disseminated Intravascular Coagulation, Dog tapeworm, Donovanosis, Donovanosis (Granuloma inguinale), Dracontiasis, Dracunculosis, Duke's disease, Dum Dum Disease, Durand-Nicholas-Favre disease, Dwarf tapeworm, E, Coli infection (E. Coli), Eastern equine encephalitis, Ebola Hemorrhagic Fever (Ebola virus disease EVD), Ectothrix, Ehrlichiosis (Sennetsu fever), Encephalitis, Endemic Relapsing fever, Endemic syphilis, Endophthalmitis, Endothrix, Enterobiasis (Pinworm infection), Enterotoxin-B Poisoning (Staph Food Poisoning), Enterovirus Infection, Epidemic Keratoconjunctivitis, Epidemic Relapsing fever, Epidemic typhus, Epiglottitis, Erysipelis, Ervsipeloid (Erysipelothricosis), Erythema chronicum migrans, Erythema infectiosum, Erythema marginatum, Enrthema multiforme, Erythema nodosum, Erythema nodosum leprosum Erythrasma, Espundia, Euniycotic mycetoma, European blastomycosis, Exanthem subitumn (Sixth disease), Eyeworm, Far Eastern tick, Fascioliasis, Fievre boutonneuse (Tick typhus), Fifth Disease (erythema infectiosum), Filatow-Dukes' Disease (Scalded Skin Syndrome; Ritter's Disease), Fish tapeworm, Fitz-Hugh-Curtis syndrome—Perihepatitis, Flinders Island Spotted Fever, Flu (Influenza), Folliculitis, Four Corners Disease, Four Corners Disease (Human Pulmonary Syndrome (HPS)), Frambesia, Francis disease, Furunculosis, Gas gangrene, Gastroenteritis, Genital Herpes, Genital Warts, German measles, Gerstmann-Straussler-Scheinker (GSS), Giardiasis, Gilchrist's disease, Gingivitis, Gingivostomatitis, Glanders, Glandular fever (infectious mononucleosis), Gnathostomiasis, Gonococcal Infection (Gonorrhea), Gonorrhea, Granuloma inguinale (Donovanosis), Guinea Worm, Haemophilus Influenza disease, Hamburger disease, Hansen's disease—leprosy, Hantaan disease, Hantaan-Korean hemorrhagic fever, Hantavirus Pulmonary Syndrome, Hantavirus Pulmonary Syndrome (HPS), Hard chancre, Hard measles, Haverhill fever—Rat bite fever, Head and Body Lice, Heartland fever, Helicobacterosis, Hemolytic Uremic Syndrome (HUS), Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, Hepatitis E, Herpangina, Herpes—genital, Herpes labialis, Herpes—neonatal, Hidradenitis, Histoplasmosis, Histoplasmosis infection (Histoplasmosis), His-Werner disease, HIV infection, Hookworm infections, Hordeola, Hordeola (Stye), HTLV, HTLV-associated myelopathy (HAM), Human granulocytic ehrlichiosis, Human monocytic ehrlichiosis, Human Papillomavirus (HPV), Human Pulmonary Syndrome, Hydatid cyst, Hydrophobia, Impetigo, Including congenital (German Measles), Inclusion conjunctivitis, Inclusion conjunctivitis+Swimming Pool conjunctivitis—Pannus, Infantile diarrhea, Infectious Mononucleosis, Infectious myocarditis, Infectious pericarditis, Influenza, Isosporiasis, Israeli spotted fever, Japanese Encephalitis, Jock itch, Jorge Lobo disease—Iobomycosis, Jungle yellow fever, Junin Argentinian hemorrhagic fever, Kala Azar, Kaposi's sarcoma, Keloidal blastomycosis, Keratoconjunctivitis, Kuru, Kyasanur forest disease, LaCrosse encephalitis, Lassa hemorrhagic fevter, Legionellosis (Legionnaires Disease), Legionnaires pneumonia, Lemierre's Syndrome (Postanginal septicemia), Lemming fever, Leprosy, Leptospirosis (Nanukayami fever: Well's disease), Listeriosis (Listeria), Liver fluke infection, Lobo's mycosis, Lockjaw, Loiasis, Louping Ill, Ludwig's angina, Lung fluke infection, Lung fluke infection (Paragonimiasis), Lyme disease, Lymphogranuloma venereum infection (LGV), Machupo Bolivian hemorrhagic fever, Madura foot, Mal del pinto, Malaria, Malignant pustule, Malta fever, Marburg hemorrhagic fever, Masters disease, Maternal Sepsis (Puerperal fever), Measles, Mediterannean spotted fever, Melioidosis (Whitmore's disease), Meningitis, Meningococcal Disease, MERS, Milker's nodule, Molluscum contagiosum, Moniliasis, monkeypox, Mononucleosis, Mononucleosis-like syndrome, Montezuma's Revenge, Morbillih, MRSA (methicillin-resistant Staphylococcus aureus) infection, Mucormycosis-Zygonmycosis, Multiple Organ Dysfunction Syndrome or MODS, Multiple-system atrophy (MSA), Mumps, Murine typhus, Murray Valley Encephalitis (MVE), Mycoburuli ulcers, Mycoburuli ulcers-Buruli ulcers, Mycotic vulvovaginitis, Myositis, Nanukavami fever, Necrotizing fasciitis, Necrotizing fasciitis—Type 1, Necrotizing fasciitis—Type 2, Negishi, New world spotted fever, Nocardiosis, Nongonococcal urethritis, Non-Polio (Non-Polio Enterovirus), Norovirus infection, North American blastonmycosis, North Asian tick typhus, Norwalk virus infection, Norwegian itch, O'Hara disease, Omsk hemorrhagic fever, Onchocerciasis, Onychomycosis, Opisthorchiasis, Opthalmia neonatorium, Oral hairy leukoplakia, Orf, Oriental Sore, Oriental Spotted Fever, Omithosis (Parrot fever; Psittacosis), Oroya fever, Otitis externa, Otitis media, Pannus, Paracoccidioidomycosis, Paragonimiasis, Paralytic Shellfish Poisoning (Paralytic Shellfish Poisoning), Paronychia (Whitlow), Parotitis, PCP pneumonia, Pediculosis, Peliosis hepatica, Pelvic Inflammatory Disease, Pertussis (also called Whooping cough), Phaeohyphomycosis, Pharyngoconjunctival fever, Piedra (White Piedra), Piedra(Black Piedra), Pigbel, Pink eye conjunctivitis, Pinta, Pinworm infection, Pitted Keratolysis, Pityriasis versicolor (Tinea versicolor), Plague; Bubonic, Pleurodynia, Pneumococcal Disease, Pneumocystosis, Pneumonia, Pneumonic (Plague), Polio or Poliominvelitis, Polycystic hydatid, Pontiac fever, Pork tapeworm, Posada-Wemicke disease, Postanginal septicemia, Powassan, Progressive multifocal leukencephalopathy, Progressive Rubella Panencephalitis, Prostatitis, Pseudomembranous colitis, Psittacosis, Puerperal fever, Pustular Rash diseases (Small pox), Pyelonephritis, Pylephlebitis, Q-Fever, Quinsy, Quintana fever (5-day fever), Rabbit fever, Rabies, Racoon roundworm infection, Rat bite fever, Rat tapeworm, Reiter Syndrome, Relapsing fever, Respiratory syncytial virus (RSV) infection, Rheumatic fever, Rhodotorulosis, Ricin Poisoning, Rickettsialpox, Rickettsiosis, Rift Valley Fever, Ringworm, Ritter's Disease, River Blindness, Rocky Mountain spotted fever, Rose Handler's disease (Sporotrichosis), Rose rash of infants, Roseola, Ross River fever, Rotavirus infection, Roundworm infections, Rubella, Rubeola, Russian spring, Salmonellosis gastroenteritis, San Joaquin Valley fever, Sao Paulo Encephalitis, Sao Paulo fever, SARS, Scabies Infestation (Scabies) (Norwegian itch), Scalded Skin Syndrome, Scarlet fever (Scarlatina), Schistosomiasis, Scombroid, Scrub typhus, Sennetsu fever, Sepsis (Septic shock), Severe Acute Respiratory Syndrome, Severe Acute Respiratory Syndrome (SARS), Shiga Toxigenic Escherichia coli (STEC/VTEC), Shigellosis gastroenteritis (Shigella), Shinbone fever, Shingles, Shipping fever, Siberian tick typhus, Sinusitis, Sixth disease, Slapped cheek disease, Sleeping sickness, Smallpox (Variola), Snail Fever, Soft chancre, Southern tick associated rash illness, Sparganosis, Spelunker's disease, Sporadic typhus, Sporotrichosis, Spotted fever, Spring, St, Louis encephalitis, Staphylococcal Food Poisoning, Staphylococcal Infection, Strep, throat, Streptococcal Disease, Streptococcal Toxic-Shock Syndrome, Strongyloiciasis, Stye, Subacute Sclerosing Panencephalitis, Subacute Sclerosing Panencephalitis (SSPE), Sudden Acute Respiratory Syndrome, Sudden Rash, Swimmer's ear, Swimmer's Itch, Swimming Pool conjunctivitis, Sylvatic yellow fever, Syphilis, Systemic Inflammatory Response Syndrome (SIRS), Tabes dorsalis (tertiary syphilis), Taeniasis, Taiga encephalitis, Tanner's disease, Tapeworm infections, Temporal lobe encephalitis, Temporal lobe encephalitis, tetani (Lock Jaw), Tetanus Infection, Threadwonn infections, Thrush, Tick, Tick typhus, Tinea barbae, Tinea capitis, Tinea corporis, Tinea cruris, Tinea manuum, Tinea nigra, Tinea pedis, Tinea unguiunm, Tinea versicolor, Torulopsosis, Torulosis, Toxic Shock Syndrome, Toxoplasmosis, transmissible spongioform (CJD), Traveler's diarrhea, Trench fever 5, Trichinellosis, Trichomoniasis, Trichomycosis axillaris, Trichuriasis, Tropical Spastic Paraparesis (TSP), Trypanosomiasis, Tuberculosis (TB), Tuberculousis, Tularemia, Typhoid Fever, Typhus fever, Ulcus molle, Undulant fever, Urban yellow fever, Urethritis, Vaginitis, Vaginosis, Vancomycin Intermediate (VISA), Vancomycin Resistant (VRSA), Varicella, Venezuelan Equune encephalitis, Verruga peruana, Vibrio cholerae (Cholera), Vibriosis (Vibrio), Vincent's disease or Trench mouth, Viral conjunctivitis, Viral Meningitis, Viral meningoencephalitis, Viral rash, Visceral Larval Migrans, Vornito negro, Vulvovaginitis, Warts, Waterhouse, Weil's disease, West Nile Fever, Western equine encephalitis, Whipple's disease, Whipworm infection, White Piedra, Whitlow, Whitmore's disease, Winter diarrhea, Wolhynia fever, Wool sorters' disease, Yaws, Yellow Fever, Yersinosis, Yersinosis (Yersinia), Zahorsky's disease, Zika virus disease, Zoster, Zygornmcosis, John Cunningham Virus (JCV), Human immunodeficiency virus (HIV), Influenza virus, Hepatitis B, Hepatitis C, Hepatitis D, Respiratory syncytial virus (RSV), Herpes simplex virus 1 and 2, Human Cytomegalovirus, Epstein-Barr virus, Varicella zoster virus, Coronaviruses, Poxviruses, Enterovirus 71, Rubella virus, Human papilloma virus, Streptococcus pneumoniae, Streptococcus viridans, Staphylococcus aureus (S. aureus), Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-intermediate Staphylococcus aureus (VISA), Vancomycin-resistant Staphylococus aureus (VRSA), Staphylococcus epidermidis (S. epidermidis), Clostridium teltani, Bordetella pertussis, Bordetelia paratussis, Mycobacterium, Francisella yularensis, Toxoplasma gondii, Candida ((C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei and C. lusiltaniae) and/or any other infectious diseases, disorders or syndromes.


Various toxins may be treated with the pharmaceutical compositions, AAV particles, of the present invention. Non-limited examples of toxins include Ricin, Bacillus anthracis, Shiga toxin and Shiga-like toxin, Botulinum toxins.


Various tropical diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. Non-limited examples of tropical diseases include Chikungunya fever. Dengue fever. Chagas disease, Rabies, Malaria. Ebola virus, Marburg virus, West Nile Virus, Yellow Fever, Japanese encephalitis virus. St Louis encephalitis virus.


Various foodborne illnesses and gastroenteritis may be treated with pharmaceutical compositions, AAV particles, of the present invention. Non-limited examples of foodborne illnesses and gastroenteritis include Rotavirus, Norwalk virus (Norovirus), Campylobacter jejuni, Clostridium difficile, Entamoeba histolytica, Helicobacter pylori, Enterotoxin B of Staphylococcus aureus, H-lepatitis A virus (HAV), Hepatitis E. Listeria monocytogenes, Salmonella, Clostridium perfringens, and Salmonella.


Various infectious agents may be treated with pharmaceutical compositions, AAV particles, of the present invention. Non-limited examples of infectious agents include adenoviruses. Anaplasma phagocytophilium, Ascaris lumbricoides, Bacillus anthracis, Bacillus cereus, Bacteroides sp, Barmah Forest virus, Bartonella bacilliformis, Bartonella henselae, Bartonella quintana, beta-toxin of Clostridium perifingens, Bordetella pertussis, Bordetella parapertussis, Borrelia burgdorferi, Borrelia miyamotoi, Borrelia recurrentis, Borreha sp., Botulinum toxin, Brucella sp., Burkholderia pseudomallei, California encephalitis virus, Campylobacter, Candida albicans, chikungunya virus, Chlamydia psittaci, Chlamydia trachomatis, Clonorchts sinensis, Clostridium difficile bacteria, Clostridium tetani, Colorado tick fever virus, Corynebacterium diphtheriae, Corynebacterium minutissimum, Coxiella burneii, coxsackie A, coxsackie B, Crimean-Congo hemorrhagic fever virus, cytomegalovirus, dengue virus, Eastern Equine encephalitis virus, Ebola viruses, echovirus, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia sp., Entamoeba histolytica, Enterobacter sp., Enterococcus feacalis, Enterovirus 71, Epstein-Barr virus (EBV), Erysipelothrix rhusioplathiae, Escherichia coli, Flavivirus, Fusobacterium necrophorum, Gardnerella vaginalis, Group B streptococcus, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenzae, hantavirus, Helicobacter pylori, Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, Hepatitis E, herpes simplex virus 1 and 2, human herpes virus 6, human herpes Virus 8, human immunodeficiency virus 1 and 2, human T-cell leukemia viruses 1 and 11, influenza viruses (A, B, C), Jamestown Canyon virus, Japanese encephalitis antigenic, Japanese encephalitis virus, John Cunningham virus, juninvirus, Kaposi's Sarcoma-associated Herpes Virus (KSHV), Klebsiella granulomatis, Klebsiella sp., Kyasanur Forest Disease virus, La Crosse virus, Lassavirus, Legionella pneumophila, Leptospira interrogans, Listeria monocytogenes, lymphocytic choriomeningitis virus, lyssavirus, Machupovirus, Marburg virus, measles virus, MERS coronavirus (MERS-CoV), Micrococcus sedentarius, Mobiliuncus sp., Molluscipeoxvirus, Moraxella catarrhalis, Morbilli-Ruheola virus, Mumpsvirus, Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma genitalium, Mycoplasma sp. Nairovirus, Neisseria gonorrhoeae, Neisseria menigitidis, Nocardia, Norwalk virus, norovirus, Onmsk hemorrhagic fever virus, papilloma virus, parainfluenza viruses 1-3, parapoxvirus, parvovirus B19, Peptostreptococccus sp., Plasmodium sp., polioviruses types 1, 11, and III, Proteus sp., Pseudomonas aeruginosa, Pseudomonas pseudomallei, Pseudomonas sp., rabies virus, respiratory syncytial virus, ricin toxin, Rickettsia australis, Rickettsia conori, Rickettsia honei, Rickettsia prowazekii, Ross River Virus, rotavirus, rubellavirus, Saint Louis encephalitis, Salmonella typhi, Sarcoptes scabiei, SARS-associated coronavirus (SARS-CoV), Serratia sp., Shiga toxin and Shiga-like toxin, Shigella sp., Sin Nombre Virus, Snowshoe hare virus, Staphylococcus aureus, Staphylococcus epidermidis, Streptobacillus moniliformis, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus agalacticae, Streptococcus group A-H, Streptococcus pneumoniae, Streptcoccus pyogenes, Treponema pallidum subsp. Pallidum, Treponema pallidum var. carateum, Treponema pallidum var. endemicum, Tropheryma whippelii, Ureaplasma urealytcum, Varicella-Zoster virus, variola virus, Vibrio cholerae, West Nile virus, yellow fever virus, Yersinia enterocolitica, Yersinia pestis, and Zika virus.


Various rare diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As used herein, the term “rare disease” refers to any disease that affects a small percentage of the population. As a non-limiting example, the rare disease may be Acrocephalosyndactylia, Acrodermatitis, Addison Disease, Adie Syndrome, Alagille Syndrome, Amylose, Amyotrophic Lateral Sclerosis, Angelman Syndrome, Angiolymphoid Hyperplasia with Eosinophilia, Arnold-Chiari Malformation, Arthritis, Juvenile Rheumatoid, Asperger Syndrome, Bardet-Biedl Syndrome, Barrett Esophagus, Beckwith-Wiedemann Syndrome, Behcet Syndrome, Bloom Syndrome, Bowen's Disease, Brachial Plexus Neuropathies, Brown-Sequard Syndrome, Budd-Chiari Syndrome, Burkitt Lymphoma, Carcinoma 256, Walker, Caroli Disease, Charcot-Marie-Tooth Disease, Chediak-Hiigashi Syndrome, Chiari-Frommel Syndrome, Chondrodysplasia Punctata, Colonic Pseudo-Obstruction, Colorectal Neoplasms, Hereditary Nonpolyposis, Craniofacial Dysostosis, Creutzfeldt-Jakob Syndrome, Crohn Disease, Cushing Syndrome, Cystic Fibrosis, Dandy-Walker Syndrome, De Lange Syndrome, Dementia, Vascular, Dermatitis Herpetiformis, DiGeorge Syndrome, Diffuse Cerebral Sclerosis of Schilder, Duane Retraction Syndrome, Dupuytren Contracture, Ebstein Anomaly, Eisenmenger Complex, Ellis-Van Creveld Syndrome, Encephalitis, Enchondromatosis, Epidermal Necrolysis, Toxic, Facial Hemiatrophy, Factor XII Deficiency, Fanconi Anemia, Felty's Syndrome, Fibrous Dyvsplasia, Polvostotic, Fox-Fordyce Disease, Friedreich Ataxia, Fusobacterium, Gardner Syndrome, Gaucher Disease, Gerstmann Syndrome, Giant Lymph Node Hyperplasia, Glycogen Storage Disease Type I, Glycogen Storage Disease Type II, Glycogen Storage Disease Type IV, Glycogen Storage Disease Type V, Glycogen Storage Disease Type VII, Goldenhar Syndrome, Guillain-Barre Syndrome, Hallermann's Syndrome, Hamartoma Syndrome, Multiple, Hartnup Disease, Hepatolenticular Degeneration, Hepatolenticular Degeneration, Hereditary Sensory and Motor Neuropathy, Hirschsprung Disease, Histiocytic Necrotizing Lymphadenitis, Histiocytosis, Langerhans-Cell, Hodgkin Disease, Homer Syndrome, Huntington Disease, Hyperaldosteronism, Hyperhidrosis, Hyperostosis, Diffuse Idiopathic Skeletal, Hypopituitarism, Inappropriate ADH Syndrome, Intestinal Polyps, Isaacs Syndrome, Kartagener Syndrome, Keams-Sayre Syndrome, Klippel-Feil Syndrome, Klippel-Trenaunay-Weber Syndrome, Kluver-Bucy Syndrome, Korsakoff Syndrome, Lafora Disease, Lambert-Eaton Myasthenic Syndrome, Landau-Kleffner Syndrome, Langer-Giedion Syndrome, Leigh Disease, Lesch-Nyhan Syndrome, Leukodystrophy, Globoid Cell, Li-Fraumeni Syndrome, Long QT Syndrome, Machado-Joseph Disease, Mallory-Weiss Syndrome, Marek Disease, Marfan Syndrome, Meckel Diverticulum, Meige Syndrome, Melkersson-Rosenthal Syndrome, Meniere Disease, Mikulicz' Disease, Miller Fisher Syndrome, Mobius Syndrome, Moyamoya Disease, Mucocutaneous Lymph Node Syndrome, Mucopoly saccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis III, Mucopolysaccharidosis IV, Mucopolysaccharidosis VI, Multiple Endocrine Neoplasia Type 1, Munchausen Syndrome by Proxy, Muscular Atrophy, Spinal, Narcolepsy, Neuroaxonal Dystrophies, Neuromyelitis Optica, Neuronal Ceroid-Lipofuscinoses, Niemann-Pick Diseases, Noonan Syndrome, Optic Atrophies, Hereditary, Osteitis Deformans, Osteochondritis, Osteochondrodysplasias, Osteolysis, Essential, Paget Disease Extramammary, Paget's Disease, Mammary, Panuuculitis, Nodular Nonsuppurative, Papillon-Lefevre Disease, Paralysis, Pelizaeus-Merzbacher Disease, Pemphigus, Benign Familial, Penile Induration, Pericarditis, Constrictive, Peroxisomal Disorders, Peutz-Jeghers Syndrome, Pick Disease of the Brain, Pierre Robin Syndrome, Pigmentation Disorders, Pityriasis Lichenoides, Polycystic Ovary Syndrome, Polyendocrinopathies, Autoimmune, Prader-Willi Syndrome, Pupil Disorders, Rett Syndrome, Reye Syndrome, Rubinstein-Taybi Syndrome, Sandhoff Disease, Sarcoma, Ewing's, Schnitzler Syndrome, Sjogren's Syndrome, Sjogren-Larsson Syndrome, Smith-Lemli-Opitz Syndrome, Spinal Muscular Atrophies of Childhood, Sturge-Weber Syndrome, Sweating, Gustatory, Takayasu Arteritis, Tangier Disease, Tay-Sachs Disease, Thromboangiitis Obliterans, Thyroiditis, Autoimmune, Tietze's Syndrome, Togaviridae Infections, Tolosa-Hunt Syndrome, Tourette Syndrome, Uveomeningoencephalitic Syndrome, Waardenburg's Syndrome, Wegener Granulomatosis, Weil Disease, Werner Syndrome, Williams Syndrome, Wilms Tumor, Wolff-Parkinson-White Syndrome, Wolfram Syndrome, Wolman Disease, Zellweger Syndrome, Zollinger-Ellison Syndrome, and von Willebrand Diseases.


Various autoimmune diseases and autoimmune-related diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As used herein, the term “autoimmune disease” refers to a disease in which the body produces antibodies that attack its own tissues. As a non-limiting example, the autoimmune disease may be Acute Disseminated Encephalomyelitis (ADEM), Acute necrotizing hemorrhagic leukoencephalitis, Addison's disease, Agammaglobulinemia, Alopecia areata, Amyloidosis, Ankylosing spondylitis, Anti-GBM/Anti-TBM nephritis, Antiphospholipid syndrome (APS), Autoimmune angioedema, Autoimmune aplastic anemia, Autoimmune dysautonomia, Autoimmune hepatitis, Autoimmune hyperlipidemia, Autoimmune immunodeficiency, Autoimmune inner ear disease (AIED), Autoimmune myocarditis, Autoimmune oophoritis, Autoimmune pancreatitis, Autoimmune retinopathy, Autoimmune thrombocytopenic purpura (ATP), Autoimmune thyroid disease, Autoimmune urticaria, Axonal & neuronal neuropathies, Balo disease, Behcet's disease, Bullous pemphigoid, Cardiomyopathy, Castleman disease, Celiac disease, Chagas disease, Chronic fatigue syndrome**, Chronic inflammatory demyelinating polyneuropathy (CIDP), Chronic recurrent multifocal ostomyelitis (CRMO), Churg-Strauss syndrome, Cicatricial pemphigoid/benign mucosal pemphigoid, Crohn's disease, Cogans syndrome, Cold agglutinin disease, Congenital heart block, Coxsackle myocarditis, CREST disease, Essential mixed cryoglobulinemia, Demyelinating neuropathies, Dermatitis herpetiformis, Dermatomyositis, Devic's disease (neuromyelitis optica), Discoid lupus, Dressler's syndrome, Endometriosis, Eosinophilic esophagitis, Eosinophilic fasciitis, Erythema nodosum, Experimental allergic encephalomyelitis, Evans syndrome, Fibromyalgia**, Fibrosing alveolitis, Giant cell arteritis (temporal arteritis), Giant cell myocarditis, Glomerulonephritis, Goodpasture's syndrome, Granulomatosis with Polyangiitis (GPA) (formerly called Wegener's Granulomatosis), Graves' disease, Guillain-Barre syndrome, Hashimoto's encephalitis, Hashimoto's thyroiditis, Hemolytic anemia, Henoch-Schonlein purpura, Herpes gestationis, Hypogammaglobulinemia, Idiopathic thrombocytopenic purpura (ITP), IgA nephropathy, IgG4-related sclerosing disease, Immunoregulatory lipoproteins, Inclusion body myositis, Interstitial cystitis, Juvenile arthritis, Juvenile diabetes (Type 1 diabetes), Juvenile myositis, Kawasaki syndrome, Lambert-Eaton syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Ligneous conjunctivitis, Linear IgA disease (LAD), Lupus (SLE), Lyme disease, chronic, Meniere's disease, Microscopic polyangiitis, Mixed connective tissue disease (MCTD), Mooren's ulcer, Mucha-Habermann disease, Multiple sclerosis, Myasthenia gravis, Myositis, Narcolepsy, Neurormelitis optica (Devic's), Neutropenia, Ocular cicatricial pemphigoid, Optic neuritis, Palindromic rheumatism, PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus), Paraneoplastic cerebellar degeneration, Paroxysmal nocturnal hemoglobnuria (PNH), Parry Romberg syndrome, Parsonnage-Turner syndrome, Pars planitis (peripheral uveitis), Pemphigus, Peripheral neuropathy, Perivenous encephalomyelitis, Pernicious anemia, POEMS syndrome, Polyarteritis nodosa, Type I, II, & III autoimmune polyglandular syndromes, Polymyalgia rheumatica, Polymyositis, Postmyocardial infarction syndrome, Postpericardiotomy syndrome, Progesterone dermatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Psoriasis, Psoriatic arthritis, Idiopathic pulmonary fibrosis, Pyoderma gangrenosum, Pure red cell aplasia, Raynauds phenomenon, Reactive Arthritis, Reflex sympathetic dystrophy, Reiter's syndrome, Relapsing polychondritis, Restless legs syndrome, Retroperitoneal fibrosis, Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleritis, Scleroderma, Sjogren's syndrome, Sperm & testicular autoimmunity, Stiff person syndrome, Subacute bacterial endocarditis (SBE), Susac's syndrome, Sympathetic ophthalmia, Takayasu's arteritis, Temporal arteritis/Giant cell arteritis, Thrombocy topenic purpura (TTP), Tolosa-Hunt syndrome, Transverse myelitis, Ulcerative colitis, Undifferentiated connective tissue disease (UCTD), Uveitis, Vasculitis, Vesiculobullous dermatosis, Vitiligo, and Wegener's granulomatosis (now termed Granulomatosis with Polyangiitis (GPA).


Various kidney diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the kidney disease Abderhalden-Kaufmann-Lignac syndrome (Nephropathic Cystinosis), Abdominal Compartment Syndrome, Acute Kidney Failure/Acute Kidney Injury, Acute Lobar Nephronia, Acute Phosphate Nephropathy, Acute Tubular Necrosis, Adenine Phosphoribosyltransferase Deficiency, Adenovirus Nephritis, Alport Syndrome, Amyloidosis, ANCA Vasculitis Related to Endocarditis and Other Infections, Angiomyolipoma, Analgesic Nephropathy, Anorexia Nervosa and Kidney Disease, Angiotensin Antibodies and Focal Segmental Glomerulosclerosis, Antiphospholipid Syndrome, Anti-TNF-α Therapy-related Glomerulonephritis, APOL1 Mutations, Apparent Mineralocorticoid Excess Syndrome, Aristolochic Acid Nephropathy, Chinese Herbal Nephropathy, Balkan Endemic Nephropathy, Bartter Syndrome, Beeturia, β-Thalassemia Renal Disease, Bile Cast Nephropathy, BK Polyoma Virus Nephropathy in the Native Kidney, Bladder Rupture, Bladder Sphincter Dyssynergia, Bladder Tamponade, Border-Crossers' Nephropathy, Bourbon Virus and Acute Kidney Injury, Burnt Sugarcane Harvesting and Acute Renal Dysfunction, Byetta and Renal Failure, C1q Nephropathy, Cannabinoid Hyperemesis Acute Renal Failure, Cardiorenal syndrome, Carfilzomib-Induced Renal Injury, CFHR5 nephropathy, Charcot-Marie-Tooth Disease with Glomerulopathy, Cherry Concentrate and Acute Kidney Injury, Cholesterol Emboli, Churg-Strauss syndrome, Chyluria, Colistin Nephrotoxicity, Collagenofibrotic Glomerulopathy, Collapsing Glomerulopathy, Collapsing Glomerulopathy Related to CMV, Congenital Nephrotic Syndrome, Conorenal syndrome (Mainzer-Saldino Syndrome or Saldino-Mainzer Disease), Contrast Nephropathy, Copper Sulpfate Intoxication, Cortical Necrosis, Crizotinib-related Acute Kidney Injury, Cryoglobinemia, Crystalglobulin-Induced Nephropathy, Crystal-Induced Acute Kidney injury, Cystic Kidney Disease, Acquired, Cystinuria, Dasatinib-Induced Nephrotic-Range Proteinuria, Dense Deposit Disease (MPGN Type 2), Dent Disease (X-linked Recessive Nephrolithiasis), Dialysis Disequilibrium Syndrome, Diabetes and Diabetic Kidney Disease, Diabetes Insipidus, Dietary Supplements and Renal Failure, Drugs of Abuse and Kidney Disease, Duplicated Ureter, EAST syndrome, Ebola and the Kidney, Ectopic Kidney, Ectopic Ureter, Edema, Swelling, Erdheim-Chester Disease, Fabry's Disease, Familial Hypocalciuric Hypercalcemia, Fanconi Syndrome, Fraser syndrome, Fibronectin Glomerulopathy, Fibrillary Glomerulonephritis and Immunotactoid Glomerulopathy, Fraley syndrome, Focal Segmental Glomerulosclerosis, Focal Sclerosis, Focal Glomerulosclerosis, Galloway Mowat syndrome, Giant Cell (Temporal) Arteritis with Kidney Involvement, Gestational Hypertension, Gitelman Syndrome, Glomerular Diseases, Glomerular Tubular Reflux, Glycosuria, Goodpasture Syndrome, Hair Dye Ingestion and Acute Kidney Injury, Hantavirus Infection Podocytopathy, Hematuria (Blood in Urine), Hemolytic Urermic Syndrome (HUS), Atypical Hemolytic Uremic Syndrome (aHUS), Hemophagocytic Syndrome, Hemorrhagic Cystitis, Hemorrhagic Fever with Renal Syndrome (HFRS, Hantavirus Renal Disease, Korean Hemorrhagic Fever, Epidemic Hemorrhagic Fever, Nephropathis Epidemica), Hemosiderosis related to Paroxysmal Nocturnal Hemoglobinuria and Hemolytic Anemia, Hepatic Glomerulopathy, Hepatic Veno-Occlusive Disease, Sinusoidal Obstruction Syndrome, Hepatitis C-Associated Renal Disease, Hepatorenal Syndrome, Herbal Supplements and Kidney Disease, High Blood Pressure and Kidney Disease, HIV-Associated Nephropathy (HIVAN), Horseshoe Kidney (Renal Fusion), Hunner's Ulcer, Hyperaldosteronism, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypermanesemia, Hypernatremia, Hyperoxaluria, Hyperphosphatemia, Hypocalcemia, Hypokalemia, Hypokalemia-induced renal dysfunction, Hypokalemic Periodic Paralysis, Hypomagnesemia, Hyponatremia, Hypophosphatemia, IgA Nephropathy, IgG4 Nephropathy, Interstitial Cystitis, Painful Bladder Syndrome (Questionnaire), Interstitial Nephritis, Ivemark's syndrome, Ketamine-Associated Bladder Dysfunction, Kidney Stones, Nephrolithiasis, Kombucha Tea Toxicity, Lead Nephropathy and Lead-Related Nephrotoxicity, Leptospirosis Renal Disease, Light Chain Deposition Disease, Monoclonal Immunoglobulin Deposition Disease, Liddle Syndrome, Lightwood-Albright Syndrome, Lipoprotein Glomerulopathy, Lithium Nephrotoxicity, LMXIB Mutations Cause Hereditary FSGS, Loin Pain Hematuria, Lupus, Systemic Lupus Erythematosis, Lupus Kidney Disease, Lupus Nephritis, Lupus Nephritis with Antineutrophil Cytoplasmic Antibody Seropositivity, Lyme Disease-Associated Glomerulonephritis, Malarial Nephropathy, Malignancy-Associated Renal Disease, Malignant Hypertension, Malakoplakia, Meatal Stenosis, Medullary Cystic Kidney Disease, Medullary Sponge Kidney, Megaureter, Melamine Toxicity and the Kidney, Membranoproliferative Glomerulonephritis, Membranous Nephropathy, MesoAmerican Nephropathy, Metabolic Acidosis, Metabolic Alkalosis, Methotrexate-related Renal Failure, Microscopic Polyangiitis, Milk-alkalai syndrome, Minimal Change Disease, MDMA (Molly, Ecstacy; 3,4-Methylenedioxymnethamphetamine) and Kidney Failure, Multicystic dysplastic kidney, Multiple Myeloma, Myeloproliferative Neoplasms and Glomerulopathy, Nail-patella Syndrome, Nephrocalcinosis, Nephrogenic Systemic Fibrosis, Nephroptosis (Floating Kidney, Renal Ptosis), Nephrotic Syndrome, Neurogenic Bladder, Nodular Glomerulosclerosis, NonGonococcal Urethritis, Nutcracker syndrome, Orofaciodigital Syndrome, Orotic Aciduria, Orthostatic Hypotension, Orthostatic Proteinurina, Osmotic Diuresis, Ovarian Hyperstimulation Syndrome, Page Kidney, Papillary Necrosis, Papillorenal Syndrome (Renal-Coloboma Syndrome, Isolated Renal Hypoplasia), Parvovirus B19 and the Kidney, The Peritoneal-Renal Syndrome, Posterior Urethral Valve, Post-infectious Glomerulonephritis, Post-streptococcal Glomerulonephritis, Polyarteritis Nodosa, Polycystic Kidney Disease, Posterior Urethral Valves, Preeclampsia, Propofol infusion syndrome, Proliferative Glomerulonephritis with Monoclonal IgG Deposits (Nasr Disease), Propolis (Honeybee Resin) Related Renal Failure, Proteinuria (Protein in Urine), Pseudohyperaldosteronism, Pseudohypobicarbonatemia, Pseudohypoparathyroidism, Pulmonary-Renal Syndrome, Pyelonephritis (Kidney Infection), Pyonephrosis, Radiation Nephropathy, Ranolazine and the Kidney, Refeeding syndrome, Reflux Nephropathy, Rapidly Progressive Glomerulonephritis, Renal Abscess, Peripnephric Abscess, Renal Agenesis, Renal Arcuate Vein Microthrombi-Associated Acute Kidney Injury, Renal Artery Aneurysm, Renal Artery Stenosis, Renal Cell Cancer, Renal Cyst, Renal Hypouricemia with Exercise-induced Acute Renal Failure, Renal Infarction, Renal Osteodystrophy, Renal Tubular Acidosis, Renin Secreting Tumors (Juxtaglomerular Cell Tumor), Reset Osmostat, Retrocaval Ureter, Retroperitoneal Fibrosis, Rhabdomyolysis, Rhabdomyolysis related to Bariatric Sugery, Rheumatoid Arthritis-Associated Renal Disease, Sarcoidosis Renal Disease, Salt Wasting, Renal and Cerebral, Schistosomiasis and Glomerular Disease, Schimke immuno-osseous dysplasia, Scleroderma Renal Crisis, Serpentine Fibula-Polycystic Kidney Syndrome, Exner Syndrome, Sickle Cell Nephropathy, Silica Exposure and Chronic Kidney Disease, Sri Lankan Farmers' Kidney Disease, Sjögren's Syndrome and Renal Disease, Synthetic Cannabinoid Use and Acute Kidney Injury, Kidney Disease Following Hematopoietic Cell Transplantation, Kidney Disease Related to Stem Cell Transplantation, Thin Basement Membrane Disease, Benign Familial Hematuria, Trigonitis, Tuberculosis, Genitourinary, Tuberous Sclerosis, Tubular Dysgenesis, Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border, Tumor Lysis Syndrome, Uremia, Uremic Optic Neuropathy, Ureteritis Cystica, Ureterocele, Urethral Caruncle, Urethral Stricture, Urinary Incontinence, Urinary Tract Infection, Urinary Tract Obstruction, Vesicointestinal Fistula, Vesicoureteral Reflux, Volatile Anesthetics and Acute Kidney Injury, Von Hippel-Lindau Disease, Waldenstrom's Macroglobulinemic Glomerulonephritis, Warfarin-Related Nephropathy, Wasp Stings and Acute Kidney Injury, Wegener's Granulomatosis, Granulomatosis with Polyangiitis, West Nile Virus and Chronic Kidney Disease, and Wunderlich syndrome.


Various cardiovascular diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the cardiovascular disease may be Ischemic heart disease also known as coronary artery disease, cerebrovascular disease (Stroke), Peripheral vascular disease, Heart failure, Rheumatic heart disease, and Congenital heart disease.


Various antibody deficiencies may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the antibody deficiencies may be X-Linked Agammaglobulinemia (XLA), Autosomal Recessive Agammaglobulinemia (ARA), Common Variable Immune Deficiency (CVID), IgG (IgG1, IgG2, IgG3 and IgG4) Subclass Deficiency, Selective IgA Deficiency, Specific Antibody Deficiency (SAD). Transient Hypogammaglobulinemia of Infancy, Antibody Deficiency with Normal or Elevated Immunoglobulins, Selective IgM Deficiency, Immunodeficiency with Thymoma (Good's Syndrome), Transcobalamin II Deficiency, Warts, Hypogammaglobulinemia, Infection, Myelokathexis (WHIM) Syndrome, Drug-Induced Antibody Deficiency, Kappa Chain Deficiency, Heavy Chain Deficiencies, Post-Meiotic Segregation (PMS2) Disorder, and Unspecified Hypogammaglobulinemia.


Various ocular diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the ocular disease may be thyroid eye disease (TED), Graves' disease (GD) and orbitopathy, Retina Degeneration. Cataract, optic atrophy, macular degeneration, Leber congenital amaurosis, retinal degeneration, cone-rod dystrophy, Usher syndrome, leopard syndrome, photophobia, and photoaversion.


Various neurological diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the neurological disease may be Absence of the Septum Pellucidum, Acid Lipase Disease, Acid Maltase Deficiency, Acquired Epileptiform Aphasia, Acute Disseminated Encephalomyelitis, Attention Deficit-Hyperactivity Disorder (ADHD), Adie's Pupil, Adle's Syndrome, Adrenoleukodystrophy, Agenesis of the Corpus Callosum, Agnosia, Aicardi Syndrome, Aicardi-Goutieres Syndrome Disorder, AIDS—Neurological Complications, Alexander Disease, Alpers' Disease, Alternating Hemiplegia, Alzheimer's Disease, Amyotrophic Lateral Sclerosis (ALS), Anencephaly, Aneurysm, Angelman Syndrome, Angiomatosis, Anoxia, Antiphospholipid Syndrome, Aphasia, Apraxia, Arachnoid Cysts, Arachnoiditis, Amold-Chiari Malformation, Arteriovenous Malformation, Asperger Syndrome, Ataxia, Ataxia Telangiectasia, Ataxias and Cerebellar or Spinocerebellar Degeneration, Atrial Fibrillation and Stroke, Attention Deficit-Hyperactivity Disorder, Autism Spectrum Disorder, Autonomic Dysfunction, Back Pain, Barth Syndrome, Batten Disease, Becker's Myotonia, Behcet's Disease, Bell's Palsy, Benign Essential Blepharospasm, Benign Focal Amyotrophy, Benign Intracranial Hypertension, Bernhardt-Roth Syndrome, Binswanger's Disease, Blepharospasm, Bloch-Sulzberger Syndrome, Brachial Plexus Birth Injuries, Brachial Plexus Injuries, Bradbury-Eggleston Syndrome, Brain and Spinal Tumors, Brain Aneurysm, Brain Injury, Brown-Sequard Syndrome, Bulbospinal Muscular Atrophy, Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy (CADASIL), Canavan Disease, Carpal Tunnel Syndrome, Causalgia, Cavernomas, Cavernous Angioma, Cavernous Malformation, Central Cervical Cord Syndrome, Central Cord Syndrome, Central Pain Syndrome, Central Pontine Myelinolysis, Cephalic Disorders, Ceramidase Deficiency, Cerebellar Degeneration, Cerebellar Hypoplasia, Cerebral Aneurysms, Cerebral Arteriosclerosis, Cerebral Atrophy, Cerebral Beriberi, Cerebral Cavernous Malformation, Cerebral Gigantism, Cerebral Hypoxia, Cerebral Palsy, Cerebro-Oculo-Facio-Skeletal Syndrome (COFS), Charcot-Mane-Tooth Disease, Chian Malformation, Cholesterol Ester Storage Disease, Chorea, Choreoacanthocytosis, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Chronic Orthostatic Intolerance, Chronic Pain, Cockayne Syndrome Type II, Coffin Lowry Syndrome, Colpocephaly, Coma, Complex Regional Pain Syndrome, Congenital Facial Diplegia, Congenital Myasthenia, Congenital Myopathy, Congenital Vascular Cavernous Malformations, Corticobasal Degeneration, Cranial Arteritis, Craniosynostosis, Cree encephalitis, Creutzfeldt-Jakob Disease, Cumulative Trauma Disorders, Cushing's Syndrome, Cytomegalic Inclusion Body Disease, Cytomegalovirus Infection, Dancing Eyes-Dancing Feet Syndrome, Dandy-Walker Syndrome, Dawson Disease, De Morsier's Syndrome, Dejerine-Klumpke Palsy, Dementia, Dementia—Multi-Infarct, Dementia—Semantic, Dementia—Subcortical, Dementia With Lewy Bodies, Dentate Cerebellar Ataxia, Dentatorubral Atrophy, Dermatomyositis, Developmental Dyspraxia, Devic's Syndrome, Diabetic Neuropathy, Diffuse Sclerosis, Dravet Syndrome, Dysautonomia, Dysgraphia, Dyslexia, Dysphagia, Dyspraxia, Dyssynergia Cerebellaris Myoclonica, Dyssynergia Cerebellaris Progressiva, Dystonias, Early Infantile Epileptic Encephalopathy, Empty Sella Syndrome, Encephalitis, Encephalitis Lethargica, Encephaloceles, Encephalopathy, Encephalopathy (familial infantile), Encephalotrigeminal Anglomatosis, Epilepsy, Epileptic Hermplegia, Erb's Palsy, Erb-Duchenne and Dejerine-Klumpke Palsies, Essential Tremor, Extrapontine Myelinolysis, Fabry Disease, Fahr's Syndrome, Fainting, Familial Dysautonomia, Familial Hemangioma, Familial Idiopathic Basal Ganglia Calcification, Familial Periodic Paralyses, Familial Spastic Paralysis, Farber's Disease, Febrile Seizures, Fibromuscular Dysplasia, Fisher Syndrome, Floppy Infant Syndrome, Foot Drop, Friedreich's Ataxia, Frontotemporal Dementia, Gaucher Disease, Generalized Gangliosidoses, Gerstmann's Syndrome, Gerstmann-Straussler-Scheinker Disease, Giant Axonal Neuropathy, Giant Cell Arteritis, Giant Cell Inclusion Disease, Globoid Cell Leukodystrophy, Glossopharyngeal Neuralgia, Glycogen Storage Disease, Guillain-Barre Syndrome, Hallervorden-Spatz Disease, Head Injury, Headache, Hemicrania Continua, Hemifacial Spasm, Hemiplegia Alterans, Hereditary Neuropathies, Hereditary Spastic Paraplegia, Heredopathia Atactica Polyneuritiformis, Herpes Zoster, Herpes Zoster Oticus, Hirayama Syndrome, Holmes-Adie syndrome, Holoprosencephaly, HTLV-1 Associated Myelopathy, Hughes Syndrome, Huntington's Disease, Hydranencephaly, Hydrocephalus, Hydrocephalus—Normal Pressure, Hydromyelia, Hypercortisolism, Hypersomnia, Hypertonia, Hypotonia, Hypoxia, Immune-Mediated Encephalomyelitis, Inclusion Body Myositis, Incontinentia Pigmenti, Infantile Hypotonia, Infantile Neuroaxonal Dystrophy, Infantile Phytanic Acid Storage Disease, Infantile Refsum Disease, Infantile Spasms, Inflammatory Myopathies, Iniencephaly, Intestinal Lipodystrophy, Intracranial Cysts, Intracranial Hypertension, Isaacs' Syndrome, Joubert Syndrome, Kearns-Savre Syndrome, Kennedy's Disease, Kinsbourne syndrome, Kleine-Levin Syndrome, Klippel-Feil Syndrome, Klippel-Trenaunay Syndrome (KTS), Klüver-Bucy Syndrome, Korsakoff's Amnesic Syndrome, Krabbe Disease, Kugelberg-Welander Disease, Kuru, Lambert-Eaton Myasthenic Syndrome, Landau-Kleffner Syndrome, Lateral Femoral Cutaneous Nerve Entrapment, Lateral Medullary Syndrome, Learning Disabilities, Leigh's Disease, Lennox-Gastaut Syndrome, Lesch-Nyhan Syndrome, Leukodystrophy, Levine-Critchley Syndrome, Lewy Body Dementia, Lipid Storage Diseases, Lipoid Proteinosis, Lissencephaly, Locked-In Syndrome, Lou Gehrig's Disease, Lupus—Neurological Sequelae, Lyme Disease—Neurological Complications, Machado-Joseph Disease, Macrencephaly, Megalencephaly, Melkersson-Rosenthal Syndrome, Meningitis, Meningitis and Encephalitis, Menkes Disease, Meralgia Paresthetica, Metachromatic Leukodystrophy, Microcephaly, Migraine, Miller Fisher Syndrome, Mini Stroke, Mitochondrial Myopathy, Moebius Syndrome, Monomelic Amyotrophy, Motor Neuron Diseases, Moyamoya Disease, Mucolipidoses, Mucopolysaccharidoses, Multi-Infarct Dementia, Multifocal Motor Neuropathy, Multiple Sclerosis, Multiple System Atrophy, Multiple System Atrophy with Orthostatic Hypotension, Muscular Dystrophy, Myasthenia—Congenital, Myasthenia Gravis, Myelinoclastic Diffuse Sclerosis, Myoclonic Encephalopathy of Infants, Myoclonus, Myopathy, Myopathy—Congenital, Myopathy—Thyrotoxic, Myotonia, Myotonia Congenita, Narcolepsy, Neuroacanthocytosis, Neurodegeneration with Brain Iron Accumulation, Neurofibromatosis, Neuroleptic Malignant Syndrome, Neurological Complications of AIDS, Neurological Complications of Lyme Disease, Neurological Consequences of Cytomegalovirus Infection, Neurological Manifestations of Pompe Disease, Neurological Sequelae Of Lupus, Neuromyelitis Optica, Neuromyotonia, Neuronal Ceroid Lipofuscinosis, Neuronal Migration Disorders, Neuropathy—Hereditary, Neurosarcoidosis, Neurosyphilis, Neurotoxicity, Nevus Cavernosus, Niemann-Pick Disease, O'Sullivan-McLeod Syndrome, Occipital Neuralgia, Ohtahara Syndrome, Olivopontocerebellar Atrophy, Opsoclonus Myoclonus, Orthostatic Hypotension, Overuse Syndrome, Pain—Chronic, Pantothenate Kinase-Associated Neurodegeneration, Paraneoplastic Syndromes, Paresthesia, Parkinson's Disease, Paroxysmal Choreoathetosis, Paroxysmal Hemicrania, Parry-Romberg, Pelizaeus-Merzbacher Disease, Pena Shokeir II Syndrome, Perineural Cysts, Periodic Paralyses, Peripheral Neuropathy, Periventricular Leukomalacia, Persistent Vegetative State, Pervasive Developmental Disorders, Phytanic Acid Storage Disease, Pick's Disease, Pinched Nerve, Piriformis Syndrome, Pituitary Tumors, Polymyositis, Pompe Disease, Porencephaly, Post-Polio Syndrome, Postherpetic Neuralgia, Postinfectious Encephalomyelitis, Postural Hypotension, Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Primary Dentatum Atrophy, Primary Lateral Sclerosis, Primary Progressive Aphasia, Prion Diseases, Progressive Hemifacial Atrophy, Progressive Locomotor Ataxia, Progressive Multifocal Leukoencephalopathy, Progressive Sclerosing Poliodystrophy, Progressive Supranuclear Palsy, Prosopagnosia, Pseudo-Torch syndrome, Pseudotoxoplasmosis syndrome, Pseudotumor Cerebri, Psychogenic Movement, Ramsay Hunt Syndrome I, Ramsay Hunt Syndrome II, Rasmussen's Encephalitis, Reflex Sympathetic Dystrophy Syndrome, Refsum Disease, Refsum Disease—Infantile, Repetitive Motion Disorders, Repetitive Stress Injuries, Restless Legs Syndrome, Retrovirus-Associated Myelopathy, Rett Syndrome, Reye's Syndrome, Rheumatic Encephalitis, Riley-Day Syndrome, Sacral Nerve Root Cysts, Saint Vitus Dance, Salivary Gland Disease, Sandhoff Disease, Schilder's Disease, Schizencephaly, Seitelberger Disease, Seizure Disorder, Semantic Dementia, Septo-Optic Dysplasia, Severe Myoclonic Epilepsy of Infancy (SMEI), Shaken Baby Syndrome, Shingles, Shy-Drager Syndrome, Sjögren's Syndrome, Sleep Apnea, Sleeping Sickness, Sotos Syndrome, Spasticity, Spina Bifida, Spinal Cord Infarction, Spinal Cord Injury, Spinal Cord Tumors, Spinal Muscular Atrophy, Spinocerebellar Atrophy, Spinocerebellar Degeneration, Steele-Richardson-Olszewski Syndrome, Stiff-Person Syndrome, Striatonigral Degeneration, Stroke, Sturge-Weber Syndrome, Subacute Sclerosing Panencephalitis, Subcortical Arteriosclerotic Encephalopathy, Short-lasting, Unilateral, Neuralgiform (SUNCT) Headache, Swallowing Disorders, Sydenham Chorea, Syncope, Syphilitic Spinal Sclerosis, Syringohydromyelia, Syrmgomyella, Systemic Lupus Erythematosus, Tabes Dorsalis, Tardive Dyskinesia, Tarlov, Cysts, Tay-Sachs Disease, Temporal Arteritis, Tethered Spinal Cord Syndrome, Thomsen's Myotonia, Thoracic Outlet Syndrome, Thyrotoxic Myopathy, Tic Douloureux, Todd's Paralysis, Tourette Syndrome, Transient Ischemic Attack, Transmissible Spongiform Encephalopathies, Transverse Myelitis, Traumatic Brain Injury, Tremor, Trigeminal Neuralgia, Tropical Spastic Paraparesis, Troyer Syndrome, Tuberous Sclerosis, Vascular Erectile Tumor, Vasculitis Syndromes of the Central and Peripheral Nervous Systems, Von Economo's Disease, Von Hippel-Lindau Disease (VHL), Von Recklinghausen's Disease, Wallenberg's Syndrome, Werdnig-Hoffman Disease, Wernicke-Korsakoff Syndrome, West Syndrome, Whiplash, Whipple's Disease, Williams Syndrome. Wilson Disease. Wolman's Disease. X-Linked Spinal and Bulbar Muscular Atrophy.


Various psychological disorders may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the psychological disorders may be Aboulia, Absence epilepsy, Acute stress Disorder, Adjustment Disorders, Adverse effects of medication NOS, Age related cognitive decline, Agoraphobia, Alcohol Addiction, Alzheimer's Disease, Amnesia (also known as Amnestic Disorder), Amphetamine Addiction, Anorexia Nervosa, Anterograde amnesia, Antisocial personality disorder (also known as Sociopathy), Anxiety Disorder (Also known as Generalized Anxiety Disorder), Anxiolytic related disorders, Asperger's Syndrome (now part of Autism Spectrum Disorder), Attention Deficit Disorder (Also known as ADD), Attention Deficit Hyperactivity Disorder (Also known as ADHD), Autism Spectrum Disorder (also known as Autism), Autophagia, Avoidant Personality Disorder, Barbiturate related disorders, Benzodiazepine related disorders, Bereavement, Bibliomania, Binge Eating Disorder, Bipolar disorder (also known as Manic Depression, includes Bipolar I and Bipolar II), Body Dysmorphic Disorder, Borderline intellectual functioning, Borderline Personality Disorder, Breathing-Related Sleep Disorder, Brief Psychotic Disorder, Bruxism, Bulimia Nervosa, Caffeine Addiction, Cannabis Addiction, Catatonic disorder, Catatonic schizophrenia, Childhood amnesia, Childhood Disintegrative Disorder (now part of Autism Spectrum Disorder), Childhood Onset Fluency Disorder (formerly known as Stuttering), Circadian Rhythm Disorders, Claustrophobia, Cocaine related disorders, Communication disorder, Conduct Disorder, Conversion Disorder, Cotard delusion, Cyclothymia (also known as Cyclothymic Disorder), Delerium, Delusional Disorder, dementia, Dependent Personality Disorder (also known as Asthenic Personality Disorder), Depersonalization disorder (now known as Depersonalization/Derealization Disorder), Depression (also known as Major Depressive Disorder), Depressive personality disorder, Derealization disorder (now known as Depersonalization/Derealization Disorder), Dermotillomania, Desynchronosis, Developmental coordination disorder, Diogenes Syndrome, Disorder of written expression, Dispareunia, Dissocial Personality Disorder, Dissociative Amnesia, Dissociative Fugue, Dissociative Identity Disorder (formerly known as Multiple Personality Disorder), Down syndrome, Dyslexia, Dyspareunia, Dysthymia (now known as Persistent Depressive Disorder), Eating disorder NOS, Ekbom's Syndrome (Delusional Parasitosis), Emotionally unstable personality disorder, Encopresis, Enuresis (bedwetting), Erotomania, Exhibitionistic Disorder, Expressive language disorder, Factitious Disorder, Female Sexual Disorders, Fetishistic Disorder, Folie à deux, Fregoli delusion, Frotteuristic Disorder, Fugue State, Ganser syndrome, Gambling Addiction, Gender Dysphoria (formerly known as Gender Identity Disorder), Generalized Anxiety Disorder, General adaptation syndrome, Grandiose delusions, Hallucinogen Addiction, Haltlose personality disorder, Histrionic Personality Disorder, Primary hypersomnia, IHuntington's Disease, Hypoactive sexual desire disorder, Hypochondriasis, Hypomania, Hyperkinetic syndrome, Hypersomnia, Hysteria, Impulse control disorder, Impulse control disorder NOS, Inhalant Addiction, Insomnia, Intellectual Development Disorder, Intermittent Explosive Disorder, Joubert syndrome, Kleptomania, Korsakoff's syndrome, Lacunar amnesia, Language Disorder, Learning Disorders, Major Depression (also known as Major Depressive Disorder), major depressive disorder, Male Sexual Disorders, Malingering, Mathematics disorder, Medication-related disorder, Melancholia, Mental Retardation (now known as Intellectual Development Disorder), Misophonia, Morbid jealousy, Multiple Personality Disorder (now known as Dissociative Identity Disorder), Munchausen Syndrome, Munchausen by Proxy, Narcissistic Personality Disorder, Narcolepsy, Neglect of child, Neurocognitive Disorder (formerly known as Dementia), Neuroleptic-related disorder, Nightmare Disorder, Non Rapid Eye Movement, Obsessive-Compulsive Disorder, Obsessive-Compulsive Personality Disorder (also known as Anankastic Personality Disorder), Oneirophrenia, Onychophagia, Opioid Addiction, Oppositional Defiant Disorder, Orthorexia (ON), Pain disorder, Panic attacks, Panic Disorder, Paranoid Personality Disorder, Parkinson's Disease, Partner relational problem, Passive-aggressive personality disorder, Pathological gambling, Pedophilic Disorder, Perfectionism, Persecutory delusion, Persistent Depressive Disorder (also known as Dysthymia), Personality change due to a general medical condition, Personality disorder, Pervasive developmental disorder (PDD), Phencyclidine related disorder, Phobic disorder, Phonological disorder, Physical abuse, Pica, Polysubstance related disorder, Postpartum Depression, Post-traumatic embitterment disorder (PTED), Post Traumatic Stress Disorder, Premature ejaculation, Premenstrual Dysphoric Disorder, Psychogenic amnesia, Psychological factor affecting medical condition, Psychoneurotic personality disorder, Psychotic disorder, not otherwise specified, Pyromania, Reactive Attachment Disorder, Reading disorder, Recurrent brief depression, Relational disorder, REM Sleep Behavior Disorder, Restless Leg Syndrome, Retrograde amnesia, Retts Disorder (now part of Autism Spectrum Disorder), Rumination syndrome, Sadistic personality disorder, Schizoaffective Disorder, Schizoid Personality Disorder, Schizophrenia, Schizophreniform disorder, Schizotypal Personality Disorder, Seasonal Affective Disorder, Sedative, Hypnotic, or Anxiolytic Addiction, Selective Mutism, Self-defeating personality disorder, Separation Anxiety Disorder, Sexual Disorders Female, Sexual Disorders Male, Sexual Addiction, Sexual Masochism Disorder, Sexual Sadism Disorder, Shared Psychotic Disorder, Sleep Arousal Disorders, Sleep Paralysis, Sleep Terror Disorder (now part of Nightmare Disorder, Social Anxiety Disorder, Somatization Disorder, Specific Phobias, Stendhal syndrome, Stereotypic movement disorder, Stimulant Addiction, Stuttering (now known as Childhood Onset Fluency Disorder), Substance related disorder, Tardive dyskinesia, Tobacco Addiction, Tourettes Syndrome, Transient tic disorder, Transient global amnesia, Transvestic Disorder, Trichotillomania, Undifferentiated Somatoform Disorder, Vaginismus, and Voyeunstic Disorder.


Various lung diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the lung diseases may be Asbestosis, Asthma, Bronchiectasis, Bronchitis, Chronic Cough, Chronic Obstructive Pulmonary Disease (COPD), Croup, Cystic Fibrosis, Hantavirus, Idiopathic Pulmonary Fibrosis, Pertussis, Pleurisy, Pneumonia, Pulmonary Embolism, Pulmonary Hypertension, Sarcoidosis, Sleep Apnea, Spirometry, Sudden Infant Death Syndrome (SIDS), Tuberculosis, Alagille Syndrome, Autoimmune Hepatitis, Biliary Atresia, Cirrhosis, ERCP (Endoscopic Retrograde Cholangiopancreatography), and Hemochromatosis, Nonalcoholic Steatohepatitis, Porphyria, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis.


Various bone diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the bone diseases may be osteoporosis, neurofibromatosis, osteogenesis imperfecta (OI), rickets, osteosarcoma, achondroplasia, fracture, osteomyelitis, Ewing tumour of bone, osteomalacia, hip dysplasia, Paget disease of bone, marble bone disease, osteochondroma, bone cancer, bone disease, osteochondrosis, osteoma, fibrous dysplasia, cleidocranial dysostosis, osteoclastoma, bone cyst, metabolic bone disease, melorheostosis, callus, Caffey syndrome, and mandibulofacial dysostosis.


Various blood diseases may be treated with pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the blood diseases may be Anemia and CKD (for health care professionals), Aplastic Anemia and Myelodysplastic Syndromes, Deep Vein Thrombosis, Hemochromatosis, Hemophilia, Henoch-Schönlein Purpura, Idiopathic Thrombocytopenic Purpura, Iron-Deficiency Anemia, Pernicious Anemia, Pulmonary Embolism, Sickle Cell Anemia, Sickle Cell Trait and Other Hemoglobminopathies, Thalassemia, Thrombotic Thrombocytopenic Purpura, and Von Willebrand Disease.


Various diseases associated with TNF-alpha may be treated with the pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the disease may be respiratory disorder; asthma; allergic and nonallergic asthma; asthma due to infection; asthma due to infection with respiratory syncytial virus (RSV); chronic obstructive pulmonary disease (COPD); a condition involving airway inflammation; eosinophilia; fibrosis and excess mucus production; cystic fibrosis; pulmonary fibrosis; an atopic disorder; atopic dermatitis; urticaria, eczema; allergic rhinitis; allergic enterogastritis; an inflammatory and/or autoimmune condition of the skin; an inflammatory and/or autoimmune condition of gastrointestinal organs, inflammatory bowel diseases (IBD); ulcerative colitis; Crohn's disease; an inflammatory and/or autoimmune condition of the liver; liver cirrhosis; liver fibrosis; liver fibrosis caused by hepatitis B and/or C virus, scleroderma; tumors or cancers; hepatocellular carcinoma, glioblastoma; lymphoma; Hodgkin's lymphoma; a viral infection; a bacterial infection; a parasitic infection; HTLV-1 infection; suppression of expression of protective type 1 immune responses, and suppression of expression of a protective type 1 immune response during vaccination, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, septic arthritis, Lyme arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, inflammatory bowel disease, insulin dependent diabetes mellitus, thyroiditis, asthma, allergic diseases, psoriasis, dermatitis scleroderma, graft versus host disease, organ transplant rejection, acute or chronic immune disease associated with organ transplantation, sarcoidosis, atherosclerosis, disseminated intravascular coagulation, Kawasaki's disease, Grave's disease, nephrotic syndrome, chronic fatigue syndrome, Wegener's granulomatosis, Henoch-Schoenlein purpurea, microscopic vasculitis of the kidneys, chronic active hepatitis, uveitis, septic shock, toxic shock syndrome, sepsis syndrome, cachexia, infectious diseases, parasitic diseases, acquired immunodeficiency syndrome, acute transverse myelitis, Huntington's chorea, Parkinson's disease, Alzheimer's disease, stroke, primary biliary cirrhosis, hemolytic anemia, malignancies, heart failure, myocardial infarction, Addison's disease, sporadic, polyglandular deficiency type I and polyglandular deficiency type II, Schmidt's syndrome, adult (acute) respiratory distress syndrome, alopecia, alopecia greata, seronegative arthropathy, arthropathy, Reiter's disease, psoriatic arthropathy, ulcerative colitic arthropathy, enteropathic synovitis, chlamydia, yersinia and salmonella associated arthropathy, spondyloarthropathy, atheromatous disease/arteriosclerosis, atopic allergy, autoimmune bullous disease, pemphigus vulgaris, pemphigus foliaceus, pemphigoid, linear IgA disease, autoimmune haemolytic anaemia, Coombs positive haemolytic anaemia, acquired pernicious anaemia, juvenile pernicious anaemia, myalgic encephalitis/Royal Free Disease, chronic mucocutaneous candidiasis, giant cell arteritis, primary sclerosing hepatitis, cyptogenic autoimmune hepatitis, Acquired Immunodeficiency Disease Syndrome, Acquired Immunodeficiency Related Diseases, hepatitis B, hepatitis C, common varied immunodeficiency (common variable hypogammaglobulinemia), dilated cardiomyopathy, female infertility, ovarian failure, premature ovarian failure, fibrotic lung disease, cryptogenic fibrosing alveolitis, post-inflammatory interstitial lung disease, interstitial pneumonitis, connective tissue disease associated interstitial lung disease, mixed connective tissue disease associated lung disease, systemic sclerosis associated interstitial lung disease, rheumatoid arthritis associated interstitial lung disease, systemic lupus erythematosus associated lung disease, dermatomyositis/polymyositis associated lung disease, Sjögren's disease associated lung disease, ankylosing spondylitis associated lung disease, vasculitic diffuse lung disease, haemosiderosis associated lung disease, drug-induced interstitial lung disease, fibrosis, radiation fibrosis, bronchiolitis obliterans, chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease, postinfectious interstitial lung disease, gouty arthritis, autoimmune hepatitis, type-1 autoimmune hepatitis (classical autoimmune or lupoid hepatitis), type-2 autoimmune hepatitis (anti-LKM antibody hepatitis), autoimmune mediated hypoglycemia, type B insulin resistance with acanthosis nigricans, hypoparathyroidism, acute immune disease associated with organ transplantation, chronic immune disease associated with organ transplantation, osteoarthrosis, primary sclerosing cholangitis, psoriasis type 1, psoriasis type 2, idiopathic leucopaenia, autoimmune neutropaenia, renal disease NOS, glomerulonephritides, microscopic vasculitis of the kidneys, Lyme disease, discoid lupus erythematosus, male infertility idiopathic or NOS, sperm autoimmunity, multiple sclerosis (all subtypes), sympathetic ophthalmia, pulmonary hypertension secondary to connective tissue disease, Goodpasture's syndrome, pulmonary manifestation of polyarteritis nodosa, acute rheumatic fever, rheumatoid spondylitis, Still's disease, systemic sclerosis, Sjörgren's syndrome, Takayasu's disease/arteritis, autoimmune thrombocytopaenia, idiopathic thrombocytopaenia, autoimmune thyroid disease, hyperthyroidism, goitrous autoimmune hypothyroidism (Hashimoto's disease), atrophic autoimmune hypothyroidism, primary myxoederma, phacogenic uveitis, primary vasculitis, vitiligo acute liver disease, chronic liver diseases, alcoholic cirrhosis, alcohol-induced liver injury, choleostasis, idiosyncratic liver disease, drug-Induced hepatitis, non-alcoholic steatohepatitis, allergy and asthma, group B streptococci (GBS) infection, mental disorders (e.g., depression and schizophrenia), Th2 Type and Th1 Type mediated diseases, acute and chronic pain (different forms of pain), and cancers such as lung, breast, stomach, bladder, colon, pancreas, ovarian, prostate and rectal cancer and hematopoietic malignancies (leukemia and lymphoma) abetalipoproteinemia, acrocyanosis, acute and chronic parasitic or infectious processes, acute leukemia, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute or chronic bacterial infection, acute pancreatitis, acute renal failure, adenocarcinomas, aerial ectopic beats, AIDS dementia complex, alcohol-induced hepatitis, allergic conjunctivitis, allergic contact dermatitis, allergic rhinitis, allograft rejection, alpha-1-antitrypsin deficiency, amyotrophic lateral sclerosis, anemia, angina pectoris, anterior horn cell degeneration, anti-CD3 therapy, antiphospholipid syndrome, anti-receptor hypersensitivity reactions, aortic and peripheral aneurysms, aortic dissection, arterial hypertension, arteriosclerosis, arteriovenous fistula, ataxia, atrial fibrillation (sustained or paroxysmal), atrial flutter, atrioventricular block, B cell lymphoma, bone graft rejection, bone marrow transplant (BMT) rejection, bundle branch block, Burkitt's lymphoma, burns, cardiac arrhythmias, cardiac stun syndrome, cardiac tumors, cardiomyopathy, cardiopulmonary bypass inflammation response, cartilage transplant rejection, cerebellar cortical degenerations, cerebellar disorders, chaotic or multifocal atrial tachycardia, chemotherapy associated disorders, chronic myelocytic leukemia (CML), chronic alcoholism, chronic inflammatory pathologies, chronic lymphocytic leukemia (CLL), chronic obstructive pulmonary disease (COPD), chronic salicylate intoxication, colorectal carcinoma, congestive heart failure, conjunctivitis, contact dermatitis, corpulmonale, coronary artery disease, Creutzfeldt-Jakob disease, culture negative sepsis, cystic fibrosis, cytokine therapy associated disorders, dementia pugilistica, demyelinating diseases, dengue hemorrhagic fever, dermatitis, dermatologic conditions, diabetes, diabetes mellitus, diabetic arteriosclerotic disease, Diffuse Lewy body disease, dilated congestive cardiomyopathy, disorders of the basal ganglia, Down's Syndrome in middle age, drug-induced movement disorders induced by drugs which block CNS dopamine receptors, drug sensitivity, eczema, encephalomyelitis, endocarditis, endocrinopathy, epiglottitis, Epstein-Barr virus infection, erythromelalgia, extrapyramidal and cerebellar disorders, familial hemophagocytic lymphohistiocytosis, fetal thymus implant rejection, Friedreich's ataxia, functional peripheral arterial disorders, fungal sepsis, gas gangrene, gastric ulcer, glomerular nephritis, graft rejection of any organ or tissue, gram negative sepsis, gram positive sepsis, granulomas due to intracellular organisms, hairy cell leukemia, Hallervorden-Spatz disease, Hashimoto's thyroiditis, hay fever, heart transplant rejection, hemochromatosis, hemodialysis, hemolytic uremic syndrome/thrombolytic thrombocytopenic purpura, hemorrhage, hepatitis (A), His bundle arrhythmias, HIV infection/HIV neuropathy, Hodgkin's disease, hyperkinetic movement disorders, hypersensitivity reactions, hypersensitivity pneumonitis, hypertension, hypokinetic movement disorders, hypothalamic-pituitary-adrenal axis evaluation, idiopathic Addison's disease, idiopathic pulmonary fibrosis, antibody mediated cytotoxicity, asthenia, infantile spinal muscular atrophy, inflammation of the aorta, influenza a, ionizing radiation exposure, iridocyclitis/uveitis/optic neuritis, ischemia-reperfusion injury, ischemic stroke, juvenile rheumatoid arthritis (JRA), juvenile spinal muscular atrophy, Kaposi's sarcoma, kidney transplant rejection, legionella, leishmaniasis, leprosy, lesions of the corticospinal system, lipedema, liver transplant rejection, lymphedema, malaria, malignant lymphoma, malignant histiocytosis, malignant melanoma, meningitis, meningococcemia, metabolic/idiopathic, migraine headache, mitochondrial multi-system disorder, mixed connective tissue disease, monoclonal gammopathy, multiple myeloma, multiple systems degenerations (Menzel, Dejerine-Thomas, Shy-Drager, and Machado-Joseph), myasthenia gravis, Mycobacterium avium intracellulare, nmycobacterium tuberculosis, myelodysplastic syndrome, myocardial infarction, myocardial ischemic disorders, nasopharyngeal carcinoma, neonatal chronic lung disease, nephritis, nephrosis, neurodegenerative diseases, neurogenic I muscular atrophies, neutropenic fever, non-Hodgkins lymphoma, occlusion of the abdominal aorta and its branches, occlusive arterial disorders, OKT3® therapy, orchitis/epidydimitis, orchitis/vasectomy reversal procedures, organomegaly, osteoporosis, pancreas transplant rejection, pancreatic carcinoma, paraneoplastic syndrome/hypercalcemia of malignancy, parathyroid transplant rejection, pelvic inflammatory disease, perennial rhinitis, pericardial disease, peripheral atherosclerotic disease, peripheral vascular disorders, peritonitis, pernicious anemia, Pneumocystis carinii pneumonia, pneumonia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome), post perfusion syndrome, post pump syndrome, post-MI cardiotomy syndrome, preeclampsia, progressive supranucleo palsy, primary pulmonary hypertension, radiation therapy, Raynaud's phenomenon and disease, Raynaud's disease, Refsum's disease, regular narrow QRS tachycardia, renovascular hypertension, reperfusion injury, restrictive cardiomyopathy, sarcomas, scleroderma, senile chorea, senile dementia of Lewy body type, seronegative arthropathies, shock, sickle cell anemia, skin allograft rejection, skin changes syndrome, small bowel transplant rejection, solid tumors, specific arrhythmias, spinal ataxia, spinocerebellar degenerations, streptococcal myositis, structural lesions of the cerebellum, subacute sclerosing panencephalitis, syncope, syphilis of the cardiovascular system, systemic anaphylaxis, systemic inflammatory response syndrome, systemic onset juvenile rheumatoid arthritis, T-cell or FAB ALL, telangiectasia, thromboangitis obliterans, thrombocytopenia, toxicity, transplants, trauma/hemorrhage, type III hypersensitivity reactions, type IV hypersensitivity, unstable angina, uremia urosepsis, urticaria, valvular heart diseases, varicose veins, vasculitis, venous diseases, venous thrombosis, ventricular fibrillation, viral and fungal infections, viral encephalitis/aseptic meningitis, viral-associated hemophagocytic syndrome, Wemicke-Korsakoff syndrome, Wilson's disease, xenograft rejection of any organ or tissue, acute coronary syndromes, acute idiopathic polyneuritis, acute inflammatory demyelinating polyradiculoneuropathy, acute ischemia, adult Still's disease, alopecia greata, anaphylaxis, anti-phospholipid antibody syndrome, aplastic anemia, arteriosclerosis, atopic eczema, atopic dermatitis, autoimmune dermatitis, autoimmune disorder associated with streptococcus infection, autoimmune enteropathy, autoimmune hearing loss, autoimmune lymphoproliferative syndrome (ALPS), autoimmune myocarditis, autoimmune premature ovarian failure, blepharitis, bronchiectasis, bullous pemphigoid, cardiovascular disease, catastrophic antiphospholipid syndrome, celiac disease, cervical spondylosis, chronic ischemia, cicatricial pemphigoid, clinically isolated syndrome (CIS) with risk for multiple sclerosis, conjunctivitis, childhood onset psychiatric disorder, chronic obstructive pulmonary disease (COPD), dacryocytitis, dermatomyositis, diabetic retinopathy, diabetes mellitus, disk herniation, disk prolapse, drug induced immune hemolytic anemia, endocarditis, endometriosis, endophthalmitis, episcleritis, erythema multiforme, erythema multiforme major, gestational pemphigoid, Guillain-Barré syndrome (GBS), hay fever, Hughes syndrome, idiopathic Parkinson's disease, idiopathic interstitial pneumonia, IgE-mediated allergy, immune hemolytic anemia, inclusion body myositis, infectious ocular inflammatory disease, inflammatory demyelinating disease, inflammatory heart disease, inflammatory kidney disease, IPF/UIP, iritis, keratitis, keratojunctivitis sicca, Kussmaul disease or Kussmaul-Meier disease, Landry's paralysis, Langerhan's cell histiocytosis, livedo reticularis, macular degeneration, microscopic polyangiitis, morbus bechterev, motor neuron disorders, mucous membrane pemphigoid, multiple organ failure, myasthenia gravis, myelodysplastic syndrome, myocarditis, nerve root disorders, neuropathy, non-A non-B hepatitis, optic neuritis, osteolysis, ovarian cancer, pauciarticular JRA, peripheral artery occlusive disease (PAOD), peripheral vascular disease (PVD), peripheral artery disease (PAD), phlebitis, polyarteritis nodosa (or periarteritis nodosa), polychondritis, polymyalgia rheumatica, poliosis, polyarticular JRA, polyendocrine deficiency syndrome, polymyositis, polymyalgia rheumatica (PMR), post-pump syndrome, primary Parkinsonism, prostate and rectal cancer and hematopoietic malignancies (leukemia and lymphoma), prostatitis, pure red cell aplasia, primary adrenal insufficiency, recurrent neuromyelitis optica, restenosis, rheumatic heart disease, sapho (synovitis, acne, pustulosis, hyperostosis, and osteitis), scleroderma, secondary amyloidosis, shock lung, scleritis, sciatica, secondary adrenal insufficiency, silicone associated connective tissue disease, Sneddon-Wilkinson dermatosis, spondylitis ankylosans, Stevens-Johnson syndrome (SJS), systemic inflammatory response syndrome, temporal arteritis, toxoplasmic retinitis, toxic epidermal necrolysis, transverse myelitis, TRAPS (tumor necrosis factor receptor associated periodic syndrome), type 1 allergic reaction, type II diabetes, urticaria, usual interstitial pneumonia (UIP), vasculitis, vernal conjunctivitis, viral retinitis, Vogt-Koyanagi-Harada syndrome (VKH syndrome), wet macular degeneration, wound healing, yersinia or salmonella associated arthropathy.


Various receptor for advanced gly cation endproducts (RAGE) diseases may be treated with the pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the disease may be Amytropic Lateral Sclerosis, Brachial Plexus Injury, Brain Injury, including traumatic brain injury, Cerebral Palsy, Friedrich's Ataxia, Guillain Barre, Leukodystrophies, Multiple Sclerosis, Post Polio, Spina Bifida, Spinal Cord Injury, Spinal Muscle Atrophy, Spinal Tumors, Stroke, Transverse Myelitits, dementia, senile dementia, mild cognitive impairment, Alzheimer-related dementia, Huntington's chorea, tardive dyskinesia, hyperkinesias, manias, Morbus Parkinson, steel-Richard syndrome, Down's syndrome, myasthenia gravis, nerve trauma, vascular amyloidosis, cerebral hemorrhage I with amyloidosis, brain inflammation, Friedrich's ataxia, acute confusion disorder, amyotrophic lateral sclerosis, glaucoma, Alzheimer's disease, diabetic nephropathy, sepsis, rheumatoid arthritis and related inflammatory diseases.


Various neurite degenerative diseases may be treated with the pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the disease may be multiple sclerosis, Parkinson's disease, Alzheimer's disease, Tay-Sachs disease, Niemann-Pick disease, Gaucher's disease, Hurler's syndrome, Huntington's disease, amyotrophic lateral sclerosis, idiopathic inflammatory demyelinating diseases, vitamin B12 deficiency, central pontine myelinolysis, tabes dorsalis, transverse myelitis, Devic's disease, progressive multifocal leukoencephalopathy, optic neuritis, traumatic injury to the CNS, an ischemic cerebral stroke, glaucoma, diabetic retinopathy, age-dependent macular degeneration, and a leukodystrophy.


Various neurological diseases may be treated with the pharmaceutical compositions, AAV particles, of the present invention. As a non-limiting example, the disease may be Amyotrophic Lateral Sclerosis, Brachial Plexus Injury, Brain Injury, including traumatic brain injury, Cerebral Palsy, Guillain Barre, Leukodystrophies, Multiple Sclerosis, Post Polio, Spina Bifida, Spinal Cord Injury, Spinal Muscle Atrophy, Spinal Tumors, Stroke, Transverse Myelitis; dementia, senile dementia, mild cognitive impairment, Alzheimer-related dementia, Huntington's chorea, tardive dyskinesia, hyperkinesias, manias, Morbus Parkinson, steel-Richard syndrome, Down's syndrome, myasthenia gravis, nerve trauma, vascular amyloidosis, cerebral hemorrhage I with amyloidosis, brain inflammation, acute confusion disorder, amyotrophic lateral sclerosis, glaucoma and Alzheimer's disease.


Various cancers may be treated with pharmaceutical compositions, AAV particles, of the present invention. As used herein, the term “cancer” refers to any of various malignant neoplasms characterized by the proliferation of anaplastic cells that tend to invade surrounding tissue and metastasize to new body sites and also refers to the pathological condition characterized by such malignant neoplastic growths. Cancers may be tumors or hematological malignancies, and include but are not limited to, all types of lymphomas/leukemias, carcinomas and sarcomas, such as those cancers or tumors found in the anus, bladder, bile duct, bone, brain, breast, cervix, colon/rectum, endometrium, esophagus, eye, gallbladder, head and neck, liver, kidney, larynx, lung, mediastinum (chest), mouth, ovaries, pancreas, penis, prostate, skin, small intestine, stomach, spinal marrow, tailbone, testicles, thyroid and uterus.


Types of carcinomas which may be treated with the AAV particles of the present invention include, but are not limited to, papilloma/carcinoma, choriocarcinoma, endodermal sinus tumor, teratoma, adenoma/adenocarcinoma, melanoma, fibroma, lipoma, leiomyoma, rhabdomyoma, mesothelioma, angioma, osteoma, chondroma, glioma lymphoma/leukemia, squamous cell carcinoma, small cell carcinoma, large cell undifferentiated carcinomas, basal cell carcinoma and sinonasal undifferentiated carcinoma.


Types of sarcomas which may be treated with the AAV particles of the present invention include, but are not limited to, soft tissue sarcoma such as alveolar soft part sarcoma, angiosarcoma, dermatofibrosarcoma, desmoid tumor, desmoplastic small round cell tumor, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, tibrosarcoma, hemangiopericytoma, hemangiosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma lymphosarcoma, malignant fibrous histiocytoma, neurofibrosarcoma, rhabdonyosarcoma, synovial sarcoma, and Askin's tumor, Ewing's sarcoma (primitive neuroectodermal tumor), malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, and chondrosarcoma.


As a non-limiting example, the cancer which may be treated may be Acute granulocytic leukemia Acute lymphocytic leukemia, Acute myelogenous leukemia, Adenocarcinoma, Adenosarcoma, Adrenal cancer, Adrenocortical carcinoma, Anal cancer, Anaplastic astrocytoma, Angiosarcoma, Appendix cancer, Astrocytoma, Basal cell carcinoma, B-Cell lymphoma), Bile duct cancer, Bladder cancer, Bone cancer, Bowel cancer, Brain cancer, Brain stem glioma, Brain tumor, Breast cancer, Carcinoid tumors, Cervical cancer, Cholangiocarcinoma, Chondrosarcoma, Chronic lymphocytic leukemia, Chronic myelogenous leukemia, Colon cancer, Colorectal cancer, Craniopharyngioma, Cutaneous lymphoma, Cutaneous melanoma, Diffuse astrocytoma, Ductal carcinoma in situ, Endometrial cancer, Ependymoma, Epitheloid sarcoma, Esophageal cancer, Ewing sarcoma, Extrahepatic bile duct cancer, Eye cancer, Fallopian tube cancer, Fibrosarcoma, Gallbladder cancer, Gastric cancer, Gastrointestinal cancer, Gastrointestinal carcinoid cancer, Gastrointestinal stromal tumors, General, Germ cell tumor, Glioblastoma multiforme, Glioma, Hairy cell leukemia, Head and neck cancer, Hemangioendothelioma, Hodgkin lymphoma, Hodgkin's disease, Hodgkin's lymphoma, Hypopharyngeal cancer, Infiltrating ductal carcinoma, Infiltrating lobular carcinoma, Inflammatory breast cancer, Intestinal Cancer, Intrahepatic bile duct cancer, Invasive/infiltrating breast cancer, Islet cell cancer, Jaw cancer, Kaposi sarcoma, Kidney cancer, Laryngeal cancer, Leiomyosarcoma, Leptomeningeal metastases, Leukemia, Lip cancer, Liposarcoma, Liver cancer, Lobular carcinoma in situ, Low-grade astrocytoma, Lung cancer, Lymph node cancer, Lymphoma, Male breast cancer, Medullary carcinoma, Medulloblastoma, Melanoma, Meningioma, Merkel cell carcinoma, Mesenchy mal chondrosarcoma, Mesenchymous, Mesothelioma, Metastatic breast cancer, Metastatic melanoma, Metastatic squamous neck cancer, Mixed gliomas, Mouth cancer, Mucinous carcinoma, Mucosal melanoma, Multiple melanoma, Nasal cavity cancer, Nasopharyngeal cancer, Neck cancer, Neuroblastoma, Neuroendocrine tumors, Non-Hodgkin lymphoma, Non-Hodgkin's lymphoma, Non-small cell lung cancer, Oat cell cancer, Ocular cancer, Ocular melanoma, Oligodendroglioma, Oral cancer, Oral cavity cancer, Oropharyngeal cancer, Osteogenic sarcoma, Osteosarcoma, Ovarian cancer, Ovarian epithelial cancer, Ovarian germ cell tumor, Ovarian primary peritoneal carcinoma, Ovarian sex cord stromal tumor, Paget's disease, Pancreatic cancer, Papillary carcinoma, Paranasal sinus cancer, Parathyroid cancer, Pelvic cancer, Penile cancer, Peripheral nerve cancer, Peritoneal cancer, Pharyngeal cancer, Pheochromocytoma, Pilocytic astrocytoma, Pineal region tumor, Pineoblastoma, Pituitary gland cancer, Primary central nervous system lymphoma, Prostate cancer, Rectal cancer, Renal cell cancer, Renal pelvis cancer, Rhabdomyosarcoma, Salivary gland cancer, Sarcoma, Sarcoma, bone, Sarcoma, soft tissue, Sarcoma, uterine, Sinus cancer, Skin cancer, Small cell lung cancer, Small intestine cancer, Soft tissue sarcoma, Spinal cancer, Spinal column cancer, Spinal cord cancer, Spinal tumor, Squamous cell carcinoma, Stomach cancer, Synovial sarcoma, T-cell lymphoma), Testicular cancer, Throat cancer, Thymoma/thymic carcinoma, Thyroid cancer, Tongue cancer, Tonsil cancer, Transitional cell cancer, Transitional cell cancer, Transitional cell cancer, Triple-negative breast cancer, Tubal cancer, Tubular carcinoma, Ureteral cancer, Ureteral cancer, Urethral cancer, Uterine adenocarcinoma, Uterine cancer, Uterine sarcoma, Vaginal cancer, and Vulvar cancer.


The AAV particles or pharmaceutical compositions of the present invention useful in preventing or treating HIV and AIDS may alternatively, or in combination, encode an antibody that targets a different infectious agent (e.g., an infectious agent that is not HIV-1 or 2). Non-limiting examples of other target antigens include any of the following, including fragments or variants thereof, adenoviruses, Anaplasma phagocytophilium, Ascaris lumbricoides, Bacillus anthracis, Bacillus cereus, Bacteroides sp, Barmah Forest virus, Bartonella bacilliformis, Bartonella henselae, Bartonella quintona, beta-toxin of Clostridium perfringens, Bordetella pertussis, Bordetella parapertussis, Borrelia burgdorferi, Borrelia miyamotoi, Borrelia recurrentis, Borrelia sp., Botulinum toxin, Brucella sp., Burkholderia pseudomallei, California encephalitis virus, Campylobacter, Candida albicans, chikungunya virus, Chlamydia psittaci, Chlamydia trachomatis, Clonorchis sinensis, Clostridium difficile bacteria, Clostridium tetani, Colorado tick fever virus, Corynebacterium diphtheriae, Corynebacterium minutissimum, Coxiella burnetii, coxsackie A, coxsackie B, Crimean-Congo hemorrhagic fever virus, cytomegalovirus, dengue virus, Eastern Equine encephalitis virus, Ebola viruses, echovirus, Ehrlichia chaffeensis, Ehrlichia equi, Ehrlichia sp. Entamoeba histolytica, Enterobacter sp., Enterococcus feacalis, Enterovirus 71, Epstein-Barr virus (EBV), Erysipelothrix rhusiopathiae, Escherichia coli, Flavivirus, Fusobacterium necrophorum, Gardnerella vaginalis, Group B streptococcus, Haemophilus aegyptius, Haemophilus ducreyi, Haemophilus influenzae, hantavirus, Helicobacter pylori, Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, Hepatitis E, herpes simplex virus 1 and 2, human herpes virus 6, human herpes Virus 8, human immunodeficiency virus 1 and 2, human T-cell leukemia viruses I and II, influenza viruses (A, B, C), Jamestown Canyon virus, Japanese encephalitis antigenic, Japanese encephalitis virus, John Cunninham virus, juninvirus, Kaposi's Sarcoma-associated Herpes Virus (KSHV), Klebsiella granulomatis, Klebsiella sp., Kyasanur Forest Disease virus, La Crosse virus, Lassavirus, Legionella pneumophila, Leptospira interrogans, Listeria monocytogenes, lymphocytic choriomeningitis virus, lyssavirus, Machupovirus, Marburg virus, measles virus, MERS coronavirus (MERS-CoV), Mictococcus sedentarius, Mobiluncus sp., Molluscipoxvirus, Moraxella catarrhalis, Morbilli-Rubeola virus, Mumpsvirus, Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma genitalium, Mycoplasma sp, Nairovirus, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia, Norwalk virus, norovirus, Omsk hemorrhagic fever virus, papilloma virus, parainfluenza viruses 1-3, parapoxvirus, parvovirus B19, Peptostreptococccus sp., Plasmodium sp., polioviruses types I, II, and III, Proteus sp., Pseudomonas aeruginosa, Pseudomonas pseudomallei, Pseudomonas sp., rabies virus, respiratory syncytial virus, ricin toxin, Rickettsia australis, Rickettsia conori, Rickettsia honei, Rickettsia prowazekii, Ross River Virus, rotavinrus, rubellavirus, Saint Louis encephalitis, Salmonella typhi, Sarcoptes scabiei, SARS-associated coronavirus (SARS-CoV), Serrana sp., Shiga toxin and Shiga-like toxin, Shigella sp., Sin Nombre Virus, Snowshoe hare virus, Staphylococcus aureus, Staphylococcus epidermidis, Streptobacillus moniliformis, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus agalactiae, Streptococcus group A-H, Streptococcus pneumoniae, Streptococcus pyogenes, Treponema pallidum subsp. Pallidum, Treponema palladium var. carateum, Treponema pallidum var. endemicum, Tropheryma whippelii, Ureaplasma urealyticum, Varicella-Zoster virus, variola virus, Vibrio cholerae, West Nile virus, yellow fever virus, Yersinia enterocolitica, Yersinia pestis, Zika virus.


Diagnostic Applications

The AAV particles of the present invention may be used for diagnostic purposes or as diagnostic tools for any of the aforementioned diseases or disorders. As a non-limiting example, the AAV particles of the present invention or the antibodies encoded within the viral genome therein may be used as a biomarker for disease diagnosis. As a second non-limiting example, the AAV particles of the present invention or the antibodies encoded within the viral genome therein may be used for diagnostic imaging purposes, e.g., MRI. PET, CT or ultrasound.


Preventative Applications

The AAV particles of the present invention or the antibodies encoded by the viral genome therein may be used to prevent disease or stabilize the progression of disease. In one embodiment, the AAV particles of the present invention are used to as a prophylactic to prevent a disease or disorder in the future. In one embodiment, the AAV particles of the present invention are used to halt further progression of a disease or disorder. As a non-limiting example, the AAV particles of the invention may be used in a manner similar to that of a vaccine.


Research Applications

The AAV particles of the present invention or the antibodies encoded by the viral genome therein may also be used as research tools. The AAV particles of the invention may be used as in any research experiment, e.g., in vivo or in vitro experiments. In a non-limiting example, the AAV particles of the invention may be used in cultured cells. The cultured cells may be derived from any origin known to one with skill in the art, and may be as non-limiting examples, derived from a stable cell line, an animal model or a human patient or control subject. In a non-limiting example, the AAV particles of the invention may be used in in vivo experiments in animal models (i.e., mouse, rat, rabbit, dog, cat, non-human primate, guinea pig, ferret, c-elegans, drosophila, zebrafish, or any other animal used for research purposes, known in the art). In another non-limiting example, the AAV particles of the invention may be used in human research experiments or human clinical trials.


Combination Applications

The AAV particles of the invention may be used as a combination therapy with any other therapeutic molecule known in the art. The therapeutic molecule may be approved by the US Food and Drug Administration or may be in clinical trial or at the preclinical research stage. The therapeutic molecule may utilize any therapeutic modality known in the art, with non-limiting examples including gene silencing or interference (i.e., miRNA, siRNA, RNAi, shRNA), gene editing (i.e., TALEN, CRISPRCas9 systems, zinc finger nucleases), and gene, protein or enzyme replacement.


Therapeutic Applications: Infectious Diseases

AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat infectious disease. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Tables 21-42 (SEQ ID NO: 4138-9220).


The methods, components and compositions of the present invention may be used to diagnose, prevent, treat and/or manage infectious diseases. Infectious diseases, also known as transmissible diseases or communicable diseases, are caused by invasion and multiplication of agents in the body. Infection agents are species typically not present within the body and may be, but are not limited to, viruses, bacteria, prions, nematodes, fungus, parasites or arthropods. Additionally, an infection or symptoms associated with an infection may be caused by one or more toxins produced by such agents. Humans, and other mammals, react to infections with an innate immune system response, often involving an inflammation. The illnesses and symptoms involved with infections vary according to the infectious agent. Many infections may be subclinical without presenting any definite or observable symptoms, whereas some infections cause severe symptoms, require hospitalization or may be life-threatening. Some infections are localized, whereas some may overcome the body through blood circulation or lymphatic vessels Some infections have long-term effects on wellbeing of infected individuals.


Infectious agents may be transmitted to humans via different routes. For example, infection agents may be transmitted by direct contact with an infected human, an infected animal, or an infected surface Infections may be transmitted by direct contact with bodily fluids of an infected human or an animal, e.g. blood, saliva, sweat, tears, mucus, female ejaculate, semen, vomit or urine. For example, infection may be transmitted by a fecal-oral route, referring to an infected person shedding the virus in fecal particles which then enters to person's mouth causing infection. The fecal-oral route is especially common transmission route in environments with poor sanitation and hygiene. Non-limiting examples of agents transmitted by the fecal-oral route include bacteria, e.g. shigella, Salmonella typhii and Vibrio Cholerae, virus, e.g. norovirus, rotavirus, enteroviruses, and hepatitis A, fungi, e.g. Entamadeba histolytica, parasites, tape worms, transmitted by contaminated food or beverage, leading to food poisoning or gastroenteritis. Infections may be transmitted by a respiratory route, referring to agents that are spread through the air. Typical examples include agents spread as small droplets of liquid or as aerosols, e.g. respiratory droplets expelled from the mouth and nose while coughing and sneezing. Typical examples of respiratory transmitted diseases include the common cold mostly implicated to rhinoviruses, influenza caused by influenza viruses, respiratory tract infections caused by e.g. respiratory syncytial virus (RSV). Infections may be transmitted by a sexual transmission route. Examples of common sexually transmitted infections include e.g. human immunodeficiency virus (HIV) causing acquired immune deficiency syndrome (AIDS), chlamydia caused by Neisseria gonorrhoeae bacteria, fungal infection Candidiasis caused by Candida yeast, and Herpes Simplex disease caused by herpes simplex virus Infections may be transmitted by an oral transmission route, e.g. by kissing or sharing a drinking glass. A common infection transmitted by oral transmission is an infectious mononucleosis caused by Epstein-Barr virus Infections may be transmitted by a vertical transmission, also known as “mother-to-child transmission.” from mother to an embryo, fetus or infant during pregnancy or childbirth. Examples of infection agents that may be transmitted vertically include HIV, chlamydia, rubella, Toxoplasma gondii, and herpes simplex virus. Infections may be transmitted by an iatrogenic route, referring to a transmission by medical procedures such as injection (contaminated reused needles and syringes), or transplantation of infected material, blood transfusions, or infection occurring during surgery. For example, methicillin-resistant Staphylococcus aureus (MRSA), which may cause several severe infections, may be transmitted via iatrogenic route during surgery. Infections may also be transmitted by vector-borne transmission, where a vector may be an organism transferring the infection agents from one host to another. Such vectors may be triatomine bugs, e.g. trypanosomes, parasites, animals, arthropods including e.g. mosquitos, flies, lice, flees, tick and mites or humans. Non-limiting examples of mosquito-borne infections include Dengue fever, West Nile virus related infections, Yellow fever and Chikungunya fever. Non-limiting examples of parasite-borne diseases include malaria, Human African trypanosomiasis and Lyme disease. Non-limiting examples of diseases spread by humans or mammals include HIV. Ebola hemorrhagic fever and Marburg fever.


Traditionally infectious diseases are treated with medications and/or good supportive care. Medical prevention, treatment and/or management of bacterial infections may include administration of antibiotics. Antibiotics may inhibit the colonization of bacteria or kill the bacteria. Antibiotics include e.g. penicillins, cephalosporins, macrolides, fluoroquinolones, sulfonamides, tetracyclines, and aminoglycosides. Antibiotics may be specific to a certain bacteria or act against broad spectrum of bacteria. Some types of bacteria are especially susceptible to antibiotics, whereas some bacteria are more resistant. Development of bacterial strain mutations that are resistant to antibiotics is an increasing concern. Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) and Klebsiella pneumoniae carbapenemase-producing bacteria (KPC) are examples of bacteria that are resistant to most general antibiotics. Due to the emerging resistance, unnecessary administration and overdosing of antibiotics should be avoided. Medical prevention, treatment and/or management of viral infections may include administration of antiviral medications. Antiviral medications may be specific to a certain bacteria or act against a broad spectrum of viruses. Currently antiviral medications are available for e.g. HIV, influenza, hepatitis B and C Medical prevention, treatment and/or management of viral infections may include administration of antifungal medication. Antifungal medication kills or prevents the growth of fungi. Types of antifungal medications include e.g. imidazoles, triazoles and thiazoles, allylamines, and echinocandins. Development of antifungal medication capable of targeting fungal cells without affecting human cells is a challenge due to the similarities of human and fungal cell on the molecular level. Typically, medical treatment is combined with good supportive care, which includes provision of fluids, bed rest, medication to relieve pain and lower fever, supportive alternative medicine such as vitamins, antioxidants and other supplements important for wellbeing of patients.


Antibody therapies for infectious diseases have also been developed. Examples of commercial therapeutic antibodies include raxibacumab (developed by Cambridge Antibody Technology and Human Genome Sciences) which is an antibody for the prophylaxis and treatment of inhaled anthrax. SHIGAMAB™ (developed by Bellus Health Inc.) is a monoclonal antibody for treatment of Shiga toxin induced hemolytic uremic syndrome, and actoxumab and bezlotoxumab (developed by Medarex Inc, and the University of Massachusetts Medical School) are commercial human monoclonal antibodies targeting C. difficile toxin A and toxin B, respectively.


Infectious diseases and/or infection related diseases, disorders, and/or conditions that may be treated by methods, components and compositions of the present invention include, but are not limited to, 14-day measles, 5-day fever, acne, acquired immunodeficiency syndrome (AIDS), acrodermatitis chronica atrophicans (ACA), acute hemorrhagic conjunctivitis, acute hemorrhagic cystitis, acute rhinosinusitis, adult T-cell leukemia-lymphoma (ATLL). African sleeping sickness, alveolar hydatid, amebiasis, amebic meningoencephalitis, anaplasmosis, anthrax, arboviral, ascariasis, aseptic meningitis, Athlete's foot, Australian tick typhus, avian Influenza, babesiosis, bacillary angiomatosis, bacterial meningitis, bacterial vaginosis, balanitis, balantidiasis, Bang's disease, Barmah Forest virus, bartonellosis, bat lyssavirus, Bay sore, Baylisascaris, beaver fever, beef tapeworm, bejel, biphasic meningoencephalitis, black bane, black death, black piedra, Blackwater fever, blastomycosis, blennorrhea of the newborn, blephantis, boils, Bomholm disease, borrelia miyamotoi disease, botulism, boutonneuse fever, Brazilian purpuric fever, break bone fever, brill, bronchiolitis, bronchitis, brucellosis, bubonic, bubonic plague, bullous impetigo, Burkholderia mallei, Burkholderia pseudomallei, burly ulcers mycoburuli ulcers, Busse-Buschke disease, California group encephalitis, campylobacteriosis, candidiasis, canefield fever, canicola fever, capillariasis, carate, carbapenem-resistant enterobacteriaceae (CRE), Carrion's disease, cat scratch fever, cave disease, central Asian hemorrhagic fever, Central European tick, cervical cancer, Chagas disease, cancroid, Chicago disease, chickenpox, Chiclero's ulcer, chikungunya fever, chlamydial, cholera, chromoblastomy cosis, ciguatera, clap, clonorchiasis, Clostridium difficile, Clostridium perfringens, coccidioidomycosis fungal, coenurosis, colorado tick fever, condyloma accuminata, condyloma lata, Congo fever, Congo hemorrhagic fever virus, conjunctivitis, cowpox, crabs, Crimean disease, croup, crypto, cryptococcosis, cryptosporidiosis, cutaneous larval migrans, cyclosporiasis, cystic hydatid, cysticercosis, cystitis, Czechoslovak tick, d68 (EV-d68), dacnrocytitis, dandy fever, darling's disease, deer fly fever, dengue fever types 1, 2, 3, and 4, desert rheumatism, devil's grip, diphasic milk fever, diphtheria, disseminated intravascular coagulation, dog tapeworm, donovanosis, dracontiasis, dracunculosis, duke's disease, dum dum disease, Durand-Nicholas-Favre disease, dwarf tapeworm, E. coli, eastern equine encephalitis, Ebola hemorrhagic fever, Ebola virus disease (EVD), ectothrix, ehrlichiosis, encephalitis, endemic relapsing fever, endemic syphilis, endophthalmitis, endothrix, enterobiasis, enterotoxin-B poisoning (staph food poisoning), enterovirus, epidemic keratoconjunctivitis, epidemic relapsing fever, epidemic typhus, epiglottitis, epsilon toxin, erysipelas, erysipeloid, erysipelothricosis, erythema chronicum migrans, erythema infectiosum, erythema marginatum, erythema multiforme, erythema nodosum, erythema nodosum leprosum, erythrasma, espundia, eumycotic mycetoma, European blastomycosis, exanthem subitum, eyeworm, Far-Eastern tick, fascioliasis, fievre boutonneuse, fifth disease, Filatow-Dukes' disease, fish tapeworm, Fitz-Hugh-Curtis syndrome—perihepatitis, flinders island spotted fever, flu, folliculitis, four corners disease, frambesia, francis disease, furunculosis, gas gangrene, gastroenteritis, genital herpes, genital warts, German measles, Gerstmann-Straussler-Scheinker (GSS), giardiasis, Gilchrist's disease, gingivitis, gingivostomatitis, glanders, glandular fever, gnathostomiasis, gonococcal, gonorrhea, granuloma inguinale, guinea worm, haemophilus influenza disease, hamburger disease, Hansen's disease, Hantaan disease, Hantaan-Korean hemorrhagic fever, hantavirus pulmonary syndrome (UPS), hard chancre, hard measles, Haverhill fever, head and body lice, heartland fever, helicobacterosis, hemolytic uremic syndrome (HUS), hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, herpangina, herpes—genital, herpes labialis, herpes—neonatal, hidradenitis, histoplasmosis, histoplasmosis, his-werner disease, hiv, hookworms, hordeola, HTLV-associated myelopathy (HAM), human granulocytic ehrlichiosis, human monocytic ehrlichiosis, human papillomarivus (HPV), human pulmonary syndrome, human pulmonary syndrome (HPS), human T-cell lymphotrophic virus (HTLV), hydatid cyst, hydrophobia, impetigo, including congenital, inclusion conjunctivitis, infantile diarrhea, infectious mononucleosis, infectious myocarditis, infectious pericarditis, influenza, isosporiasis, Israeli spotted fever, Japanese encephalitis, jock itch, jorge lobo disease, jungle yellow fever, Junin Argentinian hemorrhagic fever, kala azar, Kaposi's sarcoma, keloidal blastomycosis, keratoconjunctivitis, kuru, Kyasanur forest disease, lacrosse encephalitis, lassa hemorrhagic fever, legionellosis, legionnaires disease, legionnaire's pneumonia, Lemierre's syndrome, lemming fever, leprosy, leptospirosis, listena, listeriosis, liver fluke, lobo's mycosis, lock jaw, lockjaw, loiasis, louping ill, Ludwig's angina, lung fluke, Lyme disease, lymphogranuloma venereum (LGV), Machupo Bolivian hemorrhagic fever, Madura foot, mal del pinto, malaria, malignant pustule, Malta fever, Marburg hemorrhagic fever, masters disease, maternal sepsis, measles, Mediterranean spotted fever, melioidosis, meningitis, meningococcal disease, Middle East Respiratory Syndrome (MERS), methicillin-resistant Staphylococcus aureus (MRSA), milker's nodule, molluscum contagiosum, moniliasis, monkeypox, mononucleosis, mononucleosis-like syndrome, Montezuma's revenge, morbilli, mucormycosis, multiple organ dysfunction syndrome (MODS), multiple-system atrophy (MSA), mumps, murine typhus, Murray Valley encephalitis (MVE), mycoburuli ulcers, mycotic vulvovagmitis, myositis, Nanukayami fever, necrotizing fasciitis, necrotizing fasciitis—type 1, necrotizing fasciitis—type 2, negishi, new world spotted fever, nocardiosis, nongonococcal urethritis, non-polio enterovirus, norovirus, North American blastomycosis, North Asian tick typhus, Norwalk virus, Norwegian itch, O'hara disease, Omsk hemorrhagic fever, onchoceriasis, onychomycosis, opisthorchiasis, opthalmia neonatorium, oral hairy leukoplakia, orf, oriental sore, oriental spotted fever, omithosis, Oroya fever, otitis externa, otitis media, pannus, paracoccidioidornycosis, paragonimiasis, paramfectious, paralytic shellfish poisoning, paronychia, parotitis, parrot fever, pediculosis, peliosis hepatica, pelvic inflammatory disease, pertussis, phaeohyphomycosis, pharyngoconjunctival fever, piedra, pigbel, pink eye conjunctivitis, pinta, pinworm, pitted keratolysis, pitvriasis versicolor, plague, pleurodynia, pneumococcal disease, pneumocystis pneumonia, pneumocystosis, pneumonia, polio, poliomyelitis, polycystic hydatid, Pontiac fever, pork tapeworm, Posada-Wernicke disease, postanginal septicemia, Powassan, progressive multifocal leukencephalopathy (PML), progressive rubella panencephalitis, prostatitis, pseudomembranous colitis, psittacosis, puerperal fever, pustular rash diseases, pyelonephritis, pylephlebitis, q-fever, quinsy, quintana fever, rabbit fever, rabies, racoon roundworm, rat bite fever, rat tapeworm, Reiter syndrome, relapsing fever, respiratory syncytial virus (RSV), rheumatic fever, rhodotorulosis, ricin poisoning, rickettsialpox, rickettsiosis, Rift valley fever, ringworm, Ritter's disease, river blindness, rocky mountain spotted fever, rose handler's disease, rose rash of infants, roseola, Ross river fever, rotavirus, roundworm s, rubella, rubeola, Russian spring, salmonellosis gastroenteritis, San Joaquin valley fever, Sao Paulo encephalitis, Sao Paulo fever, scabies infestation, scalded skin syndrome, scalded skin syndrome, scarlatina, scarlet fever, schistosomiasis, scombroid, scrub typhus, sennetsu fever, sepsis, septic shock, severe acute respiratory syndrome, severe acute respiratory syndrome (SARS), shiga toxigenic Escherichia coli, shigella, shigellosis gastroenteritis, shinbone fever, shingles, shipping fever, siberian tick typhus, sinusitis, sixth disease, slapped cheek disease, sleeping sickness, small pox, smallpox, snail fever, soft chancre, southern tick associated rash illness, sparganosis, Spelunker's disease, sporadic typhus, sporotrichosis, spotted fever, spring, St. Louis encephalitis, staphylococcal food poisoning, staphylococcal, strep, throat, streptococcal disease, streptococcal toxic-shock syndrome, strongyloiciasis, stye, subacute sclerosing panencephalitis (SSAPE), sudden acute respiratory syndrome, sudden rash, swimmer's ear, swimmer's itch, swimming pool conjunctivitis, Sylvatic yellow fever, syphilis, systemic inflammatory response syndrome (SIRS), tabes dorsalis, taeniasis, taiga encephalitis, tanner's disease, tapeworm s, temporal lobe encephalitis, tertiary syphilis, tetani, tetanus, threadworms, thrush, tick, tick typhus, tinea barbae, tinea capitis, tinea corporis, tinea cruris, tinea manuum, tinea nigra, Tinea pedis, tinea unguium, tinea versicolor, torulopsosis, torulosis, toxic shock syndrome, toxoplasmosis, transmissible spongioform, traveler's diarrhea, trench fever 5, trichinellosis, trichomoniasis, trichonycosis axillaris, trichuriasis, tropical spastic paraparesis (TSP), trypanosomiasis, tuberculosis (TB), tularenua, typhoid fever, typhus fever, ulcus molle, undulant fever, urban yellow fever, urethritis, vagmitis, vaginosis, valley fever, vancomycin intermediate (VISA), vancomycin resistant (VRSA), varbuncle, varicella, variola, varrion's disease, venezuelan equine encephalitis, Verruga peruana, vibrio, Vibrio cholerae, vibriosis, vincent's disease or trench mouth, viral conjunctivitis, viral meningitis, viral meningoencephalitis, viral rash, visceral larval migrans, vomito negro, vulvovaginitis, warts, Waterhouse, Weil's disease, West Nile fever, Western equine encephalitis, Whipple's disease, whipworm, white piedra, whitlow, Whitmore's disease, whooping cough, winter diarrhea, wolhynia fever, wool sorters' disease, yaws, yellow fever, yersinosis, zahorsky's disease, zika virus disease, zoster, zygomycosis, acute bacterial rhinosinusitis, lobomycosis, and/or any other infectious diseases, disorders or conditions.


John Cunningham Virus (JCV)

John Cunningham Virus is a common human polyomavirus. The transmission route of JCV is unknown. The virus is suspected to be spread by contaminated water and may be obtained through tonsils or by the gastrointestinal tract, 70-90% of humans are estimated to be infected by the virus, and for normal healthy individuals the infection is asymptomatic. However, for patients with weakened immune system. JCV may lead to Progressive multifocal leukoencephalopathy (PMI). PML is a condition characterized by multifocal progressive damage or inflammation of the white matter of the brain. The symptoms include clumsiness, progressive weakness and changes in visual, speech and personality. PLM has a mortality rate of 30-50% and patients who survive the disease are left with severe neurological disabilities. PML occurs in patients with a severe immunodeficiency, most commonly in patients with HIV/AIDS. As many as 5% of HIV/AIDS patients are affected by PML. Individuals with other autoimmune conditions such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus are also at risk, as well as individuals going through immunosuppressive therapy for cancer, e.g lymphoma or Hodgkin's disease, or organ transplant. PML associated with immunosuppressive therapy is an increasing concern. For example, commercial antibody natalizumab (TYSABR®, developed by Biogen Idec) for treatment of multiple sclerosis increases susceptibility to PML. Other drugs associated with increased risk of PML include Rituximab (RITUXAN®, developed by IDEC Pharmaceuticals), Efalizunab (RAPTIVAR® developed by Genentech and XOMA) and Mycophenolate mofetil (CELLCEPT®, developed by Genentech).


JCV is a nonenveloped, T=7 icosahedral virus with a closed circular, double-stranded DNA genome. The major capsid component is the viral protein VP1 is made of 72 pentamers formed by VP1 monomers linked through the C terminal end. VP1 starts the infection by binding to the receptor target cells. After initial infection, typically occurring in childhood or adolescence, the virus stays quiescent in the kidneys and the lymphoid organs. In healthy individuals, the virus may replicate in kidney without causing any symptoms. However, in patients with weakened immune system, JCV may cross the blood-brain barrier into the central nervous system causing PML.


As of today, there is no known cure for PML. Current therapies focus on reversing the immune deficiency to slow down or stop the progress of the disease. There remains a need for therapies neutralizing JVC for prevention, management and treatment of JCV infection and PML Goldmann et al. demonstrated that neutralizing activity with JCV VP1 protein in sera of a rabbit (see Goldmann C. et al., 1999, J. Virol.; 73(5): 4465-4469). Therapies based on neutralizing JCV antibodies could be applied for treatment, management and/or prevention of PML. Recently, immunological approaches have been under investigation and neutralizing antibodies binding to JC virus, especially targeting the VP1 protein, have been developed e.g. as described in US Patent Publication US2015/0191530. US2015/0056188 and US2015/0050271, the contents of each of which are incorporated herein by reference in their entirety. Such antibodies may cause reduction of JCV replication, proliferation or Infectivity. Antibodies may bind to a conformational epitope of JCV VP1 protein or to the sialic acid binding pocket of VP1 protein of JCV.


In some embodiments, methods of the present invention may be used to prevent, manage and/or treat JCV infection and/or PML.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat JCV As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 26 (SEQ ID NO: 6802-6865).


Influenza Virus

Influenza viruses cause a common respiratory infection called influenza (flu). Influenza viruses are categorized into three main groups, virus A, B and C Influenza viruses are negative-sense, single-stranded, segmented RNA viruses. Influenza A contains two proteins on the surface of the viral envelope; hemagglutinm (H), which is a protein responsible for red blood cell agglutination and neuraminidase (N), which is an enzyme cleaving the glycosidic bonds of neuraminic acid. Influenza A mutates at a faster rate than types B and C Several serotypes of H and subtypes of N have been identified. Influenza Type B, similarly to Type A, contains H and N protein. Type C influenza virus is a single stranded RNA virus with glycoprotein called hemagglutinin-esterase fusion Influenza strains vary according to geographical presentation.


Influenza in general is a highly contagious disease and may be transmitted by the respiratory route. Influenza symptoms include e.g. high fever, runny nose, headache, sore throat, muscle pain, cough and occasionally nausea and vomiting. Influenza may lead to other complications such as pneumonia or sinus infections. Influenza may be dangerous to young children, the elderly, pregnant women and individuals with chronic medical conditions or weakened immune system. According to Centers for Disease Control and Prevention (CDC), the estimated annual number of flu-associated deaths in the United States ranges between 3000 and 49,000, depending on the severity of the seasonal variations.


Influenza may be treated with good supportive care and antiviral medication. Antiviral medications include neuraminidase inhibitors, e.g. oseltamivir and zanarmvir and M2 protein inhibitors. However, some strains of influenza appear to be resistant to these antiviral medications. Seasonal vaccinations to influenza are very efficient in prevention of the disease and are recommended annually.


There remains a need for prevention and treatment therapies for influenza, especially for those providing long lasting and broad neutralization Therapeutic antibodies against influenza viruses have been developed. In general, antibody responses to different subtypes and serotypes of influenza A. B and C are unique. Some therapeutic antibodies are specific to an antibody type, whereas some have a broad coverage. Navivumab (developed by Celltrion, Inc.) taught in US Patent application US20140234336, firivumab (developed by Celltrion, Inc.) taught in US Patent application US20130004505 and diridavumab (developed by Jansen Biotech, Crucell and Johnson&Johnson) taught in International Patent application WO/2008/028946 are examples of therapeutically antibodies against influenza A hemagglutinin HA.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat influenza. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 21 (SEQ ID NO: 4138-5222).


Hepatitis

Hepatitis is an inflammation of the liver. Hepatitis may be caused by an infection of hepatitis viruses A, B, C, D or E. In some cases, hepatitis may be asymptotic. A typical symptom of hepatitis is jaundice, characterized by yellowing of the skin, mucous membrane and conjunctiva. Other symptoms include loss of appetite, diarrhea, nausea and fever. Hepatitis may lead to a liver failure. Acute form of hepatitis is healed within six months of infection. The inflammation may also progress to a chronic hepatitis, which may lead to liver complications such as fibrosis, cirrhosis or hepatocellular carcinoma. There is no specific treatment for hepatitis. Typically, acute hepatitis is treated with good supportive care, including good nutritional balance, fluid and rest. Chronic hepatitis may be treated with antiviral drugs. Hepatitis may be prevented by vaccinations.


Hepatitis A (HAV) virus belongs to the family of Picornaviridae. HAV is encapsidated in an icosahedral structure formed by 60 copies of three viral structural proteins (VP1, VP2 and VP3), (see e.g. Kim et al. 2004, Virlogy; 318(2):598-607, and references therein). HAV is spread by the fecal-oral-route. Typical transmission is through contaminated food or drink or in contact with an infected individual. Improperly cooked shellfish is a common source of HAV. Hepatitis A is more abundant in developing countries with poor sanitary conditions. According to the World Health Organization (WHO), an estimated 1.4 million people are infected by HAV every year.


Vaccines for prevention of HAV infection exists and are recommended to be administered to children under 1 year of age by CDC, As of today, there is no specific treatment for HAV infection. The treatment includes supportive therapy and may last for weeks or even months. There remains a need for treatment therapies for HAV. Antibodies for prevention and/or treatment of HAV have been developed. For example, U.S. Pat. No. 763,476, International Publication WO2011114353 and Kim et al in Virology. 2004 Jan. 20:318(2).598-607, the contents of each of which are incorporated herein by reference in their entirety, teach neutralizing antibodies targeting HAV antigens.


Hepatitis B (HBV) belongs to the family of Orthohepadnaviridae. HBV comprises a 3.2 kb-partially double-stranded circular DNA genome. HBV virus may be transmitted via the sexual transmission route, vertical transmission at birth, iatrogenic route (e.g. blood transfusions, contaminated reused needles and syringes), as well as via exposure to certain body fluids of an infected individual According to the WHO, an estimated 240 million people are chronically infected with hepatitis B annually, and more than 780 000 people die to associated complications.


HBV may be prevented by vaccination. The WHO recommends vaccination for all infants, as well as for adults living in increased risk of the infection. HBV infection may be treated with antiviral medications, e.g. tenofovir and entecavir. The medication does not cure the disease but suppresses the replication of the virus. Individuals with chronic hepatitis B infection are administered antiviral medications for life. There remains a need for therapies providing long lasting management and/or cure for HBV infection. Antibodies for prevention and/or treatment of HBV infection are described e.g. in US Patent publication US20120308580 and International publication WO2013165972, the contents of each of which are herein incorporated by their reference in their entirety.


Hepatitis C (HCV) belongs to the family of Flaviviridae. HCV is a positive-sense single-stranded RNA virus with an open reading frame with 9600 nucleotide bases. HCV is most commonly transmitted by the sexual transmission route or iatrogenic route. Hepatitis C may be transmitted also via the vertical route, though uncommon. According to WHO, 130-150 million people have a chronic HCV infection and approximately half a million people die from complications associated with HCV annually.


As of today, there is no vaccine for HCV infection. Traditional treatment of hepatitis C is based on antiviral medication therapy with e.g. ribavirin and interferon. More recently, direct antiviral agents (DAA) have been developed to treat hepatitis C infections. However, there remains a need for efficient prevention and treatment therapies for HCV infection.


Hepatitis D (HDV) is a small spherical enveloped RNA virus belonging to the genus of deltaviruses. HDV infection may only replicate in the presence of a HBV virus and therefore HDV infection has a dependency on HBV. HDV virus may be transmitted as coinfection with HBV or be superimposed on chronic HBV or HBV carrier state. HDV may be transmitted similarly to HBV, e.g. via the sexual transmission route, vertical transmission at birth, iatrogenic route, as well as via exposure to certain body fluids of an infected individual. Treatment and vaccination against HBV may be applied against HDV, and there remains a need for therapies to cure both infections.


Hepatitis E (HEV) is a linear, monoparte, single-stranded RNA virus belonging to the family of Hepeviridae. HEV may be transmitted via the fecal-oral route due to contaminated food or beverage, the iatrogenic route (e.g. blood transfusions, contaminated reused needles and syringes) or the vertical transmission route during pregnancy. Contaminated drinking water is the most common source of infection. Improperly cooked shellfish are a common source of HEV. The disease is present worldwide but is more abundant in East and South Asia, and especially in environments with poor sanitation and hygiene. According to WHO, an estimated 20 million HEV infections occur annually leading to 56 600 death associated with HEV complications.


There is no specific treatment for HEV. The disease is typically cured with good supportive care. As of today, vaccinations against 1-HEV are not globally available, though development in the field has been done. There remains a need for prevention and treatment therapies for HEV infection. Antibodies for prevention and treatment of HEV have been developed. For example, neutralizing antibodies targeting HEV have been taught in U.S. Pat. No. 7,148,323, Tang et al. 2011. Proc. Natl. Acad. Sci. U.S.A. 108 (25), 10266-10271 and Gu et al. 2015, Cell Res. 25 (5), 604-620, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by HAV, HBV, HCV, HDV and/or HEV.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HAV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 6 (SEQ ID NO: 3197-3237).


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HBV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 23 (SEQ ID NO: 6311-6627).


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HDV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 23 (SEQ ID NO: 6311-6627).


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HEV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 6 (SEQ ID NO: 3197-3237).


Respiratory Syncytial Virus (RSV)

Respiratory syncytial virus (RSV) is a single-stranded RNA virus belonging to the family of Paramyxoviridae. The RSV RNA is contained in a nucleocapsid made of 11 proteins and covered with a lipid envelope (see, e.g. Piedimonte, 2015, Cleve Clin J Med.; 82(11 Suppl 1):S13-8, and references therein). RSV attaches to the epithelial cells of the host airway cells with the surface glycoproteins G and F and merges the viral envelope to the membranes of adjacent cells G and F glycoproteins are the principal antigens exposed to the host immune system.


Respiratory syncytial virus (RSV) causes infections of the respiratory tract including the lungs and breathing passages. RSV is transmitted through the respiratory transmission route, in direct contact with nasal or oral secretions of infected individuals, or indirectly e.g. by touching a contaminated surface. The symptoms include a runny nose, decrease of appetite, coughing, sneezing, fever and wheezing. The infection may progress into a pneumonia or bronchiolitis Additionally, RSV infection may have a role in triggering asthma attacks and in the inception of asthma for individuals with a family history of asthma. In healthy adults, RSV infection is typically mild and does not require hospitalization. However, the infection may be dangerous for young children and infants, and for individuals with a weakened immune system. According to the CDC, almost all children under 3 years of age will acquire an RSV infection and up to 2% of cases require hospitalization. RSV infection the most common cause for bronchiolitis and pneumonia in children younger than 1-year-old.


As of today, there is no specific medical treatment for RSV infection on the market and typically the infection is treated with good supportive care. There remains a need for prevention and treatment therapies for RSV infections and associated complications. Antibodies for treatment and prevention of RSV infection have been developed. For example, palivizumab (developed by Medimmune) taught in U.S. Pat. No. 8,153,133, the contents of which are incorporated herein by reference in their entirety, is a nearly human monoclonal antibody targeting the RSV F glycoprotein. Palivizunumab is used for passive immunity for infants at risk for severe infection, including children with hemodynamically significant congenital heart defects, profound immunodeficiency and pulmonary or neuromuscular pathologies impairing airway clearance.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by RSV.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat RSV As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 22 (SEQ ID NO: 5223-6310).


Herpes Simplex Virus 1 and 2

Herpes simplex viruses 1 and 2 (HSV1 and HSV2), also known as human herpesvirus 1 and 2 (HHV-1 and HHV-2), belong to the family of Herpesviridae. Herpesviruses in general, consist of an icosahedral capsid surrounded by a membrane envelope. The capsid contains the viral double stranded DNA. The capsid is surrounded by an amorphous tegument of 30 viral proteins. The virion is enveloped by lipids with multiple viral glycoproteins and cellular proteins (see, e.g. McAllister and Schleiss, 2014, Expert Rev Vaccines.; 13(11):1349-1360, and references therein).


HSV1 and HSV2 cause an infection known as herpes, which is characterized by blisters in the skin, or mucous membranes of the mouth, lips, also known as “cold sores”, or genitals. Typically, the symptoms are mild or asymptomatic. However, HSV1 and HSV2 are neurotropic and neuroinvasive viruses persisting in the body by becoming latent, and sustain in the cell bodies of neurons. The infection is lifelong with outbreaks, or sporadic episodes of viral reactivation, when the virus in the nerve cells become active causing new blistering. The infection may be dangerous to individuals with weakened immune system. Neonatal herpes of infants may be fatal. Occasionally HSV1 infections may lead to encephalitis or keratitis. HSV1 and HSV2 are transmitted by contact with an infected area during reactivations of the virus. HSV1 is mainly transmitted by oral-to-oral contact, skin contact or the sexual transmission route. HSV1 may also be transmitted vertically during birth. HSV2 is transmitted via the sexual transmission route and is one of the most common sexually transmitted infections. According to the WHO, an estimated 67% of world's population aged under 50 years has an HSV-1 infection. An estimated 11% of world's population aged 15-49 years has an HSV2 infection.


As of today, there is no vaccination for prevention of HSV1 and HSV2 infections on the market. HSV1 and HSV2 infections may be treated with antiviral medications, such as acyclovir, famciclovir and valacyclovir. Antiviral medications do not cure the infection, but reduce the severity and frequency of symptoms. There remains a therapy for prevention and cure for these infections. Antibodies for prevention, treatment and management of HSV1 and HSV2, targeting the viral glycoproteins, have been developed, as described e.g. in U.S. Pat. No. 8,431,118, US Patent U.S. Pat. No. 5,646,041. Haynes US Patent Publication US201410302062, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by HSV1 and HSV2.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HSV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 24 (SEQ ID NO: 6628-6736).


Human Cytomegalovirus

Human Cytomegalovirus (HCMV) also known as human herpesvirus 5 (HHV-5) belongs to the family of Herpesviridae, a sub-family of Betaherpesvirinae. HCMV is a double-stranded DNA enveloped virus composed of a nucleocapsid surrounded by structured tegument layer and bounded by a trilaminate membrane envelope.


In most occasions, an initial HCMV infection is asymptomatic, or associated with mild symptoms e.g. sore throat, fatigue, flu-like symptoms, and fever. After initial infections, HCMV virus resides in mononuclear cells without detectable symptoms. HCMV infection may be dangerous to individuals with weakened immune system. HCMV may be transmitted by contact with certain body fluids of an infected individuals (e.g. saliva, urine, semen). HCMV may be transmitted vertically, especially if acquired during pregnancy, leading to a congenital HCMV infection. According to CDC, about 1 in 150 children are born with congenital CMV infection. In about 20% of cases, congenital HCMV infection may lead to premature birth, birth defects or developmental disabilities, e.g. liver, lung, spleen problems, small head size, small body size or seizures.


As of today, there is no specific treatment or prevention therapy for HCMV infection. In severe cases of congenital HCMV infection, infants may be treated with an antiviral drug, ganciclovir, to prevent hearing loss and developmental outcomes. However, the drug has serious side effects. There remains a need for prevention therapy and improved therapies for treatment and cure of HCMV infection. Antibodies neutralizing HCMV have been developed. Such antibodies are taught e.g. in International Patent Publication WO2010007463, U.S. Pat. Nos. 9,149,524, 8,492,529 and 8,202,518, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by HCMV.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HCMV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 24 (SEQ ID NO: 6628-6736).


Epstein-Barr Virus

Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4) belongs to the family of Herpesviridae. EBV is a double-stranded DNA virus composed of a protein nucleocapsid surrounded by a tegument layer and bounded by an envelope containing lipids and surface projection of glycoproteins. EBV may enter B cells and epithelial cells.


EBV infection causes glandular fever known as infectious mononucleosis, also known as the kissing disease. Typical symptoms include e.g. sore throat, fever swollen lymph nodes in the neck, enlarged spleen, swollen liver, rash and fatigue. Additionally, EBV infection is associated with certain cancers, e.g. central nervous system lymphomas. Hodgkin's lymphoma, Burkitt's lymphoma, Guillain-Barre syndrome, multiple sclerosis, and higher susceptibility to certain autoimmune diseases. The virus is transmitted via contact with certain bodily fluids of an infected individual, especially through saliva. The infection affects majority of population. According to CDC, 90% of adult population have antibodies demonstrating current or past EBV infection.


As of today, there is no specific therapy for prevention or treatment of EBV infection on the market Typically, EBV infection is treated with good supportive care. Antibodies for prevention, management and treatment of EBV infection and associated diseases have been developed, e.g. by Wang and Fogg in US Patent publication US20150064174 and Fang et al, in Intervirology 50 (4), 254-263 (2007), the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by EBV.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat EBV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 31 (SEQ ID NO: 6898-6911).


Varicella Zoster Virus

Varicella zoster virus (VZV), also known as human herpes virus 3 (HHV-3) and chickenpox virus, belongs to the family of Herpesviridae. VZV is a linear duplex DNA molecule containing two segments (L and S) joined covalently. At least five clades of the virus have been identified.


VZV causes varicella, also known as chickenpox, which is an infection characterized by blister-like rash, itching, fatigue and fever. Chickenpox may be dangerous for babies, adults and individuals with weakened immune system. After primary phase of the infection, VZV resides in the nerves, including cranial nerve ganglia, dorsal root ganglia and autonomic ganglia, and may eventually lead to shingles, which is a viral disease characterized with a painful skin rash, blistering and occasionally nerve pain. Additionally, VZV has been associated with other complications, e.g. neurological conditions, inflammation of arteries, myelitis, Ramsay Hunt syndrome. Mollaret's meningitis VZV is transmitted by direct contact or by the respiratory route. VZV is highly contagious. According to CDC, before VZV vaccination, about 4 million people would be affected by chickenpox in the US annually, with more than 10,00KK hospitalized.


VZV infection may be prevented by a vaccination, which is recommended by CDC to all children and unvaccinated adults. Chickenpox may be treated with antiviral medications, e.g. acyclovir, valacyclovir and famciclovir, or with other symptom relieving medications and therapies. However, the present antiviral medications may have undesirable side effects. There remains a need for improved therapies to treat VZV infection, and its reactivation stages Antibodies targeting VZV have been developed, e.g. as described in U.S. Pat. No. 5,506,132, and US Patent application US20100074906, the contents of which are herein incorporated by their reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by VZV.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat VZV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 31 (SEQ ID NO: 6898-6911).


Corona Viruses

Coronaviruses are a diverse group of enveloped viruses belonging to the family of Coronaviridae. Coronaviruses contain an envelope, a helical capsid, and a single-stranded, positive-sense RNA genome. Coronaviruses have a characteristic structure with viral spike-shaped glycoprotein populating the surface of the virus and causing an appearance resembling the solar corona. Coronaviruses are a common cause of mammalian and avian infections causing upper respiratory tract, gastrointestinal and central nervous system diseases.


Human coronavirus 229E, OC-43, NL63, and HKU1 are a cause a behind typical, short term ‘common cold’ and affect individuals all over the world. Typical symptoms of the infections include coughing, sneezing, fatigue and fever. Occasionally the viruses can cause lower-respiratory tract illnesses, such as pneumonia. The viruses are spread by direct contact or by the respiratory route. The infections may be dangerous to the elderly and individuals with weakened immune system. There is no specific treatment or prevention therapy for these coronavirus infections.


Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) causes a viral respiratory illness. Typical symptoms of the infection include a high fever, headache, body aches, dry coughing and eventually pneumonia SARS-CoV was identified in 2003 in an outbreak starting from Asia. SARS-CoV is transmitted by direct contact with an infected individual or by the respirator route. According to the WHO, during the 2003 outbreak of SARS-CoV, 8098 people worldwide were infected with symptoms and out of them, 774 died. As of today, there is no specific treatment or prevention therapy for SARS on the market. Antiviral medication and steroids may be prescribed to certain patients. Antibodies targeting SARS-CoV have been developed, e.g. as described in U.S. Pat. No. 7,728,110 and US Patent publication US20110159001, the contents of each of which are herein incorporated by their reference in their entirety.


Middle East Respiratory syndrome coronavirus (MERS-CoV) causes an acute severe respiratory infection affecting the lungs and breathing tubes. MERS-CoV was identified in 2012. Typical symptoms include fever, cough and shortness of breath, eventually pneumonia and additionally gastrointestinal symptoms. MERS-CoV is highly dangerous to humans. According to the WHO, 36% of the infections are fatal. MERS-CoV is a zoonotic virus transmitted to humans from animals, e.g. bats and camels, or from human to human Camels are suggested to be a reservoir for MERS-CoV. Majority of MERS-CoV infection have occurred in the Arabian Peninsula, and especially in Saudi Arabia. As of today, no specific treatment of prevention therapy for MERS-CoV infection is available on the market. Antibodies targeting MERS-CoV have been developed, e.g. as described in International publication WO2015057942, the contents of which are herein incorporated by their reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by SARS-CoV. MERS-CoV and/or other coronaviruses.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat coronaviruses. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 25 (SEQ ID NO: 6737-6801).


Poxviruses

Poxviruses affecting humans include orthopoxvirus, parapoxvirus, yatapoxvirus and mollusipoxvirus. Poxviruses are typically brick-shaped, enveloped, single, liner or double-stranded viruses with DNA genome. Typically, poxvirus infections cause lesions, skin nodules, or disseminated rash Poxviruses may be transmitted by direct contact with contaminated humans, animals or materials. Diseases caused by poxviruses include e.g. smallpox, monkeypox, molluscum conagiosum, vaccinia virus and orf virus infection.


Smallpox virus infection is highly fatal, and though it does not occur in nature anymore, smallpox virus is considered to be a potential chemical or biological warfare agent. The threat of terrorism has created a need for efficient and improved methods for treatment and/or prevention of smallpox infection. The traditional vaccination for smallpox, also applicable against monkeypox, has a rare but severe side effect due to vaccinia virus, which is the active constituent of the vaccine that eradicated smallpox. Vaccinia Immune Globulin (VIG) is the only licensed therapeutic treatment for smallpox, but is highly variable and available in limited quantities Antibodies against smallpox have been developed, as described e.g. in U.S. Pat. No. 8,623,370 and US Patent publication US20140186370, the contents of each of which are herein incorporated by their reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by smallpox virus and/or other poxviruses.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat poxvirus. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 27 (SEQ ID NO: 6866-6875).


Enterovirus 71

Enterovirus 71 (EV71) belongs to the family of Picornaviridae Enterovirus 71 is a single-stranded RNA positive sense virus. The virus has approximately 7411 nucleotides. The RNA genome is enclosed in an icosahedral capsid of structural proteins VP1-VP4. (see, e.g. Tan et al., 2014, J. Biomed Sci; 21(1):140, and references therein).


EV71 infections typically cause hand, foot and mouth (HFMD), which is characterized by fever, mouth ulcers, and vesicles on the palms of the hands and feet. Additionally, EV7 causes severe neurological manifestations, including poliomyelitis-like acute flaccid paralysis, brainstem encephalitis in infants and children. These neurological manifestations may be fatal, or cause permanent neurological consequences, such as delayed neurodevelopment or reduced cognitive function in children. EV71 is transmitted through direct contact with certain bodily fluids, such as saliva, or the respiratory route, or the fecal-to-mouth route. Outbreaks of EV71 have been reported by WHO in the US, Europe, and more frequently in Asia-Pacific region in the past 30 year.


As of today, no specific treatment or prevention therapy for EV71 is on the market. Antiviral drugs, e.g. pleconaris and other capsid-function inhibitors (see, e.g. Tan et al J Biomed Sci. 2014; 21(1): 140), may be prescribed against EV71 infections, though their effectiveness is not well established. There remains a need for prevention and treatment therapies for EV71 infection. Antibodies neutralizing EV71 have been developed. Non-limiting examples include the anti-EV71 antibody MAB979 (developed by Merck Millipore) and those taught by Carderosa et al. in International Patent Publication WO2015092668, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by EV71.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat EV71. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 28 (SEQ ID NO: 6876-6891).


Rubella Virus

Rubella virus belongs to the family of Togaviridae. Rubella virus is a positive sense, single-stranded RNA virus with spike-like, hemagglutinin containing surface projections. The virus core is enveloped by glycosylated E1 and E2 proteins.


Rubella, also known as German measles or three-day measles, is a viral infection typically characterized by a rash, low fever, nausea, swollen lymph glands behind the ears and the neck, and mild conjunctivitis. At later stage, the infection may develop arthritis and pain in the joints. Typical symptoms of rubella infection are mild and affect children and young adults. Rubella virus is transmitted by the respiratory route and the virus replicates in the nasopharyngeal mucosa and local lymph nodes. However, when an infection is acquired during pregnancy, the virus is transmitted through vertical route with 90% chance and may cause fetal death or congenital defects known as congenital rubella syndrome (CRS). Infants with CRS may have hearing impairments, eye and heart defects, diabetes mellitus, thyroid dysfunction and/or autism. According to the WHO, about 10,000 infants with CRS are born every year, majority occurring in countries with low vaccine coverage.


As of today, there is no specific treatment for rubella. Rubella may be prevented with vaccination, and rubella has been part of the vaccination program for the past 40 years. However, the infection still persists and an increasing concern related to the life-time of vaccine efficiency exists. There remains a need for long lasting prevention therapy, as well as treatment for rubella virus infection. Antibodies against rubella have been described e.g. in US Patent US20100143376, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by rubella.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Rubella. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 29 (SEQ ID NO: 6892-6895).


Human Papilloma Virus

Human papilloma virus (HPV) is a non-enveloped double-stranded DNA virus belonging to the family of Papillomaviridae. Over 170 types of HPV have been identified.


HPV infections may be asymptomatic, or cause infection related to warts (e.g. plantar, flat or anogenital warts), oral infections such as papillomas or multifocal epithelial hyperplasia. The infection may be undetected, and clears from the body to low levels within two years. Infections caused by human papillomavirus (HPV) have been associated with certain cancers of stratified epithelial tissues, e.g. cervical, anal, vaginal, vulvar and penile cancers, lung and throat cancers. Especially HPV 16 and HPV 18 are known to be carcinogenic. According to the WHO, persistent genital HPV infection may cause cervical cancer which is the second most common cancer in women worldwide. In developing countries, cervical cancer counts for 13% of all female cancers, and survivor rate worldwide is approximately 50%. HPV is very common. CDC estimates that every one in four individuals in the US has an HPV infection Most commonly HPV is transmitted by the sexual route, but also the vertical transmission route, or by direct contact to infected blood, or objects may occur.


Cancers caused by HPV may be prevented by vaccines developed against certain HPV types. The vaccines are available worldwide and are recommended by CDC for all preteen aged children. As of today, there are no specific treatment for HPV infection. There remains a need for prevention and treatment therapy affecting a broad range of HPV infections Antibodies for HPV have been developed, e.g. as described in International publication WO2015096269, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by HPV


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat HPV. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 30 (SEQ ID NO: 6896 and 6897).



Pseudomonas aeruginosa



Pseudomonas Aeruginosa (P. aeruginosa) is a common Gram-negative, aerobic, rod-shaped bacterium belonging to the family of Pseudomonodaceae. P. aeruginosa is found in soil, water, skin, flora, and in most man-made environments around the world P. aeruginosa is considered as an opportunistic pathogen taking advantage of a weakened immune system.



P. aeruginosa may cause a variety of mild infections, such as, urinary tract infections, respiratory, system infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections, gastrointestinal infections, blood infections, ear infections, skin rash, eye infections and a variety of systemic infections. P. aeruginosa is transmitted through water, contaminated hands, materials or objects. In general, P. aeruginosa infections in healthy individuals are very mild or asymptomatic. However, the infections expose a significant risk for individuals with weakened immunity, such as patients with other underlying illnesses or complications, and especially when in a hospital environment. For example, patients with cystic fibrosis have a susceptibility towards loss of lung function due to respiratory tract infection with the bacterium. Patients attached to breathing machines, patients with catheters, or with surgery wounds or burn wounds are potentially at risk for serious and life-threatening infections. P. Aeruginosa infection may lead to a fatal sepsis. According to CDC, approximately 51,000 health-care associated infection occur in the US every year, leading to approximately 400 deaths.


As of today, there are no prevention therapies for P. aeruginosa infection on the market. Some strains of P. aeruginosa may be treated with antibiotics, e.g. gentamicin, tobramycin, colistin, and amikacin. However, an increasing number of strains of P. aeruginosa, especially those affecting hospitalized patients, are resistant to antibiotics and no specific treatment therapy exists. There remains a need for improved treatment and prevention therapies against P. aeruginosa infections. Antibodies against P. aeruginosa have been developed, such as, panobacumab (developed by Kenta Biotech Inc.), which is an antibacterial antibody against P. aeruginosa.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by P. aeruginosa.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat P. aeruginosa. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 32 (SEQ ID NO: 6912-7196).



Streptococcus Bacteria


Streptococcus is a genus of gram-positive bacteria belonging to the family of Streptoccaceae. Species of Streptococcus are divided into alpha- and beta-hemolytic species Alpha-hemolytic species cause oxidation of iron in hemoglobin molecules within the red blood cells. Alpha-hemolytic streptococci include e.g. Streptococcus pneumoniae and Streptococcus virilans. Beta-hemolytic species cause complete rupture of the red blood cells and include e.g Lancefield groups A and B, also known as ‘group A strep’ and ‘group B strep’. Streptococcus genus includes overall more than 50 species. Streptococcus bacteria cause a variety of infections in humans, including dental caries, pneumonia, endocarditis, meningitis, respiratory tract infections, urinary tract infections, neonatal meningitis, pharyngitis and/or sepsis.



Streptococcus pneumoniae is a common bacterium causing, i.e. pneumonia, meningitis, bronchitis, acute sinusitis, conjunctivitis, osteomyelitis, endocarditis and/or septic arthritis. The bacteria is transmitted by direct contact or via the respiratory route. The bacteria resides in the nasopharynx of healthy carriers and proceeds into an infection under certain circumstances. The infection may be prevented by vaccines, e.g. conjugate vaccine or polysaccharide vaccines. The infection may be treated with antibiotics, e.g. broad-spectrum cephalosporin, and vancomycin, but there is a concern over increasing resistant towards antibodies. According to CDC, Streptococcus pneumoniae is currently resistant to one or more antibiotics in 30% of infections. Streptococcus pneumoniae is resistant to e.g. penicillins. There remains a need for improved, non-antibiotic, therapies for treatment of Streptococcus pneumoniae and other Streptococcus infections Antibodies for Streptococcus have been developed, as described e.g. in U.S. Pat. No. 5,686,070 and US Patent publication US20070003561, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Streptococcus pneumoniae and other Streptococcus bacteria.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Streptococcus pneumoniae. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 33 (SEQ ID NO: 6900-6902, 6905-6907, 6911, 7197-7229).



Staphylococcus Bacteria


Staphylococcus is a genus of gram-positive bacteria belonging to the family of Staphylococcacea. The genus includes overall approximately 40 species. Most species of the genus are harmless and reside in the skin and mucous membranes of humans. Staphylococcus bacteria may also be found in the soil. The bacteria may cause diseases either through toxin production or penetration. Staphylococcal toxins are a common cause of food poisoning. Staphylococcus bacteria may cause a variety of diseases, e.g. localized or diffuse skin infection, gastroenteritis, ear infections, septic arthritis, osteomrnyelitis, sinusitis, infective endocarditis and/or toxic shock syndrome.



Staphylococcus aureus (S. aureus) is typically residing in human nose asymptotically. In certain circumstances. S. aureus infections may affect many tissues and organs. Individuals with chronic conditions, e.g. diabetes, cancer, vascular disease, eczema and lung disease, have an increased susceptibility towards S. aureus infections. S. aureus may cause skin infections, such as, pimples, impetigo, atopic dermatitis, cellulitis folliculitis. More serious forms of infections include pneumonia, meningitis, osteomyelitis and endocarditis. S. aureus may also cause food poisoning. In severe cases, S. aureus infection may enter the blood stream causing bacteremia and/or sepsis. As of today, there is no medical therapy for prevention of the infection Some strains of S. aureus may be treated with antibiotics. However, increasing resistance towards antibiotics is a concern. Currently several antibiotic resistant forms of S aureus exist, including, but not limited to, Methicillin-resistant Staphylococcus aureus (MRSA). Vanconmycin-intermediate Staphylococcus aureus (VISA) and Vancomycin-resistant Staphylococcus aureus (VRSA) The drug resistant forms of S. aureus are more frequent in hospital environments.



Staphylococcus epidermidis (S. epidermidis) resides in the normal human skin flora and may cause an infection to individuals with weakened immune system, and to individuals who have catheters, prostheses or surgical implants. S. epidermidis has an ability to colonize on plastic materials or devices placed within the body. The infection may be treated with some antibiotics, but they do not remove the infection and can only be used to manage such infections. Many S. epidermis strains are resistant to antibiotics, such as penicillin, methicillin and/or amoxicillin, and increasing resistance to antibiotics in a concern.


There remains a need for prevention and/or improved treatment therapies against Staphylococcal infections. Antibodies targeting Staphylococcal bacteria have been developed. As an example, pagadaximab (developed by Medimnunune and AstraZeneca) is a monoclonal antibody for prevention of staphylococcal sepsis and may be administered to infants with low birth weight.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Staphylococcus bacteria.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Staphylococcal infections. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 34 (SEQ ID NO: 7230-7478).



Clostridium tetani



Clostridium tetani (C. tetani) is a rod-shaped, anaerobic, Gram-positive bacteria belonging to the family of Clostridiaccae. A matured bacterium develops a terminal spore, which is resistant to heat and common antiseptics. C. tetani produces tetanospasmin toxin. C. tetani is found as spores in soil and in the gastrointestinal tract of animals.



C. tetani infection spreads the tetanospamin toxin to the body, causing tetanus, also known as lock jaw. Tetanus is a dangerous disease characterized by painful tightening of the muscles. The disease may lead to locking of the jaw and neck, leading to inability to open mouth or swallow. The tightening may affect the whole body. In severe cases, the infection may lead to breathing difficulties, pneumonia, or pulmonary embolism. Even more serious is an infection acquired during pregnancy, leading to almost always fatal neonatal tetanus of an infant. The bacteria is typically transmitted through broken skin by direct contact with contaminated soil or objects, or saliva or feces of a contaminated animal. Especially susceptible are individuals with burns, puncture wounds, crush injuries or injuries with dead tissue, individuals having animal bites or scratches. Tetanus is fairly uncommon in developed countries. However, the WHO reported an estimated 50, 000 neonatal tetanus deaths in year 2008. A program form elimination of tetanus was started in 1989 by the WHO.


Tetanus may be prevented efficiently by a four vaccine combination, DTaP, Tdap, DT, and Td, given to children and adults. For adequate immunity, the primary vaccine is adrministered during childhood, a booster dose during adolescence and every 10 years thereafter during adulthood C. tetani infection may be treated with antibiotics, wound care and with human tetanus immune globulin (an antitoxin) Despite the existing treatment methods, approximately 10% of tetanus infections lead to death, according to CDC, There remains a need for longer lasting vaccine as well as improved treatment therapies against C. tetani infections. Antibodies against C. tetani have been developed, as described e.g. by Larrick. J. W. et al., 1992, Immunol Rev. 130, 69-85, and de Krulf. J. et al., 2009, J. Mol Biol. 387 (3), 548-558, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by C. tetani.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat C. tetani. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 35 (SEQ ID NO: 7479-7535).



Bordetella


Bordetella is a genus of Gram-negative, coccobacilli belonging to the family of Alcaliigenaceac. The structure of the bacteria consists of an outer membrane with lipopolysaccharides and phospholipids forming a capsule Bordetelia bacteria affecting humans include, but are not limited to, B. pertussis, B. parapertussis and B. bronchiseptica, B. pertussis resides in the upper air pathways, mostly the trachea and the bronchii, of humans. B. parapertussis resides in the upper air pathways of mammals. The bacteria release toxins that cause damage and swelling of the respiratory pathways.


Pertussis, also known as whooping cough, is a highly contagious infection of the respiratory track caused most commonly by B. pertussis, and occasionally by B. parapertussis. Typical symptoms of the infection include severe coughing and difficulty to breathe accompanied by a runny nose, apnea and fever. Additional complications for infants include pneumonia, convulsions, apnea, and encephalopathy. The bacteria are transmitted through the respiratory tract route. The disease is especially dangerous for infants According to CDC, about 30,0K00 infections were reported in the US in 2014. CDC reports 277 deaths occurring from 2000 through 2014, out of which 241 where infants less than 3 months of age.


Pertussis may be treated with antibiotics, such as, erythromycin, clarithromycin or azithromycin. However, an increasing resistance to antibiotics is a concern. Pertussis caused B. pertussis may be prevented by vaccination, e.g. by DTaP combination vaccine, which is recommended routinely for infants by CDC and WHO. Despite the widespread vaccination, the disease has insisted. The protection provided by the traditional vaccination is estimated to be 3-6 years. There remains a need for prevention therapies providing a longer lasting immunity, as well as for improved, non-antibiotic, treatments. Antibodies for prevention and/or treatment of pertussis have been developed, as described e.g. in International publication WO2014160098, and Hussein, A. H et al, 2007, Infect. Immun. 75 (11), 5476-5482, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by B. pertussis, B. parapertussis and/or other Bordetella bacteria.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Bordetella infection. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 36 (SEQ ID NO: 7536-7560).



Mycobacterium


Mycobacterium is a genus of nonmotile and aerobic bacteria, belonging to its own family of Myobacteriaceae. Mycobacteria have an outer membrane, and a hydrophobic and waxy cell wall with mycolic acid/mycolates. The cell wall is neither truly Gram-positive nor—negative. In general, the infections are difficult to treat and the bacteria is naturally resistant to many antibiotics, e.g. penicillin, due to the cell wall. Mycobacteria includes species, such as, but not limited to, M. tuberculosis, Nontuberculous mycobacteria (NTM), M. leprae, M. bovis, M. africanum, and M. micron.



M. tuberculosis is a genetically diverse bacterium and most common and dangerous of the mycobacteria family species. M. tuberculosis causes tuberculosis (TB) which is an infection mainly affecting the lungs. Typical early symptoms include cough, fever, night sweat, and weight loss. The disease may be mild for a period of time and therefore early diagnosis is difficult. Eventually the symptoms get more severe and coughing sputum and blood may occur. TB may be transmitted by the respiratory tract. TB affects all ages of the population, but is most dangerous to children, and individuals with weakened immune systems, e.g. HIV patients. According to the WHO, TB is referred to as a top infectious disease killer worldwide. WHO reports an estimated 9.6 million infections of TB in 2014, out of which 1.5 million cases were fatal. The disease is globally spread, but it is most abundant in the South-East Asia and Western Pacific Regions.


TB may be prevented by vaccinations, i.e. Bacille Clamette-Guerin vaccine. The vaccine is provided for children and adults exposed to environments with high risk of infection. However, the vaccine is not always efficient against TB, e.g. due to the diversity of strains geographically. TB may be treated with a 6 to 9 month course of combinational antimicrobial drug therapy Antimicrobial drugs effective against TB include e.g. isoniazid, rifampin, ethambutol, and pyrazinamide. However, an increasing resistance towards the medication is a concern. Certain strains of existing TB are identified as multi-drug resistant TB strains, which do not respond to therapy with e.g. isoniazid, rifampicin, or other common drugs. WHO reports an estimated 480 000 multidrug-resistant TB infections in 2014. There remains a need for prevention therapies protecting against broad spectrum of strains, as well as for improved treatment of M. tuberculosis and/or other mycobacteria. Antibodies against mycobacteria have been developed, as described e.g. in US Patent publications US20130309237, US20130309237, US20600229438, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by M. tuberculosis and/or other mycobacteria.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat mycobacterium related diseases. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 37 (SEQ ID NO: 7561-7576).



Francisella Tularensis


Francisella tularensis (F. tuliarensis) is a facultative intracellular Gram-negative, rod-shaped bacterium belonging to the family of Francisellaceae. F. tularensis resides in invertebrates, birds, reptiles, fish, and mammals, including humans. It is one of the most infectious and pathogenic bacteria known (see, e.g. Pechous et al., 2009, Microbiol Mol Biol Rev.; 73(4): 684-711).



F. yularensis causes infection called Tularemia. Severity of tularemia varies from mild to fatal. F. Tularensis may be transmitted to a human by direct skin or eye contact, by the respiratory route or by consumption of contaminated food or drink. Most commonly, the infection is acquired while handling infected animals Most common form of tularemia is ulceroglandular tularemia, characterized by skin ulcers on the site of infection accompanied by swelling or regional lymph glands. Ulceroglandular tularemia is typically acquire by a tick, or deer fly bite. Pneumonic tularemia is an infection of the respiratory tract characterized by a cough, chest pain, and difficulty of breathing. Pneumonic tularemia is transmitted through the respiratory route and may be fatal if not treated. Oropharyngeal tularemia is transmitted by contaminated food or beverage and causes a sore throat, mouth ulcers, tonsillitis and swelling of lymph glands in the neck. Other forms of tularemia include glandular, oculoglandular (affecting the eyes) and typhoidal (combination of the general symptoms). F. tularensis is considered to be a potential biological and chemical warfare agent.


As of today, there is not preventive therapy for tularemia infection on the market. Some vaccines have been under development (see, e.g. Pechous et al., Microbiol Mol Biol Rev. 2009 December; 73(4): 684-711). Tularemia may be treated with antibiotics, such as, streptomycin, gentamicin, doxycycline, and ciprofloxacin. However, increasing resistance against antibiotics is a concern There remains a need for improved prevention and treatment therapies for F. tularensis infections. Antibodies against F. tularensis have been developed, e.g. as described by Rynkiewicz, M. J. et al., 2012, Biochemistry, 51 (28), 5684-5694 and Lu. Z., et al., 2013. Immunology, 140 (3), 374-389, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by F. tularensis.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat F. tularensis related infections. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 38 (SEQ ID NO: 7577-7592).



Toxoplasma gondii



Toxoplasma gondii is a parasitic protozoan infecting warm-blooded animals, including humans. Domestic cats and other felines are the most desired hosts for Toxoplasma gondii, as they are the only hosts where the protozoan is capable of sexual reproduction. According to CDC, more than 60 million people in the US may be infected by Toxoplasma gondii.



Toxoplasma gondii causes toxoplasmosis, which is typically asymptomatic in healthy individuals and is controlled by the natural immune system. The infection may be obtained from undercooked, contaminated food, especially pork, lamb and venison, from food contaminated by utensils, or contaminated hands, occasionally from contaminated drinking water, or by the fecal-to-oral route from cat feces. Toxoplasma gondii may also be transmitted by vertical route, especially when the protozoan is acquired during pregnancy. Children infected during or just prior to pregnancy may have eye problems, or brain damage at birth, or may develop symptoms later in their lives. Toxoplasmosis may be dangerous to individuals with a weakened immune system, such as patients with AIDS, undergoing certain chemotherapies or having organ transplants.


Toxoplasmosis may be treated with certain medications such as antibiotics called sulfadiazine and pyrimethamine, which is an anti-parasite medication used for e.g. malaria. However, resistance to both of the medications is an increasing concern. There remains a need for improved treatment methods as well as prevention therapies against Toxoplasma gondii infection. Antibodies targeting Toxoplasma gondii have been developed, as described by e.g. Graille, M. et al., 2005, J. Mol. Biol. 354 (2), 447-458, the contents of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Toxoplasma gondii.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Toxoplasma gondii related infections. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 40 (SEQ ID NO: 7617 and 7618).



Candida Yeast

Typically, species of yeast are commensals and endosymbionts of human hosts, but may cause an infection under certain circumstances. C. albicans is a yeast belonging to the family of Saccharomycetaceae C. albicans causes infection of the mouth characterized by white patches on the tongue, mouth and throat. The infection of the mouth is most typical with new born babies, the elderly and individuals with weakened immune system, e.g. HIV/AIDS patients. Optionally, the infection may affect the nails, leading o brittle and defected nails. Optionally, the infection may cause an infection of the vagina, leading to genital burning or uncomfortable discharge. Typically, Candida albicans infections are mild and localized. However, the infection may be severe or fatal for individuals with underlying health problems and left untreated. Invasive candidiasis refers to an infection spreading to many parts of the body, including the heart, brain, eyes, bones and/or joints. Candidemia refers to an infection where candida yeast is present in the blood stream. Severe forms of C. albicans infections affect individuals in health care environments, e.g. patients with central venous catheter, patients treated at an intensive care unit, patients undergoing antibiotic treatments, treatments for kidney failure, recovering from a surgery, and patients with chronic diseases, e.g. diabetes and/or HIV/AIDS. C. albicans is typically transmitted from mother to an infant during childbirth and it remains as a species of human's normal microflora. It may also be transmitted through the sexual transmission route. Other species of candida yeast family include, e.g., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei and C. lusitaniae.



C. albicans infection may be treated with antifungal drugs, e.g. nystatin, clotrimazole, amphotericin B oral suspension) or systemic oral azoles (e.g. fluconazole, itraconazole, or posaconazole). Despite the medical therapy available, some forms of C. albicans infections are dangerous, or life-threatening. There remains a need for improved prevention, and/or treatment therapies against C. albicans infections, for example by antibody therapies. Efungumab (developed by NeuTec Pharma) is an antibody for treatment of invasive C. albicans infection.


In some embodiment, methods of the present invention may be used to prevent and/or treat C. albicans infections.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat C. albicans related infections. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 41 (SEQ ID NO: 7619).


Human Immunodeficiency Virus (HIV)

Human immunodeficiency virus (HIV) is a roughly spherical enveloped RNA virus belonging to the family of Retroviridae. HIV is composed of two positive single-stranded RNA copies. The viral core contains a viral capsule protein, p24, which surrounds the two single stranded RNAs and the enzymes for HIV replication. The viral envelope consists of two lipid layers, the outer layer glycoprotein 120 (gp 120) and the transmembrane glycoprotein 41 (gp41). Gp 120 attached to the host cell whereas gp41 has a role in the cell fusion process. For replication, the virus needs a host cell and the RNA first transcribes into DNA by enzyme reverse transcriptase. HIV infects the CD4 lymphocyte (T cell) leading to depletion of CD4+ T cells and loss of CD4+ T-cell function, as infected cell loses its function and converts to a HIV-replicating cell. (see, e.g. Okoye and Picker, 2013, Immunol Rev.; 254(1): 54-64, and references therein) Additionally, HIV infection leads to B lymphocyte (B cell) hyper-activation and dysfunction (see, e.g. Moir and Fauci, 2009, Nat Rev Immunol.; 9(4): 235-245, and references therein). The virus may be transmitted through sexual transmission route, vertical transmission route, iatrogenic (medical procedure) route, or in direct contact with certain body fluids with high concentration of HIV, including e.g. blood, breast milk, semen, vaginal, and rectal secretions. Two types of HIV (HIV-1 and HIV-2) have been identified. HIV-1 has higher infectivity and has spread around the globe whereas HIV-2 is more localized to West Africa According to CDC, there is about 36.9 million people in the world with HIV/AIDS with about 2 million cases arising every year. The infection is most abundant in Sub-Saharan Africa.


In acute HIV infection stage, within 2-4 weeks after infection, infected patients experience flu-like illness. In the second stage the infection is asymptomatic and the HIV replication is at low level. The second stage may last for years or decades, especially when treated with HIV medication. Eventually, HIV causes acquired immune deficiency syndrome (AIDS), which is a clinical condition characterized by severe immunosuppression attacking the CD4 cells, making individuals susceptible to life-threatening malignancies and infections. Complications associated with HIV/AIDS include common bacterial and viral infections, parasite infections, certain cancers (e.g. Kaposi's sarcoma, Non-Hodgkin's lymphoma, and angiosarcoma), progressive multifocal leukoencephalopathy (PML) and wasting.


As of today, there is no prevention therapy or cure for HIV/AIDS. However, with antiretroviral (ART) therapy, the disease may be managed for a long period of time. ART therapy comprises of five classes of drugs used in different combinations to treat HIV. The drugs target the different phases of the retrovirus life-cycle. However, there remains a need for improved therapies for prevention, management and/or treatment of HIV/AIDS.


Antibodies for treatment and prevention of HIV infection have been developed. For example, commercial antibody Ibalizumab (developed by Taimed Biologics Inc.) is a non-immunosuppressive monoclonal antibody binding to CD4, Anaplasma phagocytophilium inhibiting the viral entry process. As another example, suvizumab (developed by Kaktsuden, Chemo-Sero Therapeutic Research Institute) is a humanized antibody targeting the HIV-1 envelope glycoprotein GP120. As a non-limiting example, any of the antibodies in Table 42, variants or fragments thereof may be used in the treatment and/or prevention of HIV.


Antibodies neutralizing HIV-1 and HIV-1 strains have been identified, but as of today, the researchers have not been able to develop a vaccination for HIV. HIV has a capability to evolve with unusually high somatic mutation and recombination rate. So far, conventional vaccines have not succeeded in eliciting analogues of the broadly neutralizing antibodies. An alternative approach suggested involves using adeno-associated vectored gene delivery for expression of antibodies from muscle tissue (e.g. Balasz et al, 2012. Nature Letter, 481, 81-84, Balasz et al. 2014, Nat Med.; 20(3): 296-300, Saunders et al., 2015, J Virol.; 89(16):8334-45, and US Patent publication US20030219733, the contents of which are herein incorporated by reference in their entirety). The studies have demonstrated efficient and long lasting protection from HIV infection by e.g. intravenous or mucosal surface transmission.


AAV Particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat I-IV infection and AIDS. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 42 (SEQ ID NO: 7620-9220).


Therapeutic Applications: Toxins

AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat infectious disease. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Tables 14-17 (SEQ ID NO: 3549-3914).


Toxins are a group of substances that are highly poisonous and dangerous to humans. Toxins are infectious agents in form of bacteria, viruses, fungi, proteins, and other chemical and/or biological substances. Toxins may lead to fatal conditions Toxins are produced by nature, and may be produced synthetically. Exposure to toxins may be unintentional and occur when in contact with toxic plants, or contaminated food, water, livestock or animals. Due to the life-threatening impact of toxins, they are considered to be potential biological and/or chemical warfare agents that may be applied as weapons of mass destruction in war field. They also impose a threat to be used as means for terrorist attacks.


Ricin

Is a naturally occurring carbohydrate-binding lectin protein produced by castor oil plant growing in Eastern Africa, India, Southeastern Mediterranean basin area, and in tropical regions. Ricin may also be manufactured from the waste products when processing castor beans. Ricin has a globular structure with two toxin chains, chain A and chain B, which both need to be present for the cytotoxic affect. Ricin kills cells by inhibiting protein synthesis. Chain B penetrates to the cell whereas the disulfide bond joining chain A to chain B lectin has an affinity to bind to cell surface carbohydrates, (see, e.g. Friedman and Rasooly, 2013, Toxins (Basel); 5(4): 743-775). Ricin is highly toxic to humans with median lethal dose (LD50) of 22 micrograms per kilogram of body weight. The exposure to Racin may be by inhaling, ingestion or by injection. The symptoms are dependent of the method of exposure. When inhaled, ricing causes severe inflammation of the lungs, causing would has symptoms including coughing, difficulty breathing, muscle ache and nausea. When ingested, ricin induces internal bleeding of the stomach and intestines leading to pain, vomiting and bloody diarrhea, and eventual failure of the kidneys, liver and spleen. When injected, ricin induces failure of the muscles and lymph nodes, and eventually failure of the liver, kidney and spleen. There is no known treatment for Ricin poisoning.


Unintentional poisoning by Ricin is uncommon. However, Ricin is a potential biological and chemical warfare agent creating a need for treatment and prevention therapies for ricin poisoning. Antibodies targeting ricin have been developed, as described e.g. in International publication WO2015100409, the contents of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by ricin.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Ricin related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 14 (SEQ ID NO: 3549-3568).



Bacillus anthracis



Bacillus anthracis is a Gram-positive, rod-shaped bacterium causing anthrax disease (see, e.g. Spencer, 2003, J Clin Pathol.; 56(3): 182-187, and references therein). Most animals, especially herbivores, are susceptible to infection of Bacillus anthracis. Anthrax may be infected via respiratory exposure, skin contact or eating contaminated food, in most cases meat. Inhaled anthrax causes flu-like symptoms, pneumonia and severe respiratory collapse. Gastrointestinal anthrax causes severe diarrhea, acute inflammation of the intestinal tract, and vomiting of blood. Skin exposure to the bacteria will lead to boil-like skin lesions forming an ulcer with black center. Typically, infection to humans occurs by eating contaminated meat or while handling infected animals or their product, such as skin, wool or meat. Bacillus anthracis is a potential biological warfare agent. In 2001, weeks following the September 11 terrorist attacks, letters containing Bacillus anthracis were mailed to news media offices and two U.S. Senators resulting in death of five people and infected many more.


Anthrax may be treated with antibiotics, such as penicillin and amoxicillin, and may be prevented by vaccines, developed both for humans and animals. However, due to increased threat of biological warfare and terrorism, improved methods of treatment are in demand. Anthrax may also be treated by antibody therapy. For example. Raxibacumab (developed by Cambridge Antibody Technology and Human Genome Sciences) is an antibody for the prophylaxis and treatment of inhaled anthrax.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Bacillus anthracis.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Bacillus anthracis related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 15 (SEQ ID NO: 3569-3813).


Shiga Toxin and Shiga-Like Toxin

Shiga toxin, including two major types Stx1 and Stx2, is a toxin produced by Shigella dysenteriae, a rod-shaped bacteria belonging to bacterial genus Shigella. Shiga toxin inhibits protein synthesis within cells. The toxin enters cell via a marcopinosome and inhibits the protein synthesis by cleaving a specific nucleobase RNA of the 60S subunit of ribosome. Shiga-like toxins 1 and 2 are structurally similar to Stx1 and Stx2 and are produced by enterohemorrhagic strains of Escherichia coli (EHEC) strains. (see, e.g. Friedman and Rasooly, Toxins (Basel). 2013 April; 5(4): 743-775) EHEC type 0157 is the most common pathogen causing E. Coli outbreaks in the US. Stx2 is considered to be orders of magnitude more toxic that Stx1. The severity of Shiga toxin foodborne illnesses range from mild diarrhea to a life-threatening complication known as hemolytic uremic syndrome (HUS). HUS is a disease associated with hemolytic anemia, acute kidney failure and low platelet count. Cattle is the major source or infection to humans, but the disease may be spread by birds or pigs. Shiga infection is typically obtained from contaminated food or drink, such as meat, unpasteurized milk, or contaminated water, or by contact with cattle Shiga toxin and Shiga-like toxins considered to be potential chemical and biological warfare agents.


As of today, there is no prevention therapy or specific treatment for Shiga and Shiga-like toxins. Recent developments have been made in antibody therapy of Shiga toxin induced HUS. For example, SHIGAMAB® (developed by Bellus Health Inc.) is a monoclonal antibody for treatment of Shiga toxin induced HUS.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Shigella dysenteriae.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Shigella dysenteriae related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 17 (SEQ ID NO: 3844-3914).


Botulinum Toxins

Botulinum toxins are neurotoxins produced by Clostridium bacteria and they cause a disease called botulism which is characterized by weakness, problems in vision, tiredness, and problems with speech, followed by weakness of the arms, chest muscles and legs. Botulism may be fatal. There are seven different botulinum neurotoxins with a four-domain structure varying in antigenic properties and interactions with intracellular targets. L-chain enters the cytosol, cleaves the synaptosomal protein and blocks neurotransmitter release resulting in peripheral neuromuscular blockade and flaccid paralysis in humans. (see, e.g. Friedman and Rasooly. Toxins (Basel) 2013 April; 5(4): 743-775) Botulinum neurotoxins are highly dangerous to humans, serotype A having a median lethal dose (LD50) of 0.8 micrograms for a human of 70 kg weight. The bacteria is common in soil and water and may produce the botulinum toxins when exposed to low oxygen levels and certain temperatures. Outbreaks of foodborne botulism occur occasionally. Most susceptible to contamination by botulinum are baked products, fresh mussels, canned fruit and vegetables. Infant botulism occurs when the toxins are produced and released by bacteria in the infant's intestines. Botulism may also occur in wounds where the bacteria in the absence of oxygen produces and releases the toxins. Wound botulism is most common in cases where contaminated needles are used for injection. Botulinum toxins are potential biological and chemical warfare agents.


As of today, there is no prevention therapy for botulism. Botulism may be treated with antitoxins that block the circulation of toxins in the blood and prevent worsening of the disease. However, the antitoxins are expensive and not easily available. In cases of wound botulism, the area infected may be removed surgically. Additionally, good supportive care therapy is applied There remains a need for therapies to prevent and treat botulism. Antibodies targeting botulinum toxins are developed, as described e.g. in US Patent publication US20130058962, and International publication WO2015100409, the contents of each of which are herein incorporated by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by botulinum toxins.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat botulinum toxin related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 16 (SEQ ID NO: 3814-3843).


Therapeutic Applications: Neglected Tropical Diseases (NTDs)

AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat infectious disease. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Tables 10-13 (SEQ ID NO: 3327-3548).


Neglected Tropical diseases (NTDs) are a diverse category of communicable diseases present in tropical and subtropical environments. NTDs affect more than one billion people in about 150 countries. NTDs are a significant public health problem costing the involved developing economies billions of dollars annually. The diseases affect mostly the populations with inadequate sanitation, and those in contact with infectious vectors, domestic animals and livestock. In May 2013, the 66th WHO Assembly announced resolution WHA66.12 to integrate measures and plan investments to improve the wellbeing of populations affected by NTDs. NTDs include Buruli ulcer, Chagas disease, Dengue and Chikungunya, Dracunculiasis (guinea-worm disease). Echinococcosis, Endemic treponematoses (Yaws), Foodborne trematodiases, Human African trypanosomiasis (sleeping sickness), Leishmaniasis, Leprosy (Hansen disease), Lymphatic filariasis, Onchocerciasis (river blindness), Rabies, Schistosomiasis. Soil-transmitted helminthiases, Taeniasis/Cysticercosis and Trachoma.


Chikungunya Virus

Chikungunya virus is an arbovirus belonging to the Togoviridae family. The genome is a single-strand RNA molecule encoding four non-structural and three structural glycoproteins (C, E1, E2) (see, e.g. Caglioti et al., 2013, New Microbiol.; 36(3):211-27, and references therein). Chikungunya fever is a mosquito-borne disease caused by chikungunya virus. The symptoms include a fever lasting 2-7 days, rash and flu-like symptoms accompanied by a joint pain that may last for weeks, months or even years. The disease may be dangerous for the elderly and individuals with chronic medical problems. Chikungunya virus is spread by Aedes albopictus and Aedes aegypti. Outbreaks of chikungunya fever have occurred in Africa, Asia, Europe and Indian and Pacific Oceans, and more recently in islands in the Caribbean. As an example, according to the WHO, an outbreak of 1.9 million cases in India, Indonesia, Maldives, Myanmar and Thailand since 2005 has been reported. More recently, as of April 2015 more than million cases have reported in Caribbean Islands. Latin American countries and the United States.


As of today, there is no specific treatment or vaccination for chikungunya fever. The disease is typically treated with supportive care therapy, as well as anti-inflammatory drugs and medicines to relieve the symptoms. Research and development on vaccinations has been done but none has been approved for commercial use so far Antibodies for detection and treatment of Chikungunya have been developed. E.g. fully human antibodies binding to an epitope located in an antigenic site of the chikungunya virus E1 and E2 envelope proteins were in US Patent Publication US20130189279, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by chikungunya virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat chikungunya virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 13 (SEQ ID NO: 3543-3548).


Dengue virus


Dengue virus belongs to the family of Flaviviridae, genus of Flavivirus. It is an enveloped, positive strand RNA virus containing two integral membrane proteins envelope (E) and premembrane (prM) Dengue virus is closely related to e.g. Yellow fever. West Nile virus and St. Louis and Japanese encephalitis viruses. There are five serotypes of the virus that can cause dengue fever, which is a mosquito-borne tropical disease. Neutralizing antibodies target the protein E as it binds to the cellular receptors and mediates the viral entry into cells Infection with a serotype may produce a lifelong immunity to that serotype but no long-term immunity against other serotypes, (see e.g., Wahala and de Silva, 2011, Viruses.; 3(12): 2374-2395, and references therein). In fact, an infection by a second serotype may lead to a more severe form of disease, due to the complexity of the antibody respond and possible antibody dependent enhancement (ADE), which hypothesizes that weakly neutralizing antibodies from the first infection bind to the second serotype and enhance the infection. The symptoms of dengue fever are similar to flu, including fever, headache, muscle and joint pain and skin rash. The disease may also manifest as a potentially lethal complication called severe dengue, also known as dengue hemorrhagic fever. The disease may be dangerous to individuals with chronic diseases, such as diabetes or asthma, or children and the elderly. Dengue virus is spread by several mosquito species, out of which Aedes aegypti is the most common. Dengue may also be transmitted via infected blood or organ donation or by the vertical transmission route. According to the WHO, the estimated number of dengue infections annually could be as high as 390 million.


As of today, there is no specific treatment or prevention therapy for dengue fever. Antibodies targeting dengue virus have been developed. As an example, antibodies neutralizing four serotypes of dengue virus have been in US Patent publication US20150225474. US20150218255 and in U.S. Pat. No. 9,073,981, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by dengue virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Dengue virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 10 (SEQ ID NO: 3327-3449).



Trypanosoma cruzi



Trypanosoma cruzi (T. cruzi) is a species of parasitic euglenoid protozoan. T. cruzi causes Chagas disease, also known as American trypanosomiasis, which is a tropical parasitic disease. The symptoms of Chagas disease at the early stage include fever, swollen lymph nodes, headaches or local swelling at the site of bite. The chronic phase of Chagas starts after 8-12 weeks, which may be symptomless, or include enlargement of the ventricles of the heart, which may result in heart failure, or to an enlarged esophagus or enlarged colon. The severity of Chagas disease varies from almost unnoticeable to fatal. Chagas disease is spread by an insect vector triatomine bug. These bugs get infected with T. cruzi by feeding on the blood of an infected human or animals, and they spread it further by bites and ingestion of blood. The triatomine bug is also known as a “kissing bug” referring to its tendency to feed on people's faces T. cruzi may also be transmitted through blood transfusions or through breast milk. Chagas disease is present mainly in 12 Latin American countries, but has also spread to other continents. According The WHO, over 10 000 people die every year from Chagas disease, and 25 million people are in the risk of infection.


As of today, there is no specific prevention or treatment therapy for Chagas disease. The traditional therapies for Chagas have been involved with attempts to kill the parasite and treatment of the symptoms. For example, azole and nitro-derivative drugs have been used, but have not been successful in removal of the parasite fully. Other mechanisms to treat the disease have been under research. After infection in mammals, the parasite incorporates a charged carbohydrate (sialic acid) to survive to the chronic phase of the disease. To do so, the parasite scavenged sialic acid it from the host's sialoglycococonjugates, through a transglycosylation reaction catalyzed by an enzyme called trans-sialidase. The trans-sialidase has been identified as a potential target for drug development Buschiazzo et al. have reported an antibody inhibiting the T. cruzi trans-sialidase enzyme providing an antibody therapy mechanism for Chagas disease (see, Buschiazzo et al., 2012, PLoS Pathol. 8 (1), E1002474, and references therein).


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Chagas disease.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Chagas disease. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 12 (SEQ ID NO: 3541 and 3542).


Rabies Virus

Lyssaviruses are a genus of RNA viruses belonging to the family of Rhabdoviridae. Rabies virus is a neurotropic virus with cylindrical morphology After infection, rabies virus enters the peripheral nervous system, and further to central nervous system by retrograde axonal transport Rabies virus and Australian bat lyssavirus cause rabies Rabies affects humans and warm-blooded animals. The early stage symptoms include flu-like signs, but later the disease manifests as paralysis, anxiety, insomnia, abnormal behavior, hallucinations. Humans and animals infected may also experience hydrophobia, “fear of water”, which is considered a characteristic symptom of the disease Eventually the disease affects the central nervous system and brain, causing death. Humans are typically infected by being bitten, scratched or licked by an animal with the disease. Most commonly the infection is by dogs. Whereas efficient vaccination programs for animals have been able to reduce or even eliminate rabies in developing countries, the disease still affects poor population mainly in Africa and Asia. According to the WHO, post-bite treatment and vaccination is provided for 15 million people annually.


Rabies is a vaccine-preventable disease and especially systematic vaccination of dogs has been a cost-effective strategy for prevention of rabies. Post-exposure prophylaxis (PEP), the treatment of bite victims immediately after the exposure, includes local treatment of the wound, rabies vaccination and administration of rabies immunoglobulin. Though efficient vaccines for rabies have been developed, there remains a need for treatment/or management of rabies to prevent death after rabies virus has entered the central nervous system (see, e.g., Hicks et al., 2012, Clin Exp Immunol.; 169(3): 199-204, and references therein). The genome of rabies virus codes for five viral proteins. Out of the five. G protein, which is an external surface glycoprotein, forms protrusions that cover the outer surface of the virion envelope and is known to induce neutralizing antibodies. Also, nucleoprotein (N) molecules and the phospho-protein (NS) participate in immune responses. G protein has been the target of antibody developments. For example, therapeutic antibodies against rabies virus are taught in U.S. Pat. Nos. 7,071,319, 6,890,532, and 9,005,624, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by rabies virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat rabies virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 11 (SEQ ID NO: 3450-3540).


Therapeutic Applications: Tropical Diseases (TDs) and Vector-Borne Diseases

AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat infectious disease. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Tables 10-13 (SEQ ID NO: 3327-3548).



Plasmodium falciparum



Plasmodium falciparum (P. falciparum) is a protozoan parasite belonging to Plasmodium parasite family. P. falciparum is the main cause of malaria and responsible for nearly all death cases in malaria. P. falciparum is released to the human bloodstream through mosquito saliva. The parasite has a high rate of replication and capability to alter. P. falciparum, among other Plasmodium parasites, cause malaria, which is a mosquito borne tropical disease. The early stage symptoms include fever, headache, chills and vomiting. If not treated at the early stage, malaria can progress to a life-threatening condition involving multiple organs, resulting in skin yellowing, seizures and coma. In children, malaria may cause severe anemia, respiratory distress in relation to metabolic acidosis, and/or cerebral malaria. The disease is especially dangerous for young children, pregnant women and individuals without immunity to the disease, such as travelers from non-malaria areas. An infection may develop a partial immunity, allowing the following infections to be asymptomatic According to the WHO, about half of world's population are at risk of malaria. Sub-Saharan Africa carries the highest density of malaria. In 2015, 88% of malaria cases and 90% of malaria deaths was in Sub-Saharan Africa Malaria is spread by female Anopheles mosquitos and caused by 5 different parasite species, out of which Plasmodium falciparum is the most prevalent and responsible for the severe cases of malaria.


Despite tremendous efforts, there is no commercial vaccination for malaria. Traditional treatment for malaria consists of antimalarial medicine therapies, such as artemisinin-based combination therapies, which consists of artemisinin combined with antimalarial drugs such as amodiaquine, lumefantrine, mefloquine and sulfadoxine/pyrimethamine. However, drug resistance has been a serious challenge in malaria treatment. Currently resistance is common for all antimalarial medications apart from artemisinin combination therapy. The cost of artemisinin treatment is high and there remains a need for prevention therapies and improved treatment against malaria.


Due to the polymorphic nature and high replication rate of P. falciparum, tolerance to malaria is achieved only after years of repeated infections Antibodies for prevention and treatment of malaria have been developed. For example, antibodies against P. falciparum are taught in U.S. Pat. No. 7,811,569, in US Patent publication US20150197562 and in International Patent publication WO2014087007, the contents of each of which are incorporated herein by reference in their entirety. A need for mechanism to deliver constant, effective concentration of malaria antibody for a long period is still in need Studies by Deal et al, demonstrate results on vectored immunoprophylaxis delivery of malaria antibodies to mice (see. Deal et al. PNAS, 2014, 111(34), 12528-12532).


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by P. falciparum.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat P. falciparum related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 18 (SEQ ID NO: 3915-3971).


Ebola Virus

Genus of Ebola virus includes five viruses. Zaire, Reston, Sudan. Tai Forest and Bundibygvo Ebola viruses, is a negative-sense RNA virus belonging to the family of filoviridae. The West Africa outbreak has been associated with Zaire Ebola virus. The genome of Ebolavirus encodes seven genes. The glycoprotein GP gene encodes two distinct gene products: sGP which is a dimeric and secreted glycoprotein and less abundant GP, which is a trimeric-virion attached, membrane embedded envelope glycoprotein and responsible for the virus attachment, fusion and entry during infection. Ebola virus disease is a hemorrhagic fever disease caused. The early symptoms include fever, sore throat, muscular pain, followed by a diarrhea and rash. Eventually the disease will affect the liver and kidney function, and cause internal bleeding. The disease is highly fatal, as about 50% infected individuals die. The Ebola virus is transmitted by direct contact with the blood and body fluids and tissues of an infected person or an animal, most commonly a chimpanzee, gorilla, fruit bat, monkey, forest antelope and porcupine. The disease is also transmitted when handling dead bodies of infected animals or humans. Also, sexual transmittance of the disease has been suggested. The WHO has reported more than 28 000 infections and 11 000 deaths in Ebola virus disease outbreak in West Africa (2014-present), mainly affecting Guinea, Sierra Leone and Liberia.


As of today, there is no licensed treatment or prevention therapy proven to neutralize the virus. Typically. Ebola virus disease is treated with a good supportive care. A variety of blood, immunological and drug therapies are under investigation, as well as preventive vaccines undergoing evaluations. However, a demand for effective therapies for treatment and prevention of Ebola virus disease remain.


Viral surface of GP has been identified as a target for neutralizing antibodies. Antibodies targeting GP of Ebola virus have been taught, e.g. in International Patent publication WO2015127136 and Olal. D., et al., 2012. J. Virol. 86 (5), 2809-2816, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Ebola virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Ebola related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 19 (SEQ ID NO: 3972-4024).


Marburg Virus

Marburg virus belongs to the filoviridae family of viruses with coiled, toroid or branched structures with seven proteins. The structure of Marburg virus is similar to Ebola virus, however, the involved antigens are different. The filoviruses express a single glycoprotein on their surface. The glycoprotein is responsible for the infection, as it is involved in the attachment and entry of the viruses causing infection. Marburg virus disease is a hemorrhaging fever disease caused by Marburg virus. It is highly fatal disease and related to Ebola virus diseases. The early symptoms of the disease include severe headache and malaise. Severe hemorrhagic manifestations in later stages include bleeding from multiple sites. The Marburg virus is transmitted by direct contact with the blood and body fluids and tissues of infected persons or animals, most commonly fruit bats and monkeys. The disease is also transmitted when handling dead the bodies of infected animals or humans. Marburg virus disease is uncommon, but outbreaks typically have a high rate of fatality. According to the WHO, the death rate was as high 80% in outbreaks of 1998-2000 in Democratic Republic of Congo and 2005 in Angola.


As of today, there is no preventive or treatment therapy for Marburg virus disease. The current treatment methods include good supportive treatment. The surface glycoprotein has been a target for development of antibodies for Marburg disease vaccines and treatments. For example, International Patent publication WO02015127140, and US Patent publication US20140356354, the contents of which are incorporated herein by reference in their entirety, teach therapeutic antibodies that recognize glycoprotein of filoviruses for different strains of Marburg, as well as Ebola.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Marburg virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Marburg related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Tables 3-42 (SEQ ID NO: 2948-9220).


West Nile Virus

West Nile virus (WNV) is a positive-stranded RNA of the flavivirus genome and member of the Japanese encephalitis serocomplex of flaviviruses. (see Throsby, M. J. Virol. 80 (14), 6982-6992 (2006)). Two lineages of the virus have been identified. The genome of the virus encodes a single polyprotein producing three structural proteins, capsid C, precursor membrane prM and envelope E as well as seven nonstructural proteins. WNV causes mosquito-borne infections with a variety of manifestations. Tough about 80% of WNV infections are symptomless and not harmful, in certain cases, the disease may lead to fatal neurological diseases. Infection of MNV may lead to a West Nile fever, which causes flu-like symptoms accompanied by high fever, headache, chills, excessive sweating, fatigue, weakness, swollen lymph nodes, and joint pains Infection by MNV may also occur as cutaneous manifestations, including rashes that may include punctate erythematous, macular and popular eruptions. West Nile infections may also affect the central nervous system resulting in West Nile neuroinvasive diseases, including meningitis, encephalitis, meningoencephalitis and poliomyelitis-like syndrome. These neuroinvasive forms of NWV infections occur in only about 1% of infections, but they may be life-threatening. WNV is commonly found in Africa. Europe, the Middle East. North America and West Asia. WNV is typically transmitted to humans and other mammals by mosquitos and is maintained in nature in a cycle involving transmission between birds and mosquitoes WNV is carried by different types of mosquitos, dependent on geographical distribution. Transmission to humans may also occur from birds, horses or other humans.


As of today, there is no specific treatment or prevention therapy for MNV infections. Current methods of treatment include good supportive care. Due to severity of some of the manifestations, there remains a need for such therapies. Envelope E has been a target of most antibody related studies. Antibodies targeting M and the first non-structural protein have also been investigated. As an example. Thorsby et al, 2006, J. Virol. 80 (14), 6982-6992, the contents of which are incorporated herein by reference in their entirety, teaches antibodies binding to E and prM proteins. U.S. Pat. Nos. 8,663,950 and 7,527,973, the contents of each of which are incorporated herein by reference in their entirety, teach antibodies binding to E protein of WNV.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by West Nile virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat West Nile virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 20 (SEQ ID NO: 3333, 3359, 3393, 3418, 3442, 4025-4137).


Yellow Fever Virus

Yellow fever virus is an enveloped RNA virus belonging to the Flavivirus family Yellow fever, also known as Yellow Jack. Yellow Plague or Bronze John, is a mosquito-borne viral hemorrhagic disease. In most cases, the symptoms include fever, headache, chills, loss of appetite, nausea, and muscle pain. In some occasions, the disease progresses to a second stage which includes fever accompanied by abdominal pains, liver damage resulting in jaundice, kidney problems and/or bleeding. The disease is spread primarily by Aedes and Haemogogus type mosquitos. The disease is most typical in tropical environments. According to the WHO, there are 200 000 annual cases of yellow fever resulting in 30 000 deaths mainly in Africa and Latin America, 90% of cases occur in Africa.


Preventive live-attenuated vaccines for yellow fever are available. However, concern related to post-vaccine adverse events has decreased the popularity of the vaccines. The vaccination is not recommended to infants younger than 9 months, pregnant women and individuals with an immune deficiency. As of today, there is no specific treatment for yellow fever. Current methods for treatment involve with supportive care to treat dehydration, respiratory failure and fever There is a need for improved prevention and treatment therapies against yellow fever virus.


Envelope E glycoprotein of yellow fever virus has been identified as a potential target for antibody therapies. Neutralizing antibodies for yellow fever virus have been reported by Thibodeaux, B. A. et al, 2012, Antiviral Res. 94 (1), 1-8 and Daffis, S. et al., 2005, Virology, 337 (2), 262-272, the contents of each of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by yellow fever virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat yellow fever virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 20 (SEQ ID NO: 3333, 3359, 3393, 3418, 3442, 4025-4137)


Japanese Encephalitis Virus

Japanese encephalitis virus is an enveloped positive sense single-stranded RNA virus belonging to Flavivirus family and closely related to St. Louis encephalitis and West Nile virus. The virus causes Japanese encephalitis, also known as Japanese B encephalitis. In majority of cases, the disease is symptomless. However, in less than 1% of infections, the disease leads to a life-threatening encephalitis. The early stage symptoms include fever, headache and malaise. As the disease progresses into an acute encephalitis, the symptoms include neck rigidity, cachexia, hemiparesis, convulsions and fever, accompanied by lifelong neurological problems such as deafness, and/or mental retardation. The disease is transmitted to humans via mosquitos of the Culex species. The virus exists in a transmission cycle between mosquitos, pigs, and water birds. The disease affects 24 countries in the South-East Asia and Western Pacific. According to the WHO, an estimated 68 000 clinical cases are reported annually, with case-fatality rate as high as 30%. Major outbreaks of the disease occur every 2-15 years.


The disease may be prevented by a vaccination, most common vaccination being a live attenuated vaccine. In general, the vaccines initially show high effectiveness, but the protection decreases over time. As of today, there is no specific treatment for the disease. Current treatment therapies include good supportive care. There remains a need for longer lasting, improved prevention therapies, and treatment for Japanese encephalitis virus infections.


Antibodies for treatment of Japanese encephalitis have been developed. For example, Hsieh et al, teach antibodies that target cellular receptors and interrupts their function in flavivirus infections in US Patent publication US20080292644, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Japanese encephalitis virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Japanese encephalitis virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 20 (SEQ ID NO: 3333, 3359, 3393, 3418, 3442, 4025-4137).


St. Louis Encephalitis Virus


St. Louis encephalitis virus is a positive-stranded RNA virus and member of the Flavivirus family and closely related to Japanese encephalitis virus St Louis encephalitis is a mosquito-borne disease caused by the virus. In majority of cases, the disease is symptomless. However, in less than 1% of the cases, the disease may lead to encephalitis, which may be life-threatening, especially for the elderly. The early stage symptoms include fever, headache, dizziness, malaise and nausea. If the disease progresses to the central nervous system, symptoms include stiff neck, confusion, disorientation, dizziness, tremor and unsteadiness, and in severe cases coma or even death. St. Louis encephalitis virus is transmitted to humans through Culex mosquitos. The virus exists in a transmission cycle between mosquitos and birds. The disease mainly affects the USA, especially eastern and central states. The disease has also spread to Canada and Mexico.


As of today, there is no vaccine or specific treatment for St. Louis encephalitis. Current treatment therapies include good supportive care. There is a demand for preventive and treatment therapies for the disease. Neutralizing antibodies for St. Louis encephalitis virus have been reported in Thibodeaux, B. A. et al, 2012, Antiviral Res 94 (1), 1-8 and Daffis, S. et al., 2005, Virology 337 (2), 262-272, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by St. Louis encephalitis virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat St. Louis encephalitis virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 20 (SEQ ID NO: 3333, 3359, 3393, 3418, 3442, 4025-4137).


Therapeutic Application: Foodborne Illness and Gastroenteritis

AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat infectious disease. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Tables 3-9 (SEQ ID NO: 2948-3326).


Foodborne illnesses, also known as food poisoning, are a common and costly public health problem. The illnesses are typically transmitted by the fecal-oral-route. The transmission to humans is by consuming contaminated food or beverage More than 250 different foodborne diseases, mostly infections caused by viruses, bacteria, parasites or fungus, are identified by the CDC, CDC estimates that approximately 48 million individuals are affected by foodborne illnesses annually in the United States. Gastroenteritis is an inflammation of the gastrointestinal tract involving stomach and small intestine. Gastroenteritis is also caused by an infection caused by viruses, bacteria, parasites or fungus. The transmission to humans is by person-to-person contact, or by consuming contaminated food or beverage. Foodborne illnesses and gastroenteritis have similar symptoms including diarrhea, vomiting, abdominal pain, dehydration. In some cases, the diseases may require hospitalization or be fatal. Both illnesses are best prevented by proper hand hygiene, proper hygiene while preparing food, treatments to kill bacteria such as pasteurizing, cooking or heating food, and proper methods to store food.


Rotavirus

Rotavirus is a double-stranded RNA virus belonging to the family of Reoviridae. The rotavirus genome consists of 10 segments coding for a single protein, and segment 11 coding for two proteins. The virions are non-enveloped, triple-layered and icosahedral in structure (see, e.g. Aiyegbo et al., 2013, Plos One 8, 61101, and references therein). The virus is spread by the fecal-oral-route. Rotavirus is very common especially among infants and young children and spreads easily. Almost all children worldwide are infected with rotavirus by the age of 5, and the disease leads to death of half a million children annually. Rotavirus causes rotavirus gastroenteritis with symptoms including nausea, vomiting, diarrhea and fever. Rotavirus is associated with dehydration. The disease is milder in adults and more severe in young children, infants and the elderly. Though infection does not provide full immunity to the virus, the first infection is typically the most severe in symptoms.


As of today, there is no specific treatment rotavirus infections. Present treatment includes good supportive care including drinking of fluids to prevent dehydration. In severe cases, the rotavirus gastroenteritis requires hospital care e.g. treatment with intravenous fluids. Vaccines for prevention of the disease have been developed and CDC recommends rotavirus vaccination for infants as part of the routine vaccinations There remains a need for medical treatment therapies for the infection. Development has been done in the field of antibodies. E.g. Aiyegbo et al., in Plos One 8, 61101 (2013, teach antibodies targeting the intermediate capsid layer of VP6 of the triple-layered particle and Frenken et al, teach anti-rotavirus antibodies in U.S. Pat. No. 8,105,592, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by rotavirus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat rotavirus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 8 (SEQ ID NO: 3286-3310).


Norwalk Virus/Norovirus

Norwalk virus, also known as winter vomiting bug, is the only member of genus norovirus belonging to the family of Caliciviridae Norwalk virus is a single-stranded RNA with three open-reading frames that encode a polyprotein precursor to non-structural proteins, and two polypeptides of different sizes (see e.g. Jiang et al., 1993, Virology; 195(1):51-61, and references therein) Norwalk virus is spread by the fecal-oral-route Norwalk virus is extremely contagious and can be transmitted through contaminated food or drink, touching contaminated surfaces or objects or from a contact with an infected individual. The Norwalk virus causes an inflammation of stomach and/or intestines. The symptoms associated with the infection include stomach pain, nausea, vomiting and diarrhea. The disease can be dangerous, especially for your children or young adults. According to CDC, every year 19-21 million infections occur leading to 570-800 deaths in the US.


As of today, there is no vaccine or specific treatment for Norwalk virus associated gastroenteritis. Antibodies for prevention and treatment of Norwalk virus have been developed. For example, International Patent publication WO2014126921 and WO2014183052, the contents of each of which are incorporated herein by reference in their entirety, teach neutralizing antibodies binding to the polypeptides of Norwalk virus.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by Norwalk virus.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat Norwalk virus related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 7 (SEQ ID NO. 3238-3285).



Campylobacter jejuni



Campylobacter jejuni (C. jejuni) is an oxidase-positive, catalase-positive, nonfermentative Gram-negative bacteria with a helical shape. The C. jejuni inhabits in the intestinal tract of animals (e.g. poultry, cattle, pigs, sheep, ostriches and shellfish), and in pets (e.g. cats and dogs). The bacteria may be transmitted to humans foodborne, e.g, when eating contaminated food or drink, such as unpasteurized milk. According to the WHO, campylobacter is the most common cause of gastroenteritis worldwide C. jejuni causes campylobacteriosis infection. The typical symptoms include diarrhea with blood in the feces, abdominal pain, fever, headache, nausea and/or vomiting. The infection may be dangerous to young children, the elderly and individuals with immunodeficiency and is most abundant with malnourished children. C. jejuni infections have been associated with severe long-term complications such as Guillain-Barre Syndrome, inflammatory bowel disease and reactive arthritis (see, e.g., Platts-Mills and Kosek, 2014, Curr Opin Infect Dis; 27(5): 444-450, and references therein).


Typically, C. jejuni infection does not require specific treatment in addition to good supportive care. In more severe cases, in humans and in poultry, the infection has been treated with antibiotics such as fluoroquinoles and macrolides. However, spread of antibiotic-resistant strains is an increasing concern. The treatment with antibiotics is recommended in cases where the bacteria has invaded the intestinal mucosa cell and damaged the tissues, or to eliminate the carrier state. There remains a need for prevention therapies, as well as improved, non-antibiotic, therapies for treatment of the infection Antibodies targeting C. jejuni have been taught e.g. in International Patent publication WO2014063253, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by C. jejuni.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat C. jejuni related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 4 (SEQ ID NO: 3089-3098).



Clostridium difficile



Clostridium difficile bacteria (C. difficile) is a Gram-positive, anaerobic spore-forming bacteria belonging to the genus of Clostridium. C. difficile inhabits in the soil. C. difficile produces toxins, most commonly enterotoxin A and cytotoxin B. Toxins A and B both have a C-terminal receptor-binding domain containing repeating sequences, a central hydrophobic domain and N-terminal glucosyltranferase domain. The toxins bind to the intestinal epithelial cells leading to glucosylation of target Rho GTPases, disruption of the cytoskeleton and cell death. C. difficile toxins A and B are a common cause C. difficile associated diarrhea and Clostridium difficile colitis, which is an inflammation of the large intestine. Typical symptoms of the colitis include flu-like symptoms, bloating, diarrhea, and/or abdominal pain. The disease may lead to dehydration, kidney failure, bowel perforation, toxic megacolon resulting in colon rupture. The elderly and individuals with a weakened immunity are more susceptible to severe and recurring infections which can be life-threatening. C. difficile is transmitted by the fecal-oral-route. Due to the ability to form heat-resistant spores, the bacteria is not killed by alcohol-based cleansers or routine surface cleaning. The bacteria may be cultured on almost any surface and survives in clinical environments, such as hospitals. C. difficile is one of the most common and severe healthcare-associated infections. According to CDC, an estimated about half a million infections occur in the United States annually. In 2011, 29, 000 deaths related to C. difficile were reported.


Currently C. difficile infections are treated with antibiotics such as vanconmycin and metronidazole. However, increasing an antibiotic-resistance to the bacteria is a concern. Especially in cases of recurring infections, antibiotic treatments have an incomplete response and they disrupt the normal colonic flora. There remains a need for prevention and improved treatment therapies for the infection. Antibodies targeting C. difficile have been developed. For example, actoxumab and bezlotoxumab (developed by Medarex Inc and the University of Massachusetts Medical School) are human monoclonal antibodies targeting C. difficile toxin A and toxin B, respectively. The antibodies may be administered as a combination for the prevention of recurring C. difficile infection.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by C. difficile.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat C. difficile related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 3 (SEQ ID NO: 2948-3088).



Entamoeba histolytica



Entamoeba histolytica (E. histolytica) is an anaerobic one-celled parasite protozoan belonging to the genus of Entamoeba. The active stage of the protozoan exists only in the host and in fresh feces. Cysts survive outside the host in water, soil and food in moist conditions. E. histolytica causes an infection called amebiasis, also known as ameobiasis or entamoebiasis. In majority of cases, amebiasis is symptomless. In 10-20% of individuals infected have symptoms that include loose feces, stomach pain and cramping. The severe more form of amebiasis called amebic dysentery is associated with stomach pain, blood stools and fever. In rare cases. E. histolytica invades the liver, forms an abscess and may spread to other parts of the body, such as the lungs or brain. The transmission to humans is mostly via the fecal-oral-route. The disease is typically caused by ingestion of mature cysts in contaminated food, water or via hands. The disease may also be transmitted in close person-to-person contact, e.g. sexual contact. E. histolytica infections are most common in tropical areas and especially in poor sanitary conditions. It is estimated that 50 million cases of amebiasis occur annually, leading to 100, 000 deaths.


As of today, there are no preventive vaccines for E. histolytica infections, though cellular immunity is important for the prevention of liver invasive amebiasis. Amebiasis is typically treated with amebicides, which are medicines targeting E. histolytica at specific parts of the body, e.g. the intestine tissue or liver. Optionally, the treatment may involve one or more antibiotics, as well as steroids. However, increasing antibiotic-resistance of E. histolytica is a concern. There remains a need for prevention therapy as well as for improved treatments. Antibodies targeting E. histolytica are taught in, e.g., 2009, Infect. Immun.; 77(1): 549-556, and Tachibana et al., 1999, Clin Diagn Lab Immunol.; 6(3):383-7, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by E. histolytica.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat E. histolytica related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 9 (SEQ ID NO: 3311-3326).



Helicobacter pylori



Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped microaerophilic bacterium. H. pylori infection is typically asymptomatic and is suggested to be transmitted through the fecal-oral route or oral-oral route. According to CDC, two-thirds of the world's population is infected with H. pylori. The infection may cause chronic active, chronic, persistent, and atrophic gastritis, duodenal and gastric ulcers and is associated with cancer. CDC reposts 25 million Americans suffering from an ulcer during their lifetime. Typical symptoms associated with ulcer are gnawing or burning pain in the epigastrium, especially between meals. Additional symptoms include nausea, vomiting, loss of appetite, internal bleeding leading to anemia and fatigue.


Typical treatment for H. pylori infection involves antibiotics. Increasing antibiotic resistance and patient noncompliance are major challenges associated with the antibiotic treatment. There remains a need for improved, non-antibiotic, treatment and prevention therapies targeting H. pylori. Antibodies targeting H. pylori infection have been developed. For example. Boren et al, teach antibodies targeting the BAbA antigen expressed by H. pylori in US patent U.S. Pat. No. 8,025,880, the contents of which are incorporated herein by reference in their entirety.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by H. pylori.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat H. pylori related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 5 (SEQ ID NO: 3099-3196).


Enterotoxin B

Enterotoxin B is a toxin produced by certain strains of Gram-positive bacteria Staphylococcus aureus and is a common cause for food poisoning. Staphylococcus species thrive and produce toxins in unrefrigerated meats, dairy, and bakery products. The symptoms associated with enterotoxin B infection are severe diarrhea, nausea and intestinal cramping. The toxin may remain active in the human body after the bacteria has been killed. Enterotoxin B is a so-called superantigen. Superantigens are toxins that may activate T cells by forming a bridge between a MHC II on antigen presenting cells (APCs) and the T cell receptors (TCR). Due to binding of enterotoxin B, the T cells release large amount of cytokines leading to an inflammation and gastroenteritis. Though enterotoxin B infection is typically not life threatening, enterotoxin B has been identified as a potential chemical and biological warfare agent.


As of today, there is no specific prevention or treatment for enterotoxin B infection. Antibodies that neutralize enterotoxin B have been investigated, e.g. as described in U.S. Pat. No. 8,895,704.


In some embodiment, methods of the present invention may be used to prevent, manage and/or treat infections and complications caused by enterotoxin B.


AAV particles and methods of using the AAV particles described in the present invention may be used to prevent, manage and/or treat enterotoxin B related infections and/or conditions. As a non-limiting example, the AAV particles of the present invention comprise a nucleic acid sequence encoding at least one of the sequences described in Table 5 (SEQ ID NO: 3099-3196).


V. Kits and Devices
Kits

In one embodiment, the invention provides a variety of kits for conveniently and/or effectively carrying out methods of the present invention. Typically, kits will comprise sufficient amounts and/or numbers of components to allow a user to perform multiple treatments of a subject(s) and/or to perform multiple experiments.


Any of the AAV particles of the present invention may be comprised in a kit. In some embodiments, kits may further include reagents and/or instructions for creating and/or synthesizing compounds and/or compositions of the present invention. In some embodiments, kits may also include one or more buffers. In some embodiments, kits of the invention may include components for making protein or nucleic acid arrays or libraries and thus, may include, for example, solid supports.


In some embodiments, kit components may be packaged either in aqueous media or in lyophilized form. The container means of the kits will generally include at least one vial, test tube, flask, bottle, syringe or other container means, into which a component may be placed, and preferably, suitably aliquoted. Where there is more than one kit component. (labeling reagent and label may be packaged together), kits may also generally contain second, third or other additional containers into which additional components may be separately placed. In some embodiments, kits may also comprise second container means for containing sterile, pharmaceutically acceptable buffers and/or other diluents. In some embodiments, various combinations of components may be comprised in one or more vial. Kits of the present invention may also typically include means for containing compounds and/or compositions of the present invention, e.g., proteins, nucleic acids, and any other reagent containers in close confinement for commercial sale. Such containers may include injection or blow-molded plastic containers into which desired vials are retained.


In some embodiments, kit components are provided in one and/or more liquid solutions. In some embodiments, liquid solutions are aqueous solutions, with sterile aqueous solutions being particularly preferred. In some embodiments, kit components may be provided as dried powder(s). When reagents and/or components are provided as dry powders, such powders may be reconstituted by the addition of suitable volumes of solvent. In some embodiments, it is envisioned that solvents may also be provided in another container means. In some embodiments, labeling dyes are provided as dried powders. In some embodiments, it is contemplated that 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 120, 130, 140, 150, 160, 170, 180, 190, 200, 300, 400, 500, 600, 700, 800, 900, 1000 micrograms or at least or at most those amounts of dried dye are provided in kits of the invention. In such embodiments, dye may then be resuspended in any suitable solvent, such as DMSO.


In some embodiments, kits may include instructions for employing kit components as well the use of any other reagent not included in the kit. Instructions may include variations that may be implemented.


Devices

In one embodiment, the AAV particles may delivered to a subject using a device to deliver the AAV particles and a head fixation assembly. The head fixation assembly may be, but is not limited to, any of the head fixation assemblies sold by MRI interventions. As a non-limiting example, the head fixation assembly may be any of the assemblies described in U.S. Pat. Nos. 8,099,150, 8,548,569 and 9,031,636 and International Patent Publication Nos. WO201108495 and WO2014014585, the contents of each of which are incorporated by reference in their entireties. A head fixation assembly may be used in combination with an MRI compatible drill such as, but not limited to, the MRI compatible drills described in International Patent Publication No. WO2013181008 and US Patent Publication No US20130325012, the contents of which are herein incorporated by reference in its entirety.


In one embodiment, the AAV particles may be delivered using a method, system and/or computer program for positioning apparatus to a target point on a subject to deliver the AAV particles. As a non-limiting example, the method, system and/or computer program may be the methods, systems and/or computer programs described in U.S. Pat. No. 8,340,743, the contents of which are herein incorporated by reference in its entirety. The method may include: determining a target point in the body and a reference point, wherein the target point and the reference point define a planned trajectory line (PTL) extending through each; determining a visualization plane, wherein the PTL intersects the visualization plane at a sighting point; mounting the guide device relative to the body to move with respect to the PTL, wherein the guide device does not intersect the visualization plane; determining a point of intersection (GPP) between the guide axis and the visualization plane; and aligning the GPP with the sighting point in the visualization plane.


In one embodiment, the AAV particles may be delivered using an MRI-guided device Non-limiting examples of MRI-guided devices are described in U.S. Pat. Nos. 9,055,884, 9,042,958, 8,886,288, 8,768,433, 8,396,532, 8,369,930, 8,374,677 and 8,175,677 and US Patent Application No. US20140024927 the contents of each of which are herein incorporated by reference in their entireties. As a non-limiting example, the MRI-guided device may be able to provide data in real time such as those described in U.S. Pat. Nos. 8,886,288 and 8,768,433, the contents of each of which is herein incorporated by reference in its entirety. As another non-limiting example, the MRI-guided device or system may be used with a targeting cannula such as the systems described in U.S. Pat. Nos. 8,175,677 and 8,374,677, the contents of each of which are herein incorporated by reference in their entireties. As yet another non-limiting example, the MRI-guided device includes a trajectory guide frame for guiding an interventional device as described, for example, in U.S. Pat. No. 9,055,884 and US Patent Application No. US20140024927, the contents of each of which are herein incorporated by reference in their entireties.


In one embodiment, the AAV particles may be delivered using an MRI-compatible tip assembly. Non-limiting examples of MRI-compatible tip assemblies are described in US Patent Publication No. US20140275980, the contents of which is herein incorporated by reference in its entirety.


In one embodiment, the AAV particles may be delivered using a cannula which is MRI-compatible. Non-limiting examples of MRI-compatible cannulas include those taught in International Patent Publication No. WO2011130107, the contents of which are herein incorporated by reference in its entirety.


In one embodiment, the AAV particles may be delivered using a catheter which is MRI-compatible. Non-limiting examples of MRI-compatible catheters include those taught in International Patent Publication No. WO02012116265, U.S. Pat. No. 8,825,133 and US Patent Publication No. US20140024909, the contents of each of which are herein incorporated by reference in their entireties.


In one embodiment, the AAV particles may be delivered using a device with an elongated tubular body and a diaphragm as described in US Patent Publication Nos US20140276582 and US20140276614, the contents of each of which are herein incorporated by reference in their entireties.


In one embodiment, the AAV particles may be delivered using an MRI compatible localization and/or guidance system such as, but not limited to, those described in US Patent Publication Nos. US20150223905 and US20150230871, the contents of each of which are herein incorporated by reference in their entireties. As a non-limiting example, the MRI compatible localization and/or guidance systems may comprise a mount adapted for fixation to a patient, a targeting cannula with a lumen configured to attach to the mount so as to be able to controllably translate in at least three dimensions, and an elongate probe configured to snugly advance via slide and retract in the targeting cannula lumen, the elongate probe comprising at least one of a stimulation or recording electrode.


In one embodiment, the AAV particles may be delivered to a subject using a trajectory frame as described in US Patent Publication Nos. US20150031982 and US20140066750 and International Patent Publication Nos. WO2015057807 and WO2014039481, the contents of each of which are herein incorporated by reference in their entireties.


In one embodiment, the AAV particles may be delivered to a subject using a gene gun.


VI. Definitions

At various places in the present specification, substituents of compounds of the present disclosure are disclosed in groups or in ranges. It is specifically intended that the present disclosure include each and every individual subcombination of the members of such groups and ranges.


About: As used herein, the term “about” means+/−10% of the recited value.


Adeno-associated virus. The term “adeno-associated virus” or “AAV” as used herein refers to members of the dependovirus genus comprising any particle, sequence, gene, protein, or component derived therefrom.


AAV Particle: As used herein, an “AAV particle” is a virus which comprises a viral genome with at least one payload region and at least one ITR region, AAV vectors of the present disclosure may be produced recombinantly and may be based on adeno-associated virus (AAV) parent or reference sequences, AAV particle may be derived from any serotype, described herein or known in the art, including combinations of serotypes (i.e., “pseudotyped” AAV) or from various genomes (e.g., single stranded or self-complementary). In addition, the AAV particle may be replication defective and/or targeted.


Activity: As used herein, the term “activity” refers to the condition in which things are happening or being done. Compositions of the invention may have activity and this activity may involve one or more biological events.


Administered in combination: As used herein, the term “administered in combination” or “combined administration” means that two or more agents are administered to a subject at the same time or within an interval such that there may be an overlap of an effect of each agent on the patient. In some embodiments, they are administered within about 60, 30, 15, 10, 5, or 1 minute of one another. In some embodiments, the administrations of the agents are spaced sufficiently closely together such that a combinatorial (e.g., a synergistic) effect is achieved.


Amelioration: As used herein, the term “amelioration” or “ameliorating” refers to a lessening of severity of at least one indicator of a condition or disease. For example, in the context of neurodegeneration disorder, amelioration includes the reduction of neuron loss.


Animal: As used herein, the term “animal” refers to any member of the animal kingdom. In some embodiments. “animal” refers to humans at any stage of development. In some embodiments, “animal” refers to non-human animals at any stage of development. In certain embodiments, the non-human animal is a mammal (e.g. a rodent, a mouse, a rat, a rabbit, a monkey, a dog, a cat, a sheep, cattle, a primate, or a pig). In some embodiments, animals include, but are not limited to, mammals, birds, reptiles, amphibians, fish, and worms. In some embodiments, the animal is a transgenic animal, genetically-engineered animal, or a clone.


Antibody: As used herein, the term “antibody” is referred to in the broadest sense and specifically covers various embodiments including, but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g. bispecific antibodies formed from at least two intact antibodies), and antibody fragments (e.g., diabodies) so long as they exhibit a desired biological activity (e.g., “functional”). Antibodies are primarily amino-acid based molecules but may also comprise one or more modifications (including, but not limited to the addition of sugar moieties, fluorescent moieties, chemical tags, etc.). Non-limiting examples of antibodies or fragments thereof include VH and VL domains, scFvs, Fab, Fab′, F(ab′)2, Fv fragment, diabodies, linear antibodies, single chain antibody molecules, multispecific antibodies, bispecific antibodies, intrabodies, monoclonal antibodies, polyclonal antibodies, humanized antibodies, codon-optimized antibodies, tandem scFv antibodies, bispecific T-cell engagers, mAb2 antibodies, chimeric antigen receptors (CAR), tetravalent bispecific antibodies, biosynthetic antibodies, native antibodies, miniaturized antibodies, unibodies, maxibodies, antibodies to senescent cells, antibodies to conformers, antibodies to disease specific epitopes or antibodies to innate defense molecules.


Antibody-based composition: As used herein, “antibody-based” or “antibody-derived” compositions are monomeric or multi-meric polypeptides which comprise at least one amino-acid region derived from a known or parental antibody sequence and at least one amino acid region derived from a non-antibody sequence, e.g., mammalian protein.


Approximately: As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).


Associated with: As used herein, the terms “associated with.” “conjugated.” “linked.” “attached.” and “tethered.” when used with respect to two or more moieties, means that the moieties are physically associated or connected with one another, either directly or via one or more additional moieties that serves as a linking agent, to form a structure that is sufficiently stable so that the moieties remain physically associated under the conditions in which the structure is used, e.g. physiological conditions. An “association” need not be strictly through direct covalent chemical bonding. It may also suggest ionic or hydrogen bonding or a hybridization based connectivity sufficiently stable such that the “associated” entities remain physically associated.


Bifunctional. As used herein, the term “bifunctional” refers to any substance, molecule or moiety which is capable of or maintains at least two functions. The functions may effect the same outcome or a different outcome. The structure that produces the function may be the same or different.


Biocompatible: As used herein, the term “biocompatible” means compatible with living cells, tissues, organs or systems posing little to no risk of injury, toxicity or rejection by the immune system.


Biodegradable: As used herein, the term “biodegradable” means capable of being broken down into innocuous products by the action of living things.


Biologically active: As used herein, the phrase “biologically active” refers to a characteristic of any substance that has activity in a biological system and/or organism. For instance, a substance that, when administered to an organism, has a biological effect on that organism, is considered to be biologically active. In particular embodiments, an AAV particle of the present invention may be considered biologically active if even a portion of the encoded payload is biologically active or mimics an activity considered biologically relevant.


Capsid: As used herein, the term “capsid” refers to the protein shell of a virus particle.


Chimeric antigen receptor (C4R). As used herein, the term “chimeric antigen receptor” or “CAR” refers to an artificial chimeric protein comprising at least one antigen specific targeting region (ASTR), a transmembrane domain and an intracellular signaling domain, wherein the antigen specific targeting region comprises a full-length antibody or a fragment thereof. As a non-limiting example the ASTR of a CAR may be any of the antibodies listed in Tables 3-42, antibody-based compositions or fragments thereof. Any molecule that is capable of binding a target antigen with high affinity can be used in the ASTR of a CAR, The CAR may optionally have an extracellular spacer domain and/or a co-stimulatory domain. A CAR may also be used to generate a cytotoxic cell carrying the CAR.


Complementary and substantially complementary: As used herein, the term “complementary” refers to the ability of polynucleotides to form base pairs with one another. Base pairs are typically formed by hydrogen bonds between nucleotide units in antiparallel polynucleotide strands. Complementary polynucleotide strands can form base pair in the Watson-Crick manner (e.g., A to T, A to U, C to G), or in any other manner that allows for the formation of duplexes. As persons skilled in the art are aware, when using RNA as opposed to DNA, uracil rather than thy mine is the base that is considered to be complementary to adenosine However, when a U is denoted in the context of the present invention, the ability to substitute a T is implied, unless otherwise stated. Perfect complementarity or 100% complementarity refers to the situation in which each nucleotide unit of one polynucleotide strand can form hydrogen bond with a nucleotide unit of a second polynucleotide strand. Less than perfect complementarity refers to the situation in which some, but not all, nucleotide units of two strands can form hydrogen bond with each other. For example, for two 20-mers, if only two base pairs on each strand can form hydrogen bond with each other, the polynucleotide strands exhibit 10% complementarity. In the same example, if 18 base pairs on each strand can form hydrogen bonds with each other, the polynucleotide strands exhibit 90% complementarity. As used herein, the term “substantially complementary” means that the siRNA has a sequence (e.g., in the antisense strand) which is sufficient to bind the desired target mRNA, and to trigger the RNA silencing of the target mRNA.


Compound Compounds of the present disclosure include all of the isotopes of the atoms occurring in the intermediate or final compounds. “Isotopes” refers to atoms having the same atomic number but different mass numbers resulting from a different number of neutrons in the nuclei. For example, isotopes of hydrogen include tritium and deuterium.


The compounds and salts of the present disclosure can be prepared in combination with solvent or water molecules to form solvates and hydrates by routine methods.


Comprehensive Positional Evolution (CPE™): As used herein, the term “comprehensive positional evolution” refers to an antibody evolution technology that allows for mapping of the effects of amino acid changes at every position along an antibody variable domain's sequence. This comprehensive mutagenesis technology can be used to enhance one or more antibody properties or characteristics.


Comprehensive Protein Synthesis (CPS™): As used herein, the term “comprehensive protein synthesis” refers to a combinatorial protein synthesis technology that can be used to optimize antibody properties or characteristics by combining the best properties into a new, high-performance antibody.


Conditionally active: As used herein, the term “conditionally active” refers to a mutant or variant of a wild-type polypeptide, wherein the mutant or variant is more or less active at physiological conditions than the parent polypeptide. Further, the conditionally active polypeptide may have increased or decreased activity at aberrant conditions as compared to the parent polypeptide. A conditionally active polypeptide may be reversibly or irreversibly inactivated at normal physiological conditions or aberrant conditions.


Conserved: As used herein, the term “conserved” refers to nucleotides or amino acid residues of a polynucleotide sequence or polypeptide sequence, respectively, that are those that occur unaltered in the same position of two or more sequences being compared. Nucleotides or amino acids that are relatively conserved are those that are conserved amongst more related sequences than nucleotides or amino acids appearing elsewhere in the sequences.


In some embodiments, two or more sequences are said to be “completely conserved” if they are 100% identical to one another. In some embodiments, two or more sequences are said to be “highly conserved” if they are at least 70% identical, at least 80% identical, at least 90% identical, or at least 95% identical to one another. In some embodiments, two or more sequences are said to be “highly conserved” if they are about 70% identical, about 80% identical, about 90% identical, about 95%, about 98%, or about 99% identical to one another. In some embodiments, two or more sequences are said to be “conserved” if they are at least 30% identical, at least 40% identical, at least 50% identical, at least 60% identical, at least 70% identical, at least 80% identical, at least 90% identical, or at least 95% identical to one another. In some embodiments, two or more sequences are said to be “conserved” if they are about 30% identical, about 40% identical, about 50% identical, about 60% identical, about 70% identical, about 80% identical, about 90% identical, about 95% identical, about 98% identical, or about 99% identical to one another. Conservation of sequence may apply to the entire length of a polynucleotide or polypeptide or may apply to a portion, region or feature thereof.


Control Elements: As used herein, “control elements”, “regulatory control elements” or “regulatory sequences” refers to promoter regions, polyadenylation signals, transcription termination sequences, upstream regulatory domains, origins of replication, internal ribosome entry sites (“IRES”), enhancers, and the like, which provide for the replication, transcription and translation of a coding sequence in a recipient cell. Not all of these control elements need always be present as long as the selected coding sequence is capable of being replicated, transcribed and/or translated in an appropriate host cell.


Controlled Release: As used herein, the term “controlled release” refers to a pharmaceutical composition or compound release profile that conforms to a particular pattern of release to effect a therapeutic outcome.


Cytostatic: As used herein, “cytostatic” refers to inhibiting, reducing, suppressing the growth, division, or multiplication of a cell (e.g., a mammalian cell (e.g., a human cell)), bacterium, virus, fungus, protozoan, parasite, prion, or a combination thereof.


Cytotoxic: As used herein, “cytotoxic” refers to killing or causing injurious, toxic, or deadly effect on a cell (e.g., a mammalian cell (e.g., a human cell)), bacterium, virus, fungus, protozoan, parasite, prion, or a combination thereof.


Delivery: As used herein, “delivery” refers to the act or manner of delivering an AAV particle, a compound, substance, entity, moiety, cargo or pay load.


Delivery Agent: As used herein, “delivery agent” refers to any substance which facilitates, at least in part, the in vivo delivery of an AAV particle to targeted cells.


Destabilized: As used herein, the term “destable,” “destabilize,” or “destabilizing region” means a region or molecule that is less stable than a starting, wild-type or native form of the same region or molecule.


Detectable label: As used herein. “detectable label” refers to one or more markers, signals, or moieties which are attached, incorporated or associated with another entity that is readily detected by methods known in the art including radiography, fluorescence, chermluminescence, enzymatic activity, absorbance and the like. Detectable labels include radioisotopes, fluorophores, chromophores, enzymes, dyes, metal ions, ligands such as biotin, avidin, streptavidin and haptens, quantum dots, and the like. Detectable labels may be located at any position in the peptides or proteins disclosed herein. They may be within the amino acids, the peptides, or proteins, or located at the N- or C-termini.


Digest: As used herein, the term “digest” means to break apart into smaller pieces or components. When referring to polypeptides or proteins, digestion results in the production of peptides.


Distal: As used herein, the term “distal” means situated away from the center or away from a point or region of interest.


Dosing regimen: As used herein, a “dosing regimen” is a schedule of administration or physician determined regimen of treatment, prophylaxis, or palliative care.


Encapsulate: As used herein, the term “encapsulate” means to enclose, surround or encase.


Engineered: As used herein, embodiments of the invention are “engineered” when they are designed to have a feature or property, whether structural or chemical, that varies from a starting point, wild type or native molecule.


Effective Amount: As used herein, the term “effective amount” of an agent is that amount sufficient to effect beneficial or desired results, for example, clinical results, and, as such, an “effective amount” depends upon the context in which it is being applied. For example, in the context of administering an agent that treats cancer, an effective amount of an agent is, for example, an amount sufficient to achieve treatment, as defined herein, of cancer, as compared to the response obtained without administration of the agent.


Epitope: As used herein, an “epitope” refers to a surface or region on a molecule that is capable of interacting with a biomolecule. For example, a protein may contain one or more amino acids, e.g., an epitope, which interacts with an antibody, e.g., a biomolecule. In some embodiments, when referring to a protein or protein module, an epitope may comprise a linear stretch of amino acids or a three-dimensional structure formed by folded amino acid chains.


EvoMap™: As used herein, an EvoMap™ refers to a map of a polypeptide, wherein detailed informatics are presented about the effects of single amino acid mutations within the length of the polypeptide and their influence on the properties and characteristics of that polypeptide.


Expression: As used herein, “expression” of a nucleic acid sequence refers to one or more of the following events: (1) production of an RNA template from a DNA sequence (e.g., by transcription); (2) processing of an RNA transcript (e.g. by splicing, editing, 5′ cap formation, and/or 3′ end processing), (3) translation of an RNA into a polypeptide or protein, and (4) post-translational modification of a polypeptide or protein.


Feature: As used herein, a “feature” refers to a characteristic, a property, or a distinctive element.


Formulation: As used herein, a “formulation” includes at least one AAV particle and a delivery agent.


Fragment: A “fragment,” as used herein, refers to a portion. For example, fragments of proteins may comprise polypeptides obtained by digesting full-length protein isolated from cultured cells.


Functional: As used herein, a “functional” biological molecule is a biological molecule in a form in which it exhibits a property and/or activity by which it is characterized.


Gene expression: The term “gene expression” refers to the process by which a nucleic acid sequence undergoes successful transcription and in most instances translation to produce a protein or peptide. For clarity, when reference is made to measurement of “gene expression”, this should be understood to mean that measurements may be of the nucleic acid product of transcription, e.g. RNA or mRNA or of the amino acid product of translation, e.g., polypeptides or peptides. Methods of measuring the amount or levels of RNA, mRNA, polypeptides and peptides are well known in the art.


Homology: As used herein, the term “homology” refers to the overall relatedness between polymeric molecules, e.g. between polynucleotide molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. In some embodiments, polymeric molecules are considered to be “homologous” to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical or similar. The term “homologous” necessarily refers to a comparison between at least two sequences (polynucleotide or polypeptide sequences). In accordance with the invention, two polynucleotide sequences are considered to be homologous if the polypeptides they encode are at least about 50%, 60%, 70%, 80%, 90%, 95%, or even 99% for at least one stretch of at least about 20 amino acids. In some embodiments, homologous polynucleotide sequences are characterized by the ability to encode a stretch of at least 4-5 uniquely specified amino acids. For polynucleotide sequences less than 60 nucleotides in length, homology is determined by the ability to encode a stretch of at least 4-5 uniquely specified amino acids. In accordance with the invention, two protein sequences are considered to be homologous if the proteins are at least about 50%, 60%, 70%, 80%, or 90% identical for at least one stretch of at least about 20 amino acids.


Heterologous Region: As used herein the term “heterologous region” refers to a region which would not be considered a homologous region.


Homologous Region: As used herein the term “homologous region” refers to a region which is similar in position, structure, evolution origin, character, form or function.


Identity: As used herein, the term “identity” refers to the overall relatedness between polymeric molecules, e.g., between polynucleotide molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. Calculation of the percent identity of two polynucleotide sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second nucleic acid sequences for optimal alignment and non-identical sequences can be disregarded for comparison purposes). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the length of the reference sequence. The nucleotides at corresponding nucleotide positions are then compared. When a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. For example, the percent identity between two nucleotide sequences can be determined using methods such as those described in Computational Molecular Biology, Lesk, A. M., ed. Oxford University Press, New York; 1988; Biocomputing: Informatics and Genome Projects, Smith, D. W, ed., Academic Press, New York, 1993; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; Computer Analysis of Sequence Data, Part I. Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press. New York, 1991; each of which is incorporated herein by reference. For example, the percent identity between two nucleotide sequences can be determined using the algorithm of Meyers and Miller (CABIOS, 1989, 4:11-17), which has been incorporated into the ALIGN program (version 2.0) using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The percent identity between two nucleotide sequences can, alternatively, be determined using the GAP program in the GCG software package using an NWSgapdna.CMP matrix. Methods commonly employed to determine percent identity between sequences include, but are not limited to those disclosed in Carillo, H., and Lipman, D., SIAM J Applied Math., 48:1073 (1988); incorporated herein by reference. Techniques for determining identity are codified in publicly available computer programs. Exemplary computer software to determine homology between two sequences include, but are not limited to, GCG program package, Devereux, J., et al., Nucleic Acids Research, 12(1), 387 (1984)). BLASTP. BLASTN, and FASTA Altschul, S. F. et al., J. Molec. Biol., 215, 403 (1990)).


Inhibit expression of a gene: As used herein, the phrase “inhibit expression of a gene” means to cause a reduction in the amount of an expression product of the gene. The expression product can be an RNA transcribed from the gene (e.g., an mRNA) or a polypeptide translated from an mRNA transcribed from the gene. Typically, a reduction in the level of an mRNA results in a reduction in the level of a polypeptide translated therefrom. The level of expression may be determined using standard techniques for measuring mRNA or protein.


In vitro: As used herein, the term “in vitro” refers to events that occur in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, in a Petri dish, etc., rather than within an organism (e.g., animal, plant, or microbe).


In vivo: As used herein, the term “in vivo” refers to events that occur within an organism (e.g., animal, plant, or microbe or cell or tissue thereof).


Isolated: As used herein, the term “isolated” refers to a substance or entity that has been separated from at least some of the components with which it was associated (whether in nature or in an experimental setting) Isolated substances may have varying levels of purity in reference to the substances from which they have been associated. Isolated substances and/or entities may be separated from at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more of the other components with which they were initially associated. In some embodiments, isolated agents are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. As used herein, a substance is “pure” if it is substantially free of other components.


Substantially isolated: By “substantially isolated” is meant that a substance is substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the substance or AAV particles of the present disclosure. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99%, by weight of the compound of the present disclosure, or salt thereof. Methods for isolating compounds and their salts are routine in the art.


Linker: As used herein “linker” refers to a molecule or group of molecules which connects two molecules, such as a VH chain and VL chain or an antibody. A linker may be a nucleic acid sequence connecting two nucleic acid sequences encoding two different polypeptides. The linker may or may not be translated. The linker may be a cleavable linker.


MicroRNA (miRNA) binding site: As used herein, a microRNA (miRNA) binding site represents a nucleotide location or region of a nucleic acid transcript to which at least the “seed” region of a miRNA binds.


Modified: As used herein “modified” refers to a changed state or structure of a molecule of the invention. Molecules may be modified in many ways including chemically, structurally, and functionally.


Naturally Occurring: As used herein. “naturally occurring” or “wild-type” means existing in nature without artificial aid, or involvement of the hand of man.


Non-human vertebrate: As used herein, a “non-human vertebrate” includes all vertebrates except Homo sapiens, including wild and domesticated species. Examples of non-human vertebrates include, but are not limited to, mammals, such as alpaca, banteng, bison, camel, cat, cattle, deer, dog, donkey, gayal, goat, guinea pig, horse, llama, mule, pig, rabbit, reindeer, sheep water buffalo, and yak.


Off-target: As used herein, “off target” refers to any unintended effect on any one or more target, gene, or cellular transcript.


Open reading frame: As used herein, “open reading frame” or “ORF” refers to a sequence which does not contain a stop codon in a given reading frame.


Operably linked: As used herein, the phrase “operably linked” refers to a functional connection between two or more molecules, constructs, transcripts, entities, moieties or the like.


Particle: As used herein, a “particle” is a virus comprised of at least two components, a protein capsid and a polynucleotide sequence enclosed within the capsid.


Patient: As used herein. “patient” refers to a subject who may seek or be in need of treatment, requires treatment, is receiving treatment, will receive treatment, or a subject who is under care by a trained professional for a particular disease or condition.


Payload: As used herein, “payload” or “payload region” refers to one or more polynucleotides or polynucleotide regions encoded by or within a viral genome or an expression product of such polynucleotide or polynucleotide region, e.g., a transgene, a polynucleotide encoding a polypeptide or multi-polypeptide or a modulatory nucleic acid or regulatory nucleic acid.


Payload construct: As used herein, “payload construct” is one or more polynucleotide regions encoding or comprising a payload that is flanked on one or both sides by an inverted terminal repeat (ITR) sequence. The payload construct is a template that is replicated in a viral production cell to produce a viral genome.


Payload construct vector. As used herein, “payload construct vector” is a vector encoding or comprising a payload construct, and regulatory regions for replication and expression in bacterial cells.


Payload construct expression vector: As used herein, a “payload construct expression vector” is a vector encoding or comprising a payload construct and which further comprises one or more polynucleotide regions encoding or comprising components for viral expression in a viral replication cell.


Peptide: As used herein, “peptide” is less than or equal to 50 amino acids long, e.g., about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 amino acids long.


Pharmaceutically acceptable: The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.


Pharmaceutically acceptable excipients: The phrase “pharmaceutically acceptable excipient.” as used herein, refers any ingredient other than the compounds described herein (for example, a vehicle capable of suspending or dissolving the active compound) and having the properties of being substantially nontoxic and non-inflammatory in a patient. Excipients may include, for example: antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (colors), emollients, emulsifiers, fillers (diluents), film formers or coatings, flavors, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, sorbents, suspensing or dispersing agents, sweeteners, and waters of hydration. Exemplary excipients include, but are not limited to: butylated hydroxytoluene (BHT), calcium carbonate, calcium phosphate (dibasic), calcium stearate, croscarmellose, crosslinked poly vinyl pyrrolidone, citric acid, crospovidone, cysteine, ethylcellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methyl paraben, microcrystalline cellulose, polyethylene glycol, polyvinyl pyrrolidone, povidone, pregelatinized starch, propyl paraben, retinyl palmitate, shellac, silicon dioxide, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E, vitamin C, and xylitol.


Pharmaceutically acceptable salts: The present disclosure also includes pharmaceutically acceptable salts of the compounds described herein. As used herein. “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form (e.g., by reacting the free base group with a suitable organic acid). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines: alkali or organic salts of acidic residues such as carboxylic acids; and the like. Representative acid addition salts include acetate, acetic acid, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzene sulfonic acid, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two: generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences. 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418. Pharmaceutical Salts: Properties. Selection, and Use, P. H Stahl and C. G. Wermuth (eds.). Wiley-VCH, 2008, and Berge et al., Journal of Pharmaceutical Science, 66, 1-19 (1977), each of which is incorporated herein by reference in its entirety.


Pharmaceutically acceptable solvate: The term “pharmaceutically acceptable solvate,” as used herein, means a compound of the invention wherein molecules of a suitable solvent are incorporated in the crystal lattice. A suitable solvent is physiologically tolerable at the dosage administered. For example, solvates may be prepared by crystallization, recrystallization, or precipitation from a solution that includes organic solvents, water, or a mixture thereof. Examples of suitable solvents are ethanol, water (for example, mono-, di-, and tri-hydrates), N-methylpyrrolidinone (NMP), dimethyl sulfoxide (DMSO), N,N′-dimethylformamide (DMF), N,N′-dimethylacetamide (DMAC), 1,3-dimethyl-2-imidazolidinone (DMEU), 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPU), acetonitrile (ACN), propylene glycol, ethyl acetate, benzyl alcohol, 2-pyrrolidone, benzyl benzoate, and the like. When water is the solvent, the solvate is referred to as a “hydrate.”


Pharmacokinetic: As used herein, “pharmacokinetic” refers to any one or more properties of a molecule or compound as it relates to the determination of the fate of substances administered to a living organism. Pharmacokinetics is divided into several areas including the extent and rate of absorption, distribution, metabolism and excretion. This is commonly referred to as ADME where: (A) Absorption is the process of a substance entering the blood circulation; (D) Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body: (M) Metabolism (or Biotransformation) is the irreversible transformation of parent compounds into daughter metabolites; and (E) Excretion (or Elimination) refers to the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.


Physicochemical: As used herein, “physicochemical” means of or relating to a physical and/or chemical property.


Preventing: As used herein, the term “preventing” refers to partially or completely delaying onset of an infection, disease, disorder and/or condition; partially or completely delaying onset of one or more symptoms, features, or clinical manifestations of a particular infection, disease, disorder, and/or condition, partially or completely delaying onset of one or more symptoms, features, or manifestations of a particular infection, disease, disorder, and/or condition, partially or completely delaying progression from an infection, a particular disease, disorder and/or condition; and/or decreasing the risk of developing pathology associated with the infection, the disease, disorder, and/or condition.


Proliferate: As used herein, the term “proliferate” means to grow, expand or increase or cause to grow, expand or increase rapidly. “Proliferative” means having the ability to proliferate. “Anti-proliferative” means having properties counter to or inapposite to proliferative properties.


Prophylactic: As used herein, “prophylactic” refers to a therapeutic or course of action used to prevent the spread of disease.


Prophylaxis: As used herein, a “prophylaxis” refers to a measure taken to maintain health and prevent the spread of disease.


Protein of interest: As used herein, the terms “proteins of interest” or “desired proteins” include those provided herein and fragments, mutants, variants, and alterations thereof.


Proximal: As used herein, the term “proximal” means situated nearer to the center or to a point or region of interest.


Purified: As used herein, “purify,” “purified,” “purification” means to make substantially pure or clear from unwanted components, material defilement, admixture or imperfection. “Purified” refers to the state of being pure. “Purification” refers to the process of making pure.


Region: As used herein, the term “region” refers to a zone or general area. In some embodiments, when referring to a protein or protein module, a region may comprise a linear sequence of amino acids along the protein or protein module or may comprise a three-dimensional area, an epitope and/or a cluster of epitopes. In some embodiments, regions comprise terminal regions. As used herein, the term “terminal region” refers to regions located at the ends or termini of a given agent. When referring to proteins, terminal regions may comprise N- and/or C-termini. N-termini refer to the end of a protein comprising an amino acid with a free amino group. C-termini refer to the end of a protein comprising an amino acid with a free carboxyl group. N- and/or C-terminal regions may there for comprise the N- and/or C-termini as well as surrounding amino acids. In some embodiments. N- and/or C-terminal regions comprise from about 3 amino acid to about 30 amino acids, from about 5 amino acids to about 40 amino acids, from about 10 amino acids to about 50 amino acids, from about 20 amino acids to about 100 amino acids and/or at least 100 amino acids. In some embodiments, N-terminal regions may comprise any length of amino acids that includes the N-terminus, but does not include the C-terminus. In some embodiments. C-terminal regions may comprise any length of amino acids, which include the C-terminus, but do not comprise the N-terminus.


In some embodiments, when referring to a polynucleotide, a region may comprise a linear sequence of nucleic acids along the polynucleotide or may comprise a three-dimensional area, secondary structure, or tertiary structure. In some embodiments, regions comprise terminal regions. As used herein, the term “terminal region” refers to regions located at the ends or termini of a given agent. When referring to polynucleotides, terminal regions may comprise 5′ and 3′ termini, 5′ termini refer to the end of a polynucleotide comprising a nucleic acid with a free phosphate group, 3′ termini refer to the end of a polynucleotide comprising a nucleic acid with a free hydroxyl group, 5′ and 3′ regions may there for comprise the 5′ and 3′ termini as well as surrounding nucleic acids. In some embodiments, 5′ and 3′ terminal regions comprise from about 9 nucleic acids to about 90 nucleic acids, from about 15 nucleic acids to about 120 nucleic acids, from about 30 nucleic acids to about 150 nucleic acids, from about 60 nucleic acids to about 300 nucleic acids and/or at least 300 nucleic acids. In some embodiments, 5′ regions may comprise any length of nucleic acids that includes the 5′ terminus, but does not include the 3′ terminus. In some embodiments, 3′ regions may comprise any length of nucleic acids, which include the 3′ terminus, but does not comprise the 5′ terminus.


RNA or RN4 molecule: As used herein, the term “RNA” or “RNA molecule” or “ribonucleic acid molecule” refers to a polymer of ribonucleotides; the term “DNA” or “DNA molecule” or “deoxyribonucleic acid molecule” refers to a polymer of deoxyribonucleotides. DNA and RNA can be synthesized naturally, e.g., by DNA replication and transcription of DNA, respectively; or be chemically synthesized. DNA and RNA can be single-stranded (i.e., ssRNA or ssDNA, respectively) or multi-stranded (e.g., double stranded, i.e., dsRNA and dsDNA, respectively). The term “mRNA” or “messenger RNA”, as used herein, refers to a single stranded RNA that encodes the amino acid sequence of one or more polypeptide chains.


Sample: As used herein, the term “sample” or “biological sample” refers to a subset of its tissues, cells or component parts (e.g. body fluids, including but not limited to blood, mucus, lymphatic fluid, synovial fluid, cerebrospinal fluid, saliva, amniotic fluid, amniotic cord blood, urine, vaginal fluid and semen). A sample further may include a homogenate, lysate or extract prepared from a whole organism or a subset of its tissues, cells or component parts, or a fraction or portion thereof, including but not limited to, for example, plasma, serum, spinal fluid, lymph fluid, the external sections of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, milk, blood cells, tumors, organs. A sample further refers to a medium, such as a nutrient broth or gel, which may contain cellular components, such as proteins or nucleic acid molecule.


Self-complementary viral particle: As used herein, a “self-complementary viral particle” is a particle comprised of at least two components, a protein capsid and a polynucleotide sequence encoding a self-complementary genome enclosed within the capsid.


Signal Sequences: As used herein, the phrase “signal sequences” refers to a sequence which can direct the transport or localization of a protein.


Single unit dose: As used herein, a “single unit dose” is a dose of any therapeutic administered in one dose/at one time/single route/single point of contact, i.e., single administration event. In some embodiments, a single unit dose is provided as a discrete dosage form (e.g., a tablet, capsule, patch, loaded syringe, vial, etc.).


Similarity: As used herein, the term “similarity” refers to the overall relatedness between polymeric molecules, e.g. between polynucleotide molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. Calculation of percent similarity of polymeric molecules to one another can be performed in the same manner as a calculation of percent identity, except that calculation of percent similarity takes into account conservative substitutions as is understood in the art.


Split dose: As used herein, a “split dose” is the division of single unit dose or total daily dose into two or more doses.


Stable: As used herein “stable” refers to a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and preferably capable of formulation into an efficacious therapeutic agent.


Stabilized: As used herein, the term “stabilize”, “stabilized,” “stabilized region” means to make or become stable.


Subject. As used herein, the term “subject” or “patient” refers to any organism to which a composition in accordance with the invention may be administered, e.g., for experimental, diagnostic, prophylactic, and/or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and humans) and/or plants.


Substantially: As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and/or proceed to completeness or achieve or avoid an absolute result. The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.


Substantially equal: As used herein as it relates to time differences between doses, the term means plus/minus 2%.


Substantially simultaneously: As used herein and as it relates to plurality of doses, the term means within 2 seconds.


Suffering from: An individual who is “suffering from” a disease, disorder, and/or condition has been diagnosed with or displays one or more symptoms of a disease, disorder, and/or condition.


Susceptible to: An individual who is “susceptible to” a disease, disorder, and/or condition has not been diagnosed with and/or may not exhibit symptoms of the disease, disorder, and/or condition but harbors a propensity to develop a disease or its symptoms. In some embodiments, an individual who is susceptible to a disease, disorder, and/or condition (for example, cancer) may be characterized by one or more of the following: (1) a genetic mutation associated with development of the disease, disorder, and/or condition: (2) a genetic polymorphism associated with development of the disease, disorder, and/or condition: (3) increased and/or decreased expression and/or activity of a protein and/or nucleic acid associated with the disease, disorder, and/or condition; (4) habits and/or lifestyles associated with development of the disease, disorder, and/or condition: (5) a family history of the disease, disorder, and/or condition; and (6) exposure to and/or infection with a microbe associated with development of the disease, disorder, and/or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and/or condition will develop the disease, disorder, and/or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and/or condition will not develop the disease, disorder, and/or condition.


Sustained release. As used herein, the term “sustained release” refers to a pharmaceutical composition or compound release profile that conforms to a release rate over a specific period of time.


Synthetic: The term “synthetic” means produced, prepared, and/or manufactured by the hand of man. Synthesis of polynucleotides or polypeptides or other molecules of the present invention may be chemical or enzymatic.


Targeting: As used herein, “targeting” means the process of design and selection of nucleic acid sequence that will hybridize to a target nucleic acid and induce a desired effect.


Targeted Cells: As used herein. “targeted cells” refers to any one or more cells of interest. The cells may be found in vitro, in vivo, in situ or in the tissue or organ of an organism. The organism may be an animal, preferably a mammal, more preferably a human and most preferably a patient.


Therapeutic Agent: The term “therapeutic agent” refers to any agent that, when administered to a subject, has a therapeutic, diagnostic, and/or prophylactic effect and/or elicits a desired biological and/or pharmacological effect.


Therapeutically effective amount: As used herein, the term “therapeutically effective amount” means an amount of an agent to be delivered (e.g., nucleic acid, drug, therapeutic agent, diagnostic agent, prophylactic agent, etc.) that is sufficient, when administered to a subject suffering from or susceptible to an infection, disease, disorder, and/or condition, to treat, improve symptoms of, diagnose, prevent, and/or delay the onset of the infection, disease, disorder, and/or condition. In some embodiments, a therapeutically effective amount is provided in a single dose. In some embodiments, a therapeutically effective amount is administered in a dosage regimen comprising a plurality of doses. Those skilled in the art will appreciate that in some embodiments, a unit dosage form may be considered to comprise a therapeutically effective amount of a particular agent or entity if it comprises an amount that is effective when administered as part of such a dosage regimen.


Therapeutically effective outcome: As used herein, the term “therapeutically effective outcome” means an outcome that is sufficient in a subject suffering from or susceptible to an infection, disease, disorder, and/or condition, to treat, improve symptoms of, diagnose, prevent, and/or delay the onset of the infection, disease, disorder, and/or condition.


Total daily dose: As used herein, a “total daily dose” is an amount given or prescribed in 24 hr period. It may be administered as a single unit dose.


Transfection: As used herein, the term “transfection” refers to methods to introduce exogenous nucleic acids into a cell. Methods of transfection include, but are not limited to, chemical methods, physical treatments and cationic lipids or mixtures.


Treating: As used herein, the term “treating” refers to partially or completely alleviating, ameliorating, improving, relieving, delaying onset of, inhibiting progression of, reducing severity of, and/or reducing incidence of one or more symptoms or features of a particular infection, disease, disorder, and/or condition. For example, “treating” cancer may refer to inhibiting survival, growth, and/or spread of a tumor Treatment may be administered to a subject who does not exhibit signs of a disease, disorder, and/or condition and/or to a subject who exhibits only early signs of a disease, disorder, and/or condition for the purpose of decreasing the risk of developing pathology associated with the disease, disorder, and/or condition.


Unmodified: As used herein, “unmodified” refers to any substance, compound or molecule prior to being changed in any way Unmodified may, but does not always, refer to the wild type or native form of a biomolecule. Molecules may undergo a series of modifications whereby each modified molecule may serve as the “unmodified” starting molecule for a subsequent modification.


Vector: As used herein, a “vector” is any molecule or moiety which transports, transduces or otherwise acts as a carrier of a heterologous molecule. Vectors of the present invention may be produced recombinantly and may be based on and/or may comprise adeno-associated virus (AAV) parent or reference sequence Such parent or reference AAV sequences may serve as an original, second, third or subsequent sequence for engineering vectors. In non-limiting examples, such parent or reference AAV sequences may comprise any one or more of the following sequences: a polynucleotide sequence encoding a polypeptide or multi-polypeptide, which sequence may be wild-type or modified from wild-type and which sequence may encode full-length or partial sequence of a protein, protein domain, or one or more subunits of a protein; a polynucleotide comprising a modulatory or regulatory nucleic acid which sequence may be wild-type or modified from wild-type; and a transgene that may or may not be modified from wild-type sequence. These AAV sequences may serve as either the “donor” sequence of one or more codons (at the nucleic acid level) or amino acids (at the polypeptide level) or “acceptor” sequences of one or more codons (at the nucleic acid level) or amino acids (at the polypeptide level).


Viral genome: As used herein, a “viral genome” or “vector genome” is a polynucleotide comprising at least one inverted terminal repeat (ITR) and at least one encoded payload. A viral genome encodes at least one copy of the payload.


Described herein are compositions, methods, processes, kits and devices for the design, preparation, manufacture and/or formulation of AAV particles. In some embodiments, payloads, such as but not limited to AAV polynucleotides, may be encoded by payload constructs or contained within plasmids or vectors or recombinant adeno-associated viruses (AAVs).


The details of one or more embodiments of the invention are set forth in the accompanying description below. Although any materials and methods similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred materials and methods are now described. Other features, objects and advantages of the invention will be apparent from the description. In the description, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the case of conflict, the present description will control.


The present invention is further illustrated by the following non-limiting examples.


VII. EXAMPLES
Example 1. Production and Purification of AAV Particles

AAV particles described herein may be produced using methods known in the art, such as, for example, triple transfection or baculovirus mediated virus production. Any suitable permissive or packaging cell known in the art may be employed to produce the vectors Mammalian cells are often preferred. Also preferred are trans-complementing packaging cell lines that provide functions deleted from a replication-defective helper virus, e.g., 293 cells or other E1a trans-complementing cells.


The gene cassette may contain some or all of the parvovirus (e.g., AAV) cap and rep genes. Preferably, however, some or all of the cap and rep functions are provided in trans by introducing a packaging vector(s) encoding the capsid and/or Rep proteins into the cell. Most preferably, the gene cassette does not encode the capsid or Rep proteins. Alternatively, a packaging cell line is used that is stably transformed to express the cap and/or rep genes


Recombinant AAV virus particles are, in some cases, produced and purified from culture supernatants according to the procedure as described in US20160032254, the contents of which are incorporated by reference Production may also involve methods known in the art including those using 293T cell, sf9 insect cells, triple transfection or any suitable production method.


In some cases, 293 cells are transfected with CaPO4 with plasmids required for production of AAV, i.e., AAV2 rep, an adenoviral helper construct and a ITR flanked transgene cassette. The AAV2 rep plasmid also contains the cap sequence of the particular virus being studied. Twenty-four hours after transfection, which occurs in serum containing DMEM, the medium is replaced with fresh medium with or without serum. Three (3) days after transfection, a sample is taken from the culture medium of the 293 adherent cells. Subsequently cells are scraped and transferred into a receptacle. After centrifugation to remove cellular pellet, a second sample is taken from the supernatant after scraping. Next cell lysis is achieved by three consecutive freeze-thaw cycles (−80 C. to 37 C.). Cellular debris is removed and sample 3 is taken from the medium. The samples are quantified for AAV particles by DNase resistant genome titration by Taqman™ PCR, The total production yield from such a transfection is equal to the particle concentration from sample 3.


AAV vector titers are measured according to genome copy number (genome particles per milliliter). Genome particle concentrations are based on Taqman® PCR of the vector DNA as previously reported (Clark et al. (1999) Hum. Gene Ther., 10:1031-1039; Veldwijk et al. (2002) Mol. Ther., 6:272-278).


Example 2. Tissue Specific Expression

To evaluate the expression of various encoded antibody payloads in tissues, a series of AAV particles carrying the encoded antibody sequences driven by a panel of ubiquitous and tissue-specific promoters are made. These particles are administered to the specific tissue, e.g., intramuscularly, via an appropriate route, e.g., a single injection in the gastrocnemius muscle and expression is monitored to determine the relative expression potential of the payload as well as of each promoter in this target tissue. Measurement of antibody production is performed using standard techniques, for example by ELISA.


In some cases, the cytomegalovirus immediate early promoter (CMV), chimeric chicken-beta-actin (CAG), and ubiquitin C (UBC), CBA, H1 promoters provide robust expression.


Example 3. Generation of Antibodies
Antibody Production by Hybridoma Technology

Host animals (e.g. mice, rabbits, goats, and llamas) are immunized by an injection with an antigenic protein to elicit lymphocytes that specifically bind to the antigen Lymphocytes are collected and fused with immortalized cell lines to generate hybridomas. Hybridomas are cultured in a suitable culture medium that is enriched with appropriate selection agents to promote growth.


Antibodies produced by the cultured hybridomas are subjected to analysis to determine binding specificity of the antibodies for the target antigen Once antibodies with desirable characteristics are identified, corresponding hybridomas are subcloned through limiting dilution procedures and grown by standard methods. Antibodies produced by these cells are isolated and purified using standard immunoglobulin purification procedures


Recombinant Antibody Production

Recombinant antibodies are produced using heavy and light chain variable region cDNA sequences selected from hybridomas or from other sources. Sequences encoding antibody variable domains expressed by hybridomas are determined by extracting RNA molecules from antibody-producing hybridoma cells and producing cDNA by reverse transcriptase polymerase chain reaction (PCR). PCR is used to amplify cDNA using primers specific for heavy and light chain sequences. PCR products are then subcloned into plasmids for sequence analysis. Antibodies are produced by insertion of resulting variable domain sequences into expression vectors.


Recombinant antibodies are also produced using phage display technology. Target antigens are screened, in vitro, using phage display libraries having millions to billions of phage particles expressing unique single chain variable fragments (scFvs) on their viral coat. Precipitated phage particles are analyzed and sequences encoding expressed scFvs are determined. Sequences encoding antibody variable domains and/or CDRs are inserted into expression vectors for antibody production.


Recombinant antibodies are further produced using yeast surface display technology, wherein antibody variable domain sequences are expressed on the cell surface of Saccharomyces cerevisae. Recombinant antibodies are developed by displaying the antibody fragment of interest as a fusion to e.g. Aga2p protein on the surface of the yeast, where the protein interacts with proteins and small molecules in a solution, scFvs with affinity towards desired receptors are isolated from the yeast surface using magnetic separation and flow cytometry. Several cycles of yeast surface display and isolation will be done to attain scFvs with desired properties through directed evolution.


Example 4. Optimization of the Encoded Antibody

To design an optimal framework for the expression of an antibody, the heavy and light chains of several antibodies separated by an F2A self-processing peptide sequence are cloned into a mammalian expression vector under the control of the CMV promoter. 293T cells or any suitable cell line transfected with these vectors exhibit secretion of human IgG into the culture supernatant that is then detected by ELISA.


To increase expression, the antibody chains and/or the processing peptide are codon optimized for mammalian expression. In some instances, a furin cleavage site at the N-terminus is inserted for better processing.


To improve secretion of the antibody, the endogenous signal sequences are replaced with a sequence which may or may not be codon optimized, derived from any gene. In some cases, the human growth hormone signal sequence is used. Any of the heavy, light or both chains may be driven by any signal sequence, whether the same or different. Antibody expression is confirmed using standard immunohistochemical techniques, including ELISA


Example 5. Vectored Antibodies

Viral genomes are designed for AAV delivery of antibodies to cells. The viral genome comprises a payload region and at least one inverted terminal repeat (ITR) region. The payload region may optionally encode regulatory elements e.g., a promoter region, an intronic region, or a polyadenylation sequence. The payload region comprises a sequence encoding one or more polypeptides selected from the group consisting of those listed in Table 3 An exemplary payload region comprises a sequence encoding an antibody heavy chain, a region encoding an antibody light chain and a region encoding a linker connecting the heavy and light chain sequences or polypeptides before further processing. A promoter is selected to target the desired tissue or for desired regulation of expression, or both. The promoter may be selected from human EF1α, CMV, CBA, and its derivative CAG, GUSB, UBC, or any other promoter known to one with skill in the art, or combinations thereof. The 5′ and 3′ ITRs may or may not be of the same serotype as the capsid of the AAV particle.


Payload regions may optionally encode a linker between light and heavy antibody chain sequences or polypeptides. Sequence encoding linkers are derived from an internal ribosome entry site (IRES; SEQ ID NO: 899), foot and mouth disease virus 2A (F2A, SEQ ID NO: 900), porcine teschovirus-1 virus 2A (P2A; SEQ ID NO:901), a furin cleavage site (F: SEQ ID NO: 902), or a 5xG4S (SEQ ID NO: 9221 encoded by SEQ ID NO: 903) linker sequence. In various payload regions, the order of heavy and light chains is alternated with respect to 5′ to 3′ direction. Payloads are further designed to encode protein signal sequences (to aid in protein processing, localization, and/or secretion) as well as an untranslated poly A tail.


Each viral genome is then incorporated into an AAV cloning vector to create payload expression vectors.


The payload expression vectors are expressed in e.g. Expi 293 cells. The supernatants are collected and expressed antibodies are purified using protein A/G beads. Supernatants are diluted with a loading buffer and applied to a column prepared with A/C beads. Unbound proteins are washed through with loading buffer Elution buffer is added to the column, fractions collected, and fractions containing proteins of interest are identified with absorption spectroscopy technique, pooled together, and neutralized. Western blotting techniques are used to identify payload regions producing the antibody proteins of interest Purified antibodies are then tested for their affinity to their specific target by e.g. ELISA essay technique and antibodies with the highest affinity are identified and selected.


Finally, the rAAVs are produced using, for example, HEK293T cells. The cells are transfected simultaneously with the viral genome of the present invention, a viral genome encoding helper proteins and a viral genome encoding replication and capsid proteins.


Example 6. In Vivo Expression and Efficacy of Antibody Payloads

To determine the efficacy or comparative expression of encoded antibodies, dose-dependent expression is determined at a series of time points. Samples from mice treated with AAV particles encoding antibodies or luciferase at various levels are examined for expression using standard techniques such as nucleic acid analyses for RNA levels, protein analyses for antibody levels and compared to the expression of the luciferase control.


Example 7. Treatment of Infectious Disease

AAV particles of the current invention encoding an antibody are administered to a patient who has been diagnosed with an infectious disease, disorder or condition. The purpose of the treatment may be aimed to manage the disease, prevent or slow the progression of the disease, treat the symptoms associated with the disease and/or cure the disease.


The AAV particles may be administered through an intramuscular injection to the skeletal muscle. The administration may include one or more injections over a period of time. The level and distribution of AAV particles and antibody expression is monitored by standard diagnostic techniques known in the art. Such diagnostic techniques include e.g. (e.g. from blood, urine, or saliva), cerebrospinal fluid (CSF) testing, or any other testing useful for monitoring antibody levels in the body.


Additionally, the progression of the disease and the health of the patient is monitored by standard diagnostic techniques known in the art. Such techniques may include diagnostic imaging (e.g. X-ray, MRA scans, Ultrasound scans, PET scans. Nuclear scans, mammography), biopsy, laboratory tests (e.g. from blood, urine, or saliva), cerebrospinal fluid (CSF) testing, vital signs, clinical tests (cognitive, motor or reflex tests) and other relevant techniques. Treatment with the AAV particles may results in cure of the non-infectious disease, slowing down or stabilizing the progression of the disease, or have no effect on the progression of the disease. Additionally, the treatment may reduce severity of one or more symptoms associated with the disease, eliminate one or more symptoms associated with the disease or have no effect on the symptoms.


Example 8. Treatment of HIV or AIDS

AAV particles of the current invention encoding an antibody are administered to a patient who has been diagnosed with HIV or AIDS. The purpose of the treatment may be aimed to manage the disease, prevent or slow the progression of the disease, treat the symptoms associated with the disease and/or cure the disease.


The AAV particles may be administered through an intramuscular injection to the skeletal muscle. The administration may include one or more injections over a period of time. The level and distribution of AAV particles and antibody expression is monitored by standard diagnostic techniques known in the art. Such diagnostic techniques include e.g. (e.g. from blood, urine, or saliva), cerebrospinal fluid (CSF) testing, or any other testing useful for monitoring antibody levels in the body.


Additionally, the progression of the disease and the health of the patient is monitored by standard diagnostic techniques known in the art. Such techniques may include diagnostic imaging (e.g. X-ray, MRA scans, Ultrasound scans, PET scans. Nuclear scans, mammography), biopsy, laboratory tests (e.g. from blood, urine, or saliva), cerebrospinal fluid (CSF) testing, vital signs, clinical tests (cognitive, motor or reflex tests) and other relevant techniques. Treatment with the AAV particles may results in cure of the non-infectious disease, slowing down or stabilizing the progression of the disease, or have no effect on the progression of the disease. Additionally, the treatment may reduce severity of one or more symptoms associated with the disease, eliminate one or more symptoms associated with the disease or have no effect on the symptoms.


VIII. Equivalents and Scope

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments in accordance with the invention described herein. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the appended claims.


In the claims, articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or the entire group members are present in, employed in, or otherwise relevant to a given product or process.


It is also noted that the term “comprising” is intended to be open and permits but does not require the inclusion of additional elements or steps. When the term “comprising” is used herein, the term “consisting of” is thus also encompassed and disclosed.


Where ranges are given, endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.


In addition, it is to be understood that any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Since such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the compositions of the invention (e.g., any antibiotic, therapeutic or active ingredient; any method of production; any method of use: etc.) can be excluded from any one or more claims, for any reason, whether or not related to the existence of prior art.


It is to be understood that the words which have been used are words of description rather than limitation, and that changes may be made within the purview of the appended claims without departing from the true scope and spirit of the invention in its broader aspects.


While the present invention has been described at some length and with some particularity with respect to the several described embodiments, it is not intended that it should be limited to any such particulars or embodiments or any particular embodiment, but it is to be construed with reference to the appended claims so as to provide the broadest possible interpretation of such claims in view of the prior art and, therefore, to effectively encompass the intended scope of the invention.

Claims
  • 1. An AAV particle comprising a capsid and a viral genome, said viral genome comprising at least one inverted terminal repeat (ITR) region and a payload region, said payload region comprising a regulatory sequence operably linked to at least a first nucleic acid segment, said first nucleic acid segment encoding one or more polypeptides selected from the group consisting of any member given in Tables 3-42 and fragments thereof.
  • 2. The AAV particle of claim 1, wherein the capsid is selected from the group of serotypes consisting of Table 1.
  • 3. The AAV particle of claim 2, wherein the regulatory sequence comprises a promoter.
  • 4. The AAV particle of claim 3, wherein the promoter is selected from the group consisting of human elongation factor 1α-subunit (EF1α), cytomegalovirus (CMV) immediate-early enhancer and/or promoter, chicken β-actin (CBA) and its derivative CAG, β glucuronidase (GUSB), or ubiquitin C (UBC). Tissue-specific expression elements can be used to restrict expression to certain cell types such as, but not limited to, muscle specific promoters, B cell promoters, monocyte promoters, leukocyte promoters, macrophage promoters, pancreatic acinar cell promoters, endothelials cell promoters, lung tissue promoters, astrocyte promoters, or nervous system promoters which can be used to restrict expression to neurons, astrocytes, or oligodendrocytes.
  • 5. The AAV particle of claim 1, wherein the viral genome is single stranded.
  • 6. The AAV particle of claim 1, wherein the viral genome is self-complementary.
  • 7. The AAV particle of claim 1, wherein at least one region of the viral genome is codon-optimized.
  • 8. The AAV particle of claim 7, wherein the first nucleic acid segment is codon-optimized.
  • 9. The AAV particle of any of claims 1-8, wherein the first nucleic acid segment encodes one or more polypeptides selected from the group consisting of an antibody heavy chain, an antibody light chain, a linker, and combinations thereof.
  • 10. The AAV particle of claim 9, wherein any of the polypeptides encoded by first nucleic acid segment of the payload region is humanized.
  • 11. The AAV particle of claim 9, wherein the linker is selected from one or more of the members of the group given in Table 2.
  • 12. The AAV particle of claim 9, wherein the first nucleic acid segment encodes from 5′ to 3′, an antibody heavy chain, a linker, and an antibody light chain.
  • 13. The AAV particle of claim 9, wherein the first nucleic acid segment encodes from 5′ to 3′, an antibody light chain, a linker, and an antibody heavy chain.
  • 14. The AAV particle of claim 9, wherein the first nucleic acid segment encodes one or more antibody heavy chains.
  • 15. The AAV particle of claim 14, wherein the first nucleic acid segment encodes one or more antibody heavy chains selected from those listed in Tables 3-42.
  • 16. The AAV particle of claim 9, wherein the first nucleic acid segment encodes one or more antibody light chains.
  • 17. The AAV particle of claim 16, wherein the first nucleic acid segment encodes one or more antibody light chains selected from those listed in Tables 3-42.
  • 18. The AAV particle of claim 9, wherein the first nucleic acid segment encodes one or more antibody heavy chains and one or more antibody light chains and, optionally one or more linkers.
  • 19. The AAV particle of any of claims 9-18, wherein said linker is selected from the group consisting of Table 2 and combinations thereof.
  • 20. The AAV particle of claim 1, wherein the first nucleic acid segment encodes an antibody, having at least 95% identity to any of the sequences selected from the group consisting of SEQ ID NO: 2948-9220 (Tables 3-42).
  • 21. An AAV particle comprising a capsid and a viral genome, said viral genome comprising at least one inverted terminal repeat (ITR) region and a payload region comprising a regulatory sequence operably linked to at least a first nucleic acid segment, said first nucleic acid segment encoding a bispecific antibody derived from any of the sequences listed in Tables 3-42 or portions or fragments thereof.
  • 22. The AAV particle of claim 21, wherein the bispecific antibody comprises a light and a heavy chain selected from two different starting antibodies selected from the group consisting of SEQ ID NO: 2948-9220 (Tables 3-42).
  • 23. A method of producing a functional antibody in a subject in need thereof, comprising administering to said subject the AAV particle of any of claims 1-22.
  • 24. The method of claim 23, wherein the level or amount of the functional antibody in the target cell or tissue after administration to the subject is from about 0.001 ug/mL to 100 mg/mL.
  • 25. The method of claim 23, wherein the functional antibody is encoded by a single first nucleic acid segment of a viral genome within said AAV particle.
  • 26. The method of claim 23, wherein the functional antibody is encoded by two different viral genomes, said two different viral genomes packaged in separate capsids.
  • 27. A pharmaceutical composition comprising an AAV particle of any of the preceding claims in a pharmaceutically acceptable excipient.
  • 28. The pharmaceutical composition of claim 27, wherein the pharmaceutically acceptable excipient is saline.
  • 29. The pharmaceutical composition of claim 27, wherein the pharmaceutically acceptable excipient is 0.001% pluronic in saline.
  • 30. A method of expressing an antibody in a cell or tissue comprising administering the AAV particle of any of claims 1-29 via a delivery route selected from the group consisting of enteral (into the intestine), gastroenteral, epidural (into the dura mater), oral (by way of the mouth), transdermal, intracerebral (into the cerebrum), intracerebroventricular (into the cerebral ventricles), epicutaneous (application onto the skin), intradermal, (into the skin itself), subcutaneous (under the skin), nasal administration (through the nose), intravenous (into a vein), intravenous bolus, intravenous drip, intra-arterial (into an artery), intramuscular (into a muscle), intracardiac (into the heart), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intraparenchymal (into brain tissue), intraperitoneal, (infusion or injection into the peritoneum), intravesical infusion, intravitreal, (through the eye), intracavernous injection (into a pathologic cavity) intracavitary (into the base of the penis), intravaginal administration, intrauterine, extra-amniotic administration, transdermal (diffusion through the intact skin for systemic distribution), transmucosal (diffusion through a mucous membrane), transvaginal, insufflation (snorting), sublingual, sublabial, enema, eye drops (onto the conjunctiva), or in ear drops, auricular (in or by way of the ear), buccal (directed toward the cheek), conjunctival, cutaneous, dental (to a tooth or teeth), electro-osmosis, endocervical, endosinusial, endotracheal, extracorporeal, hemodialysis, infiltration, interstitial, intra-abdominal, intra-amniotic, intra-articular, intrabiliary, intrabronchial, intrabursal, intracartilaginous (within a cartilage), intracaudal (within the cauda equine), intracisternal (within the cisterna magna cerebellomedularis), intracorneal (within the cornea), dental intracornal, intracoronary (within the coronary arteries), intracorporus cavernosum (within the dilatable spaces of the corporus cavernosa of the penis), intradiscal (within a disc), intraductal (within a duct of a gland), intraduodenal (within the duodenum), intradural (within or beneath the dura), intraepidermal (to the epidermis), intraesophageal (to the esophagus), intragastric (within the stomach), intragingival (within the gingivae), intraileal (within the distal portion of the small intestine), intralesional (within or introduced directly to a localized lesion), intraluminal (within a lumen of a tube), intralymphatic (within the lymph), intramedullary (within the marrow cavity of a bone), intrameningeal (within the meninges), intramyocardial (within the myocardium), intraocular (within the eye), intraovarian (within the ovary), intrapericardial (within the pericardium), intrapleural (within the pleura), intraprostatic (within the prostate gland), intrapulmonary (within the lungs or its bronchi), intrasinal (within the nasal or periorbital sinuses), intraspinal (within the vertebral column), intrasynovial (within the synovial cavity of a joint), intratendinous (within a tendon), intratesticular (within the testicle), intrathecal (within the cerebrospinal fluid at any level of the cerebrospinal axis), intrathoracic (within the thorax), intratubular (within the tubules of an organ), intratumor (within a tumor), intratympanic (within the aurus media), intravascular (within a vessel or vessels), intraventricular (within a ventricle), iontophoresis (by means of electric current where ions of soluble salts migrate into the tissues of the body), irrigation (to bathe or flush open wounds or body cavities), laryngeal (directly upon the larynx), nasogastric (through the nose and into the stomach), occlusive dressing technique (topical route administration which is then covered by a dressing which occludes the area), ophthalmic (to the external eye), oropharyngeal (directly to the mouth and pharynx), parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, respiratory (within the respiratory tract by inhaling orally or nasally for local or systemic effect), retrobulbar (behind the pons or behind the eyeball), soft tissue, subarachnoid, subconjunctival, submucosal, topical, transplacental (through or across the placenta), transtracheal (through the wall of the trachea), transtympanic (across or through the tympanic cavity), ureteral (to the ureter), urethral (to the urethra), vaginal, caudal block, diagnostic, nerve block, biliary perfusion, cardiac perfusion, photopheresis and spinal.
  • 31. The method of claim 30, wherein the delivery route is intramuscular.
  • 32. The method of claim 31, wherein the intramuscular administration is to at least one limb.
  • 33. The method of claim 30, wherein the delivery route is intravascular.
  • 34. The method of claim 30, wherein the delivery route is intrathecal.
  • 35. The method of claim 30, wherein the delivery route is intracerebroventricular.
  • 36. The method of claim 30, wherein the delivery route is intraparenchymal.
  • 37. The method of claim 30, wherein the AAV particle is encapsulated in a nanoparticle.
  • 38. The method of claim 30, wherein the AAV particle is delivered by a device.
  • 39. The method of claim 38, wherein the device is a gene gun.
  • 40. A method of preventing a disease or disorder in a subject comprising administering to said subject the pharmaceutical composition of any of claims 27-29.
  • 41. The method of claim 40, wherein the administration is at a prophylactically effective dose.
  • 42. The method of claim 41, wherein the dose is from about 1 ug/mL to about 500 ug/mL of expressed polypeptide or 1=10e4 to 1×10e16 V G/mL from the pharmaceutical composition.
  • 43. The method of claim 42, wherein the pharmaceutical composition is administered once.
  • 44. The method of claim 42, wherein the pharmaceutical composition is administered more than once.
  • 45. The method of claim 42, wherein the pharmaceutical composition is administered daily, weekly, monthly or yearly.
  • 46. The method of claim 42, wherein the pharmaceutical composition is co-administered as part of a combination therapy.
  • 47. A method of treating a disease or disorder in a subject in need thereof comprising administering to said subject the pharmaceutical composition of any of claims 27-29.
  • 48. The method of claim 47, wherein said disease or disorder is selected from the group consisting of diseases caused by John Cunningham Virus (JCV), influenza, hepatitis A, hepatitis B, hepatitis D, hepatitis E, respiratory syncytial virus (RSV), herpes simplex virus 1, herpes simplex virus 2, hyman cytomegalovirus, Epstein-Barr virus, Varicella zoster virus, Coronavirus, Poxvirus, Enterovirus 71, rubella virus, human papilloma virus, Pseudomonas Aeruginosa, Streptococcus bacteria, Staphylococcus bacteria, Clostridium tetani, Bordetella, Mycobacterium, Francisella tularensis, Toxoplasma gondii, Candida yeast, ricin, Bacillus anthracis, shiga toxin, shiga-like toxin, botulinum toxins, chikungunya virus, dengue virus, trypasnosoma cruzi, rabies virus, Plasmodium falciparum, ebola virus, Marburg virus, West Nile virus, Yellow Fever virus, Japanese encephalitis virus, St. Louis encephalitis virus, rotavirus, Norwalk virus, Campylobacter jejuni, Clostridium difficile, Entamoeba histolytica, Helicobacter pyrolii, and Enterotoxin B.
  • 49. The AAV particle of claim 1, wherein the viral genome comprises 2 ITR regions.
  • 50. The AAV particle of claim 1, wherein the at least one ITR region is derived from the same parental serotype as the capsid.
  • 51. The AAV particle of claim 1, wherein the at least one ITR region is derived from a different serotype as the capsid.
  • 52. The AAV particle of claim 1, wherein the at least one ITR region is derived from AAV2.
  • 53. The AAV particle of claim 1, wherein the at least one ITR region is 100-150 nucleotides in length.
  • 54. The AAV particle of claim 1, wherein the at least one ITR region is 102 nucleotides in length.
  • 55. The AAV particle of claim 1, wherein the at least one ITR region is 140-142 nucleotides in length.
  • 56. The AAV particle of claim 1, wherein the at least one ITR region is 140 nucleotides in length.
  • 57. The AAV particle of claim 1, wherein the at least one ITR region is 141 nucleotides in length.
  • 58. The AAV particle of claim 1, wherein the at least one ITR region is 142 nucleotides in length.
  • 59. The AAV particle of claim 1, wherein the viral genome further comprises an intron or stuffer sequence.
  • 60. A method of producing an antibody in a subject comprising administering the AAV particle of claim 1 to said subject, with the proviso that the antibody is not a virus neutralizing antibody.
  • 61. A method of producing an antibody in a subject comprising administering the AAV particle of claim 1 to said subject, with the proviso that the antibody is not an HIV or HCV virus neutralizing antibody.
  • 62. The AAV particle of claim 1, wherein the payload region of the viral genome comprises a second nucleic acid segment, said second nucleic acid segment encoding an aptamer, siRNA, saRNA, ribozyme, microRNA, mRNA or combination thereof.
  • 63. The AAV particle of claim 62, wherein the second nucleic acid segment encodes an siRNA and said siRNA is designed to target the mRNA that encodes the target of the antibody encoded by the first nucleic acid segment.
  • 64. The AAV particle of claim 62, wherein the second nucleic acid segment encodes a microRNA and said microRNA is selected to target the mRNA that encodes the target of the antibody encoded by the first nucleic acid segment.
  • 65. The AAV particle of claim 62, wherein the second nucleic acid segment encodes an mRNA and said mRNA encodes one or more peptides inhibitors of the same target of the antibody encoded by the first nucleic acid segment.
  • 66. The AAV particle of claim 1 or 62, wherein the payload region of the viral genome comprises a third nucleic acid segment.
  • 67. The AAV particle of claim 66, wherein the third nucleic acid segment encodes a nuclear export signal.
  • 68. The AAV particle of claim 66, wherein the third nucleic acid segment encodes a polynucleotide or polypeptide which acts as a regulator of expression of the viral genome in which it is encoded.
  • 69. The AAV particle of claim 66, wherein the third nucleic acid segment encodes a polynucleotide or polypeptide which acts as a regulator of expression of the payload region of the viral genome in which it is encoded.
  • 70. The AAV particle of claim 66, wherein the third nucleic acid segment encodes a polynucleotide or polypeptide which acts as a regulator of expression of the first nucleic acid segment of the payload region of the viral genome in which it is encoded.
CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent Application No. 62/329,468, filed on Apr. 29, 2016, entitled Compositions for the Treatment of Disease, and U.S. Provisional Patent Application No. 62/329,479, filed on Apr. 29, 2016, entitled Compositions for the Treatment of Disease, the contents of each of which are herein incorporated by reference in their entireties.

PCT Information
Filing Document Filing Date Country Kind
PCT/US17/30061 4/28/2017 WO 00
Provisional Applications (2)
Number Date Country
62329468 Apr 2016 US
62329479 Apr 2016 US