ANTIBODIES AGAINST INTEGRIN ALPHA 11 BETA 1

Information

  • Patent Application
  • 20230050972
  • Publication Number
    20230050972
  • Date Filed
    December 18, 2020
    3 years ago
  • Date Published
    February 16, 2023
    a year ago
  • Inventors
  • Original Assignees
    • Momenta Pharmaceuticals, Inc. (Titusville, NJ, US)
Abstract
The present disclosure includes antibodies that specifically bind integrin alpha 11 beta 1 (α11β1), as well as methods of making and using such antibodies.
Description
BACKGROUND

Fibrosis is a process of scarring that manifests itself in many tissues in the body, typically as a result of inflammation or tissue damage. Increased production of extracellular matrix results in organ failure and, often, death. Diseases associated with fibrosis account for approximately 45% of all deaths in industrialized nations (Wynn, T. A., 2008, J Pathol. 214:199-210). One such disease is Systemic Sclerosis (SSc). SSc is a complex autoimmune disease with a chronic progressive course and high interpatient variability. It is characterized by inflammation, vascular dysfunction and fibrosis. Fibrosis of the skin and visceral organs results in irreversible scarring and ultimately organ failure, accounting for high mortality. There is currently no approved targeted therapy with disease-modifying potential.


SUMMARY

The present disclosure provides novel, function-blocking antibodies against type I collagen receptor integrin alpha 11 beta 1 (α11β1). The present disclosure also provides use of such antibodies to treat fibrotic disorders and/or cancers.


In one aspect, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-443. In another aspect, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising a CDR sequence encompassed within any one of SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. In another aspect, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 encompassed within any one of SEQ ID NO: 103-206, or 413-435. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 103-114, 207-311 or 436-442, and 312-435 or 443. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises a CDR sequence encompassed within any one of SEQ ID NO: 103-114, 207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises one or more CDR sequences encompassed within any one of SEQ ID NO: 103-114, or 413-434. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises CDR1, CDR2, and CDR3 encompassed within any one of SEQ ID NO: 103-114 or 413-434.


In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, is a monoclonal antibody, or antigen-binding fragment thereof. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, is a humanized antibody, or antigen-binding fragment thereof. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, reduces interaction of α11β1 with collagen in human α11β1-expressing cells. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, competes with an antibody, or antigen-binding fragment thereof, described herein.


In another aspect, the present disclosure provides a nucleic acid, comprising a nucleic acid sequence encoding an antibody, or antigen-binding fragment thereof, described herein. In some embodiments, a nucleic acid sequence comprises a sequence selected from a group consisting of SEQ ID NO: 1-102.


In another aspect, the present disclosure provides a vector comprising a nucleic acid described herein.


In another aspect, the present disclosure provides a host cell comprising a nucleic acid described herein or a vector described herein.


In another aspect, the present disclosure provides a method of producing an antibody, or antigen-binding fragment thereof, comprising culturing a host cell described herein under conditions suitable for expression of the antibody or antigen-binding fragment thereof.


In another aspect, the present disclosure provides a method of treating a subject having or at risk of a fibrotic disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of an antibody, or antigen-binding fragment thereof, described herein. In some embodiments, a fibrotic disorder is idiopathic pulmonary fibrosis (IPF), chronic kidney disease, diabetic cardiomyopathy, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD/NASH), Crohn's disease, ulcerative colitis, or systemic sclerosis.


In another aspect, the present disclosure provides a method of treating a subject having or at risk of cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of an antibody, or antigen-binding fragment thereof, described herein. In some embodiments, the cancer is one or more of head and neck squamous cell carcinomas, pancreatic ductal adenocarcinoma, non-small cell lung cancer, adrenocortical carcinoma, acute myeloid leukemia, bladder urothelial carcinoma, invasive breast carcinoma, cervical squamous cell carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, glioblastoma multiforme, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, mesothelioma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, sarcoma, stomach adenocarcinoma, testicular germ cell tumors, thymoma, thyroid carcinoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, uveal melanoma, kidney renal clear cell carcinoma, kidney chromophobe, and kidney renal papillary cell carcinoma.





BRIEF DESCRIPTION OF THE DRAWING

The present teachings described herein will be more fully understood from the following description of various illustrative embodiments, when read together with the accompanying drawings. It should be understood that the drawings described below are for illustration purposes only and are not intended to limit the scope of the present teachings in any way.



FIG. 1 shows representations of an integrin structure. The panels illustrate the structure of collagen-binding integrins and three different conformations integrins can exist in on the surface of a cell.



FIG. 2A shows a chart illustrating an ELISA analysis of binding of exemplary mouse monoclonal antibodies to human α11β1.



FIG. 2B shows a chart illustrating an exemplary ELISA analysis of binding of mouse monoclonal antibodies to mouse α11β1.



FIG. 3A shows a graph illustrating an ELISA analysis of binding of exemplary rat monoclonal antibodies to a human α11β1 I domain.



FIG. 3B shows a graph illustrating an ELISA analysis of binding of exemplary mouse monoclonal antibodies to a human α11β1 I domain.



FIG. 4A shows a graph illustrating an FACS analysis of binding of exemplary rat monoclonal antibodies to CHO-K1 cells expressing human α11β1.



FIG. 4B shows a graph illustrating an FACS analysis of binding of exemplary mouse monoclonal antibodies to CHO-K1 cells expressing human α11β.



FIG. 5 shows graphs illustrating a FACS analysis of binding of exemplary mouse monoclonal antibodies to human pulmonary fibroblasts (HPFs) and myofibroblasts (MF).



FIG. 6A shows graphs illustrating the ability of exemplary rat monoclonal antibodies to inhibit adhesion of CHO-K1 cells expressing human α11 to rat tail type I collagen.



FIG. 6B shows graphs illustrating the ability of exemplary rabbit monoclonal antibodies to inhibit adhesion of CHO-K1 cells expressing human α11 to rat tail type I collagen.



FIG. 6C shows graphs illustrating the ability of exemplary mouse monoclonal antibodies to inhibit adhesion of CHO-K1 cells expressing human α11 to rat tail type I collagen.



FIG. 7A shows a graph illustrating the ability of exemplary rat monoclonal antibodies to inhibit Fibroblast-to-Myofibroblasts Transition (FMT) as measured by percent inhibition of αSMA upregulation.



FIG. 7B shows a graph illustrating the ability of exemplary rabbit monoclonal antibodies to inhibit Fibroblast-to-Myofibroblasts Transition (FMT) as measured by percent inhibition of αSMA upregulation.



FIG. 7C shows a graph illustrating the ability of exemplary mouse monoclonal antibodies to inhibit Fibroblast-to-Myofibroblasts Transition (FMT) as measured by percent inhibition of αSMA upregulation.



FIG. 8 shows graphs illustrating the ability of exemplary monoclonal antibodies to inhibit CHO-K1 human α11-mediated rat tail type I collagen gel contraction.



FIG. 9 shows graphs illustrating the affinity of exemplary monoclonal antibodies for human α11β1 via surface plasmon resonance (SPR).



FIG. 10A and FIG. 10B show graphs illustrating the affinity of exemplary monoclonal antibodies for human α11β1 via surface plasmon resonance (SPR).



FIG. 11A and FIG. 11B show graphs illustrating the binding ability of selected rabbit, rat, mouse and human monoclonal antibodies to α11β1 expressed on the surface of CHO cells.



FIG. 12 shows graphs illustrating a FACS analysis of binding of exemplary monoclonal antibodies to human pulmonary fibroblasts (HPFs) and myofibroblasts (MF).



FIG. 13 shows a graph and table illustrating a FACS analysis of binding of exemplary monoclonal antibodies to human myofibroblasts (MF).



FIG. 14 shows a graph illustrating the binding ability of selected monoclonal antibodies to α11β1 expressed on the surface of CHO cells.



FIG. 15A and FIG. 15B show graphs illustrating the ability of exemplary monoclonal antibodies to inhibit adhesion of CHO cells expressing human α11 to rat tail type I collagen.



FIG. 16 shows a graph illustrating the effect of exemplary monoclonal antibodies on xenograft growth in SCID mice.



FIG. 17A, FIG. 17B and FIG. 17 C illustrate the effect of exemplary monoclonal antibodies on soluble pro-fibrogenic markers from Precision-Cut Liver Slices (PCLS).





DETAILED DESCRIPTION

The present disclosure is based, in part, on the discovery of novel antibodies that selectively bind to α11β1. The disclosure also relates to nucleic acids encoding said antibodies and methods of use in the treatment of fibrosis and diseases comprising a fibrotic component.


Fibrosis and Diseases

Fibrosis is a process of scarring that manifests itself in many tissues in the body, typically as a result of inflammation or tissue damage. Increased production of extracellular matrix results in organ failure and, often, death. Diseases associated with fibrosis account for approximately 45% of all deaths in industrialized nations (Wynn, T. A., 2008, J Pathol. 214:199-210). One such disease is Systemic Sclerosis (SSc). SSc is a complex autoimmune disease with a chronic progressive course and high interpatient variability. It is characterized by inflammation, vascular dysfunction and fibrosis. Fibrosis of the skin and visceral organs results in irreversible scarring and ultimately organ failure, accounting for high mortality. There is currently no approved targeted therapy with disease-modifying potential.


The cells responsible for producing extracellular matrix (ECM) for tissue repair (and in fibrosis) are a specialized type of fibroblasts called myofibroblasts (MF). Although mechanisms of fibrosis have been extensively studied, this complex process is far from well understood. In order to focus on the most important drivers of fibrosis, published patient-derived datasets (SSc patient data and normal controls) were interrogated using an in-house derived novel data analysis methodology. This analysis lead to the identification of the type I collagen-binding integrin alpha 11 beta 1 (α11β1) as one of the top targets for modulating fibrosis.


To this date, there are no truly disease-modifying therapeutics for fibrosis. Two of the approved therapies for idiopathic pulmonary fibrosis (IPF), nintedanib and pirfenidone, work poorly and do not modify the disease, and there is no approved therapy for systemic sclerosis (SSc) to date. In some embodiments, a fibrotic disorder is or comprises idiopathic pulmonary fibrosis (IPF), chronic kidney disease, diabetic cardiomyopathy, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD/NASH), Crohn's disease, ulcerative colitis, or systemic sclerosis (SSc). In some embodiments, a fibrotic disorder is or comprises atrial fibrosis, endomyocardial fibrosis, arthrofibrosis, mediastinal fibrosis, myelofibrosis, progressive massive fibrosis, retroperitoneal fibrosis or skeletal muscle fibrosis.


One clinical feature of the tumor microenvironment is the interaction between tumor and stroma, which mainly relies on various integrins that interact with ECM components as well as growth factors. Such interaction can influence tumor survival, progression and eventually metastasis. α11β1 has been reported to be overexpressed in cancer-associated fibroblasts (CAFs) of metastatic tumors, and its expression has been correlated with aggressive tumors in patients. For example, integrin α11 was overexpressed in the stroma of most head and neck squamous cell carcinomas (HNSCC) and correlated positively with alpha smooth muscle actin expression (Parajuli et al., J. Oral Pathol. Med. 46:267-275 (2017)). Integrin α11 was also overexpressed by CAFs in Pancreatic Ductal Adenocarcinoma (PDAC) stroma (Schnittert et al., FASEB J. 33:6609-6621 (2019)). In addition, integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), and high expression of ITGA11 (gene encoding integrin alpha-11 in humans) was associated with lower recurrence-free survival in all NSCLC patients; the same study showed that all overexpression in lung cancer cell lines resulted in increased migration and invasion (Ando et al., Cancer Sci. 111:200-208 (2020)).


Integrins

Integrins are a large family of type I transmembrane heterodimeric glycoprotein receptors and act as major receptors for cell adhesion. The integrin family of receptors plays key roles in modulating signal transduction pathways that control cell adhesion, migration, proliferation, differentiation and apoptosis. There are 18 α and 8 β subunits, which combine to form 24 integrin heterodimers. Each integrin receptor comprises two non-covalently bound subunits, α and β. Integrins α1β1, α2β1, α10β1, and α11β1 are the primary collagen receptors. α and β subunits are transmembrane proteins with large, modular, extracellular domains, single transmembrane helices, and short cytoplasmic regions, which mediate cytoskeletal interactions. Extracellular domain of integrins are generally large, approximately 80-150 kDa structures. The extracellular domains can be seen as comprising a headpiece connected to two legs (see FIG. 1 for structure of collagen-binding integrins). Collagen binding integrins contain an I domain, which serves as the ligand-binding site. The αI-domain contains a conserved “metal-ion-dependent adhesion site” (MIDAS) that binds divalent metal cations (Mg2+) and plays important role in ligand binding.


Integrins can exist in three different conformations: 1) a resting, low affinity state (bent conformation, FIG. 1, panel A) where the head piece containing ligand binding site is turned towards the membrane; 2) an extended, intermediate affinity state, where the integrin is extended but the head piece remains ‘closed’ (FIG. 1, panel B) and 3) an extended, high affinity state where the integrin is fully activated and readily binds the ligand. The complexity of the different integrin states allows for both allosteric and ligand-blocking ways of inhibiting integrin function. As marked with a star in FIG. 1, one of the allosteric ways to block the function of an integrin is to generate a monoclonal antibody that prevents the integrin from reaching the fully extended conformation from the extended intermediate conformation. Another allosteric option is to bind an integrin in its bent/inactive conformation and to keep it from extending to either of the two other states. A non-allosteric way of inhibiting integrin function is to bind to the I domain a prevent the integrin from attaching to collagen. Binding to the ligand binding site directly runs the risk of generating a recombinant activator of integrin function.


As cell surface receptors, integrins sense the stiffness of the surrounding matrix, triggering the cells to further produce and remodel connective tissue, which can perpetuate a fibrotic phenotype. Many integrins are overexpressed in fibrosis, but it is not clear which alpha subunit is sufficient for fibrosis to occur. α11β1 integrin is specifically expressed on a subset of fibroblasts and myofibroblasts (i.e., terminal scar producing cells). Recent literature has provided strong evidence that α11β1 is one of the main drivers of a fibrotic phenotype in cardiac tissue, liver, lungs and kidney (Romaine, A. et. al. Overexpression of integrin alpha 11 induces cardiac fibrosis in mice. Acta Physiol February 2018, 222(2); Bansal, R. et. al. Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases. Exp Mol Med. 2017 November 17:49(11)). Blocking α11β1 function may inhibit myofibroblast differentiation and extracellular matrix deposition (i.e., the major event in scar formation) and blocking α11β1 function may provide a mechanism for local, injury-specific attenuation of fibrosis which could fundamentally change fibrotic microenvironment and modify disease progression in all diseases that have a fibrotic component.


In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, of the present disclosure reduces interaction of α11β1 with collagen in human α11β1-expressing cells. In some embodiments, reducing interaction of α11β1 with collagen in human α11β1-expressing cells comprises an anti-α11β1 antibody, or antigen-binding fragment thereof, interacting with α11β1 that is in a resting, low affinity state (bent conformation). In some embodiments, reducing interaction of α11β1 with collagen in human α11β1-expressing cells comprises an anti-α11β1 antibody, or antigen-binding fragment thereof, interacting with α11β1 that is in an extended, intermediate affinity state. In some embodiments, reducing interaction of α11β1 with collagen in human α11β1-expressing cells comprises an anti-α11β1 antibody, or antigen-binding fragment thereof, interacting with α11β1 that is in an extended, high affinity state.


Antibodies

The term “antibody” is used herein in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and/or antibody fragments (preferably those fragments that exhibit the desired antigen-binding activity). An antibody described herein can be an immunoglobulin, heavy chain antibody, light chain antibody, LRR-based antibody, or other protein scaffold with antibody-like properties, as well as other immunological binding moiety known in the art, including, e.g., a Fab, Fab′, Fab′2, Fab2, Fab3, F(ab′)2, Fd, Fv, Feb, scFv, SMIP, antibody, diabody, triabody, tetrabody, minibody, maxibody, tandab, DVD, BiTe, TandAb, or the like, or any combination thereof. The subunit structures and three-dimensional configurations of different classes of antibodies are known in the art.


A “monoclonal antibody” or “mAb” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and/or bind the same epitope, except for possible variant antibodies (e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation), such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen.


An “antigen-binding fragment” refers to a portion of an intact antibody that binds the antigen to which the intact antibody binds. An antigen-binding fragment of an antibody includes any naturally occurring, enzymatically obtainable, synthetic, or genetically engineered polypeptide or glycoprotein that specifically binds an antigen to form a complex. Exemplary antibody fragments include, but are not limited to, Fv, Fab, Fab′, Fab′-SH, F(ab′)2; diabodies; linear antibodies; single-chain antibody molecules (e.g. scFv or VHH or VH or VL domains only); and multispecific antibodies formed from antibody fragments. In some embodiments, the antigen-binding fragments of the antibodies described herein are scFvs. As with full antibody molecules, antigen-binding fragments may be mono-specific or multispecific (e.g., bispecific). A multispecific antigen-binding fragment of an antibody may comprise at least two different variable domains, wherein each variable domain is capable of specifically binding to a separate antigen or to a different epitope of the same antigen.


A “multispecific antibody” refers to an antibody comprising at least two different antigen binding domains that recognize and specifically bind to at least two different antigens. A “bispecific antibody” is a type of multispecific antibody and refers to an antibody comprising two different antigen binding domains that recognize and specifically bind to at least two different antigens.


A “different antigen” may refer to different and/or distinct proteins, polypeptides, or molecules; as well as different and/or distinct epitopes, which epitopes may be contained within one protein, polypeptide, or other molecule.


The term “epitope” refers to an antigenic determinant that interacts with a specific antigen binding site in the variable region of an antibody molecule known as a paratope. A single antigen may have more than one epitope. Thus, different antibodies may bind to different areas of an antigen and may have different biological effects. The term “epitope” also refers to a site of an antigen to which B and/or T cells respond. It also refers to a region of an antigen that is bound by an antibody. Epitopes may be defined as structural or functional. Functional epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity of the interaction. Epitopes may also be conformational, that is, composed of non-linear amino acids. In certain embodiments, epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics.


As used herein, “selective binding”, “selectively binds” “specific binding”, or “specifically binds” refers, with respect to an antigen binding moiety and an antigen target, preferential association of an antigen binding moiety to an antigen target and not to an entity that is not the antigen target. A certain degree of non-specific binding may occur between an antigen binding moiety and a non-target. In some embodiments, an antigen binding moiety selectively binds an antigen target if binding between the antigen binding moiety and the antigen target is greater than 2-fold, greater than 5-fold, greater than 10-fold, or greater than 100-fold as compared with binding of the antigen binding moiety and a non-target. In some embodiments, an antigen binding moiety selectively binds an antigen target if the binding affinity is less than about 10−5 M, less than about 10−6 M, less than about 10−7 M, less than about 10−8 M, or less than about 10−9 M.


In some embodiments, antibodies or fragments thereof that selectively bind to an identical epitope or overlapping epitope that will often cross-compete for binding to an antigen. Thus, in some embodiments, the disclosure provides an antibody or fragment thereof that cross-competes with an exemplary antibody or fragment thereof as disclosed herein. In some embodiments, to “cross-compete”, “compete”, “cross-competition”, or “competition” means antibodies or fragments thereof compete for the same epitope or binding site on a target. Such competition can be determined by an assay in which the reference antibody or fragment thereof prevents or inhibits specific binding of a test antibody or fragment thereof, and vice versa. Numerous types of competitive binding assays can be used to determine if a test molecule competes with a reference molecule for binding. Examples of assays that can be employed include solid phase direct or indirect radioimmunoassay (RIA), solid phase direct or indirect enzyme immunoassay (EIA), sandwich competition assay (see, e.g., Stahli et al. (1983) Methods in Enzymology 9:242-253), solid phase direct biotin-avidin EIA (see, e.g., Kirkland et al., (1986) J. Immunol. 137:3614-9), solid phase direct labeled assay, solid phase direct labeled sandwich assay, Luminex (Jia et al. “A novel method of Multiplexed Competitive Antibody Binning for the characterization of monoclonal antibodies” J. Immunological Methods (2004) 288, 91-98) and surface plasmon resonance (Song et al. “Epitope Mapping of Ibalizumab, a Humanized Anti-CD4 Monoclonal Antibody with Anti-HIV-1 Activity in Infected Patients” J. Virol. (2010) 84, 6935-42). Usually, when a competing antibody or fragment thereof is present in excess, it will inhibit binding of a reference antibody or fragment thereof to a common antigen by at least 50%, 55%, 60%, 65%, 70%, or 75%. In some instances, binding is inhibited by at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more.


An antibody can be an immunoglobulin molecule of four polypeptide chains, e.g., two heavy (H) chains and two light (L) chains. In some embodiments, a light chain is a lambda light chain. In some embodiments, a light chain is a kappa light chain. A heavy chain can include a heavy chain variable domain and a heavy chain constant domain. A heavy chain constant domain can include CH1, hinge, CH2, CH3, and in some instances CH4 regions. A light chain can include a light chain variable domain and a light chain constant domain. A light chain constant domain can include a CL.


A heavy chain variable domain of a heavy chain and a light chain variable domain of a light chain can typically be further subdivided into regions of variability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Such heavy chain and light chain variable domains can each include three CDRs and four framework regions, arranged from amino-terminus to carboxyl-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4, one or more of which can be engineered as described herein. The CDRs in a heavy chain are designated “CDRH1”, “CDRH2”, and “CDRH3”, respectively, and the CDRs in a light chain are designated “CDRL1”, “CDRL2”, and “CDRL3”.


There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively.


Exemplary Antibodies


The present disclosure provides antibodies that can include various heavy chains and light chains described herein. In some embodiments, an antibody comprises two heavy chains and light chains. In some embodiments, the present disclosure encompasses an antibody including at least one heavy chain and/or light chain as disclosed herein, at least one heavy chain and/or light chain framework domain as disclosed herein, at least one heavy chain and/or light chain CDR domain as disclosed herein, and/or any heavy chain and/or light chain constant domain as disclosed herein.


In some embodiments, an antibody disclosed herein is a homodimeric monoclonal antibody. In some embodiments, an antibody disclosed herein is a heterodimeric antibody. In some embodiments, an antibody is, e.g., a typical antibody or a diabody, triabody, tetrabody, minibody, maxibody, tandab, DVD, BiTe, scFv, TandAb scFv, Fab, Fab2, Fab3, F(ab′)2, or the like, or any combination thereof.


The present disclosure provides, among other things, an anti-integrin alpha 11 beta 1 (α11β1) antibody, or antigen-binding fragment thereof. In some embodiments, an α11β1 antibody, or antigen-binding fragment thereof, comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 103-443. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises a CDR sequence encompassed within any one of SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises CDR1, CDR2, and CDR3 encompassed within any one of SEQ ID NO: 103-206, or 413-435. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 103-114, 207-311 or 436-442, and 312-435 or 443. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises a CDR sequence encompassed within any one of SEQ ID NO: 103-114, 207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises one or more CDR sequences encompassed within any one of SEQ ID NO: 103-114, or 413-434. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises CDR1, CDR2, and CDR3 encompassed within any one of SEQ ID NO: 103-114, or 413-434. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, is a monoclonal antibody, or antigen-binding fragment thereof. In some embodiments, an anti-α11 antibody, or antigen-binding fragment thereof, is a humanized antibody, or antigen-binding fragment thereof. In some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, reduces interaction of α11β1 with collagen in human α11β1-expressing cells. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, that competes with an antibody, or antigen-binding fragment thereof, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-443. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, that competes with an antibody, or antigen-binding fragment thereof, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-443.


In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising a heavy chain provided herein and a light chain provided herein. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable domain provided herein and a light chain variable region provided herein. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising a specific combination of heavy chain variable domain and light chain variable domain. For example, in some embodiments, an anti-α11β1 antibody, or antigen-binding fragment thereof, comprises a combination of heavy chain variable domain and light chain variable domain selected from Table 1.









TABLE 1







Combinations of 16E10 variant heavy chain variable


regions and light chain variable regions









Light Chain
Heavy Chain



Variable Region
Variable Region
Description





16E10_VL
16E10_VH
Parental light chain variable


(SEQ ID NO: 428)
(SEQ ID NO: 421)
region; Parental heavy




chain variable region


16E10_VL_1
16E10_VH_1
Conservatively humanized


(SEQ ID NO: 429)
(SEQ ID NO: 422)
light chain variable




region; Conservatively




humanized heavy chain




variable region


16E10_VL_2
16E10_VH_2
Humanized light chain


(SEQ ID NO: 430)
(SEQ ID NO: 423)
variable region; humanized




heavy chain variable region


16E10_VL_3
16E10_VH_1
Deimmunized conservatively


(SEQ ID NO: 431)
(SEQ ID NO: 422)
humanized light chai




variable region; Conservatively




humanized heavy




chain variable region


16E10_VL_4
16E10_VH_2
Deimmunized humanized


(SEQ ID NO: 432)
(SEQ ID NO: 423)
light chain variable




region; Humanized heavy




chain variable region


16E10_VL_1
16E10_VH_3
Conservatively humanized


(SEQ ID NO: 429)
(SEQ ID NO: 424)
light chain variable




region; Deimmunized




conservatively humanized




heavy chain variable region


16E10_VL_2
16E10_VH_4
Humanized light chain


(SEQ ID NO: 430)
(SEQ ID NO: 425)
variable region;




Deimmunized humanized




heavy chain variable region


16E10_VL_3
16E10_VH_3
Deimmunized conservatively


(SEQ ID NO: 431)
(SEQ ID NO: 424)
humanized light chain variable




region; Deimmunized




conservatively humanized




heavy chain variable region


16E10_VL_4
16E10_VH_4
Deimmunized humanized


(SEQ ID NO: 432)
(SEQ ID NO: 425)
light chain variable region;




Deimmunized humanized




heavy chain




variable region


16E10_VL_5
16E10_VH_3
De-risked deimmunized


(SEQ ID NO: 433)
(SEQ ID NO: 424)
conservatively humanized




light chain variable region;




Deimmunized conservatively




humanized heavy chain




variable region


16E10_VL_6
16E10_VH_4
De-risked deimmunized


(SEQ ID NO: 434)
(SEQ ID NO: 425)
humanized light chain




variable region; Deimmunised




humanised heavy




chain variable region


16E10_VL_3
16E10_VH_5
Deimmunised conservatively


(SEQ ID NO: 431)
(SEQ ID NO: 426)
humanised light chain




variable region; De-risked




deimmunised conservatively




humanised heavy chain




variable region


16E10_VL_4
16E10_VH_6
Deimmunised humanised


(SEQ ID NO: 432)
(SEQ ID NO: 427)
light chain variable




region; De-risked




deimmunised humanised




heavy chain variable region


16E10_VL_5
16E10_VH_5
De-risked deimmunised


(SEQ ID NO: 433)
(SEQ ID NO: 426)
conservatively humanised




light chain variable region;




De-risked deimmunised




conservatively humanised




heavy chain variable region


16E10_VL_6
16E10_VH_6
De-risked deimmunised


(SEQ ID NO: 434)
(SEQ ID NO: 427)
humanised light chain




variable region; De-risked




deimmunised humanised




heavy chain variable region









In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising between 1 and 30 (e.g., 1, 2, 3, 4, 5, 10, or more) additions, deletions, or substitutions relative to an anti-α11β1 antibody, or antigen-binding fragment thereof, wherein the anti-α11β1 antibody comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 103-158, 413, 414 and 421-434 and, e.g., the antibody or fragment selectively binds α11β1. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising between 1 and 30 additions, deletions, or substitutions relative to an anti-α11β1 antibody, or antigen-binding fragment thereof, wherein the anti-α11β1 antibody comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 103-114, 413, 414 and 421-434 and, e.g., the antibody or fragment selectively binds α11β1. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to an amino acid sequence selected from a group consisting of SEQ ID NO: 103-158, 413, 414 and 421-434 and, e.g., the antibody or fragment selectively binds α11β1. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from a group consisting of SEQ ID NO: 103-114, 413, 414 and 421-434 and, e.g., the antibody or fragment selectively binds α11β1.


In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising between 1 and 90 (e.g., between 1 and 50, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) additions, deletions, or substitutions relative to an anti-α11β1 antibody, or antigen-binding fragment thereof, wherein the anti-α11β1 antibody, or antigen-binding fragment thereof comprises an amino acid sequence selected from a group consisting of SEQ ID NO: 159-206 and 415-420 and, e.g., the antibody or fragment selectively binds α11β1. In some embodiments, the present disclosure provides an anti-α11β1 antibody, or antigen-binding fragment thereof, comprising an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 159-206 and 415-420 and, e.g., the antibody or fragment selectively binds α11β1.


In some embodiments, the disclosure provides an antibody or fragment thereof that selectively binds α11β1, wherein the antibody or fragment comprises one or more CDR sequences depicted in the list of exemplary sequences provided herein. For example, in some embodiments, an antibody or fragment thereof comprises one or more CDRs from SEQ ID NOs: 103-114. In some embodiments, the disclosure provides an antibody or fragment thereof that selectively binds α11β1, wherein the antibody or fragment comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to one or more CDRs from SEQ ID NOs: 103-114. In some embodiments, an antibody or fragment comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to one of SEQ ID NOs: 103-114, wherein the antibody comprises one or more CDRs depicted in one of SEQ ID NOs: 103-114. For example, the antibody or fragment comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 103, wherein the antibody comprises one or more CDRs (e.g., 1, 2, or 3 CDRs) depicted in SEQ ID NO:103.


In some embodiments, the disclosure provides an antibody or fragment thereof that selectively binds α11β1, wherein the antibody or fragment comprises one or more CDR sequences depicted in the list of exemplary sequences provided herein. For example, in some embodiments, an antibody or fragment thereof comprises one or more CDRs from SEQ ID NOs: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. In some embodiments, the disclosure provides an antibody or fragment thereof that selectively binds α11β1, wherein the antibody or fragment comprises an amino acid sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to one or more CDRs from SEQ ID NOs: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. In some embodiments, an antibody or fragment comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to one of SEQ ID NOs: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443, wherein the antibody comprises one or more CDRs depicted in one of SEQ ID NOs: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443. For example, the antibody or fragment comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 103, wherein the antibody comprises one or more CDRs (e.g., 1, 2, or 3 CDRs) depicted in SEQ ID NO:103.


The present disclosure provides, among other things, methods of making an anti-α11β1 antibody, or antigen-binding fragment thereof. Methods of making antibodies are known in the art. In some embodiments, the present disclosure provides methods of producing an antibody, or antigen-binding fragment thereof, comprising culturing a host cell comprising a nucleic acid comprising a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-102 under conditions suitable for expression of the antibody or antigen-binding fragment thereof.


Exemplary Nucleotide Sequences


The present disclosure includes nucleotide sequences encoding one or more heavy chains, heavy chain variable domains, heavy chain framework regions, heavy chain CDRs, heavy chain constant domains, light chains, light chain variable domains, light chain framework regions, light chain CDRs, light chain constant domains, or other immunoglobulin-like sequences, antibodies, or binding molecules disclosed herein. In some embodiments, such nucleotide sequences may be present in a vector. In some embodiments such nucleotides may be present in the genome of a cell, e.g., a cell of a subject in need of treatment or a cell for production of an antibody, e.g. a mammalian cell for production of a an antibody.


In some embodiments, the present disclosure provides a nucleic acid comprising a nucleic acid sequence encoding an antibody, or antigen-binding fragment thereof, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-206. In some embodiments, the present disclosure provides a nucleic acid comprising a nucleic acid sequence encoding an antibody, or antigen-binding fragment thereof, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-114. In some embodiments, the present disclosure provides a nucleic acid comprising a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-102. In some embodiments, the present disclosure provides a vector comprising a nucleic acid comprising a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-102. In some embodiments, the present disclosure provides a host cell comprising a nucleic acid comprising a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-102. In some embodiments, the present disclosure provides a vector comprising a nucleic acid comprising a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-102.


In some embodiments, the present disclosure provides a nucleic acid comprising a nucleic acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-102.


Measuring Interactions of Antibodies and α11β1

The binding properties of an antibody described herein to α11β1 can be measured by methods known in the art, e.g., one of the following methods: BIACORE analysis, Enzyme Linked Immunosorbent Assay (ELISA), x-ray crystallography, sequence analysis and scanning mutagenesis. The binding interaction of an antibody and α11β1 can be analyzed using surface plasmon resonance (SPR). SPR or Biomolecular Interaction Analysis (BIA) detects bio-specific interactions in real time, without labeling any of the interactants. Changes in the mass at the binding surface (indicative of a binding event) of the BIA chip result in alterations of the refractive index of light near the surface. The changes in the refractivity generate a detectable signal, which are measured as an indication of real-time reactions between biological molecules. Methods for using SPR are described, for example, in U.S. Pat. No. 5,641,640; Raether (1988) Surface Plasmons Springer Verlag; Sjolander and Urbaniczky (1991) Anal. Chem. 63:2338-2345; Szabo et al. (1995) Curr. Opin. Struct. Biol. 5:699-705 and on-line resources provide by BIAcore International AB (Uppsala, Sweden). Additionally, a KinExA® (Kinetic Exclusion Assay) assay, available from Sapidyne Instruments (Boise, Id.) can also be used.


Information from SPR can be used to provide an accurate and quantitative measure of the equilibrium dissociation constant (KD), and kinetic parameters, including Kon and Koff, for the binding of an antibody to α11β1. Such data can be used to compare different molecules. Information from SPR can also be used to develop structure-activity relationships (SAR). Variant amino acids at given positions can be identified that correlate with particular binding parameters, e.g., high affinity.


In certain embodiments, an antibody described herein exhibits high affinity for binding α11β1. In various embodiments, KD of an antibody as described herein for α11β1 is less than about 10−4, 10−5, 10−6, 10−7, 10−8, 10−9, 10−10, 10−11, 10−12, 10−13, 10−14, or 10−15 M. In certain instances, KD of an antibody as described herein for α11β1 is between 0.001 and 1 nM, e.g., 0.001 nM, 0.005 nM, 0.01 nM, 0.05 nM, 0.1 nM, 0.5 nM, or 1 nM.


Methods of Treatment

In some embodiments, one or more anti-α11β1 antibodies described herein are used in a method of treating one or more disorders described herein, e.g., one or more fibrotic disorders and/or one or more cancers. In some embodiments, the method comprises administering to a subject in need thereof a therapeutically effective amount of an antibody, or antigen-binding fragment thereof, described herein. In some embodiments, a fibrotic disorder is or comprises idiopathic pulmonary fibrosis (IPF), chronic kidney disease, diabetic cardiomyopathy, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD/NASH), Crohn's disease, ulcerative colitis, or systemic sclerosis. In some embodiments, a fibrotic disorder is or comprises atrial fibrosis, endomyocardial fibrosis, arthrofibrosis, mediastinal fibrosis, myelofibrosis, progressive massive fibrosis, retroperitoneal fibrosis or skeletal muscle fibrosis.


In some embodiments, one or more anti-α11β1 antibodies described herein are used in a method of treating cancer, such as one or more of the following: head and neck squamous cell carcinomas, pancreatic ductal adenocarcinoma, non-small cell lung cancer, adrenocortical carcinoma, acute myeloid leukemia, bladder urothelial carcinoma, invasive breast carcinoma, cervical squamous cell carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, glioblastoma multiforme, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, mesothelioma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, sarcoma, stomach adenocarcinoma, testicular germ cell tumors, thymoma, thyroid carcinoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, uveal melanoma, kidney renal clear cell carcinoma, kidney chromophobe, and kidney renal papillary cell carcinoma.


Combination Therapy

In some embodiments, an anti-α11β1 antibody described herein is administered in combination with one or more additional therapeutic agents, such as a chemotherapeutic agent or an oncolytic therapeutic agent. “Combination therapy”, as used herein, refers to those situations in which two or more different pharmaceutical agents are administered in overlapping regimens so that the subject is simultaneously exposed to both agents. When used in combination therapy, two or more different agents may be administered simultaneously or separately. Administration in combination can include simultaneous administration of the two or more agents in the same dosage form, simultaneous administration in separate dosage forms, and separate administration. That is, two or more agents can be formulated together in the same dosage form and administered simultaneously. Alternatively, two or more agents can be simultaneously administered, wherein the agents are present in separate formulations. In another alternative, a first agent can be administered just followed by one or more additional agents. In the separate administration protocol, two or more agents may be administered a few minutes apart, or a few hours apart, or a few days apart.


As used herein, the term “chemotherapeutic agent” or “oncolytic therapeutic agent” (e.g., anti-cancer drug, e.g., anti-cancer therapy, e.g., immune cell therapy) has its art-understood meaning referring to one or more pro-apoptotic, cytostatic and/or cytotoxic agents, and/or hormonal agents, for example, specifically including agents utilized and/or recommended for use in treating one or more diseases, disorders or conditions associated with undesirable cell proliferation. In some embodiments, a chemotherapeutic agent and/or oncolytic therapeutic agent may be or comprise platinum compounds (e.g., cisplatin, carboplatin, and oxaliplatin), alkylating agents (e.g., cyclophosphamide, ifosfamide, chlorambucil, nitrogen mustard, thiotepa, melphalan, busulfan, procarbazine, streptozocin, temozolomide, dacarbazine, and bendamustine), antitumor antibiotics (e.g., daunorubicin, doxorubicin, idarubicin, epirubicin, mitoxantrone, bleomycin, mytomycin C, plicamycin, and dactinomycin), taxanes (e.g., paclitaxel and docetaxel), antimetabolites (e.g., 5-fluorouracil, cytarabine, premetrexed, thioguanine, floxuridine, capecitabine, and methotrexate), nucleoside analogues (e.g., fludarabine, clofarabine, cladribine, pentostatin, and nelarabine), topoisomerase inhibitors (e.g., topotecan and irinotecan), hypomethylating agents (e.g., azacitidine and decitabine), proteosome inhibitors (e.g., bortezomib), epipodophyllotoxins (e.g., etoposide and teniposide), DNA synthesis inhibitors (e.g., hydroxyurea), vinca alkaloids (e.g., vicristine, vindesine, vinorelbine, and vinblastine), tyrosine kinase inhibitors (e.g., imatinib, dasatinib, nilotinib, sorafenib, and sunitinib), nitrosoureas (e.g., carmustine, fotemustine, and lomustine), hexamethylmelamine, mitotane, angiogenesis inhibitors (e.g., thalidomide and lenalidomide), steroids (e.g., prednisone, dexamethasone, and prednisolone), hormonal agents (e.g., tamoxifen, raloxifene, leuprolide, bicaluatmide, granisetron, and flutamide), aromatase inhibitors (e.g., letrozole and anastrozole), arsenic trioxide, tretinoin, nonselective cyclooxygenase inhibitors (e.g., nonsteroidal anti-inflammatory agents, salicylates, aspirin, piroxicam, ibuprofen, indomethacin, naprosyn, diclofenac, tolmetin, ketoprofen, nabumetone, and oxaprozin), selective cyclooxygenase-2 (COX-2) inhibitors, or any combination thereof.


In certain embodiments, chemotherapeutic agents and/or oncolytic therapeutic agents for anti-cancer treatment comprise biological agents such as tumor-infiltrating lymphocytes, CAR T-cells, antibodies, antigens, therapeutic vaccines (e.g., made from a patient's own tumor cells or other substances such as antigens that are produced by certain tumors), immune-modulating agents (e.g., cytokines, e.g., immunomodulatory drugs or biological response modifiers), checkpoint inhibitors or other immunologic agents. In certain embodiments, immunologic agents include immunoglobins, immunostimulants (e.g., bacterial vaccines, colony stimulating factors, interferons, interleukins, therapeutic vaccines, vaccine combinations, viral vaccines) and/or immunosuppressive agents (e.g., calcineurin inhibitors, interleukin inhibitors, TNF alpha inhibitors). In certain embodiments, hormonal agents include agents for anti-androgen therapy (e.g., Ketoconazole, ABiraterone, TAK-700, TOK-OOl, Bicalutamide, Nilutamide, Flutamide, Enzalutamide, ARN-509).


Additional chemotherapeutic agents and/or oncolytic therapeutic agents include immune checkpoint therapeutics (e.g., pembrolizumab, nivolumab, ipilimumab, atezolizumab, avelumab, durvalumab, tremelimumab, or cemiplimab), other monoclonal antibodies (e.g., rituximab, cetuximab, panetumumab, tositumomab, trastuzumab, alemtuzumab, gemtuzumab ozogamicin, bevacizumab, catumaxomab, denosumab, obinutuzumab, ofatumumab, ramucirumab, pertuzumab, nimotuzumab, lambrolizumab, pidilizumab, siltuximab, BMS-936559, RG7446/MPDL3280A, MEDI4736), antibody-drug conjugates (e.g., brentuximab vedotin (ADCETRIS®, Seattle Genetics); ado-trastuzumab emtansine (KADCYLA®, Roche); Gemtuzumab ozogamicin (Wyeth); CMC-544; SAR3419; CDX-011; PSMA-ADC; BT-062; and IMGN901 (see, e.g., Sassoon et al., Methods Mol. Biol. 1045:1-27 (2013); Bouchard et al., Bioorganic Med. Chem. Lett. 24: 5357-5363 (2014)), or any combination thereof.


In some embodiments, combined administration of an anti-α11β1 antibody and an additional therapeutic agent results in an improvement in cancer to an extent that is greater than one produced by either the anti-α11β1 antibody or the additional therapeutic agent alone. The difference between the combined effect and the effect of each agent alone can be a statistically significant difference. In some embodiments, the combined effect can be a synergistic effect. In some embodiments, combined administration of an anti-α11β1 antibody and an additional therapeutic agent allows administration of the additional therapeutic agent at a reduced dose, at a reduced number of doses, and/or at a reduced frequency of dosage compared to a standard dosing regimen, e.g., an approved dosing regimen for the additional therapeutic agent.


In some embodiments, treatment methods described herein are performed on subjects for whom other treatments of the medical condition have failed or have had less success in treatment through other means. Additionally, the treatment methods described herein can be performed in conjunction with one or more additional treatments of the medical condition. For instance, the method can comprise administering a cancer regimen, e.g., non-myeloablative chemotherapy, surgery, hormone therapy, and/or radiation, prior to, substantially simultaneously with, or after the administration of an anti-α11β1 antibody described herein, or composition thereof.


Formulations and Administration

In various embodiments, an antibody described herein can be incorporated into a pharmaceutical composition. Such a pharmaceutical composition can be useful, e.g., for the prevention and/or treatment of diseases, e.g., fibrotic disorders. Pharmaceutical compositions can be formulated by methods known to those skilled in the art (such as described in Remington's Pharmaceutical Sciences, 17th edition, ed. Alfonso R. Gennaro, Mack Publishing Company, Easton, Pa. (1985)).


In some embodiments, a pharmaceutical composition can be formulated to include a pharmaceutically acceptable carrier or excipient. Examples of pharmaceutically acceptable carriers include, without limitation, any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. Compositions of the present invention can include a pharmaceutically acceptable salt, e.g., an acid addition salt or a base addition salt.


In some embodiments, a composition including an antibody as described herein, e.g., a sterile formulation for injection, can be formulated in accordance with conventional pharmaceutical practices using distilled water for injection as a vehicle. For example, physiological saline or an isotonic solution containing glucose and other supplements such as D-sorbitol, D-mannose, D-mannitol, and sodium chloride may be used as an aqueous solution for injection, optionally in combination with a suitable solubilizing agent, such as, for example, an alcohol such as ethanol and/or a polyalcohol such as propylene glycol or polyethylene glycol, and/or a nonionic surfactant such as polysorbate 80™ or HCO-50.


As disclosed herein, a pharmaceutical composition may be in any form known in the art. Such forms include, e.g., liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories.


Selection or use of any particular form may depend, in part, on the intended mode of administration and therapeutic application. For example, compositions containing a composition intended for systemic or local delivery can be in the form of injectable or infusible solutions. Accordingly, compositions can be formulated for administration by a parenteral mode (e.g., intravenous, subcutaneous, intraperitoneal, or intramuscular injection). As used herein, parenteral administration refers to modes of administration other than enteral and topical administration, usually by injection, and include, without limitation, intravenous, intranasal, intraocular, pulmonary, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intrapulmonary, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural, intracerebral, intracranial, intracarotid and intrasternal injection and infusion.


Route of administration can be parenteral, for example, administration by injection, transnasal administration, transpulmonary administration, or transcutaneous administration. Administration can be systemic or local by intravenous injection, intramuscular injection, intraperitoneal injection, or subcutaneous injection.


In some embodiments, a pharmaceutical composition of the present invention can be formulated as a solution, microemulsion, dispersion, liposome, or other ordered structure suitable for stable storage at high concentration. Sterile injectable solutions can be prepared by incorporating a composition described herein in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filter sterilization. Generally, dispersions are prepared by incorporating a composition described herein into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods for preparation include vacuum drying and freeze-drying that yield a powder of a composition described herein plus any additional desired ingredient (see below) from a previously sterile-filtered solution thereof. The proper fluidity of a solution can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prolonged absorption of injectable compositions can be brought about by including in the composition a reagent that delays absorption, for example, monostearate salts, and gelatin.


A pharmaceutical composition can be administered parenterally in the form of an injectable formulation comprising a sterile solution or suspension in water or another pharmaceutically acceptable liquid. For example, the pharmaceutical composition can be formulated by suitably combining the therapeutic molecule with pharmaceutically acceptable vehicles or media, such as sterile water and physiological saline, vegetable oil, emulsifier, suspension agent, surfactant, stabilizer, flavoring excipient, diluent, vehicle, preservative, binder, followed by mixing in a unit dose form required for generally accepted pharmaceutical practices. The amount of active ingredient included in a pharmaceutical preparation is such that a suitable dose within the designated range is provided. Non-limiting examples of oily liquid include sesame oil and soybean oil, and may be combined with benzyl benzoate or benzyl alcohol as a solubilizing agent. Other items that may be included are a buffer such as a phosphate buffer, or sodium acetate buffer, a soothing agent such as procaine hydrochloride, a stabilizer such as benzyl alcohol or phenol, and an antioxidant. A formulated injection can be packaged in a suitable ampule.


In various embodiments, subcutaneous administration can be accomplished by means of a device, such as a syringe, a prefilled syringe, an auto-injector (e.g., disposable or reusable), a pen injector, a patch injector, a wearable injector, an ambulatory syringe infusion pump with subcutaneous infusion sets, or other device for combining with antibody drug for subcutaneous injection.


An injection system of the present disclosure may employ a delivery pen as described in U.S. Pat. No. 5,308,341. Pen devices, most commonly used for self-delivery of insulin to patients with diabetes, are well known in the art. Such devices can comprise at least one injection needle (e.g., a 31 gauge needle of about 5 to 8 mm in length), are typically prefilled with one or more therapeutic unit doses of a therapeutic solution, and are useful for rapidly delivering solution to a subject with as little pain as possible. One medication delivery pen includes a vial holder into which a vial of a therapeutic or other medication may be received. The pen may be an entirely mechanical device or it may be combined with electronic circuitry to accurately set and/or indicate the dosage of medication that is injected into the user. See, e.g., U.S. Pat. No. 6,192,891. In some embodiments, the needle of the pen device is disposable and the kits include one or more disposable replacement needles. Pen devices suitable for delivery of any one of the presently featured compositions are also described in, e.g., U.S. Pat. Nos. 6,277,099; 6,200,296; and 6,146,361, the disclosures of each of which are incorporated herein by reference in their entirety. A microneedle-based pen device is described in, e.g., U.S. Pat. No. 7,556,615, the disclosure of which is incorporated herein by reference in its entirety. See also the Precision Pen Injector (PPI) device, MOLLY™, manufactured by Scandinavian Health Ltd.


In some embodiments, a composition described herein can be therapeutically delivered to a subject by way of local administration. As used herein, “local administration” or “local delivery,” can refer to delivery that does not rely upon transport of the composition or agent to its intended target tissue or site via the vascular system. For example, the composition may be delivered by injection or implantation of the composition or agent or by injection or implantation of a device containing the composition or agent. In certain embodiments, following local administration in the vicinity of a target tissue or site, the composition or agent, or one or more components thereof, may diffuse to an intended target tissue or site that is not the site of administration.


In some embodiments, a composition can be formulated for storage at a temperature below 0° C. (e.g., −20° C. or −80° C.). In some embodiments, the composition can be formulated for storage for up to 2 years (e.g., one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, 10 months, 11 months, 1 year, 1½ years, or 2 years) at 2-8° C. (e.g., 4° C.). Thus, in some embodiments, the compositions described herein are stable in storage for at least 1 year at 2-8° C. (e.g., 4° C.).


In some embodiments, a pharmaceutical composition can be formulated as a solution. In some embodiments, a composition can be formulated, for example, as a buffered solution at a concentration suitable for storage at 2-8° C. (e.g., 4° C.).


Compositions including one or more antibodies as described herein can be formulated in immunoliposome compositions. Such formulations can be prepared by methods known in the art. Liposomes with enhanced circulation time are disclosed in, e.g., U.S. Pat. No. 5,013,556.


In certain embodiments, compositions can be formulated with a carrier that will protect the compound against rapid release, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Many methods for the preparation of such formulations are known in the art. See, e.g., J. R. Robinson (1978) “Sustained and Controlled Release Drug Delivery Systems,” Marcel Dekker, Inc., New York.


In some embodiments, administration of an antibody as described herein is achieved by administering to a subject a nucleic acid encoding the antibody. Nucleic acids encoding a therapeutic antibody described herein can be incorporated into a gene construct to be used as a part of a gene therapy protocol to deliver nucleic acids that can be used to express and produce antibody within cells. Expression constructs of such components may be administered in any therapeutically effective carrier, e.g. any formulation or composition capable of effectively delivering the component gene to cells in vivo. Approaches include insertion of the subject gene in viral vectors including recombinant retroviruses, adenovirus, adeno-associated virus, lentivirus, and herpes simplex virus-1 (HSV-1), or recombinant bacterial or eukaryotic plasmids. Viral vectors can transfect cells directly; plasmid DNA can be delivered with the help of, for example, cationic liposomes (lipofectin) or derivatized, polylysine conjugates, gramicidin S, artificial viral envelopes or other such intracellular carriers, as well as direct injection of the gene construct or CaPO4 precipitation (see, e.g., WO04/060407). Examples of suitable retroviruses include pLJ, pZIP, pWE and pEM which are known to those skilled in the art (see, e.g., Eglitis et al. (1985) Science 230:1395-1398; Danos and Mulligan (1988) Proc Natl Acad Sci USA 85:6460-6464; Wilson et al. (1988) Proc Natl Acad Sci USA 85:3014-3018; Armentano et al. (1990) Proc Natl Acad Sci USA 87:6141-6145; Huber et al. (1991) Proc Natl Acad Sci USA 88:8039-8043; Ferry et al. (1991) Proc Natl Acad Sci USA 88:8377-8381; Chowdhury et al. (1991) Science 254:1802-1805; van Beusechem et al. (1992) Proc Natl Acad Sci USA 89:7640-7644; Kay et al. (1992) Human Gene Therapy 3:641-647; Dai et al. (1992) Proc Natl Acad Sci USA 89:10892-10895; Hwu et al. (1993) J Immunol 150:4104-4115; U.S. Pat. Nos. 4,868,116 and 4,980,286; and PCT Publication Nos. WO89/07136, WO89/02468, WO89/05345, and WO92/07573). Another viral gene delivery system utilizes adenovirus-derived vectors (see, e.g., Berkner et al. (1988) BioTechniques 6:616; Rosenfeld et al. (1991) Science 252:431-434; and Rosenfeld et al. (1992) Cell 68:143-155). Suitable adenoviral vectors derived from the adenovirus strain Ad type 5 d1324 or other strains of adenovirus (e.g., Ad2, Ad3, Ad7, etc.) are known to those skilled in the art. Yet another viral vector system useful for delivery of the subject gene is the adeno-associated virus (AAV). See, e.g., Flotte et al. (1992) Am J Respir Cell Mol Biol 7:349-356; Samulski et al. (1989) J Virol 63:3822-3828; and McLaughlin et al. (1989) J Virol 62:1963-1973.


In some embodiments, the compositions provided herein are present in unit dosage form, which unit dosage form can be suitable for self-administration. Such a unit dosage form may be provided within a container, typically, for example, a vial, cartridge, prefilled syringe or disposable pen. A doser such as the doser device described in U.S. Pat. No. 6,302,855, may also be used, for example, with an injection system as described herein.


A suitable dose of a composition described herein, which dose is capable of treating or preventing a disorder in a subject, can depend on a variety of factors including, e.g., the age, sex, and weight of a subject to be treated and the particular inhibitor compound used. For example, a different dose of one composition including an antibody as described herein may be required to treat a subject with a fibrotic disorder as compared to the dose of a different formulation of that antibody. Other factors affecting the dose administered to the subject include, e.g., the type or severity of the disorder. Other factors can include, e.g., other medical disorders concurrently or previously affecting the subject, the general health of the subject, the genetic disposition of the subject, diet, time of administration, rate of excretion, drug combination, and any other additional therapeutics that are administered to the subject. It should also be understood that a specific dosage and treatment regimen for any particular subject can also be adjusted based upon the judgment of the treating medical practitioner.


A composition described herein can be administered as a fixed dose, or in a milligram per kilogram (mg/kg) dose. In some embodiments, the dose can also be chosen to reduce or avoid production of antibodies or other host immune responses against one or more of the antigen-binding molecules in the composition. Exemplary dosages of an antibody, such as a composition described herein, include, e.g., 0.0001 to 100 mg/kg, 0.01 to 5 mg/kg, 1-1000 mg/kg, 1-100 mg/kg, 0.5-50 mg/kg, 0.1-100 mg/kg, 0.5-25 mg/kg, 1-20 mg/kg, and 1-10 mg/kg of the subject body weight. For example dosages can be 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 3.0 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 10 mg/kg or 20 mg/kg body weight or within the range of 1-20 mg/kg body weight. An exemplary treatment regime entails administration once per week, once every two weeks, once every three weeks, once every four weeks, once a month, once every 3 months or once every three to 6 months, or with a short administration interval at the beginning (such as once per week to once every three weeks), and then an extended interval later (such as once a month to once every three to 6 months).


A pharmaceutical solution can include a therapeutically effective amount of a composition described herein. Such effective amounts can be readily determined by one of ordinary skill in the art based, in part, on the effect of the administered composition, or the combinatorial effect of the composition and one or more additional active agents, if more than one agent is used. A therapeutically effective amount of a composition described herein can also vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the composition (and one or more additional active agents) to elicit a desired response in the individual, e.g., amelioration of at least one condition parameter, e.g., amelioration of at least one symptom of a fibrotic disorder. For example, a therapeutically effective amount of a composition described herein can inhibit (lessen the severity of or eliminate the occurrence of) and/or prevent a particular disorder, and/or any one of the symptoms of the particular disorder known in the art or described herein. A therapeutically effective amount is also one in which any toxic or detrimental effects of the composition are outweighed by the therapeutically beneficial effects.


Suitable human doses of any of the compositions described herein can further be evaluated in, e.g., Phase I dose escalation studies. See, e.g., van Gurp et al. (2008) Am J Transplantation 8(8):1711-1718; Hanouska et al. (2007) Clin Cancer Res 13(2, part 1):523-531; and Hetherington et al. (2006) Antimicrobial Agents and Chemotherapy 50(10): 3499-3500.


Toxicity and therapeutic efficacy of compositions can be determined by known pharmaceutical procedures in cell cultures or experimental animals (e.g., animal models of any of the fibrotic disorders described herein). These procedures can be used, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. A composition described herein that exhibits a high therapeutic index is preferred. While compositions that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue and to minimize potential damage to normal cells and, thereby, reduce side effects.


Those of skill in the art will appreciate that data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. Appropriate dosages of compositions described herein lie generally within a range of circulating concentrations of the compositions that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For a composition described herein, the therapeutically effective dose can be estimated initially from cell culture assays. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the antibody which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography. In some embodiments, e.g., where local administration (e.g., to the eye or a joint) is desired, cell culture or animal modeling can be used to determine a dose required to achieve a therapeutically effective concentration within the local site.


All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. Unless otherwise defined, 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. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described herein.


The disclosure is further illustrated by the following examples. The examples are provided for illustrative purposes only. They are not to be construed as limiting the scope or content of the disclosure in any way.


EXAMPLES
Methods
Generation of Novel Antibodies Against α11β1

Rat Immunization


Wistar rats were immunized with recombinant human α11β1 protein. An enzyme-linked immunosorbent assay (ELISA) was used to test an immune response against target human and mouse proteins. Subsequently, cell fusion (by electro fusion) was performed with animals that produced a good immune response. All fused cells were plated in a 96-well plate and supernatants were screened by ELISA against soluble human and mouse α11β1. Positive clones were counter-screened against human α1β1, α2β1 and α10β1. Clones that specifically bound to human and mouse α11β1 and did not bind to α1β1, α2β1 and α10β1 were selected, subcloned, expanded and cryopreserved. Purified antibodies were then generated from the selected clones and heavy chain and light chain variable domain sequences were obtained from each purified antibody.


Rabbit Immunization


Rabbits were immunized employing a cell-based monoclonal antibody platform. Two rabbits were immunized with recombinant human α11β1 protein. Splenocytes from the immunized rabbits were sorted and selected against human β1, in order to reduce the number of β1-specific B cell clones. Sorted splenocytes were then cultured for approximately 1 week and culture supernatants were screened for binding to human α11β1. Top results were sequenced and subsequently rabbit antibodies were recombinantly produced using a HEK cell system.


Mouse Immunization


10 mice from 5 different strains were immunized with an appropriate mixture of human α11β1, mouse α11β1 and tolerance breaking protein. Plasma titers were evaluated by ELISA against a mixture of human and mouse α11β1. Popliteal, inguinal, and iliac lymph nodes were collected. ELISA-positive anti-human/mouse α11β1 hybridomas were expanded and subjected to a secondary screen against human and mouse α11β1, control HIS protein, and a counter-screen was performed against human α11β1, α2β1 and α10β1. Supernatant IgG concentration was sufficient for functional screening. Selected hybridomas satisfying all the criteria were cloned and clonal hybridomas were confirmed by ELISA against human and mouse α11β1 and subsequently scaled-up and IgGs were purified. Heavy and light chain variable regions of selected hybridomas were then sequenced.


Phage Library Display


Phage library display was employed for generation of fully human anti-α11β1 antibodies. Fully human anti-α11β1 antibodies were discovered using single chain fragment variable (scFv) antigen-binding fragments displayed on phages (phage display library). Three rounds of selection were performed on purified human and mouse α11β1 antigen as well as deselection against α10β1, to enrich for all subunit-specific antibodies. Subsequently, optimal populations were subcloned into a bacterial soluble expression vector, recombinant antibody expression was induced and supernatant was screened for binding via ELISA assays. Antibodies with appropriate binding profiles were sequenced and subsequently converted from scFv to IgG.


ELISA

0.25 μg/mL of target antigen (recombinant human or mouse α11β1) was plated in a 96-well plate over night at 4° C. Plates were washed (PBS with 0.1% Tween-20), blocked (PBS with 2% BSA and 0.05% Tween-20) for 1 hour at room temperature and incubated with a range of antibody concentrations for 1 hour at room temperature. Subsequently, plates were washed and incubated with biotinylated anti-rabbit/mouse/human IgG in a 1:1000 dilution buffer and incubated for 1 hour at room temperature. After washing the plates, Streptavidin HRP was added at 1:200 in dilution buffer and incubated for 1 hour at room temperature. Ultra TMB ELISA substrate solution was added and the plates incubated for 5 minutes on a plate shaker. The reaction was stopped by adding stop solution to each well and plates were read at 450 nm.


FACS

Antibody Binding to CHO-K1


200,000 cells (wild-type CHO-K1 cells or CHO-K1 cells expressing human α11) were incubated with each antibody at desired concentrations in FACS buffer for 30 min at 4° C. Then, the cells were washed with FACS buffer and incubated with secondary antibody at 1:100 dilution for 30 minutes at 4° C. Cells were then washed and fixed with 1% PFA in PBS for 20 minutes at room temperature; washed again and read on a cytometer in FACS buffer.


Antibody Binding to HPF/MF


Human Pulmonary Fibroblasts (ScienCell) were cultured in complete Fibroblast Growth Medium (ScienCell) until 80% confluent in T-150 flasks. Cells were washed and harvested using Accutase. Cells were seeded into T-150 flasks at 7,500 cells/cm2 in complete FGF and cultured for 72 hours. Cells were then washed and starved in serum reduced medium for 24 hours. After starvation, cells were treated with TGFβ-1 (R&D Systems) for 72 hours. Cells were harvested using Accutase and seeded in 96-well conical bottom plates. Cells were blocked with Heat Inactived Fetal Bovine Serum (Gibco) for 30 minutes at 4° C. Cells were then incubated with anti-α11 antibodies at the doses described in each figure for 30 minutes at 4° C. A human anti-α11 antibody (Creative BioLabs) was included as a positive control as well as the appropriate IgG isotype negative controls. Cells were washed twice and incubated with PE conjugated secondary antibodies specific to the IgG class of the anti-α11 antibodies being tested for 30 minutes at 4° C. Cells were washed twice and fixed in 1% PFA for 30 minutes. Cells were acquired on a FACS Verse (Benton Dickson) binding of each antibody. Data were analyzed by gating on single cells and determining the geometric Mean Fluorescence Intensity (gMFI) in the PE channel for each sample.


Surface Plasmon Resonance (SPR)

The affinity of antibodies for human α11β1 was measured by surface plasmon resonance assay (SPR). Affinity was measured at pH 7.6 and 25° C. with a Biacore T200 instrument. Anti-HIS antibody was immobilized on the SPR sensor surface using EDC/NHS covalent attachment. HIS-tagged human α11β1 was captured on the sensor surface and a single-cycle kinetics assay was used. Increasing concentrations of test antibody were injected in series over the sensor-bound α11β1. Dissociation was monitored for 1000 seconds. A sensor surface with only anti-HIS antibody and a series of blank injections were used to double-reference subtract the data. A 1:1 Langmuir model was fit to the data to estimate the kinetic association and dissociation constants. The affinity (equilibrium dissociation constant) of the interaction was calculated by dividing the kinetic dissociation constant by the kinetic association constant. Between injection cycles α11β1 and bound antibody were removed with an injection of 10 mM glycine at pH 1.5.


Cell Adhesion Inhibition

0.6×106 cells/mL were incubated with each antibody at a range of concentrations for 20 minutes at 37° C. E-Plate VIEW 96 PET plate coated with 100 ng/mL type I collagen or PBS overnight at room temperature was blocked in 3% BSA for 1 house at room temperature. After washing the plate with PBS, cell and antibody mixture was added to the wells and the plate was places into an xCelligence machine. Cell adhesion was recorded over 6 hours. The time point of maximum cell adhesion was used for comparison relative to control.


Fibroblast-to-Myofibroblasts Transition (FMT)

Human Pulmonary Fibroblasts (ScienCell) were cultured in complete Fibroblast Growth Medium (ScienCell) until 80% confluent. Cells were washed and harvested using Accutase. Cells were seeded onto tissue culture-treated 96 well plates at 20,000 cells/well in complete Fibroblast Growth Medium. After 24 hours, cells were washed and starved in serum reduced medium for an additional 24 hours. After starvation, cells were treated with TGFβ-1 (R&D Systems) with or without anti-α11 antibodies. A polyclonal rabbit anti-human α11 antibody was used as a positive control. Appropriate IgG isotype controls were also included. After 48 hours, cells were harvested, fixed, permeabilized and stained with AlexaFluor488 Labeled Anti-αSMA (α-smooth muscle actin) (Invitrogen). Cells were acquired on a FACS Verse (Benton Dickson) to determine expression levels of αSMA. Data were analyzed by gating on single cells and determining the geometric Mean Fluorescence Intensity (gMFI) in the FITC channel for each sample. gMFI for each sample was normalized to the untreated control and presented as % inhibition.


Collagen Gel Contraction Assay

24-well plates were blocked with 2% BSA in PBS overnight at 37° C. The following day, the plates were washed 3 times with PBS before being used in the assay. Human CHO cell lines expressing α11 were harvested and resuspended at 1.25×106 in ExpiCHO Expression Medium (Gibco™ Cat #A2910002). The collagen gel solution was prepared by diluting 3 mg/mL stock collagen type I (Gibco™ Collagen I Rat Protein, Tail Cat #A1048301) to 1 mg/mL in the media containing the CHO cells. Sodium hydroxide was added to the solution to neutralize the pH and 400 μL of the collagen solution was added to each well of the 24-well plates. For the wells where the antibodies were included in the collagen gel solution, CHO cells were prepared at 2.5×106 and the antibodies were prepared at 2× final concentration in ExpiCHO media. The cells and antibodies were then combined 1:1 before the addition of the stock collagen type 1. The gels were allowed to polymerize for 60 minutes at 37° C. Antibodies were added to the ExpiCHO media, which was then layered on top of the polymerized gel (400 μL/well). The gels were incubated for 6 days at 37° C. before gel contraction was quantified. Images of each well were analyzed using Image J and gel contraction was determined as a percentage of the initial gel area.


Tumor Xenograft Model

Fifty-six female C.B-17 SCID mice were inoculated with A549 cells (5×106 cells/mouse) subcutaneously in the flank. Once tumor volume reached ˜100 mm3, animals were randomized amongst 7 groups of 8 mice each. Mice were then treated intraperitonealy every 3 days for a total of 7 doses with isotype controls or novel mAbs 79E3E3, 16E10 and 9G04 (2 and 20 mg/kg) or with docetaxel at 10 mg/kg every 4 days for a total of 6 doses. Tumor volumes and body weights were recorded twice a week with a gap of 2-3 days in between two measurements until any of the following conditions defined were observed: loss of 20% or more body weight; tumors that inhibit normal physiological function such as eating, drinking, and mobility; ulcerated tumors; tumor size greater than 2000 mm3 and clinical observations of prostration, paralysis, seizures and hemorrhages.


Precision-Cut Liver Slices (PCLS)

Precision-Cut Liver Slices (PCLS) were prepared from resected liver tissue and rested for 24 hours to allow the post-slicing stress period to elapse before experiments began. PCLS were cultured without exogenous challenge (Group 1), with 100 μg/mL control antibodies (Groups 2 and 3—either mouse IgG2a or rabbit IgG), or with a combination of TGF-β1 (3 ng/mL) and PDGF-ββ (50 ng/mL) (Groups 2-10). PCLS were cultured in the presence or absence of 10 μM Alk5i (Group 4) as a positive control or novel inhibitors (16E10, 79E3E3, and 9G05) at 2 escalating doses (10 and 100 μg/mL) in Groups 5-10. Each of the 10 groups included n=6 human PCLS prepared from a single human liver. PCLS culture media, including all stimuli and compounds, was refreshed and harvested at 24 hour intervals. Cell culture supernatant (n=⅔ paired wells) was collected every 24 hours and snap frozen for quantification of soluble outputs. All PCLS were harvested at 96 hours.


Tissue culture levels of markers of liver damage (lactate dehydrogenase (LDH) and aspartate transaminase (AST)) and hepatocyte function/viability (albumin) were quantified on all PCLS at all time points. Albumin secretion was quantified by ELISA as a marker of PCLS integrity and function. Levels of collagen 1a1, IL-6, hyaluronic acid and Timp-1 in the cell culture supernatants were quantified using R&D Duoset ELISA kits.


Total RNA extraction from PCLS was performed on all samples. RNeasy Mini kits (Qiagen) were used for RNA extraction. RNA was reverse-transcribed to cDNA and used in qPCR to measure transcript levels of Col1a1, αSMA, TIMP-1, TGF-β1, IL-6 and β-actin/GAPDH.


Example 1. Generation of Novel Monoclonal Antibodies Against α11β1 and Determination of Binding Affinity

Antibody discovery was performed by immunizing rats and rabbits with recombinant human α11β1, and by immunizing mice with both human and mouse α11β1. 51 novel anti-human α11β1 monoclonal antibodies were generated (24 rabbit, 7 rat and 20 mouse). Heavy chain and light chain variable region sequences were determined for the mouse and rat antibodies, while full heavy chain and light chain sequences were determined for the rabbit antibodies.


ELISA results illustrating exemplary binding of selected mouse monoclonal antibodies to recombinant human α11β1 are shown in FIG. 2A. Three of those mAbs also bound to mouse α11β1, as shown in FIG. 2B.


22 Data was also collected to determine whether antibodies of interest bind to the I domain of α11β1. An in-house generated I domain of α11β1 was used. The rat clones 79E3E3, 8H8E9 and 6E5C11 exhibited high, medium, and low binding, respectively, as determined by ELISA. Mouse antibodies 10-F23, 10-L15, 7-O8, 6-A12, 9-G05 and 9-E16 and rabbit antibodies 7-H-12 and 2-D3 were also tested for binding against the in-house generated α11031 domain. FIGS. 3A and 3B show graphs illustrating binding data from exemplary mAbs.


α11β1 belongs to a family of collagen receptors and has a relatively high homology to them. Therefore, the novel antibodies of this invention were counter-screened against α1β1, α2β1 and/or α10β1. Table 2 includes results of cross-reactivity to the other receptors.









TABLE 2







Data summary of tested monoclonal antibodies



























Inhibition













of

Inhibition




Human
Murine

I
CHO-


CHO-K1

of CHO-




α11β1
α11β1
Off
Domain
K1
HPF
MF
adhesion to
Inhibition
K1 gel



Clone ID
ELISA
ELISA
Target
binding
FACS
FACS
FACS
collagen
of FMT
contraction





MOUSE
10-L15
Yes
Yes
No
Yes
No
No
No
No
No




8-I14
Yes
Yes
No
No
Yes
No
Yes
No
Yes
No



3-G5
Yes
Yes/Low
No
No
No
No
No
No
No




2-A3
Yes
Yes/Low
No
No
No
No
No
No
No




8-G15
Yes
No
No
No
Yes
No
Yes
Yes
Yes




8-P20
Yes
No
No
No
Yes
No
Yes
No
No




10-F23
Yes
Yes/Low
No
Yes
Yes
No
Yes
Yes
No




7-O8
Yes
Yes/Low
Yes
Yes
Yes
No
Yes
No
No







(α10β1)










8-J17
Yes
No
Yes
No
Yes
No
Yes
No
Yes







(at high













doses)










9-E16
Yes
Yes
No
Yes
Yes
Low
Yes
Yes
Yes




9-G05
Yes
Yes
No
Yes
Yes
No
Yes
Yes
Yes
Yes



10-K10
Yes
Yes/Low
No
No
No
No
Yes
No
No




6-O12
Yes
No
No
No
No
No
No
No
No




6-A15
Yes
Yes/Low
No
No
No
No
No
No
No




6-B21
Yes
Yes/Low
No
No
No
No
No
No
No




6-A12
Yes
Yes/Low
No
Yes
Yes
No
Yes
Yes
No




6-M8
Yes
No
No
No
No
No
No
No
No




6-P20
Yes
No
No
No
Yes
No
No
No
No




6-O17
Yes
Yes/Low
No
No
Yes
No
Yes
No
No




9-B11
Yes
No
No
Yes
Yes
No
Yes
Yes
Yes
No



7-H14
Yes
Yes/Low
No
No
Yes
No
Yes
No
No



RAT
24E4G6
Yes
No/Low
No
No
Yes
No
Yes
No
Yes
Yes



40G10H11
Yes
Yes
Yes (all)
No
Yes
N/A
N/A
Yes
Yes




18E10F10
Yes
No
No
No
Yes
N/A
N/A
Yes
Yes




8H8E9
Yes
No
No
No
Yes
N/A
N/A
Yes
Yes




6E5C11
Yes
No
No
No
Yes
N/A
N/A
No
Yes




7D8B10
Yes
No
No
No
Yes
No
Yes
No
Yes




79E3E3
Yes
Yes
No
Yes
Yes
No
Yes
Yes
No
Yes


RABBIT
16E10
Yes
No
No
No
Yes
No
Yes
Yes
Yes
Yes



6F9
Yes
No
No
No
Yes
No
Yes
Yes
No




6G4
Yes
No
No
No
Yes
No
Yes
Yes
No




4E1
Yes
No
No
No
Yes
No
Yes
Yes
No




6C7
Yes
No
No
No
Yes
No
Yes
Yes
No




5D7
Yes
No
No
No
Yes
No
Yes
Yes
No




5A7
Yes
No
No
No
Yes
No
Yes
Yes
No




3B1
Yes
No
No
No
Yes
No
Yes
Yes
No




16G7
Yes
Yes
No
No
Yes
No
Yes
No
Yes
No





N/A = not tested






Since integrins are large, transmembrane receptors that exist in different conformational shapes, experiments were performed to confirm that the novel antibodies also bound cell-expressed α11β1. A CHO-K1 cell line that endogenously expressed high levels of the β1 subunit was engineered to stably express human α11 (CHO-K1 hu α11).



FIGS. 4A and 4B show selected rat and mouse mAbs that bound human α11β1 (as tested by ELISA) and also demonstrated binding ability to α11β1 expressed on the surface of CHO-K1 cells. FIGS. 11A and 11B show selected rabbit, rat, mouse and human mAbs that demonstrated binding ability to α11β1 expressed on the surface of CHO cells. Additionally, FIG. 14 shows selected fully human mAbs that demonstrated binding ability to α11β1 expressed on the surface of CHO cells. However, as shown in Table 1, there were several mAbs that were shown to bind α11β1 by ELISA, but did not bind cell-expressed α11β1.


Binding EC50 was estimated using data from Fluorescence-activated cell sorting (FACS) performed with CHO-K1 hu α11β1 cells. The results are shown in Table 3. Four out of six mAbs tested had EC50 results in the low nanomolar range (8-P20, 8-G15, 8-J17, 8-l14), while the remaining two mAbs were not as potent (9-G05 and 9-E16; both I domain binders).









TABLE 3







Estimated CHO-K1 binding EC50 for mouse mAbs











mAb
Conc. (μg/mL)
Molarity (nM)















9-G05
21.03
140.2



8-P20
0.12
0.8



8-G15
0.22
1.5



8-J17
0.33
2.2



8-I14
1.22
8.1



9-E16
42.80
285.3










As shown in FIG. 9, when antibodies 16E10, 79E3E3, 9G05 and 1994_01_C07 were tested for their affinity to human α11β1 via surface plasmon resonance (SPR), they exhibited KDs of 48 pM, 10 pM, 2.85 nM and 0.77 nM, respectively. Interestingly, 16E10 and 1994_01_C07 do not bind either the I domain or the headpiece domain of α11β1, which indicates that both might act as allosteric inhibitors by not binding to the ligand binding domain but still inhibiting α11β1 function. 9G05 and 79E3E3 do bind to the I domain (the ligand binding domain) and therefore might directly inhibit the ligand binding site. The binding affinity of antibodies for the α11β1 Headpiece and α11β1 I Domain as measured by SPR is shown in FIG. 10A and FIG. 10B, respectively.


Binding to a physiologically relevant primary human cell type was also tested. Human pulmonary fibroblasts (HPF) and TGFβ treatment were used to induce a fibroblast-to-myofibroblast transition (FMT), giving rise to myofibroblasts (MF). While HPFs do not express α11β1, significant expression of α11β1 is exhibited by MFs. Additionally, HPFs express α11 and α2β1, other collagen binding receptors, which means that HPFs can be to test cross-reactivity of antibodies of interest. Selected mAbs were assessed for binding to HPFs and MFs, and as shown in FIG. 5, FIG. 12, and FIG. 13, it is apparent that the tested antibodies bound MFs strongly while not binding HPFs, with the exception of 9-E16, which showed some HPF binding, indicative of off-target binding.


Example 2. Biological Activity of Novel Monoclonal Antibodies Against α11β1

Myofibroblasts are responsible for secreting fibrotic matrix, so blocking and/or reducing MF accumulation is an important step for treating and/or preventing fibrosis. This can be achieved by using anti-α11β1 antibodies to inhibit the fibroblast-to-myofibroblast transition. Typical functional inhibitors of a receptor block ligand binding, and while preventing the binding of α11β1 to type I collagen is a desired feature of anti-α11β1 antibodies, it may not be necessary for therapeutic efficacy. Unlike many other receptors, integrins are able to perform both “outside-in” (canonical, ligand-mediated) signaling and also “inside-out” signaling. Therefore, it might be possible for an antibody to bind α11β1 in a way that affects the structure of α11 in a way that prevents inside-out signaling and FMT, but does not affect the ability of α11β1 to bind type I collagen. For this reason, both mAbs that block ligand binding and those that do not were included these studies.


A CHO-K1 hu α11 cell line was used to assess the ability of mAbs to block α11β1-mediated binding to type I collagen. As shown in FIG. 6A, out of three rat mAbs tested, two significantly inhibited adhesion of CHO-K1 hu α11 cells to type I collagen-coated plates. In the “Untreated” condition, cells were plated on type I collagen but no antibody was added and in the “Uncoated” condition, cells were seeded onto BSA-coated wells containing no type I collagen. Statistics were performed using one-way ANOVA followed by Dunnett's multiple comparisons test. 79E3E3, which is an I-domain binder, was able to block cell adhesion with an IC50 of 9.4 nM. However, 40G10H11 strongly inhibited cell adhesion but was not found to be an I-domain binder, though it does cross-react with other collagen receptors (α1β1, a2β1 and a10β1). 24E4G6 did not bind to the I-domain nor did it inhibit cell adhesion to collagen. When rabbit mAbs were tested, eight of the nine mAbs strongly and significantly inhibited cell adhesion and none of those mAbs were found to be I-domain binders (FIG. 6B). Therefore, it is possible that these mAbs bind on an α11β1 domain that keeps the integrin in a low or intermediate affinity state. FIG. 6C shows the activity of selected mouse mAbs. Three of six mAbs significantly blocked cell adhesion, and two of those mAbs were found to be I-domain binders (9-G05 and 9-E16). 8-G15, however, is a strong blocker of cell adhesion but was not found to bind the I-domain. 8-P20, 8-J17 and 8-I14 did not block cell adhesion to type I collagen. Nine human mAbs were also tested for their ability to inhibit the binding of human CHO-α11 cells to type I collagen. As shown in FIGS. 15A and 15B, all of the human Abs inhibited cell adhesion relative to the control, with 1994-01-C07 having an IC50 of 3.3 nM. As illustrated by these data (and summarized in Table 1), some anti-α11β1 mAbs were found to strongly bind human α11β1 when tested by ELISA and FACS, but not all of those antibodies were able to block ligand interaction. Furthermore, binding to the I-domain (ligand binding domain on α11β1) was found to not be necessary for blocking the interaction of α11β1 with type I collagen.


In addition to the binding abilities described above, it is important for an anti-α11β1 antibody to inhibit the fibroblast-to-myofibroblast transition (FMT). It is now appreciated that myofibroblasts are a heterogeneous cell population, existing in different activation states, with the main function of producing and contracting collagen extracellular matrix (ECM). FMT is a multi-step event that is controlled by a changing mechanical environment in tissues undergoing repair. TGFβ is one of the potent factors that potentiates this process and alpha smooth muscle actin (αSMA) is one of the main markers that becomes overexpressed when fibroblasts are undergoing the transition to becoming myofibroblasts. The presence of αSMA enhances fibroblast contraction and guides myofibroblast activation through an intracellular feedback loop. Because αSMA is the main molecular marker of myofibroblasts, the ability of the novel anti-α11β1 mAbs to inhibit αSMA expression in TGFβ-induced FMT was tested.


As shown in FIG. 7A, two rat mAbs (40G10H11 and 24E4G6) significantly inhibited αSMA expression compared to control, but neither of the antibodies was found to be an I-domain binder. Statistics were performed using one-way ANOVA followed by Dunnett's multiple comparisons test. Furthermore, only 40G10H11 inhibited cell adhesion to type I collagen. Interestingly, the 79E3E3 mAb was found to be an I-domain binder and strongly inhibited cell adhesion to collagen but failed to decrease αSMA expression (a surrogate for myofibroblast generation). As shown in FIG. 7B, two rabbit mAbs significantly inhibited αSMA expression compared to control, but neither of the antibodies was found to be an I-domain binder. 16E10 was found to inhibit both ligand binding and FMT (% inhibition of αSMA upregulation), but 16G7 was found to inhibit FMT but didn't have an effect on cell adhesion to collagen. Finally, as shown in FIG. 7C, five of the six tested mouse mAb significantly inhibited αSMA expression compared to control. Three of the FMT inhibitors (9-G05, 8-G15, 9-E16) were also found to decrease cell adhesion to collagen and two of those (9-G05, 9-E16) also bound the I domain. Mouse antibodies 8-J17 and 8-I14 only inhibited FMT and had effect on ligand binding.


Example 3. Ability of Selected Antibodies to Inhibit Cell-Mediated Contraction of Collagen Gels

Cell-mediated contraction of CD collagen I gels is a process previously shown to be α11β1-mediated, and a more recent study showed that α11β1-mediated downstream signaling was indispensable for gel contraction to occur. Selected exemplary antibodies were tested for the ability to inhibit cell-mediated 3D gel contraction because this ability is directly linked to the functionality of the exemplary antibodies.


As can be seen in FIG. 8, rat 79E3E3, mouse 9E16, 9G05 and 8114, rabbit 16E10, and human 1994_01_C07, 2004_04_B03, 2004_04_C12, and 1994_01_D12 antibodies all inhibited CHO-hu α11-mediated collagen gel contraction. Of note, CHO-hu α11 cells were able to contract collagen gel without the addition of TGFβ, as shown in the UT (untreated) condition. In the untreated condition, cells were embedded in the collagen gel but no antibody was added. Statistics were performed using one-way ANOVA followed by Dunnett's multiple comparisons test; each treatment conditions was compared to untreated condition. Asterisks indicate statistical significance and “ns” indicates that the difference was not statistically significant.


Example 4. Assessing Effect of Selected Antibodies on Tumor Xenograpt Growth

Previous studies have shown growth of A549 cell xenografts in α11 knockout SCID mice to be significantly impeded compared to wild-type mice. In this example, studies were performed to determine if inhibition of α11β1 function with mAb results in xenograft growth inhibition. As shown in FIG. 16 and Table 4, blocking α11β1 on mouse CAFs impeded xenograft growth in SCID mice. Specifically, 79E3E3, an effectorless mAb that cross-reacts with mouse α11β1, significantly inhibited tumor growth compared to isotype control, while 16E10, a mAb that does not bind mouse α11β1, showed no significant inhibition of tumor growth. Inhibition of tumor-expressed α11β1 did not affect tumor growth as 16E10 did not show any effect.









TABLE 4







Days to volume doubling after treatment with mAbs











Days to Volume Doubling



Treatment
(ave, 95% CI)







Mouse IgG2a
7.6 (7.3, 8.0)



Docetaxel
 11.0 (10.0, 12.0)



79E3E3 2mpk
8.5 (8.0, 9.0)



79E3E3 20mpk
8.5 (8.0, 9.0)



16E10 2mpk
7.9 (7.5, 8.3)



16E10 20mpk
7.9 (7.5, 8.3)










Example 5. Effect of Anti-α11β1 Antibodies on Human Precision-Cut Liver Slices (PCLS)

Precision-Cut Liver Slices (PCLS) from human liver tissue are physiologically and structurally representative of the tissue architecture and testing therapeutic targets in human PCLS allow for assessment of their effectiveness and relevance to the clinical situation, overcoming the limitations of in vivo rodent models and in vitro 2D cell culture methods. Tissue bioreactor technology maintains viability and functionality of PCLS from human liver tissue for at least 6 days in vitro.


As shown in FIGS. 17A-17C, all anti-α11-β1 antibodies that were tested provided partial inhibition of soluble pro-fibrogenic markers (COL1A1, hyaluronic acid and TIMP1) either in a dose-dependent manner or at the highest dose tested. No toxicity was observed after treatment with any of the antibodies (i.e., no elevation in ALT, AST, or albumin; data not shown).


EXEMPLARY SEQUENCES
DNA Sequences of Anti-α11β1 Monoclonal Antibodies
Rat mAb Sequences










Signal sequence-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4



79E3E3 Heavy Chain Variable Region


Signal sequence-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4


(SEQ ID NO: 1)




ATGGATTGGTTGTGGAACTTGCTATTCCTGATGGTAGTTGCCCAAAGTGCTCAAGCACAG







ATCCAGTTGGTACAGTCTGGACCTGAAGTAAAGAAGCCTGGAGAGTCAGTGAAGAT





CTCCTGCAAGGCCTCTGGGTATACCTTCACAGACTATGCAATGAACTGGGTGAAAC





AGGCTCCAGGAAATGGCCTGAAGTGGATGGGCTGGATCAACACCCAAACTGGAAA






GCCAACATATGCGGATGATTTCAAACAACGGTTTGTCTTCTCTTTGGAAACTTCTG






CCAGAACTACATATTTGCAGATCAACAACCTCAATATTGAAGACACAGCTACATATT





TCTGTACGAGATTGGGTACAGGTAATACGAAGGGGTTTGCTTACTGGGGCCAAG





GCACTCTGGTCACTGTCTCTTCA





79E3E3 Light Chain Variable Region


(SEQ ID NO: 2)




ATGGAATCACAGACGCATGTCCTCATTTCCCTTCTGCTCTGTGTATCAGGTACCTGTGGGG







ACATTTTGATAAACCAGTCTCCAGCCTCTCTGACTGTGTCAGCAGGAGAGAGGGTCA





CTATGAGCTGCAAGTCCAGTCAGAGTCTTCTATACAGTGAAAACAACCAGGACT






ATTTGGCTTGGTACCAGCAGAAACCAGGACAGTTTCCTAAATTGCTTATCTATGGG







GCATCCAACCGGCACACTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGA






CAGACTTCACTCTGACCATCAGCAGTGTGCAGGCTGAAGACCTGGCTGATTATTATT





GTGAGCAGACCTACAGATATCCATTCACGTTCGGCTCAGGGACGAAGTTGGAAAT





AAAA





24E4G6 Heavy Chain Variable Region


(SEQ ID NO: 3)




ATGGAGTTGGAATTGAGCTTAATTTTTATTTTTTCTCTTTTAAAAGATGTCCAGTGTGA







AGTACAGCTGGTGGAGTCTGGAGGAAGCTTGGTTCAACCTGGGGGTTCTCTGAAACTCT





CCTGTGTAGCCTCAGGATACACTTTCAGTAACTACTGGATGGACTGGGTTCGGCAGT





CTCCTGGAAAGTCCCTGGAATGGATTGGAGAGATTAACACGGATGGCAGAAGGAC






CAACTATGCACCATCCATAAAGGATCGATTCACAATCTCCAGAGACAATGCCAAG






AGCACCCTGTATCTGCAGATGAGCAATGTGAAATCAGATGACACAGCCATTTATTAC





TGTACCATACTACGGGTATACCCCCACTACTTTGATTACTGGGGCCAAGGAGTCA





TGGTCACAGTCTCCTCA





24E4G6 Light Chain Variable Region


(SEQ ID NO: 4)



ATGATGAGTCCTGCCCAGTTCCTGTTTCTGCTAATGCTCTGGATCCAGGAAGCCCGC






GGAGATGTTGTGATGACCCAGACACCACCGTCTTTGTCGGTTGCCATTGGACAATCA





GTCTCCATCTCTTGCAAGTCAAGTCAGAGCCTCGTATATAGTGATGGAGAGACAT






ATTTGCATTGGTTTTTACAGAGTCCTGGCAGGTCTCCGAAGCGCCTAATTTATCACG







TGTCTAATCTGGGCTCTGGAGTCCCTGACAGGTTCAGTGGCACTGGATCACTGACA






GATTTTACACTTAGAATCAGCAGAGTGGAGGCTGAGGATTTGGGAGTTTATTACTGC






GCGCAAACTACACATTTTCCTCCCACGTTTGGAGCTGGGACCAAGCTGGAACTGA






AA





8H8E9 Heavy Chain Variable Region


(SEQ ID NO: 5)




ATGGCTGTCCTGGTGCTGTTGCTCTGCCTGGTGACATTTCCAAGCTGTGCCCTGTCCCAG







GTGCAGTTGAAGGAGTCAGGACCTGGTCTGGTGCAGCCCTCACAGACCCTGTCCCTC





ACCTGCACTGTCTCTGGGTTCTCATTAACCAGCAATAGTGTTAGCTGGGTTCGCCA





GGCTCCGGGAAAGGGTCTGGAGTGGATGGGAGCAATATGGAGTGGTGGAAGCAC






AGATTATAATTCAGCTCTCAAATCCCGACTGAGCATCAGCAGGGACACCTCCAAG






AGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGAAGACACAGCCATTTACTTC





TGTACCAGATCTCACTGGGAGCCCTTTGATTACTGGGGCCAAGGAGTCATGGTCA





CAGTCTCCTCA





8H8E9 Light Chain Variable Region


(SEQ ID NO: 6)




ATGGAATCACAAACTCAGGCCCTCATATCCCTGCTGCTCTGGGTATATGGTACCTGTGGG







GACATTGTGATGACCCAGTCTCCATTCTCCCTGGCTGTGTCAGAAGGAGAGATGGTC





ACTATAAACTGCAAGTCCAGTCAGGGTCTTTTATCCAGTGGAAACCAAAAGAAC






TACTTGGCCTGGTACCAGCAGAGACCAGGGCAGTCTCCTAAACTACTGATCTACTA







TGCATCCACTAGGCAATCAGGGGTCCCTGATCGCTTCATAGGCGGTGGATCTGGGA






CAGACTTCACTCTGACCATCAGCGATGTGCAGGCTGAAGACCTGGCAGATTATTACT





GCCTGCAGCATTACAGCTATCCTCCCACGTTCGGTTCTGGGACCAAGCTGGAGAT





CAAA





6E5C11 Heavy Chain Variable Region


(SEQ ID NO: 7)




ATGGCTGTCCTGGTGCTGTTGCTCTGCCTGGTGACATTTCCAAGCTGTGCCCTGTCCCAG







GTGCAGCTGAGGGAGTCAGGACCTGGTCTGGTGCAGCCCTCACAGACCCTGTCCCTC





ACCTGCACTGTCTCTGGGTTCTCATTGACCAGCAATAGTGTGACCTGGGTTCGCCA





GCCTCCGGGAAAGGGTCTGGAGTGGATGGGAGCGATATGGAGTGATGGAAGCAC






AGATTATAATTCAACTCTCAAATCCCGACTGAGCATCAGTAGGGACACCTCCAAG






AGCCAAGTTTTCTTAAAAATGAGCAGTCTGCAAACTGAAGACACAGCCATTTACTTC





TGTACCAGATCCCACTGGGAGCCCTTTGATTACTGGGGCCAAGGAGTCATGGTCA





CAGTCTCCTCA





6E5C11 Light Chain Variable Region


(SEQ ID NO: 8)




ATGGAATCACAAACTCAGGCCCTCATATCCCTGCTGCTCTGGGTATATGGTACCTGTGGG







GACATTGTGATGACCCAGTCTCCACTCTCCCTGGCTGTGTCAGAAGGAGAGACGGTC





ACTATGAACTGCAAGTCCAGTCAGAGTCTTTTTTCCAGTGGAAATCAAAAGAAC






TACTTGGCCTGGTACCAGCAGAAACCAGGGCAGTCTCCTAAACTACTGATCTACTA







TGCATCCACTAGGCAATCAGGGGTCCCTGATCGCTTCATAGGCAGTGGATCTGGGA






CAGACTTCACTCTGACCATCAGCGATGTGCAGACTGAAGACCTGGCAGATTATTACT





GCCTGCAGCATTACAACTATCCTCCCACGTTCGGTTCTGGGACCAAGCTGGAGA





7D8B10 Heavy Chain Variable Region


(SEQ ID NO: 9)




ATGGACTTGCGACTGACTTATGTCTTTATTGTTGCTATTTTAAAAGGTGTCTTGTGTGAG







GTGAAACTGGAGGAATCTGGGGGAGGTTTGGTGCAACCTGGAATGTCCGTGAAACTCT





CTTGTGCAACCTCTGGATTCATTTTCAGTGACTACTGGATGGAATGGGTCCGCCAG





GCTCCAGGGAAGGGGCTAGAATGGGTAGCCGAAATTAGAAACAAAGCTAATAATT






ATGCAACATACTATGGGAAGTCTATGAAAGGCAGATTCACCATCTCAAGAGATGA






TTCCAAAAGTATAGTCTACCTACAAGTGAACAGCATAAGATCTGAAGATACTGCTAT





TTATTACTGTGCACCGAATTTTGATTACTGGGGCCAAGGAGTCATGGTCACGGTCTC





CTCA





7D8B10 Light Chain Variable Region


(SEQ ID NO: 10)




ATGAGTCCTGTCCAGTCCCTGTTTTTGCTATTGCTTTGGATTCTGGGAACCCATGGTGA







AGTTGTGCTGACCCAGACTCCACCCACTTTATCGGCTACCATTGGACAATCAGTCTCTA





TCTCTTGCAGGTCAAGTCAGAGTCTCTTACATAGTACTGGAAACACCTATTTAAAT





TGGTTGCTACAGAGGCCAGGCCAACCTCCGCAACTTCTAATTTATTTGGTTTCCAG






ACTGGAATCTGGGGTCCCCAACAGGTTCAGTGCCAGTGGGTCAGGAACTGATTTCA






CACTCAAAATCAGTGGAATAGAGGCTGAGGATTTGGGGGTTTATTACTGCGTGCAA






AGTTCCCATACTCCGTACACGTTTGGGACTGGGACCAAGCTGGAACTGAAA






18E10F10 Heavy Chain Variable Region


(SEQ ID NO: 11)




ATGGACATCAGGCTCAGCTTGGTTTTCCTTGTCCTTTTTATGAAAGGTGTCCAGTGTGA







GGTGCAGTTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAAGGTCCCTGAAACTCT





CCTGTGCAGCCTCACGATTCACTTTTAGTGACTATAACATGGCCTGGGTCCGCCAG





GCTCCAAAGAAGGGTCTGGAGTGGGTCGCAACCATTTATCATGATGATAGTGGTT






CTTACTATCGAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAAATAATGCAAA






AAGCACTCTGTACCTGCAGATGGACAGTCTGAGGTCTGAGGACATGGCCACTTATTA





CTGTGCAAGACATAACAATGGCTTTGATTACTGGGGCCAAGGAGTCATGGTCACA





GTCGCCTCA





18E10F10 Light Chain Variable Region


(SEQ ID NO: 12)




ATGAAGTGGCCTGTTAGGCTGTTGGTGCTGTTCTTCTGGATTCCTGCTTCCGGGGGTGAT







GTTGTGATGACACAAACTCCAGTCTCCCTGCCTGTCCGCCTTGGAGGTCAAGCCTCT





ATCTCTTGCCGGTCAAGTCAGAGCCTGGTACACAGTAATGGAAACACCTACTTG






CATTGGTACCTACAGAAGCCAGGCCAGTCTCCACAGCTCCTCATCAATCGGGTTTC







CAACAGATTTTCTGGGGTGCCAGACAGGTTCAGTGGCAGTGGGTCAGGGACAGATT






TCACCCTCAAGATCAACAGAGTAGAGCCTGAGGACTTGGGAGATTATTACTGCTTA






CAAAGTACACATTTTCCACTCACGTTCGGTTCTGGGACCAAGCTGGAGACCAAA






40G10H11 Heavy Chain Variable Region


(SEQ ID NO: 13)




ATGGACATCAGGCTCAGCTTGGGTTTCCTTGTCCTTTTCATAAAAGGTGACCAGTGTGC







GGTGCAACTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAAGGTCCCTGAAACTC





TCCTGTGCAGCCTCAAGAATCACTTTCACTGACTATTACATGGCCTGGGTCCGCCA





GGCTCCAACGAAGGGTCTGGAGTGGGTCGCAACCATTAGTTCTGATGGTGGTGAC






ACTTTCTATCGAGACTCCGTGAAGGGCCGATTTACTATCTCCAGAGACAATGCAA






AAAGCACCCTATATTTGCAAATGGTCAGTCTGAGGTCTGAGGACACGGCCACTTATT





ACTGTTCAACAGATCGGGGAGCTCAGTTTGGTTACTGGGGCCAAGGCACTCTGGT





CACTGTCTCTTCA





40G10H11 Light Chain Variable Region


(SEQ ID NO: 14)




ATGGCTCCAGTCCAGCTCTTAGGGCTGCTGCTGATTTGGCTCCCAGCCATGAGATGTG







ACATCCAGATGACCCAGTCTCCTTCATTCCTGTCTGCATCTGTGGGAGACAGAGTCTC





TATCAACTGCAAAGCAAGTCAGAATGTTCACGAGAACCTAAACTGGTATCAGCAAA





AGCTTGGAGAAGCTCCCAAACGCCTGATATATAATACAAACAATTTGCAAACAGG





CATCCCATCAAGGTTCAGTGGCAGTGGATCTGGTGCAGATTACACACTCACCATCAG





CAGCCTGCAGCCTGAAGATTTTGCCACATATTTCTGTTTGCAGCATAATGCTTTTC






CGTACACGTTTGGACCTGGGACGAAGCTGGAACTGAAA







Mouse mAb Sequences











9-G05 Heavy Chain Variable Region



(SEQ ID NO: 15)



GAGGTCCAGCTGCAACAGTCTGGACCTGAGCTGGT






GAAGCCTGGGGCTTCAGTGAAGATACCCTGCAAGG






CTTCTGGATACACATTCCCTGACTACAACATGGAC






TGGGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTG






GATTGGATATATTAATCCTGACAATGGTGGTACTA






TCTACAACCAGAAGTTCAAGGGCAAGGCCACATTG






ACTGTAGACAAGTCCTCCAGCACAGCCTACATGGA






GCTCCGCAGCCTGACATCTGAGGACACTGCAGTCT






ATTACTGTGCAAGATTAGACAGCTCAGGCTACGGT






TACTATGCTATGGACTACTGGGGTCAAGGAACCTC






AGTCACCGTCTCCTCA






9-G05 Light Chain Variable Region



(SEQ ID NO: 16)



GACATTGTGCTGACCCAATCTCCAGCTTCTTTGGC






TGTGTCTCTAGGGCAGAGGGCCACCATCTCCTGCA






GAGCCAGCGAAAGTGTTGATAATTATGGCATTAGT






TTTATGCACTGGTACCAGCAGAAACCAGGACAGCC






ACCCAAACTCCTCATCTATCGTGCATCCAACCTAG






ACTCTGAGATCCCTGCCAGGTTCAGTGGCAGTGGG






TCTAGGACAGACTTCACCCTCACCATTGATCCTGT






GGAGACTGATGATGTTGCAACCTATTACTGTCAGC






AAAGTTATAAGGATCCTCGGACGTTCGGTGGAGGC






ACCAAGCTGGAAATCAAA






8-P20 Heavy Chain Variable Region



(SEQ ID NO: 17)



AAAGTGATGCTGGTGGAGTCTGGGGGAGCCTTAGT






GAAGCCTGGAGGGTCCCTGAAACTCTCCTGTGTAG






CCTCTGGATTCACTTTCAGTAACTATGCCATGTCT






TGGGTTCGCCAGACTCCAGAGAAGAGGCTGGAGTG






GGTCGCAACCATTAGTAGTGGTGGTTATTACACTT






ACTATCCAGACAGTGTGAAGGGTCGATTCACCATC






TCCAGAGACAATGCCAGGAACACCCTGTTCCTGCA






AATGAGCAGTCTGAGGTCTGAGGACACGGCCATGT






TTTACTGTGCAAGAGAGGATGATTACGGAAGATAT






TCCTATACTATGGACTACTGGGGTCAAGGAACCTC






AGTCACCGTCTCCTCA






8-P20 Light Chain Variable Region



(SEQ ID NO: 18)



GATGTTGTGATGACCCAAACTCCACTCTCCCTGCC






TGTCAGTCTTGGAGATCAAGTCTCCATCTCTTGCA






GATGTAGTCAGAGCCTTGTACACAGTAATGGAAAC






ACCTATTTACATTGGTACCTGCAGAAGCCAGGCCA






GTCTCCACAGCTCCTGATCTACAAAATTTCCAACC






GATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTCAAGATCAGCAG






AGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCT






CTCAAAGTACACATGTTCCGTACACGTTCGGAGGG






GGGACCGAGCTGGAAATAAAA






8-G15 Heavy Chain Variable Region



(SEQ ID NO: 19)



GAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGT






AAAGCCTGGGGCTTCAGTGAGGATATCCTGCAAGG






CTTCTGGATACACATTCACTGACTACTACATACAC






TGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAATG






CATTGGAGAGATTTATCCTGGAACTGATAATACTT






ACTACAGTAAAAAATTCAGGGGCAAGGCCACACTG






ACTGCAGACAAATCCTCCGACACAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTTCTGTGCAAGAGGAGACTACTATAGGGGGTAC






TTCGATGTCTGGGGCGCAGGGACCACGGTCACCGT






CTCCTCA






8-G15 Light Chain Variable Region



(SEQ ID NO: 20)



GATGTTGTGATGACTCAGACCTCACTCACTTTGTC






GGTTACCATTGGACAACCAGCCTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTACATAGTAATGGAAAG






ACATATTTGAATTGGTTATTACAGAGGCCAGGCCA






GTCTCCAAAGTTCCTAATCTATCTGGTGTCTAAAC






TGGAATCTGGAGTCCCTGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTGAAAATCAGCAG






AGTGGAGGCTGAGGATTTGGGGGTTTATTACTGCT






TGCAATCTACACATTTTCCTTGGACGTTCGGTGGA






GGCACCAAGCTGGAAATCAAA






8-114 Heavy Chain Variable Region



(SEQ ID NO: 21)



GAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGT






AAAGCCTGGGGCTTCAGTGAAGAAATCCTGCAAGG






CTTCTGGATACACATTCACTGACTACTACATGCAC






TGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAGTG






GATTGGAAAGATTTATCCTGGAAGTGGTAATACTC






ACTACAATGAGAAGTTCAAGGGCAAGGCCACACTG






ACTGCAGACAAATCCTCCAGCACAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTTCTGTGCAACCAATTACTACGGCTACAGGGCA






ATGAACTATTGGGGTCAAGGATCCTCAGTCACCGT






CTCCTCA






8-114 Light Chain Variable Region



(SEQ ID NO: 22)



GACATCCATTTGACCCAGTCTCCATCCTCCTTATC






TGCCTCTCTGGGAGAAAGAATCAGTCTCACTTGCC






GGGCAAGTCAGGACATTTATATTAGCTTAAACTGG






TTTCAGCAGAAACCAGATGGAACTATTAAACTCCT






GATCTACGGCACATCCAGTTTAGATTCTGGTGTCC






CCAAAAGGTTCAGTGGCAGTAGGTCTGGGTCAGAT






TATTCTCTCACCATCAGCAGCCTTGAGTCTGAAGA






TTTTGCAGACTATTACTGTCTACAATATGCTAGTT






CTCCGTACACGTTCGGAGGGGGGACCAAGCTGGAA






ATAAAA






9-E16 Heavy Chain Variable Region



(SEQ ID NO: 23)



GAGGTCCAGCTGCAGCAGTCTGGACCTGAGCTGGT






AAAGCCTGGGGCTTCAGTGAAGATATCCTGCAAGG






CTTCTGGATACACATTCACTGACTACTACATGCAC






TGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAGTG






GATTGGAGAGATTTATCCTGGAAGTGGTAATCCTT






ACTACAATGAGAAGTTCAAGGGCAAGGCCACACTG






ACTGCAGACAAATCATCCAGCTCAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTTCTGTGCAAGAACCTCCTACGGTAGAGTAGGG






ACAGGGTTTGCTTACTGGGGCCAAGGGACTCTGGT






CACTGTCTCTGCA






9-E16 Light Chain Variable Region



(SEQ ID NO: 24)



AATTTTGTGATGACCCAAACTCCACTCTCCCTGCC






TGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCA






GATCTAGTCAGAGCCTTCTACACAGTAACGGAAAC






ACCTATTTACATTGGTACCTGCAGAAGCCAGGCCA






GTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACC






GATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTCAAGATCAACAG






AGTGGAGACTGAGGATCTGGGAATTTATTTCTGCT






CTCAAAGTTCACATGTTCCCACGTTCGGTGCTGGG






ACCAAGCTGGAGCTGAAA






8-J17 Heavy Chain Variable Region



(SEQ ID NO: 25)



CAGGTCCAGCTGCAGCAGTCTGGGGCTGAACTGGC






AAAACCTGGGGCCTCAGTGAAGATGTCCTGCAAGG






CTTCTGGCTACACCTTTACTAACTACTGGATGCAC






TGGGTAAAACAGAGGCCTGGACAGGGTCTGGAATG






GATTGGATACATTAATCCTAACAATGGTTATACTG






AGTACAATCAGCGATTCAAGGACAAGGCCACATTG






ACTGCAGACAGATCCTCCACCACAGCCTACATGCA






ACTAAGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTACTGTGCAAGATCCGATATCATTACGACAGAC






TACTGGGGCCAAGGCACCACTCTCACAGTCTCCTC






A






8-J17 Light Chain Variable Region



(SEQ ID NO: 26)



GATGTTGTGATGACCCAAACTCCACTCTCCCTGCC






TGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCA






GATCTAGTCAGAGCCTTGTATATAGTAATGGAAAT






ACCTATTTACATTGGTACCTGCAGAAGCCAGGCCA






GTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACC






GATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTCAAGATAAGCAG






AGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCT






CTCAAAGTACACATGTTCCGTGGACGTTCGGTGGA






GGCACCAAGCTGGAAATCAAA






6-O12 Heavy Chain Variable Region



(SEQ ID NO: 27)



GAAGTGAAGCTTGAGGAGTCTGGAGGAGGCTTGGT






GCAACCTGGAGGATCCATGAAACTCTCTTGTGCTG






CCTCTGGATTCACTTTTAGTGACGCCTGGATGGAC






TGGGTCCGCCAGTCTCCAGAGGCGGGGCTTGAGTG






GGTTGCTGAAATTAGAAACAAAGCTCATAATCCTG






CAACATACTATGCTGAGTCTGTGAAAGGGAGATTC






ACCATCTCAAGAGATGATTCCAAAAGTAGTGTCTA






CCTGCAAATGAACAGCTTAAGAGCTGAAGACACTG






GCATTTATTACTGTACCTTAGTAGCCCCTGATGCT






ATGGACTACTGGGGTCAAGGAACCTCAGTCACCGT






CTCCTCA






6-O12 Light Chain Variable Region



(SEQ ID NO: 28)



GACATTGTGATGTCACTGTCTCCATCCTCCCTAGC






TGTGTCAGTTGGAGAGAAGGTTACTATGAGCTGCA






AGTCCAGTCAGAGCCTTTTATATAGTCGCAATCAA






AAGAACTACTTGGCCTGGTACCAGCAGAAACCAGG






GCAGTCTCCTAAACTGCTGATTTACTGGGCATCCA






CTAGGGCATCTGGAGTCCCTGATCGCTTCACAGGC






AGTGGATCTGGGACAGATTTCACTCTCACCATCAG






CAGTGTGAAGGCTGAAGACCTGGCAGTTTATTACT






GTCAGCAATATTATAGCTATCCGTACACGTTCGGA






GGGGGGACCAAGCTGGAAATAAAA






10-L15 Heavy Chain Variable Region



(SEQ ID NO: 29)



CAGGTCCAACTGCAGCAGTCTGGGCCTGAGCTGGT






GAGGCCTGGGGCTTCAGTGAAGATGTCCTGCAAGG






CTTCAGGCTATACCTTCACCAGCTACTGGATGCAC






TGGGTGAAACAGAGGCCTGGACAAGGCCTTGAGTG






GATTGGCATGATTGATCCTTCCAATAGTGAAACTT






GGTTAAATCAGAAGTTCAAGGACAAGGCCACATTG






AATGTAGACAAATCCTCCAACACAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTACTGTGCAAGATATGATGGTTACTACGACTAC






TGGGGCCAAGGCACCACTCTCACAGTCTCCTCA






10-L15 Light Chain Variable Region



(SEQ ID NO: 30)



AACATTGTGCTGACCCAATCTCCAGCTTCTTTGGC






TGTGTCTCTAGGGCAGAGGGCCACCATATCCTGCA






GAGCCAGTGAAAGTGTTGATAGTTATGGCAATAGT






TTTATGCACTGGTACCAGCAGAAACCAGGACAGCC






ACCCAAACTCCTCATCTATCTTGCATCCAACGTAG






AATCTGGGGTCCCTGCCAGGTTCAGTGGCAGTGGG






TCTAGGACAGACTTCACCCTCACCATTGATCCTGT






GGAGGCTGATGATGCTGCAACCTATTACTGTCAGC






AAAATAATGAGGATCCGTGGACGTTCGGTGGAGGC






ACCAAGCTGGAAATCAAA






7-H14 Heavy Chain Variable Region



(SEQ ID NO: 31)



CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTGGT






GAGGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGC






CTTCTGGCTACACCTTCACCAGCTACTGGATGAAC






TGGGTGAAGCAGAGGCCTGGACAAGGCCTTGAATG






GATTGGTATGATTGATCCTTCAGACAGTGAAACTC






ACTACAATCAAATGTTCAAGGACAAGGCCACATTG






ACTGTTGACAAATCCTCCAACACAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCGGTCT






ATTACTGTGCGCAGATCTACTATGCTTACGACAAG






GCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTC






TGCA






7-H14 Light Chain Variable Region



(SEQ ID NO: 32)



GACATTGTGATGTCACAGTCTCCATCCTCCCTAGC






TGTGTCAGTTGGAGAGAAGGTTACTATGAGCTGCA






AGTCCAGTCAGAGCCTTTTATATAGTAGCCATCAA






AAGAACTACTTGGCCTGGTACCAGCAGAAACCAGG






GCAGTCTCCTAAACTGCTGATTTACTGGGCATCCA






CTAGGGAATCTGGGGTCCCTGATCGCTTCACAGGC






AGTGGATCTGGGACAGATTTCAGTCTCACCATCAG






CAGTGTGAAGGCTGAAGACCTGGCAGTTTATTACT






GTCAGGAATATTATAGCTGGACGTTCGGTGGAGGC






ACCAAGCTGGAAATCAAA






6-B21 Heavy Chain Variable Region



(SEQ ID NO: 33)



GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGT






GAAGCCTGGGGCTTCAGTGAAGATATCCTGTAAGG






CTTCTGGATACACGTTCACTGACTACTACATGAAC






TGGGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTG






GATTGGAGATATTAATCCTCACAATGGTGGTACTA






GCTTCATCCAGAAGTTCAAGGGCAAGGCCACATTG






ACTGTAGACAAGTCCTCCAGCACAGCCTACATGGA






GCTCCGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTATTGTGCCCCTCTGGGACGAAAGGAGGGGTTT






GCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTC






TGCA






6-B21 Light Chain Variable Region



(SEQ ID NO: 34)



GACACTGTGCTGACACAGTCTCCTGCTTCCTTAGT






TGTATCTCTGGGGCAGAGGGCCACCATCTCATGCA






GGGCCAGCAAAAGTGTCAGTACATCTGGCTATAGT






TATATGCACTGGTACCAACAGAAACCAGGACAGCC






ACCCAAACTCCTCATCTATCTTGCATCCAACCTAG






AATCTGGGGTCCCTGCCAGGTTCAGTGGCAGTGGG






TCTGGGACAGCCTTCACCCTCAACATCCATCCTGT






GGAGGAGGAGGATGCTGCAACCTATTACTGTCAGC






ACAGTAGGGAGCTTCCGTACACGTTCGGAGGGGGG






ACCAAGCTGGAAATAAAA






10-F23 Heavy Chain Variable Region



(SEQ ID NO: 35)



CAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATT






GCAGCCCTCCCAGACCCTCAGTCTGACTTGTTCTT






TCTCTGGGTTTTCACTGAGCACTTTTGCTATGGGT






GTAGGCTGGATTCGTCAGCCTTCAGGGAAGGGTCT






GGAGTGGCTGGCACACATTTGGTGGGATGATGATA






AGTACTATAACCCAGCCCTGAAGAGCCGGCTCACA






ATCTCCAAGGATACCTCCAAAAACCATGTATTCCT






CAAGATCGCCAATGTGGACACTGCAGATACTGCCA






CATACTACTGTGCTCGAATGCCGCTAACTTTCTAC






TTTGACTACTGGGGCCAAGGCACCACTCTCACAGT






CTCCTCA






10-F23 Light Chain Variable Region



(SEQ ID NO: 36)



GATGTTTTGCTGACCCAAACTCCACTCTCCCTGCC






TGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCA






GATCTAGTCAGAGCATTGTACATAGTAATGGACAC






ACCTATTTAGAATGGTACCTGCAGAAACCAGGCCA






GTCTCCAAAGCTCCTGATCTACAAAGTTTCCAACC






GATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTCAAGATCAGCAG






AGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCT






TTCAAGGTTCACATGTTCCGTTCACGTTCGGAGGG






GGGACCAAGCTGGAAATAAAA






6-A12 Heavy Chain Variable Region



(SEQ ID NO: 37)



CAGGTTACTCTGAAAGAGTCTGGCCCTGGGATATT






GCAGCCCTCCCAGACCCTCAGTCTGACTTGTTCTT






TCTCTGGGTTTTCACTGAGAACTTTTGCTATGGGT






GTAGGCTGGATTCGTCAGCCTTCAGGGAAGGGTCT






GGAGTGGCTGGCACACATTTGGTGGGATGATGATA






AGTACTATAACCCAGCCCTGAAGAGCCGGCTCACA






ATCTCCAAGGATACCTCCAAAAACCAGGTATTCCT






CAAGATCGCCAATGTGGACACTGCAGATACTGCCA






CATACTACTGTGCTCGAATGCCGCTAACTTTCTAC






TTTGACTACTGGGGCCAAGGCACCACTCTCACAGT






CTCCTCA






6-A12 Light Chain Variable Region



(SEQ ID NO: 38)



GATGTTTTGATGACCCAAACTCCACTCTCCCTGCC






TGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGTA






GATCTAGTCAGAGCATTGTACATAGTAATGGAAAC






ACCTATTTAGAATGGTACCTGCAGAAACCAGGCCA






GTCTCCAAAGCTCCTGATCTACAAAGTTTCCACCC






GATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTCAAGATCAGCAG






AGTGGAGGCTGAGGATCTGGGAGTTTATTACTGCT






TTCAAGGTTCACATGTTCCGTTCACGTTCGGAGGG






GGGACCAAGCTGGAAATAAAA






6-M8 Heavy Chain Variable Region



(SEQ ID NO: 39)



CAGGTCCAACTGCAGCAGCCTGGGGCTGAACTTGT






GATGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGG






CTTCTGGCTACACCTTCACCAACTACTGGATGCAC






TGGGTGAAACAGAGGCCTGGACAAGGCCTTGAGTG






GATCGGAGAGATTGATCCTTCTGATAGTTATACTA






ACTACAATCAAAAGTTCAAGGGCAAGGCCACATTG






ACTGTAGACAAATCCTCCAGCACAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCGGTCT






ATTACTGTACAAGACAGGGTAGTACCTACGCGTGG






GGTCAAGGAACCTCAGTCACCGTCTCCTCA






6-M8 Light Chain Variable Region



(SEQ ID NO: 40)



GATATTGTGATGACGCAGGCTGCATTCTCCAATCC






AGTCACTCTTGGAACATCAGCTTCCATCTCCTGCA






GGTCTAGTAAGAGTCTCCTACATAGTAATGGCATC






ACTTATTTGTATTGGTATCTGCAGAAGCCAGGCCA






GTCTCCTCAGCTCCTGATTTATCAGATGTCCAACC






TTGCCTCAGGAGTCCCAGACAGGTTCAGTAGCAGT






GGGTCAGGAACTGATTTCACACTGAGAATCAGCAG






AGTGGAGGCTGAGGATGTGGGTGTTTATTACTGTG






CTCAAAATCTAGAACTTCCTCCGACGTTCGGTGGA






GGCACCAAGCTGGAAATCAAA






2-A3 Heavy Chain Variable Region



(SEQ ID NO: 41)



GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGT






GAAGCCTGGGGCTTCAGTGAAGATGTCCTGTAAGG






CTTCTGGATACACATTCACTGACTACTACATGATG






TGGGTGAAGCAGAGTCATGGAAAGAGCCTTGAGTG






GATTGGAGATATTAATCCTTACAATGGTGGTTCTA






GCTACAACCCGAAGTTCAAGGGCAGGGCCACATTG






ACTGTAGACAAATCCTCCAGCACAGCCTACATGCA






GCTCAACAGCCTGACATCTGAGGACTCTGCAGTCT






ATTACTGTGCAAGAGGGACTTACTGGGGCCAAGGG






ACTCTGGTCACTGTCTCTGCA






2-A3 Light Chain Variable Region



(SEQ ID NO: 42)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






GGTTACCATTGGACAACCAGCCTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTAGATAGTGCTGGAAAG






ACATATTTGAATTGGTTGTTACAGAGGCCAGGCCA






GTCTCCAAAGCGCCTAATGTATCTGGTGTCTAAAC






TGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGC






GGATCAGGGACAGATTTCACACTGAAAATCAGCAG






AGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCT






GGCAAGGTACACATTTTCCGTACACGTTCGGAGGG






GGGACCAAGCTGGAAATAAAA






6-O17 Heavy Chain Variable Region



(SEQ ID NO: 43)



CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTTGT






GAAGCCTGGGGCTTCAGTGAAGTTGTCCTGCAAGG






CTTCTGGCTACACCTTCACCAGCTACTGGATGCAC






TGGATAAAGCAGAGACCTGGACAAGGCCTTGAGTG






GATTGGAGAGATTAACCCTAGCAATGGTGGTTCTA






ACTACAATGAGAAGTTCAAGAGCAAGGCCACACTG






ACTGTAGACAAATCCTCCAGCACAGCCTACATGCA






ACTCAGCAGCCTGACATCTGAGGACTCTGCGGTCT






ATCACTGTAAAAGCAGAGGCTACTGGGGCCAAGGC






ACCACTCTCACAGTCTCCTCA






6-O17 Light Chain Variable Region



(SEQ ID NO: 44)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






GGTTACCATTGGACAACCAGCCTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTAGATAGTTATGGAAAG






ACATATTTGAATTGGTTGTTACAGCGGCCAGGCCA






GTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAAT






TGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGT






GGATCAGGGACAGATTTCACACTGAAAATCAGCAG






AGTGGAGGCTGAGGATTTGGGAATTTATTATTGCT






GGCAAGGTACACATTTTCCTCACACGTTCGGCTCG






GGGACAAAGTTGGAAATAAAA






3-G5 Heavy Chain Variable Region



(SEQ ID NO: 45)



CAGGTTCAGCTGCAGCAGTCTGGAGCTGAGCTGGC






GAGGCCTGGGGCTTCAGTGAAACTGTCCTGCAAGG






CTTCTGGCTACACCTTCACAAGCTATGGTATAAGC






TGGGTGAAACAGAGAACTGGACAGGGCCTTGAGTG






GATTGGAGAGATTTTTCCTAGAAGTAGTAATACTT






ACTATAATGAGAAGTTCAAGGGCAAGGCCACACTG






ACTGCAGACAAGTCCTCCAGCACAGTGTACATGGA






GTTCCGCAGCCTGACATCTGAGGACTCTGCGGTCT






ATTTCTGTGCAAGAGAGGGGGGCCTGGCCTGGTTT






GCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTC






TGCA






3-G5 Light Chain Variable Region



(SEQ ID NO: 46)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






GGTTACCATTGGACAACCAGCTTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTATATACTAATGGAAAC






ACCTATTTGAATTGGTTATTACAGAGGCCAGGCCA






GTCTCCAAAACGCCTAATCTATCTGGTGTCTAAAT






TGGACTCTGGAATCCCTGACAGGTTCAGTGGCAGT






GGATCAGGGACAGATTTCACACTGAGAATCAGCAG






AGTGGAGGCTGAGGATTTGGGAGTTTATTACTGCT






TGCAGAGTACACATTTTCCATTCACGTTCGGCTCG






GGGACAAAGTTGGAAATAAAA






6-A15 Heavy Chain Variable Region



(SEQ ID NO: 47)



GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGT






GAAGCCTGGGGCTTCAGTGAAGATGTCCTGTAAGG






CTTCTGGATACACAATCACTGACTACTACATGATG






TGGTTGAAGCAGAGTCATGGAAAGAGCCTTGAATG






GATTGGAGATATTAATCCTTACACTGGTGGTACTA






GCTACAACCAGAAGTTCAAGGGCAAGGCCACATTG






ACTGTAGACAAATCCTCCAGCACAGCCTACCTGCA






GCTCCACAGCCTGACATCTGAGGACTCTGCAGTCT






ATTACTGTGCAAGAGGGGCCTACTGGGGCCAAGGC






ACCACTCTCACAGTCTCCTCA






6-A15 Light Chain Variable Region



(SEQ ID NO: 48)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






GGTTACCATTGGACAACCAGCCTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTAGATAGTGATGGAAAG






ACATATTTGAATTGGTTGTTACAGAGGCCAGGCCA






GTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAAC






TGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGT






GGATCAGGGACAGATTTCACACTGAAAATCAGCAG






AGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCT






GGCAAGGTACACATTTTCCGTACACGTTCGGAGGG






GGGACCAAGCTGGAAATAAAA






10-K10 Heavy Chain Variable Region



(SEQ ID NO: 49)



GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGT






GAAGCCTGGGGCTTCAGTGAAGATGTCCTGTAAGG






CTTCTGGATACACAATCACTGACTACTACATGATG






TGGTTGAAGCAGAGTCATGGAAAGAGCCTTGAATG






GATTGGAGATATTAATCCTTACACTGGTGGTACTA






GCTACAACCAGAAGTTCAAGGGCAAGGCCACATTG






ACTGTAGACAAATCCTCCAGCACAGCCTACATGCA






GCTCAACAGCCTGACATCTGAGGACTCTGCAGTCT






ATTACTGTGCAAGAGGGGCCTACTGGGGCCAAGGC






ACCACTCTCACAGTCTCCTCA






10-K10 Light Chain Variable Region



(SEQ ID NO: 50)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






GGTTACCATTGGACAACCAGCCTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTAGATAGTGATGGAAAG






ACATATTTGAATTGGTTGTTACAGAGGCCAGGCCA






GTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAAC






TGGACTCTGGAGTCCCTGACAGGTTCACTGGCAGT






GGATCAGGGACAGATTTCACACTGAAAATCAGCAG






AGTGGAGGCTGAGGATTTGGGAGTTTATTATTGCT






GGCAAGGTACACATTTTCCGTACACGTTCGGAGGG






GGGACCAAGCTGGAAATAAAA






6-P20 Heavy Chain Variable Region



(SEQ ID NO: 51)



GAGGTCCAGCTGCAACAATCTGGACCTGAGCTGGT






GAAGCCTGGGGCTTCAGTGAAGATATCCTGTAAGG






CTTCTGGATACACGTTCACTGACTACTACATGAAC






TGGGTGAAGCAGAGCCATGGCAGGAGCCTTGAGTT






GATTGGAGATATTAATCCTAACAATGGTGGTTCTA






ACTTCAACCAGAAGTTCAGGGGCAAGGCCACATTG






ACTGTAGACAAGTCCTCCAGCACAGCCTATATGGA






GCTCCGCAGCCTGACATCTGAGGACTCTGCAATCT






ATTACTGTGCAAGAATGGGTTACTGGGGCCAAGGG






ACTCTGGTCACTGTCTCTGCA






6-P20 Light Chain Variable Region



(SEQ ID NO: 52)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






GGTTACCATTGGACAACCAGCCTCCATCTCTTGCA






AGTCAAGTCAGAGCCTCTTACATAGTGATGGAAAG






ACATATTTGAATTGGATGTTCCAGAGGCCAGGCCA






GTCTCCAAAGCGCCTAATCTATCTGGTGTCTAAAC






TGGACTCTGGAGTCCCTTACAGGTTCACTGGCGGT






GGATCAGGGACAGATTTCACACTGCAAATCAGCAG






AGTGGAGACTGAGGATTTGGGAGTTTATTATTGCT






GGCAAGGTACACATTTTCCTCGGACGTTCGGTGGA






GGCACCAAGCTGGAAATCAAA






7-O8 Heavy Chain Variable Region



(SEQ ID NO: 53)



GAGGTCCAGCTGCAGCAGTCTGGACCTGAACTGGT






CAAGCCTGGGGCTTCAGTGAAGATGTCCTGCAAGG






CTTCTGGATACACATTCACTGACTACTACATACAC






TGGGTGAAGCAGAAGCCTGGGCAGGGCCTTGAGTA






CATTGGAGAGATTTATCCTGGAAGTGGTAATACTT






ACTACAATGGGAAGTTCAGGGGCAAGGCCACACTG






ACTGCAGACAAGTCCTCCAGCACAGCCTACATGCA






GCTCAGCAGCCTGACATCTGAGGACTCTGCAGTCT






ATTTCTGTGGTAGTGGCTACTTTGACTACTGGGGC






CAAGGCACCACTCTCACAGTCTCCTCA






7-O8 Light Chain Variable Region



(SEQ ID NO: 54)



GATGTTGTGATGACCCAGACTCCACTCACTTTGTC






TGTTACCATTGGACAGCCAGCTTCCATTTCTTGCA






AGTCAAGTCAGAGCCTCTTATATAGTAATGGAAAA






ACCTATTTGAATTGGTTATTACAGAGTCCAGGCCA






GTCTCCAAAGCTCCTAATCTATCTGGTGTCTAAAC






TGGAATCTGGAGTCCCTGACAGATTCAGTGGCAGT






GGATCAGGGACAGATTTTACACTGAAACTCAGCAG






AGTGGAGGCTGAGGATTTGGGAGTATATTACTGCG






TGCAAGGTACACATTTCCCATTCACGTTCGGCTCG






GGGACAAAGTTGGAAATAAAA






Rabbit mAb Sequences











A11B1_16G7 Heavy Chain



(SEQ ID NO: 55)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGTTCAAAG






GTGTCCAGTGTCAGGAGCAACTGGTGGAGTCCGGGGGAGACCTGGT






CAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTC






TCCTTCAATAAGAATTATTGGATGTGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGGATGCATTTATAATGGTGATGGCAA






CACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAAA






ACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCG






CGGACACGGCCATCTATTTCTGTGCGAGACTACTTAATATGTGGGG






CCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCA






TCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCA






CGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGT






GACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACC






TTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCG






TGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGC






CCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCG






ACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGAC






CGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGAT






CTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAG






GATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGG






TGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCAC






GATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTG






AGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGG






CCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGA






GCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGC






AGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCG






ACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTA






CAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTC






TACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACG






TCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACAC






GCAGAAGTCCATCTCCCGCTCTCCGG GTAAATAG






A11B1_16G7 Light Chain



(SEQ ID NO: 56)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCC






AGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTGAGAGCATTGGCAATGCATTAGCCTGGTATCAGCAGA






AACCAGGGCAGCCTCCCAAGCTCCTGATCTATACTGCAGCCACTCT






GGCATCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACA






GAGTTCACTCTCACCATCAGTGGCGTGCAGTGTGACGATGCTGCCA






CTTACTACTGTCAAAGCTATTATTTTACTAGTGTTAGTAGTTATGG






CAATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_16E10 Heavy Chain



(SEQ ID NO: 57)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCAGAGTCTCTGGATTCTCC






TTCAGTAGCAGTTATTATATGTGTTGGGTCCGCCAGGCTCCAGGGA






AGGGGCTGGAATGGATCGCATGTATTGGTACTACTCGTGGTAGCAC






TTACTACGCGACCTGGGCGAAAGGCCGATTCACCATTTCTAAAATC






TCGTCGACCACGGTGACTCTACAAATGACCAGTCTGACAGACGCGG






ACACGGCCACCTATTTCTGTGCGAGAGATGCTACTGGTTATAGGAT






TAACACGATTGGCCTCTATTTTAATTTGTGGGGCCCAGGCACCCTG






GTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCAC






TGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGG






CTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGG






AACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCC






GGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGAC






CTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACC






AACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGC






CCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCAT






CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCC






GAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGG






TGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCG






GCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTC






AGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGT






TCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAA






AACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTAC






ACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCC






TGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGA






GTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCG






ACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCT






CAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTC






CGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATC






TCCCGCTCTCCGGGTAAATAG






A11B1_16E10 Light Chain



(SEQ ID NO: 58)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCGTTCGAATTGACCCAGACTCCATC






CTCCGTGGAGGCTGCTGTGGGAGGCACGCCCACCATCAAGTGCCAG






GCCAGTCAGACCATTTACAGTTACTTATCCTGGTATCAGCAGAAAC






CAGGGCAGCCTCCCAAGCTCCTGATCTATGAAGCGTCCAAACTGGC






CTCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACAGAC






TACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTT






ACTACTGTCAAAGCTATCATGGTACTGCTAGTACTGAATATAATAC






TTTCGGCGGGGGGACCGAGGTGGTGGTCAGAGGTGATCCAGTTGCA






CCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTG






GAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGT






CACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATC






GAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACC






TCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAA






AGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAG






AGCTTCAATAGGGGTGACTGTTAG






A11B1_15G10 Heavy Chain



(SEQ ID NO: 59)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGCAGCAGCTGGTGGAGTCCGGGGGAGGCCTGGT






CAAGCCTGGGGCAGCCCTGACATTCACCTGCACAGCCTCTGGATTC






TCCTTCAGTGGCAATTATTGGATATGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGTTGGAGTGGATCGCGTGCATTGGTACTATTACTAGTAG






GACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATTTCCAAA






ACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCG






CGGACACGGCCACGTATTTCTGTGCGAGAGGTGCGGTTGTTAGTAG






TGGTAATGCTCCCTACTACTTTACCTTGTGGGGCCCAGGCACCCTG






GTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCAC






TGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGG






CTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGG






AACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCC






GGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGAC






CTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACC






AACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGC






CCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCAT






CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCC






GAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGG






TGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCG






GCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTC






AGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGT






TCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAA






AACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTAC






ACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCC






TGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGA






GTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCG






ACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCT






CAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTC






CGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATC






TCCCGCTCTCCGGGTAAATAG






A11B1_15G10 Light Chain



(SEQ ID NO: 60)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCATTCGAATTGACGCAGACTCCATC






CTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAG






GCCAGTCAGAGCATTAGTAGTTACTTATCCTGGTATCAGCAGAAAC






CAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCACTCTGGA






ATCTGGGGTCCCATCGCGGTTTAAAGGCAGTGGATCTGGGACAGAG






TTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTT






ACTTCTGTCAAAGCTATTATGGTGTTACTTTTAGTGGTTTTGCTTT






CGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCT






ACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAA






CAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCAC






CGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAG






AACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCA






GCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGA






GTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGC






TTCAATAGGGGTGACTGTTAG






A11B1_14H1 Heavy Chain



(SEQ ID NO: 61)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCAAAGCCTCTGGAATCGAC






TTCAATAACTATTGGATAACCTGGGTCCGCCAGGCTCCAGGGAAGG






GGCTGGAGTGGATCGCATGCATTTATGTTGGAATTACCGGCCGCAC






ATGGTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAGGCC






TCGAGCACGGTGGATCTGAAAATGACCAGTCTGACAGCCGCGGACA






CGGCCACCTATTTCTGTGCGAGGAATGGTGATGGTGGTATTTATGC






TCTTAACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGG






CAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGG






ACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTA






CCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACC






AATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCT






ACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGT






CACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAG






ACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTG






AACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAA






GGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTG






GTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACA






TAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCA






GCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCG






CACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACA






ACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAG






AGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGG






GAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACG






GCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAA






GGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGAC






GGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGT






GGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTT






GCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAA






TAG






A11B1_14H1 Light Chain



(SEQ ID NO: 62)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCACATTTGCACAAGTGCTGACCCAGACTGCATC






GTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAGTTGCCAG






TCCAGTCAGAGTGTTTATAATAATAATTGGTTAGCCTGGTATCAGC






AGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCATCCAC






TCTGACATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGG






ACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTG






CCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTTACGTAAA






TGATTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTT






GCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAA






CTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGA






TGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGC






ATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACA






ACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCA






CAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTC






CAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_13G4 Heavy Chain



(SEQ ID NO: 63)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGT






CAAGCCTGGGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTC






TCCTTCAGTAATACCTACTGGGCATGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGCATGCATGAATCCTGCTAGTAGTGG






TAGCTCTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCC






AAAACCTCGTCGACCACGGTGACTCTGCACATGCCCAGTCTGACAG






CCGCGGACACGGCCACCTATTTCTGTGCGAAATGGGATACTGCTTT






CGATGTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAA






CCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACA






CACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCT






CCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACCAAT






GGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACT






CGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCAC






CTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAGACC






GTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAAC






TCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGA






CACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTG






GACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACATAA






ACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCA






GTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCAC






CAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACA






AGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGG






GCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAG






GAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCT






TCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGC






AGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGACGGC






TCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGC






AGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCA






CAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_13G4 Light Chain



(SEQ ID NO: 64)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCCGATGTTGTGATGACCCAGACTCC






ATCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTCAGAGCATTAGTAGCTACTTAGCCTGGTATCAGCAGA






AACCAGGGCAGCCTCCCAAGCTCCTGATCTATGGTGCATCCAATCT






GGAGTCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GAGTACACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTGCCA






CTTACTACTGTCAAAACTATTATGCTATTGATACTTATGGTCATGC






TTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCA






CCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTG






GAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGT






CACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATC






GAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACC






TCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAA






AGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAG






AGCTTCAATAGGGGTGACTGTTAG






A11B1_13C3 Heavy Chain



(SEQ ID NO: 65)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGT






CAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTC






TCCTTTAGTAGCAACTATCACATCTGCTGGGTCCGCCAGGCTCCAG






GAAAGGGGCTGGAGTTGATCGCATGCATTTATGTTGGTGATGGCAG






CACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAA






TCCTCGTCGACCACGGTAGCTCTGCAAATGACCAGTCTGACAGCCG






CGGACACGGCCACCTATTTCTGTGGGAGAATGTTTAACTTGTGGGG






CCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCA






TCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCA






CGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGT






GACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACC






TTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCG






TGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGC






CCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCG






ACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGAC






CGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGAT






CTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAG






GATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGG






TGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCAC






GATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTG






AGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGG






CCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGA






GCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGC






AGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCG






ACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTA






CAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTC






TACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACG






TCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACAC






GCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_13C3 Light Chain



(SEQ ID NO: 66)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCATATGTGACCCTGTGCTGACCCAGACTCCATC






CTCCGTGTCTGCGGCTGTGGGAGTCACAGTCACCATCAACTGCCAG






TCCAGTCCGAGTGTTTATAGTAACTACTTATCCTGGTATCAGCAGA






AACCAGGGCAGCCTCCCAAGCTCCTCATCTATCTGGCATCTACTCT






GGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






CAGTTCACTCTCACCATCAGCGACGTGCAGTGTGACGATGCTGCCA






CTTACTACTGTGCAGGCACTTATAGTGGTAATATTTGGTCTTTCGG






CGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACT






GTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAG






TCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGT






CACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAAC






AGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCA






GCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTA






CACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTC






AATAGGGGTGACTGTTAG






A11B1_12F2 Heavy Chain



(SEQ ID NO: 67)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGCAGCAGCTGGTGGAGTCCGGGGGAGGCCTGGT






CAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTC






TCCTTCAGTAGCGGCTATCACATGTGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGCATGCTTTGGTGTTTATACTGGTAC






CACTACCTACGCGAGCTGGGCGAAAGGTCGATTCACCATCTCCAAA






ACCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTAACAGTCG






CGGACACGGCCACCTATTTCTGTGCGAGAATCAGTGCTGAAAATGG






TGGGGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGG






CAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGG






ACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTA






CCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACC






AATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCT






ACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGT






CACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAG






ACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTG






AACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAA






GGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTG






GTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACA






TAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCA






GCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCG






CACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACA






ACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAG






AGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGG






GAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACG






GCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAA






GGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGAC






GGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGT






GGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTT






GCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAA






TAG






A11B1_12F2 Light Chain



(SEQ ID NO: 68)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGATGTTGTGATGACCCAGACTCCAGC






CTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAG






GCCAGTCAGAGCATTAGCAACTACTTTTCTTGGTATCAGCAGAAAC






CAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCGTCCACTCTGGC






ATCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACAGAG






TTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATTCTGCCACTT






ACTACTGTCAGTGCACTTATGGTAGTAGTAGTACTGGTTTTGGTTT






CGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCT






ACTGTCCCCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAA






CAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCAC






CGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAG






AACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCA






GCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGA






GTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGC






TTCAATAGGGGTGACTGTTAG






A11B1_11D10 Heavy Chain



(SEQ ID NO: 69)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCATGGCCTCTGGAATCGAC






TTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGA






AGGGACTGGAGTATATCGGATACATTGATACTGGTGATGATAACAC






ATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACC






TCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGG






ACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTG






GGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCT






CCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCT






CCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCC






AGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGC






ACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCA






GCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGT






GGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCC






TCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGG






GACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCAT






GATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGC






CAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGC






AGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAG






CACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGG






CTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCC






CGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCT






GGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGC






AGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTT






CCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAA






CTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTC






CTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCG






ACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTA






CACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_11D10 Light Chain



(SEQ ID NO: 70)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGACTCCTACTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCC






AGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTCAGAGCATTAGTAGTTACTTAGCCTGGTATCAGCAGA






AACCAGGGCAGCGTCCCAAGCTCCTGATCTACAGGGCATCCACTCT






AAAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCA






CTTATTATTGTCAAGCGTATTATCTTAGTAGTAGTATCAGTTATGG






TAATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_10F9 Heavy Chain



(SEQ ID NO: 71)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCGTCCCTGACACTCACCTGCACAGCCTCTGGATTCTCC






CTCAGTAGCGGGTATGGCATGTGCTGGGTCCGCCAGGCTCCAGGGA






AGGGACTGGAGTGGATCGGATACACTGATACTGCTACTGGTACCAT






TCACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACC






TCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGG






ACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATGGACCTCTG






GGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCT






CCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCT






CCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCC






AGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGC






ACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCA






GCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGT






GGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCC






TCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGG






GACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCAT






GATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGC






CAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGC






AGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAG






CACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGG






CTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCC






CGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCT






GGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGC






AGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTT






CCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAA






CTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTC






CTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCG






ACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTA






CACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_10F9 Light Chain



(SEQ ID NO: 72)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCC






AGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTCAGAGCATTAGTAGCTACTTAGCCTGGTATCAGCAGA






AACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGACATCCACTCT






GGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCA






CTTACTATTGTCAAAGCTATGCTTATAGTAGTAGTAGCAGTTATGG






TAATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_7H12 Heavy Chain



(SEQ ID NO: 73)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCACAGGCTCTGGAATCGAC






TTCAGTAGCAGCTACTGGATATGCTGGGTCCGCCAGGCTCCAGGGA






AGGGGCTGGAGTGGATCGCATGCATCGATGGTAGTGATGGTAACAC






TTACTACGCGAGCTGGGCGAGAGGCCGATTCACCATCTCCAAAACC






TCGTCGACCACGGTGACTCTGCAAATGGCCAGTCTGACAGCCGCGG






ACACGGCCACCTATTTCTGTACGAGAGATCTCAGGTTGTGGGGCCC






AGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCA






GTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGG






TGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGAC






CGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTC






CCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGG






TGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCA






CCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACA






TGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGT






CTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTC






ACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGAT






GACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGC






GCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGAT






CCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGG






GGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCC






CCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCC






GAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGG






TCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACA






TCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAA






GACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTAC






AGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCT






TCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCA






GAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_7H12 Light Chain



(SEQ ID NO: 74)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGCTGACCCAGACTCC






AGCCTCGGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAACTGC






CAGGCCAGTCAGAATGTTTATAGTAACAATGCCTTAGCCTGGCATC






AGCAGAAACCAGGGCAGCGTCCCAACCTCCTGATCTACAAGGCTTC






CACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCT






GGGACACAGTTTACTCTCACCATCAGCGACGTGCAGTGTGACGATG






CTGCCACTTACTACTGTCTAGGCGAATTTAGTTGTAGTAGTGGTGA






TTGTTTTGTTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGAT






CCAGTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGG






TGGCAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTT






TCCCGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACA






ACTGGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTA






CCTACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAA






CAGCCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCA






GTCGTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_7G12 Heavy Chain



(SEQ ID NO: 75)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCATGGCCTCTGGAATCGAC






TTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGA






AGGGACTGGAGTATATCGGATACATTGATACTGGTGATGATAACAC






ATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACC






TCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGG






ACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTG






GGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCT






CCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCT






CCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCC






AGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGC






ACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCA






GCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGT






GGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCC






TCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGG






GACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCAT






GATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGC






CAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGC






AGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAG






CACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGG






CTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCC






CGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCT






GGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGC






AGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTT






CCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAA






CTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTC






CTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCG






ACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTA






CACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_7G12 Light Chain



(SEQ ID NO: 76)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGACTCCTACTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCC






AGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTCAGAGCATTAGTAGTTACTTAGCCTGGTATCAGCAGA






AACCAGGGCAGCGTCCCAAGCTCCTGATCTACAGGGCATCCACTCT






AAAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GAGTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCA






CTTATTATTGTCAAGCGTATTATCTTAGTAGTAGTATCAGTTATGG






TAATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_6G4 Heavy Chain



(SEQ ID NO: 77)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGCAGCAGCTGGAGGAGTCCGGGGGAGGCCTGGT






CAAGCCTGGAGGAACCCTGACACTCACCTGCAAAGCCTCTGGAGTC






GCCCTCAATCCCTACTACTATATGTGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGCATGCGTGGATGCTGATAGTAGTGG






TAGCACTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCC






AAAACCTCGTCGACCACGGTGACTCTGAAAATGACCAGTCTGACAG






CCGCGGACACGGCCACCTATTTCTGTGCGAGAGAATCGGTTGACTA






TAGTTCTGTTGGTATTGGCTATGTACATGGTACGGATGGCTTGTGG






GGCCCAGGCACCCTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTC






CATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCTC






CACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCA






GTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGCA






CCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAG






CGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGTG






GCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCCT






CGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGGG






ACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCATG






ATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCC






AGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGCA






GGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGC






ACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGGC






TGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCCC






GGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTG






GAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGCA






GCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTTC






CGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAAC






TACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTCC






TCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGA






CGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTAC






ACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_6G4 Light Chain



(SEQ ID NO: 78)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCCGACATCGTGGTGACCCAGACTCC






ATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTCAGAGCATTAGCAACTACTTTTCTTGGTATCAGCAGA






AACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCGTCCACTCT






GGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCA






CTTACTACTGTCAATGCACTTACGGTAGAAGTAATAGTAATTTTTT






TTATGGTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_6F9 Heavy Chain



(SEQ ID NO: 79)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCCGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCCTCCCTGACACTCACCTGCACAGCCTCTGGATCCTCC






TTCAGTAGTACCTACTGGAACTGCTGGGTCCGCCAGGCTCCAGGGA






AGGGGCTGGAGTGGATCGCATGCATTAATGCTGGTAGTGGTACCAC






TTACTACGCGAGCTGGGCGAAAGGCCGATTCACCGTCTCCAAAACC






TCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGG






ACACGGCCACCTATTTCTGTACGAGAGATAGTGATGGTCGTTTTAG






TAGTGGCTACTATTTTAACTTGTGGGGCCCAGGCACCCTGGTCACC






GTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCC






CCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCT






GGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCG






GGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGT






CCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAG






CAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACC






AAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGT






GCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCC






CCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTC






ACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGT






TCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCC






GCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACC






CTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGT






GCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCAT






CTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATG






GGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCT






GCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGA






GAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTG






CTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGC






CCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGAT






GCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGC






TCTCCGGGTAAATAG






A11B1_16F9 Light Chain



(SEQ ID NO: 80)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTGCATC






CCCTGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGTCAG






TCCAGTCAGAGTGTTTATGATAACAACTGGTTAGCCTGGTATCAGC






AAAAACCAGGGCAGCCTCCCAAACTCTTGATCGACGATGCATCCAA






ATTGACATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGG






ACGCAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTG






CCACTTACTACTGTCAAGGCGCTTATTATAGTAGTGGTTGGTACTG






GGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTT






GCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAA






CTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGA






TGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGC






ATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACA






ACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCA






CAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTC






CAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_6C7 Heavy Chain



(SEQ ID NO: 81)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGCAGCAGCTGGAGGAGTCCGGGGGAGGCCTGGT






CAAGCCTGGAGGAACCCTGACACTCACCTGCAAAGCCTCTGGAATC






GACTTCAGTAGCTACTACTACATGTGTTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTTGATCGTATGTATTTATACTAGTAGTGGTGG






CACATGGTACGCGAGCTGGGTGAATGGCCGACTCACCATCTCCAGA






AGCACCAGCCTAAACACGGTGGATCTGAAAATGACCAGTCTGACAG






CCGCGGACACGGCCACCTATTTCTGTGCCAGAGGGGTTTATTCTGG






TAGTAGTGATTATCCAACTCGGTTGGATCTCTGGGGCCAGGGCACC






CTGGTCACCGTCTCCTTAGGGCAACCTAAGGCTCCATCAGTCTTCC






CACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCT






GGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACC






TGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCG






TCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGT






GACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCC






ACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCA






AGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTT






CATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACC






CCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCG






AGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGC






CCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTG






GTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGG






AGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGA






GAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTC






TACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCA






GCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGT






GGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACG






CCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGC






TCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTG






CTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCC






ATCTCCCGCTCTCCGGGTAAATAG






A11B1_6C7 Light Chain



(SEQ ID NO: 82)



ATGGACACGAGCACCTCCACTGCGCTCCTGGGGCTCCTGCTGCTCT






GGCTCACAGGTGCCAGATGTGCCATCGAGATGACCCAGTCTCCACC






CTCCCTGTCTGCATCTGTGGGAGAAACTGTCAGGATTAGGTGCCTG






GCCAGTGAGGACATTTACAGTGGTATATCCTGGTACCAACAGAAGC






CAGAGAAACCTCCTACACTCCTGATCTCTGGTGCATCCAATTTAGA






ATCTGGGGTCCCACCACGGTTCAGTGGCGGTGGATCCGGGACAGAT






TACACCCTCACCATCGGCGGCGTGCAGGCTGAAGATGTTGCCACCT






ACTACTGTCTAGGCGGTTATAGTTTCAGTAGTACCGGTTTGACTTT






TGGAGCTGGCACCAAGGTGGAAATCAAACGTGATCCAGTTGCGCCT






TCTGTCCTCCTCTTCCCACCATCTAAGGAGGAGCTGACAACTGGAA






CAGCCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCAC






CGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAG






AACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCA






GCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGA






GTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGC






TTCAATAGGGGTGACTGTTAG






A11B1_6B6 Heavy Chain



(SEQ ID NO: 83)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGCAACATCTGGTGGAGTCCGGGGGAGGCCTGGT






CAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTC






TCCTTCACTACCGGCTATCACATGTGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGCATGTTTTGGTGTTTATACTAGTAC






CACTACCTACGCGAGCTGGGCGAAAGGTCGATTCACCATCTCCAAA






ACCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTAACAGTCG






CGGACACGGCCACCTATTTCTGTGCGAGAATCAGTGCTGAAGATGG






TGGGGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCTCAGGG






CAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGG






ACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTA






CCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACC






AATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCT






ACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGT






CACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAG






ACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTG






AACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAA






GGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTG






GTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACA






TAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCA






GCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCG






CACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACA






ACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAG






AGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGG






GAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACG






GCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAA






GGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGAC






GGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGT






GGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTT






GCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAA






TAG






A11B1_6B6 Light Chain



(SEQ ID NO: 84)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGATGTTGTGATGACCCAGACTCCAGC






CTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCACGTGCCAG






GCCAGTCAGAGCATTAGCAACTACTTTTCTTGGTATCAGCAGAAAC






CAGGGCAGCCTCCCAAGCTCCTGATCTACAGGGCGTCCACTCTGGC






ATCTGGGGTCCCATCGCGGTTCAGCGGCAGTGGATCTGGGACACAG






TTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATTCTGCCACTT






ACGCCTGTCAGTGCACTTATGGTAGTAGTAGTACTGGTTTTGGTTT






CGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCT






ACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAA






CAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCAC






CGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAG






AACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCA






GCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGA






GTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGC






TTCAATAGGGGTGACTGTTAG






A11B1_5F7 Heavy Chain



(SEQ ID NO: 85)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCAAAGCCTCTGGATTCTCC






TTCAGTAGTTACTTCTGGATATGCTGGGTCCGCCAGGCTCCAGGGA






AGGGGCTGGAGTGGAGCGCATGCATCTATGGTGATAGTAGTGGTAG






TAGTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAA






ACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCG






CGGACACGGCCACCTATTTCTGTGCGAGTTATGGTAGTAGTAGTTA






TTACTACTCTAATTTATGGGGCCCAGGCACCCTGGTCACCGTCTCC






TCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCT






GCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAA






AGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACC






CTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAG






GCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCA






GCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTG






GACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCAC






CCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAA






ACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGC






GTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACAT






GGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACG






GGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCC






ATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAG






TCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAA






AGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCT






CCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGA






TCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAA






CGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGAC






AGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGA






GTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGA






GGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCG






GGTAAATAG






A11B1_5F7 Light Chain



(SEQ ID NO: 86)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCATATGTGACCCTGTGATGACCCAGACTCCATC






TTCCACGTCTGCGGCTGTGGGAGGCACAGTCACCATCAGTTGCCAG






TCCAGTCAGAGTGTTTATAATAACAACTACTTAGCCTGGTATCAGC






AGAAACCAGGGCAGCCTCCCAAACGCCTGATCTACGAATCATCCAA






ACTGGCATCTGGGGTCCCATCGCGGTTCAGAGGCAGTGGATCTGGG






GCACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTG






CCACTTACTACTGTCTAGGCGCATATTATACTACTCTTGATTTCGG






CGGAGGGACCGAGGTGGTGGTCAGAGGTGATCCAGTTGCACCTACT






GTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAG






TCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGT






CACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAAC






AGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCA






GCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTA






CACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTC






AATAGGGGTGACTGTTAG






A11B1_5D7 Heavy Chain



(SEQ ID NO: 87)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGGAGCAGTTGGTGGAGTCCGGGGGAGGCCTGGT






CCAGCCTGAGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTC






GACTTCAGTAGCAATGCAATGTGCTGGGTCCGCCAGGCTCCAGGGA






AGGGGCTGGAGTGGATCGCATGCATTTATAATGGTGATGGCAGCAC






ATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAAGACC






TCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGG






ACACGGCCACCTATTTCTGTGCGAGAGGTCTCTCTAATTGGAATAG






GGATAACTTATGGGGCCCTGGCACCCTGGTCACCGTCTCCTCAGGG






CAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGG






ACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTA






CCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTCACC






AATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCT






ACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGT






CACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGACAAG






ACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCCCTG






AACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACCCAA






GGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTGGTG






GTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGTACA






TAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCA






GCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATCGCG






CACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACA






ACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGCCAG






AGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCCCGG






GAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCAACG






GCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGGGAA






GGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGCGAC






GGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGT






GGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGCCTT






GCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAA






TAG






A11B1_5D7 Light Chain



(SEQ ID NO: 88)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTCCATC






CTCCGTGTCTGCAGCTGTGGGAGGCACAGCCACCATCAACTGCCAG






GCCAGTCAGAGTCTTTATAGTCCCAAGAATTTAGCCTGGTATCAGC






AGACACCAGGGCAGCCTCCCAAGCTCCTGATCTATTCTGCATCGAA






ACTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGG






ACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGACGATGCTG






CAATTTACTACTGTCAAGGCGAATTTAGTTGTACTACTGCTGCTTG






TTTTGCTTTTGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B 1_5A7 Heavy Chain



(SEQ ID NO: 89)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCTTTGGAGGAGTCCGGGGGAGGCCTGGTCCA






GCCTGAGGGATCCCTGACACTCGCCTGCACAGCTTCGGGATTCTCC






TTCAGTAGCTACTACTACATCTGCTGGGTCCGCCAGGCTCCAGGGA






CGGGGCTGGAGTGGATCGGATGCATTAATACTGGTAGTGATGACAC






TCACTACGCGAGCTGGTTGAAAGGCCGATTCACCTTCTCCAAGGCC






TCGTCGACCACGTTGACTCTGCAAATGACCAGTCTGACAGCCGCGG






ACACGGCCACCTATTTCTGTGCGAGATCATCTGGTAGTAGTGATGA






TGCTTATGATCTCTGGGGCCCAGGCACCCTGGTCACTGTCTCCTCA






GGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTGCG






GGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAAGG






CTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCCTC






ACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGGCC






TCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAGCC






CGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGGAC






AAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACCCC






CTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAACC






CAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCGTG






GTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATGGT






ACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGGGA






GCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCATC






GCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGTCC






ACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAAGC






CAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTCCC






CGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGATCA






ACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAACGG






GAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACAGC






GACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAGTG






AGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAGGC






CTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGGGT






AAATAG






A11B1_5A7 Light Chain



(SEQ ID NO: 90)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGATGTTGTGATGACCCAGACTCCAGC






CTCCGTGTCTGAACCTGTGGGAGGCGCAGTCACCATCAAGTGCCAG






GCCAGTCAGAGCATTGGTAGTAATTTAGCCTGGTATCAGCACAAAC






CAGGGCAGCCTCCCAAGCTCCTGATCTATTTTGCATCCAGCCTGGC






ATCTGGGGTCTCGTCGCGGTTCAAGGGCGGTAGATCTGGGACACAG






TTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTT






ACTACTGTCACTGTACTTATTATCCTCTTAGTTATGTTACTTTCGG






CGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCTACT






GTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAACAG






TCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCACCGT






CACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAGAAC






AGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCAGCA






GCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGAGTA






CACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGCTTC






AATAGGGGTGACTGTTAG






A11B1_4E1 Heavy Chain



(SEQ ID NO: 91)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGACATCCCTGACACTCTCCTGCACAGCCTCTGGATTCTCC






TTCGGTAGCTATTATTATATGTGCTGGGTCCGCCAGGCTCCAGGGA






AGGGGCTGGAGTGGATCGCATGCATTGATGTTGGTAGTAGTGGTGA






CACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCCAAA






ACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCG






CGGACACGGCCACCTATTTCTGTGCGAGAGATGATACTGCTGCTGG






TGGTTTTGGTAATTTGGAATTGTGGGGCCCAGGCACCCTGGTCACC






GTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCC






CCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCT






GGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCG






GGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGT






CCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAG






CAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACC






AAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGT






GCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCC






CCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTC






ACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGT






TCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCC






GCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACC






CTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGT






GCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCAT






CTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATG






GGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCT






GCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGA






GAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTG






CTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGC






CCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGAT






GCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGC






TCTCCGGGTAAATAG






A11B1_4E1 Light Chain



(SEQ ID NO: 92)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCATTCGAATTGACCCAGACTCCATC






CTCCGTGTCTGAACCTGTGGGAGGCACAGTCACCATCAAGTGCCAG






GCCAGTCAGAGCATTTACAGCTACTTTTCCTGGTATCAGCAGAAAC






CAGGGCAGCCTCCCAAGCGCCTGATTTACCAGGCATCCACTCTGGC






TTCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAT






TTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTT






ACTACTGTCAAAACAATTATGGTAGGGGTAGTGGTAGTTATTTTTT






TGGTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTT






GCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAA






CTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGA






TGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGC






ATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACA






ACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCA






CAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTC






CAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_3H9 Heavy Chain



(SEQ ID NO: 93)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCAAAGCCTCTGGAATCGAC






TTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGA






AGGGACTGGAGTATATCGGATACATTGATACTGGTAGTGGTAGCAC






TTACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAACC






TCGTCGACCATGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGG






ACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTG






GGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCT






CCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCT






CCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCC






AGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGC






ACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCA






GCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGT






GGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCC






TCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGG






GACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCAT






GATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGC






CAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGC






AGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAG






CACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGG






CTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCC






CGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCT






GGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGC






AGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTT






CCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAA






CTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTC






CTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCG






ACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTA






CACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_3H9 Light Chain



(SEQ ID NO: 94)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGACTCCTACTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCC






AGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGC






CAGGCCAGTCAGAGCATTAGTAGTTACTTAGCCTGGTATCAGCAGA






AACCAGGGCAGCGTCCCAAGCTCCTGATCTACAGGGCATCCACTCT






GGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GACTACACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCA






CTTATTATTGTCATACCTATTATCTTAGTAGTAGTATCAGTTATGG






TAATACTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_3G2 Heavy Chain



(SEQ ID NO: 95)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGACCTGGT






CAAGCCTGAGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTC






TCCTTCAGTAGCATCTACTGGATTTGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGCATGCACTACTGTTGTCAAAAGTGG






TAGAACTTACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCC






AAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAG






CCGCGGACACGGCCACCTATTTCTGTGCGAGAGAATTTGTTGATGG






TGGTGGTAGTAGTGGTAGGGACTTGTGGGGCCCAGGCACCCTGGTC






ACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGG






CCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCTGGGCTG






CCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAAC






TCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGC






AGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTC






AAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCCACCAAC






ACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCA






TGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTT






CCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACCCCCGAG






GTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGC






AGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGCCCGGCC






GCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGC






ACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCA






AGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGAGAAAAC






CATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACC






ATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGA






CCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTG






GGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACGCCGACC






GTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAG






TGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGT






GATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCCATCTCC






CGCTCTCCGGGTAAATAG






A11B1_3G2 Light Chain



(SEQ ID NO: 96)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCAGATGTGCCTATGATATGACCCAGACTCCAGC






CTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAG






GCCAGTCAGAGCATTAGTAGGGACTTATCCTGGTATCAGCAGAAAC






CTGGACAGCCTCCCAAGCGCCTAATCTACAAGGCATCCACTCTGGC






ATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAT






TTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTT






ACTACTGTCAACAGGGTTATAGTAGTATTGATGTTGATAATGATTT






CGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTTGCACCT






ACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAACTGGAA






CAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGATGTCAC






CGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGCATCGAG






AACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACAACCTCA






GCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCACAAAGA






GTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTCCAGAGC






TTCAATAGGGGTGACTGTTAG






A11B1_3B1 Heavy Chain



(SEQ ID NO: 97)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGGAGCAGCTGGAGGAGTCCGGGGGAGGCCTGGT






CAAGCCTGAGGGATCCCTGACACTCACCTGCAAAGCCTCTGGATTC






GACCTCAGTAGCGGCTATGACATGTGCTGGGTCCGCCAGGCTCCAG






GGAAGGGGCTGGAGTGGATCGCATGCATTTATGCTGATTATAGTGG






TAGCACATACTACGCGAGCTGGGTGAATGGCCGATTCACCATCTCC






AGCAGCACCAGCCTAAACACGGTGGATCTGAAAATGACCAGTCTGA






CAGCCGCGGACACGGCCACCTATTTCTGTGCCAGAGGGGCTACTGG






TAATGGTGGTTATGGATACTACTTTAACTTGTGGGGCCCAGGCACC






CTGGTCACCGTCTCCTCAGGGCAACCTAAGGCTCCATCAGTCTTCC






CACTGGCCCCCTGCTGCGGGGACACACCCAGCTCCACGGTGACCCT






GGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCCAGTGACCGTGACC






TGGAACTCGGGCACCCTCACCAATGGGGTACGCACCTTCCCGTCCG






TCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCAGCGTGGTGAGCGT






GACCTCAAGCAGCCAGCCCGTCACCTGCAACGTGGCCCACCCAGCC






ACCAACACCAAAGTGGACAAGACCGTTGCGCCCTCGACATGCAGCA






AGCCCATGTGCCCACCCCCTGAACTCCCGGGGGGACCGTCTGTCTT






CATCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCACGCACC






CCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCAGGATGACCCCG






AGGTGCAGTTCACATGGTACATAAACAACGAGCAGGTGCGCACCGC






CCGGCCGCCGCTACGGGAGCAGCAGTTCAACAGCACGATCCGCGTG






GTCAGCACCCTCCCCATCGCGCACCAGGACTGGCTGAGGGGCAAGG






AGTTCAAGTGCAAAGTCCACAACAAGGCACTCCCGGCCCCCATCGA






GAAAACCATCTCCAAAGCCAGAGGGCAGCCCCTGGAGCCGAAGGTC






TACACCATGGGCCCTCCCCGGGAGGAGCTGAGCAGCAGGTCGGTCA






GCCTGACCTGCATGATCAACGGCTTCTACCCTTCCGACATCTCGGT






GGAGTGGGAGAAGAACGGGAAGGCAGAGGACAACTACAAGACCACG






CCGACCGTGCTGGACAGCGACGGCTCCTACTTCCTCTACAGCAAGC






TCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCGACGTCTTCACCTG






CTCCGTGATGCACGAGGCCTTGCACAACCACTACACGCAGAAGTCC






ATCTCCCGCTCTCCGGGTAAATAG






A11B1_3B1 Light Chain



(SEQ ID NO: 98)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTACTGCTCT






GGCTCCCAGGTGCCAGATGTGCTGACATTGTGATGACCCAGACTCC






AGCCTCCGTGTCTGAACCTGTGGGAGGCACAGTCACCATCAAGTGT






CAGGCCAGTCAGAACATTAATAGCGGCTTAGCCTGGTATCAGCAGA






AACCAGGGCAGCCTCCCAAGCTCCTGATCTACAAGGCATCCACTCT






GGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACA






GAATTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCA






CTTACTACTGTCAAACCTATTATTATAGTAGTAGTAGTAGTGATAA






TGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTT






GCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAA






CTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGA






TGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGC






ATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACA






ACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCA






CAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTC






CAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_2D3 Heavy Chain



A(SEQ ID NO: 99)



TGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAGG






TGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAG






CCTGGGGCATCCCTGACACTCACCTGCACAGCTTCTGGATTCTCCT






TCAGTAGCAGTTATTGGATATGCTGGGTCCGCCAGGCTCCAGGGAA






GGGGCTGGAGTGGATCGCATGTATTTATGGTGGTAGTAGTGGTAAC






ATTGCCTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAA






CCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTGACAGCCGC






GGACACGGCCACCTATTTCTGTGCGAGAGATATTCCTAGTGATGCT






TTCACCTTAGACTTGTGGGGCCCAGGCACCCTGGTCACCGTCTCCT






CAGGGCAACCTAAGGCTCCATCAGTCTTCCCACTGGCCCCCTGCTG






CGGGGACACACCCAGCTCCACGGTGACCCTGGGCTGCCTGGTCAAA






GGCTACCTCCCGGAGCCAGTGACCGTGACCTGGAACTCGGGCACCC






TCACCAATGGGGTACGCACCTTCCCGTCCGTCCGGCAGTCCTCAGG






CCTCTACTCGCTGAGCAGCGTGGTGAGCGTGACCTCAAGCAGCCAG






CCCGTCACCTGCAACGTGGCCCACCCAGCCACCAACACCAAAGTGG






ACAAGACCGTTGCGCCCTCGACATGCAGCAAGCCCATGTGCCCACC






CCCTGAACTCCCGGGGGGACCGTCTGTCTTCATCTTCCCCCCAAAA






CCCAAGGACACCCTCATGATCTCACGCACCCCCGAGGTCACATGCG






TGGTGGTGGACGTGAGCCAGGATGACCCCGAGGTGCAGTTCACATG






GTACATAAACAACGAGCAGGTGCGCACCGCCCGGCCGCCGCTACGG






GAGCAGCAGTTCAACAGCACGATCCGCGTGGTCAGCACCCTCCCCA






TCGCGCACCAGGACTGGCTGAGGGGCAAGGAGTTCAAGTGCAAAGT






CCACAACAAGGCACTCCCGGCCCCCATCGAGAAAACCATCTCCAAA






GCCAGAGGGCAGCCCCTGGAGCCGAAGGTCTACACCATGGGCCCTC






CCCGGGAGGAGCTGAGCAGCAGGTCGGTCAGCCTGACCTGCATGAT






CAACGGCTTCTACCCTTCCGACATCTCGGTGGAGTGGGAGAAGAAC






GGGAAGGCAGAGGACAACTACAAGACCACGCCGACCGTGCTGGACA






GCGACGGCTCCTACTTCCTCTACAGCAAGCTCTCAGTGCCCACGAG






TGAGTGGCAGCGGGGCGACGTCTTCACCTGCTCCGTGATGCACGAG






GCCTTGCACAACCACTACACGCAGAAGTCCATCTCCCGCTCTCCGG






GTAAATAG






A11B1_2D3 Light Chain



(SEQ ID NO: 100)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCACATTTGCCCAAGTGCTGACCCAGACTCCATC






CTCCGTGTCTGCAGCTGTGGGAAGCACAGTCACCATCAATTGCCAG






GCCAGTCAGAGTGTTTATAAAGACAACAATTTAGCCTGGTATCAGC






AGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAAGGCTTCCAC






TCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGG






ACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGAAGATGCTG






CCACTTACTACTGTCAAGGCGAATTCAGTTGTGGTAGTGCTGATTG






TATTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCA






GTTGCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGG






CAACTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCC






CGATGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACT






GGCATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCT






ACAACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAG






CCACAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTC






GTCCAGAGCTTCAATAGGGGTGACTGTTAG






A11B1_2A7 Heavy Chain



(SEQ ID NO: 101)



ATGGAGACTGGGCTGCGCTGGCTTCTCCTGGTCGCTGTGCTCAAAG






GTGTCCAGTGTCAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAA






GCCTGGGGCATCCCTGACACTCACCTGCAAAGGCTCTGGAATCGAC






TTCAGTAGCGGCTACGGCATGTGGTGGGTCCGCCAGGCTCCAGGGA






AGGGACTGGAGTATATCGGATACATTGATACTGGTTATGGTAGCAC






TTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAGACC






TCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGTCGCGG






ACACGGCCACCTATTTCTGTGCGAAAGGGGGCGCCATAGACCTCTG






GGGCCCAGGGACCCTCGTCACCGTCTCTTCAGGGCAACCTAAGGCT






CCATCAGTCTTCCCACTGGCCCCCTGCTGCGGGGACACACCCAGCT






CCACGGTGACCCTGGGCTGCCTGGTCAAAGGCTACCTCCCGGAGCC






AGTGACCGTGACCTGGAACTCGGGCACCCTCACCAATGGGGTACGC






ACCTTCCCGTCCGTCCGGCAGTCCTCAGGCCTCTACTCGCTGAGCA






GCGTGGTGAGCGTGACCTCAAGCAGCCAGCCCGTCACCTGCAACGT






GGCCCACCCAGCCACCAACACCAAAGTGGACAAGACCGTTGCGCCC






TCGACATGCAGCAAGCCCATGTGCCCACCCCCTGAACTCCCGGGGG






GACCGTCTGTCTTCATCTTCCCCCCAAAACCCAAGGACACCCTCAT






GATCTCACGCACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGC






CAGGATGACCCCGAGGTGCAGTTCACATGGTACATAAACAACGAGC






AGGTGCGCACCGCCCGGCCGCCGCTACGGGAGCAGCAGTTCAACAG






CACGATCCGCGTGGTCAGCACCCTCCCCATCGCGCACCAGGACTGG






CTGAGGGGCAAGGAGTTCAAGTGCAAAGTCCACAACAAGGCACTCC






CGGCCCCCATCGAGAAAACCATCTCCAAAGCCAGAGGGCAGCCCCT






GGAGCCGAAGGTCTACACCATGGGCCCTCCCCGGGAGGAGCTGAGC






AGCAGGTCGGTCAGCCTGACCTGCATGATCAACGGCTTCTACCCTT






CCGACATCTCGGTGGAGTGGGAGAAGAACGGGAAGGCAGAGGACAA






CTACAAGACCACGCCGACCGTGCTGGACAGCGACGGCTCCTACTTC






CTCTACAGCAAGCTCTCAGTGCCCACGAGTGAGTGGCAGCGGGGCG






ACGTCTTCACCTGCTCCGTGATGCACGAGGCCTTGCACAACCACTA






CACGCAGAAGTCCATCTCCCGCTCTCCGGGTAAATAG






A11B1_2A7 Light Chain



(SEQ ID NO: 102)



ATGGACACGAGGGCCCCCACTCAGCTGCTGGGGCTCCTGCTGCTCT






GGCTCCCAGGTGCCACATTTGCAGCCGTGCTGACCCAGACTCCGGC






TTCCACGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGTCAG






TCCAGTCAGAGCGTGTATCGTAGCAACTGGTTAGCCTGGTATCAGC






AGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGATGTATTTAA






TTTGGCATCTGGGGTCCCATCCCGGTTCAAGGGCAGTGGATCTGGG






ACACAGTTCACTCTCACCATCAGCGGCGTGCAGTGTGCCGATGCTG






CCACTTACTACTGTCAAGGCAGTTATTATAGTGGTAATTGGTACAG






TGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAAGGTGATCCAGTT






GCACCTACTGTCCTCATCTTCCCACCAGCTGCTGATCAGGTGGCAA






CTGGAACAGTCACCATCGTGTGTGTGGCGAATAAATACTTTCCCGA






TGTCACCGTCACCTGGGAGGTGGATGGCACCACCCAAACAACTGGC






ATCGAGAACAGTAAAACACCGCAGAATTCTGCAGATTGTACCTACA






ACCTCAGCAGCACTCTGACACTGACCAGCACACAGTACAACAGCCA






CAAAGAGTACACCTGCAAGGTGACCCAGGGCACGACCTCAGTCGTC






CAGAGCTTCAATAGGGGTGACTGTTAG






Protein Sequences of Anti-α11β1 Monoclonal Antibodies
Rat mAb Sequences










Signal peptide-FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4



79E3E3 Heavy Chain Variable Region


(SEQ ID NO: 145)




MDWLWNLLFLMVVAQSAQAQIQLVQSGPEVKKPGESVKISCKASGYTFTDYAMNWVKQ







APGNGLKWMGWINTQTGKPTYADDFKQRFVFSLETSARTTYLQINNLNIEDTATYFCT





RLGTGNTKGFAYWGQGTLVTVSS





79E3E3 Light Chain Variable Region


(SEQ ID NO: 146)




MESQTHVLISLLLCVSGTCGDILINQSPASLTVSAGERVTMSCKSSQSLLYSENNQDYLA







WYQQKPGQFPKLLIYGASNRHTGVPDRFTGSGSGTDFTLTISSVQAEDLADYYCEQTY






RYPFTFGSGTKLEIK






24E4G6 Heavy Chain Variable Region


(SEQ ID NO: 147)




MELELSLIFIFSLLKDVQCEVQLVESGGSLVQPGGSLKLSCVASGYTFSNYWMDWVRQSP







GKSLEWIGEINTDGRRTNYAPSIKDRFTISRDNAKSTLYLQMSNVKSDDTAIYYCTILR






VYPHYFDYWGQGVMVTVSS






24E4G6 Light Chain Variable Region


(SEQ ID NO: 148)




MMSPAQFLFLLMLWIQEARGDVVMTQTPPSLSVAIGQSVSISCKSSQSLVYSDGETYLH







WFLQSPGRSPKRLIYHVSNLGSGVPDRFSGTGSLTDFTLRISRVEAEDLGVYYCAQTTH






FPPTFGAGTKLELK






8H8E9 Heavy Chain Variable Region


(SEQ ID NO: 149)




MAVLVLLLCLVTFPSCALSQVQLKESGPGLVQPSQTLSLTCTVSGFSLTSNSVSWVRQAPG







KGLEWMGAIWSGGSTDYNSALKSRLSISRDTSKSQVFLKMNSLQTEDTAIYFCTRSHW






EPFDYWGQGVMVTVSS






8H8E9 Light Chain Variable Region


(SEQ ID NO: 150)




MESQTQALISLLLWVYGTCGDIVMTQSPFSLAVSEGEMVTINCKSSQGLLSSGNQKNYLA







WYQQRPGQSPKLLIYYASTRQSGVPDRFIGGGSGTDFTLTISDVQAEDLADYYCLQHYS






YPPTFGSGTKLEIK






6E5C11 Heavy Chain Variable Region


(SEQ ID NO: 151)




MAVLVLLLCLVTFPSCALSQVQLRESGPGLVQPSQTLSLTCTVSGFSLTSNSVTWVRQPPG







KGLEWMGAIWSDGSTDYNSTLKSRLSISRDTSKSQVFLKMSSLQTEDTAIYFCTRSHW






EPFDYWGQGVMVTVSS






6E5C11 Light Chain Variable Region


(SEQ ID NO: 152)




MESQTQALISLLLWVYGTCGDIVMTQSPLSLAVSEGETVTMNCKSSQSLFSSGNQKNYLA







WYQQKPGQSPKLLIYYASTRQSGVPDRFIGSGSGTDFTLTISDVQTEDLADYYCLQHYN






YPPTFGSGTKLEIK






7D8B10 Heavy Chain Variable Region


(SEQ ID NO: 153)




MDLRLTYVFIVAILKGVLCEVKLEESGGGLVQPGMSVKLSCATSGFIFSDYWMEWVRQAP







GKGLEWVAEIRNKANNYATYYGKSMKGRFTISRDDSKSIVYLQVNSIRSEDTAIYYCA





PNFDYWGQGVMVTVSS





7D8B10 Light Chain Variable Region


(SEQ ID NO: 154)




MSPVQSLFLLLLWILGTHGDVVLTQTPPTLSATIGQSVSISCRSSQSLLHSTGNTYLNWLL







QRPGQPPQLLIYLVSRLESGVPNRFSASGSGTDFTLKISGIEAEDLGVYYCVQSSHTPYT





FGTGTKLELK





18E10F10 Heavy Chain Variable Region


(SEQ ID NO: 155)




MDIRLSLVFLVLFMKGVQCEVQLVESGGGLVQPGRSLKLSCAASRFTFSDYNMAWVRQA







PKKGLEWVATIYHDDSGSYYRDSVKGRFTISRNNAKSTLYLQMDSLRSEDMATYYCA





RHNNGFDYWGQGVMVTVAS





18E10F10 Light Chain Variable Region


(SEQ ID NO: 156)




MKWPVRLLVLFFWIPASGGDVVMTQTPVSLPVRLGGQASISCRSSQSLVHSNGNTYLHW







YLQKPGQSPQLLINRVSNRFSGVPDRFSGSGSGTDFTLKINRVEPEDLGDYYCLQSTHFP






LTFGSGTKLETK






40G10H11 Heavy Chain Variable Region


(SEQ ID NO: 157)




MDIRLSLGFLVLFIKGDQCAVQLVESGGGLVQPGRSLKLSCAASRITFTDYYMAWVRQA







PTKGLEWVATISSDGGDTFYRDSVKGRFTISRDNAKSTLYLQMVSLRSEDTATYYCST






DRGAQFGYWGQGTLVTVSS






40G10H11 Light Chain Variable Region


(SEQ ID NO: 158)




MAPVQLLGLLLIWLPAMRCDIQMTQSPSFLSASVGDRVSINCKASQNVHENLNWYQQKL







GEAPKRLIYNTNNLQTGIPSRFSGSGSGADYTLTISSLQPEDFATYFCLQHNAFPYTFGP





GTKLELK






Mouse mAb Sequences










FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4



9-G05 Heavy Chain Variable Region


(SEQ ID NO: 103)



EVQLQQSGPELVKPGASVKIPCKASGYTFPDYNMDWVKQSHGKSLEWIGYINPDNGGT






IYNQKFKGKATLTVDKSSSTAYMELRSLTSEDTAVYYCARLDSSGYGYYAMDYWGQG





TSVTVSS





9-G05 Light Chain Variable Region


(SEQ ID NO: 104)



DIVLTQSPASLAVSLGQRATISCRASESVDNYGISFMHWYQQKPGQPPKLLIYRASNLD







SEIPARFSGSGSRTDFTLTIDPVETDDVATYYCQQSYKDPRTFGGGTKLEIK






8-P20 Heavy Chain Variable Region


(SEQ ID NO: 105)



KVMLVESGGALVKPGGSLKLSCVASGFTFSNYAMSWVRQTPEKRLEWVATISSGGYY






TYYPDSVKGRFTISRDNARNTLFLQMSSLRSEDTAMFYCAREDDYGRYSYTMDYWGQ





GTSVTVSS





8-P20 Light Chain Variable Region


(SEQ ID NO: 106)



DVVMTQTPLSLPVSLGDQVSISCRCSQSLVHSNGNTYLHWYLQKPGQSPQLLIYKISNR







FSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPYTFGGGTELEIK






8-G15 Heavy Chain Variable Region


(SEQ ID NO: 107)



EVQLQQSGPELVKPGASVRISCKASGYTFTDYYIHWVKQKPGQGLECIGEIYPGTDNTY






YSKKFRGKATLTADKSSDTAYMQLSSLTSEDSAVYFCARGDYYRGYFDVWGAGTTVT





VSS





8-G15 Light Chain Variable Region


(SEQ ID NO: 108)



DVVMTQTSLTLSVTIGQPASISCKSSQSLLHSNGKTYLNWLLQRPGQSPKFLIYLVSKL







ESGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCLQSTHFPWTFGGGTKLEIK






8-I14 Heavy Chain Variable Region


(SEQ ID NO: 109)



EVQLQQSGPELVKPGASVKKSCKASGYTFTDYYMHWVKQKPGQGLEWIGKIYPGSGN






THYNEKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCATNYYGYRAMNYWGQGSS





VTVSS





8-I14 Light Chain Variable Region


(SEQ ID NO: 110)



DIHLTQSPSSLSASLGERISLTCRASQDIYISLNWFQQKPDGTIKLLIYGTSSLDSGVPKRF






SGSRSGSDYSLTISSLESEDFADYYCLQYASSPYTFGGGTKLEIK





9-E16 Heavy Chain Variable Region


(SEQ ID NO: 111)



EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMHWVKQKPGQGLEWIGEIYPGSGNP






YYNEKFKGKATLTADKSSSSAYMQLSSLTSEDSAVYFCARTSYGRVGTGFAYWGQGT





LVTVSA





9-E16 Light Chain Variable Region


(SEQ ID NO: 112)



NFVMTQTPLSLPVSLGDQASISCRSSQSLLHSNGNTYLHWYLQKPGQSPKLLIYKVSNR







FSGVPDRFSGSGSGTDFTLKINRVETEDLGIYFCSQSSHVPTFGAGTKLELK









8-J17 Heavy Chain Variable Region


(SEQ ID NO: 113)



QVQLQQSGAELAKPGASVKMSCKASGYTFTNYWMHWVKQRPGQGLEWIGYINPNNG







YTEYNQRFKDKATLTADRSSTTAYMQLSSLTSEDSAVYYCARSDIITTDYWGQGTTLT






VSS





8-J17 Light Chain Variable Region


(SEQ ID NO: 114)



DVVMTQTPLSLPVSLGDQASISCRSSQSLVYSNGNTYLHWYLQKPGQSPKLLIYKVSNR






FSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPWTFGGGTKLEIK





9-B11 Heavy Chain Variable Region


(SEQ ID NO: 115)



QVQLQQPGAELVRPGTSVKLSCKASGYTFTSYWMHWVQQRPGQGLEWIGVIDPSDSY







TNYNQKFKGKATLTVDTSSSSAYMQLSSLTSEDSAVYYCARDDVAMDYWGQGTSVTV






SS





9-B11 Light Chain Variable Region


(SEQ ID NO: 116)



DIVVTQSPASLAVSLGQRATISCRASESVDSYGNSFIHWYQQKPGQPPKLLIYRASNLKS






GIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPYTFGGGTKLEIK





For SEQ ID NO: 117-144, CDR3 is represented by bold and underlined text.


6-O12 Heavy Chain Variable Region


(SEQ ID NO: 117)



EVKLEESGGGLVQPGGSMKLSCAASGFTFSDAWMDWVRQSPEAGLEWVAEIRNKAHN






PATYYAESVKGRFTISRDDSKSSVYLQMNSLRAEDTGIYYCTLVAPDAMDYWGQGTS





VTVSS





6-O12 Light Chain Variable Region


(SEQ ID NO: 118)



DIVMSLSPSSLAVSVGEKVTMSCKSSQSLLYSRNQKNYLAWYQQKPGQSPKLLIYWAST






RASGVPDRFTGSGSGTDFTLTISSVKAEDLAVYYCQQYYSYPYTFGGGTKLEIK





10-L15 Heavy Chain Variable Region


(SEQ ID NO: 119)



QVQLQQSGPELVRPGASVKMSCKASGYTFTSYWMHWVKQRPGQGLEWIGMIDPSNSE






TWLNQKFKDKATLNVDKSSNTAYMQLSSLTSEDSAVYYCARYDGYYDYWGQGTTLT





VSS





10-L15 Light Chain Variable Region


(SEQ ID NO: 120)



NIVLTQSPASLAVSLGQRATISCRASESVDSYGNSFMHWYQQKPGQPPKLLIYLASNVES






GVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPWTFGGGTKLEIK





7-H14 Heavy Chain Variable Region


(SEQ ID NO: 121)



QVQLQQPGAELVRPGASVKLSCKPSGYTFTSYWMNWVKQRPGQGLEWIGMIDPSDSET






HYNQMFKDKATLTVDKSSNTAYMQLSSLTSEDSAVYYCAQIYYAYDKAYWGQGTLV





TVSA





7-H14 Light Chain Variable Region


(SEQ ID NO: 122)



DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSSHQKNYLAWYQQKPGQSPKLLIYWAST






RESGVPDRFTGSGSGTDFSLTISSVKAEDLAVYYCQEYYSWTFGGGTKLEIK





6-B21 Heavy Chain Variable Region


(SEQ ID NO: 123)



EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGKSLEWIGDINPHNGGT






SFIQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCAPLGRKEGFAYWGQGTLVTV





SA





6-B21 Light Chain Variable Region


(SEQ ID NO: 124)



DTVLTQSPASLVVSLGQRATISCRASKSVSTSGYSYMHWYQQKPGQPPKLLIYLASNLES






GVPARFSGSGSGTAFTLNIHPVEEEDAATYYCQHSRELPYTFGGGTKLEIK





10-F23 Heavy Chain Variable Region


(SEQ ID NO: 125)



QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFAMGVGWIRQPSGKGLEWLAHIWWDDDK






YYNPALKSRLTISKDTSKNHVFLKIANVDTADTATYYCARMPLTFYFDYWGQGTTLTV





SS





10-F23 Light Chain Variable Region


(SEQ ID NO: 126)



DVLLTQTPLSLPVSLGDQASISCRSSQSIVHSNGHTYLEWYLQKPGQSPKLLIYKVSNRFS






GVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPFTFGGGTKLEIK





6-A12 Heavy Chain Variable Region


(SEQ ID NO: 127)



QVTLKESGPGILQPSQTLSLTCSFSGFSLRTFAMGVGWIRQPSGKGLEWLAHIWWDDDK






YYNPALKSRLTISKDTSKNQVFLKIANVDTADTATYYCARMPLTFYFDYWGQGTTLTV





SS





6-A12 Light Chain Variable Region


(SEQ ID NO: 128)



DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSTRF






SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPFTFGGGTKLEIK





6-M8 Heavy Chain Variable Region


(SEQ ID NO: 129)



QVQLQQPGAELVMPGASVKLSCKASGYTFTNYWMHWVKQRPGQGLEWIGEIDPSDSY






TNYNQKFKGKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRQGSTYAWGQGTSVTVS





S





6-M8 Light Chain Variable Region


(SEQ ID NO: 130)



DIVMTQAAFSNPVTLGTSASISCRSSKSLLHSNGITYLYWYLQKPGQSPQLLIYQMSNLA






SGVPDRFSSSGSGTDFTLRISRVEAEDVGVYYCAQNLELPPTFGGGTKLEIK





2-A3 Heavy Chain Variable Region


(SEQ ID NO: 131)



EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYMMWVKQSHGKSLEWIGDINPYNGG






SSYNPKFKGRATLTVDKSSSTAYMQLNSLTSEDSAVYYCARGTYWGQGTLVTVSA





2-A3 Light Chain Variable Region


(SEQ ID NO: 132)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSAGKTYLNWLLQRPGQSPKRLMYLVSKL






DSGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPYTFGGGTKLEIK





6-O17 Heavy Chain Variable Region


(SEQ ID NO: 133)



QVQLQQPGAELVKPGASVKLSCKASGYTFTSYWMHWIKQRPGQGLEWIGEINPSNGGS






NYNEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYHCKSRGYWGQGTTLTVSS





6-O17 Light Chain Variable Region


(SEQ ID NO: 134)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSYGKTYLNWLLQRPGQSPKRLIYLVSKLD






SGVPDRFTGSGSGTDFTLKISRVEAEDLGIYYCWQGTHFPHTFGSGTKLEIK





3-G5 Heavy Chain Variable Region


(SEQ ID NO: 135)



QVQLQQSGAELARPGASVKLSCKASGYTFTSYGISWVKQRTGQGLEWIGEIFPRSSNTY






YNEKFKGKATLTADKSSSTVYMEFRSLTSEDSAVYFCAREGGLAWFAYWGQGTLVTV





SA





3-G5 Light Chain Variable Region


(SEQ ID NO: 136)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLYTNGNTYLNWLLQRPGQSPKRLIYLVSKLD






SGIPDRFSGSGSGTDFTLRISRVEAEDLGVYYCLQSTHFPFTFGSGTKLEIK





6-A15 Heavy Chain Variable Region


(SEQ ID NO: 137)



EVQLQQSGPELVKPGASVKMSCKASGYTITDYYMMWLKQSHGKSLEWIGDINPYTGGT






SYNQKFKGKATLTVDKSSSTAYLQLHSLTSEDSAVYYCARGAYWGQGTTLTVSS





6-A15 Light Chain Variable Region


(SEQ ID NO: 138)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSKLD






SGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPYTFGGGTKLEIK





10-K10 Heavy Chain Variable Region


(SEQ ID NO: 139)



EVQLQQSGPELVKPGASVKMSCKASGYTITDYYMMWLKQSHGKSLEWIGDINPYTGGT






SYNQKFKGKATLTVDKSSSTAYMQLNSLTSEDSAVYYCARGAYWGQGTTLTVSS





10-K10 Light Chain Variable Region


(SEQ ID NO: 140)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLDSDGKTYLNWLLQRPGQSPKRLIYLVSKLD






SGVPDRFTGSGSGTDFTLKISRVEAEDLGVYYCWQGTHFPYTFGGGTKLEIK





6-P20 Heavy Chain Variable Region


(SEQ ID NO: 141)



EVQLQQSGPELVKPGASVKISCKASGYTFTDYYMNWVKQSHGRSLELIGDINPNNGGSN






FNQKFRGKATLTVDKSSSTAYMELRSLTSEDSAIYYCARMGYWGQGTLVTVSA





6-P20 Light Chain Variable Region


(SEQ ID NO: 142)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLHSDGKTYLNWMFQRPGQSPKRLIYLVSKLD






SGVPYRFTGGGSGTDFTLQISRVETEDLGVYYCWQGTHFPRTFGGGTKLEIK





7-O8 Heavy Chain Variable Region


(SEQ ID NO: 143)



EVQLQQSGPELVKPGASVKMSCKASGYTFTDYYIHWVKQKPGQGLEYIGEIYPGSGNT






YYNGKFRGKATLTADKSSSTAYMQLSSLTSEDSAVYFCGSGYFDYWGQGTTLTVSS





7-O8 Light Chain Variable Region


(SEQ ID NO: 144)



DVVMTQTPLTLSVTIGQPASISCKSSQSLLYSNGKTYLNWLLQSPGQSPKLLIYLVSKLES






GVPDRFSGSGSGTDFTLKLSRVEAEDLGVYYCVQGTHFPFTFGSGTKLEIK






Rabbit mAb Sequences











Al1B1_16G7 Heavy Chain



(SEQ ID NO: 159)



METGLRWLLLVAVFKGVQCQEQLVESGGDLVKPGASLTLT






CTASGFSFNKNYWMCWVRQAPGKGLEWIGCIYNGDGNTYY






ASWVNGRFTISKTSSTTVTLQMTSLTVADTAIYFCARLLN






MWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCL






VKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSV






VSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPP






ELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPE






VQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQD






WLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMG






PPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYK






TTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEAL






HNHYTQKSISRSPGK*






A11B1_16G7 Light Chain



(SEQ ID NO: 160)



MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGG






TVTIKCQASESIGNALAWYQQKPGQPPKLLIYTAATLASG






VPSRFSGSGSGTEFTLTISGVQCDDAATYYCQSYYFTSVS






SYGNAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_16E10 Heavy Chain



(SEQ ID NO: 161)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






RVSGFSFSSSYYMCWVRQAPGKGLEWIACIGTTRGSTYYA






TWAKGRFTISKISSTTVTLQMTSLTDADTATYFCARDATG






YRINTIGLYFNLWGPGTLVTVSSGQPKAPSVFPLAPCCGD






TPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVR






QSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAP






STCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTC






VVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIR






VVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARG






QPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEW






EKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGD






VFTCSVMHEALHNHYTQKSISRSPGK*






A11B1_16E10 Light Chain



(SEQ ID NO: 162)



MDTRAPTQLLGLLLLWLPGARCAFELTQTPSSVEAAVGGT






PTIKCQASQTIYSYLSWYQQKPGQPPKLLIYEASKLASGV






PSRFSGSGSGTDYTLTISDLECADAATYYCQSYHGTASTE






YNTFGGGTEVVVRGDPVAPTVLIFPPAADQVATGTVTIVC






VANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNL






SSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_15G1O Heavy Chain



(SEQ ID NO: 163)



METGLRWLLLVAVLKGVQCQQQLVESGGGLVKPGAALTFT






CTASGFSFSGNYWICWVRQAPGKGLEWIACIGTITSRTYY






ASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARGAV






VSSGNAPYYFTLWGPGTLVTVSSGQPKAPSVFPLAPCCGD






TPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVR






QSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAP






STCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTC






VVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIR






VVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARG






QPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEW






EKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGD






VFTCSVMHEALHNHYTQKSISRSPGK*






A11B1_15G10 Light Chain



(SEQ ID NO: 164)



MDTRAPTQLLGLLLLWLPGARCAFELTQTPSSVEAAVGGT






VTIKCQASQSISSYLSWYQQKPGQPPKLLIYRASTLESGV






PSRFKGSGSGTEFTLTISDLECADAATYFCQSYYGVTFSG






FAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCV






ANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLS






STLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_14H1 Heavy Chain



(SEQ ID NO: 165)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






KASGIDFNNYWITWVRQAPGKGLEWIACIYVGITGRTWYA






NWAKGRFTISKASSTVDLKMTSLTAADTATYFCARNGDGG






IYALNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTV






TLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLY






SLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKP






MCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVS






QDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLP






IAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPK






VYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKA






EDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSV






MHEALHNHYTQKSISRSPGK*






A11B1_14H1 Light Chain



(SEQ ID NO: 166)



MDTRAPTQLLGLLLLWLPGATFAQVLTQTASSVSAAVGGT






VTISCQSSQSVYNNNWLAWYQQKPGQPPKLLIYRASTLTS






GVPSRFKGSGSGTQFTLTISDLECDDAATYYCAGGYSGNI






YVNDFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIV






CVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYN






LSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_13G4 Heavy Chain



(SEQ ID NO: 167)



METGLRWLLLVAVLKGVQCQEQLEESGGDLVKPGGSLTLT






CKASGFSFSNTYWACWVRQAPGKGLEWIACMNPASSGSSY






YASWAKGRFTISKTSSTTVTLHMPSLTAADTATYFCAKWD






TAFDVWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVT






LGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYS






LSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPM






CPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQ






DDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPI






AHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKV






YTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAE






DNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVM






HEALHNHYTQKSISRSPGK*






A11B1_13G4 Light Chain



(SEQ ID NO: 168)



MDTRAPTQLLGLLLLWLPGARCADVVMTQTPSSVEAAVGG






TVTIKCQASQSISSYLAWYQQKPGQPPKLLIYGASNLESG






VPSRFKGSGSGTEYTLTISGVQCDDAATYYCQNYYAIDTY






GHAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVC






VANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNL






SSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_13C3 Heavy Chain



(SEQ ID NO: 169)



METGLRWLLLVAVLKGVQCQEQLEESGGDLVKPGASLTLT






CTASGFSFSSNYHICWVRQAPGKGLELIACIYVGDGSTYY






ASWAKGRFTISKSSSTTVALQMTSLTAADTATYFCGRMFN






LWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCL






VKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSV






VSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPP






ELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPE






VQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQD






WLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMG






PPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYK






TTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEAL






HNHYTQKSISRSPGK*






A11B1_13C3 Light Chain



(SEQ ID NO: 170)



MDTRAPTQLLGLLLLWLPGAICDPVLTQTPSSVSAAVGVT






VTINCQSSPSVYSNYLSWYQQKPGQPPKLLIYLASTLASG






VPSRFKGSGSGTQFTLTISDVQCDDAATYYCAGTYSGNIW






SFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVA






NKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSS






TLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_12F2 Heavy Chain



(SEQ ID NO: 171)



METGLRWLLLVAVLKGVQCQQQLVESGGGLVKPGASLTLT






CTASGFSFSSGYHMCWVRQAPGKGLEWIACFGVYTGTTTY






ASWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCARISA






ENGGDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTV






TLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLY






SLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKP






MCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVS






QDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLP






IAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPK






VYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKA






EDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSV






MHEALHNHYTQKSISRSPGK*






A11B1_12F2 Light Chain



(SEQ ID NO: 172)



MDTRAPTQLLGLLLLWLPGARCDVVMTQTPASVEAAVGGT






VTIKCQASQSISNYFSWYQQKPGQPPKLLIYRASTLASGV






PSRFSGSGSGTEFTLTISDLECADSATYYCQCTYGSSSTG






FGFGGGTEVVVKGDPVAPTVPIFPPAADQVATGTVTIVCV






ANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLS






STLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_11D10 Heavy Chain



(SEQ ID NO: 173)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






MASGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGDDNTYYA






NWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCAKGGAI






DLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGC






LVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSS






VVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPP






PELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDP






EVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQ






DWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTM






GPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNY






KTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEA






LHNHYTQKSISRSPGK*






A11B1_11D10 Light Chain



(SEQ ID NO: 174)



MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGG






TVTIKCQASQSISSYLAWYQQKPGQRPKLLIYRASTLKSG






VPSRFKGSGSGTEYTLTISDLECADAATYYCQAYYLSSSI






SYGNTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






AllBl_10F9 Heavy Chain



(SEQ ID NO: 175)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






TASGFSLSSGYGMCWVRQAPGKGLEWIGYTDTATGTIHYA






SWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCAKGGAM






DLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGC






LVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSS






VVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPP






PELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDP






EVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQ






DWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTM






GPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNY






KTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEA






LHNHYTQKSISRSPGK*






AllBl_10F9 Light Chain



(SEQ ID NO: 176)



MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGG






TVTIKCQASQSISSYLAWYQQKPGQPPKLLIYRTSTLASG






VPSRFKGSGSGTEYTLTISDLECADAATYYCQSYAYSSSS






SYGNAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_7H12 Heavy Chain



(SEQ ID NO: 177)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






TGSGIDFSSSYWICWVRQAPGKGLEWIACIDGSDGNTYYA






SWARGRFTISKTSSTTVTLQMASLTAADTATYFCTRDLRL






WGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGCLV






KGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSSVV






SVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPPPE






LPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEV






QFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQDW






LRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGP






PREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKT






TPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEALH






NHYTQKSISRSPGK*






A11B1_7H12 Light Chain



(SEQ ID NO: 178)



MDTRAPTQLLGLLLLWLPGARCADIVLTQTPASVSAAVGG






TVTINCQASQNVYSNNALAWHQQKPGQRPNLLIYKASTLA






SGVPSRFKGSGSGTQFTLTISDVQCDDAATYYCLGEFSCS






SGDCFVFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVT






IVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCT






YNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC






*






A11B1_7G12 Heavy Chain



(SEQ ID NO: 179)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






MASGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGDDNTYYA






NWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCAKGGAI






DLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGC






LVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSS






VVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPP






PELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDP






EVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQ






DWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTM






GPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNY






KTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEA






LHNHYTQKSISRSPGK*






A11B1_7G12 Light Chain



(SEQ ID NO: 180)



MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGG






TVTIKCQASQSISSYLAWYQQKPGQRPKLLIYRASTLKSG






VPSRFKGSGSGTEYTLTISDLECADAATYYCQAYYLSSSI






SYGNTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_6G4 Heavy Chain



(SEQ ID NO: 181)



METGLRWLLLVAVLKGVQCQQQLEESGGGLVKPGGTLTLT






CKASGVALNPYYYMCWVRQAPGKGLEWIACVDADSSGSTY






YASWAKGRFTISKTSSTTVTLKMTSLTAADTATYFCARES






VDYSSVGIGYVHGTDGLWGPGTLVTVSSGQPKAPSVFPLA






PCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRT






FPSVRQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVD






KTVAPSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRT






PEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQF






NSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTI






SKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSD






ISVEWEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSE






WQRGDVFTCSVMHEALHNHYTQKSISRSPGK*






A11B1_6G4 Light Chain



(SEQ ID NO: 182)



MDTRAPTQLLGLLLLWLPGARCADIVVTQTPSSVSAAVGG






TVTIKCQASQSISNYFSWYQQKPGQPPKLLIYRASTLASG






VPSRFKGSGSGTEFTLTISDLECADAATYYCQCTYGRSNS






NFFYGFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_6F9 Heavy Chain



(SEQ ID NO: 183)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






TASGSSFSSTYWNCWVRQAPGKGLEWIACINAGSGTTYYA






SWAKGRFTVSKTSSTTVTLQMTSLTAADTATYFCTRDSDG






RFSSGYYFNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTP






SSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQS






SGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPST






CSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVV






VDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVV






STLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQP






LEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEK






NGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVF






TCSVMHEALHNHYTQKSISRSPGK*






A11B1_6F9 Light Chain



(SEQ ID NO: 184)



MDTRAPTQLLGLLLLWLPGATFAQVLTQTASPVSAAVGGT






VTINCQSSQSVYDNNWLAWYQQKPGQPPKLLIDDASKLTS






GVSSRFKGSGSGTQFTLTISGVQCDDAATYYCQGAYYSSG






WYWAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIV






CVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYN






LSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_6C7 Heavy Chain



(SEQ ID NO: 185)



METGLRWLLLVAVLKGVQCQQQLEESGGGLVKPGGTLTLT






CKASGIDFSSYYYMCWVRQAPGKGLELIVCIYTSSGGTWY






ASWVNGRLTISRSTSLNTVDLKMTSLTAADTATYFCARGV






YSGSSDYPTRLDLWGQGTLVTVSLGQPKAPSVFPLAPCCG






DTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSV






RQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVA






PSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVT






CVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTI






RVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKAR






GQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVE






WEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRG






DVFTCSVMHEALHNHYTQKSISRSPGK*






A11B1_6C7 Light Chain



(SEQ ID NO: 186)



MDTSTSTALLGLLLLWLTGARCAIEMTQSPPSLSASVGET






VRIRCLASEDIYSGISWYQQKPEKPPTLLISGASNLESGV






PPRFSGGGSGTDYTLTIGGVQAEDVATYYCLGGYSFSSTG






LTFGAGTKVEIKRDPVAPSVLLFPPSKEELTTGTATIVCV






ANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLS






STLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_6B6 Heavy Chain



(SEQ ID NO: 187)



METGLRWLLLVAVLKGVQCQQHLVESGGGLVKPGASLTLT






CTASGFSFTTGYHMCWVRQAPGKGLEWIACFGVYTSTTTY






ASWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCARISA






EDGGDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTV






TLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLY






SLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKP






MCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVS






QDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLP






IAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPK






VYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKA






EDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSV






MHEALHNHYTQKSISRSPGK*






A11B1_6B6 Light Chain



(SEQ ID NO: 188)



MDTRAPTQLLGLLLLWLPGARCDVVMTQTPASVEAAVGGT






VTITCQASQSISNYFSWYQQKPGQPPKLLIYRASTLASGV






PSRFSGSGSGTQFTLTISDLECADSATYACQCTYGSSSTG






FGFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCV






ANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLS






STLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_5F7 Heavy Chain



(SEQ ID NO: 189)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






KASGFSFSSYFWICWVRQAPGKGLEWSACIYGDSSGSSYY






ASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCASYGS






SSYYYSNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSS






TVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSG






LYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCS






KPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVD






VSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVST






LPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLE






PKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNG






KAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTC






SVMHEALHNHYTQKSISRSPGK*






A11B1_5F7 Light Chain



(SEQ ID NO: 190)



MDTRAPTQLLGLLLLWLPGAICDPVMTQTPSSTSAAVGGT






VTISCQSSQSVYNNNYLAWYQQKPGQPPKRLIYESSKLAS






GVPSRFRGSGSGAQFTLTISDLECDDAATYYCLGAYYTTL






DFGGGTEVVVRGDPVAPTVLIFPPAADQVATGTVTIVCVA






NKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSS






TLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_5D7 Heavy Chain



(SEQ ID NO: 191)



METGLRWLLLVAVLKGVQCQEQLVESGGGLVQPEGSLTLT






CKASGFDFSSNAMCWVRQAPGKGLEWIACIYNGDGSTYYA






SWVNGRFTISKTSSTTVTLQMTSLTAADTATYFCARGLSN






WNRDNLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTV






TLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLY






SLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKP






MCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVS






QDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLP






IAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPK






VYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKA






EDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSV






MHEALHNHYTQKSISRSPGK*






A11B1_5D7 Light Chain



(SEQ ID NO: 192)



MDTRAPTQLLGLLLLWLPGATFAQVLTQTPSSVSAAVGGT






ATINCQASQSLYSPKNLAWYQQTPGQPPKLLIYSASKLAS






GVPSRFKGSGSGTQFTLTISGVQCDDAAIYYCQGEFSCTT






AACFAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_5A7 Heavy Chain



(SEQ ID NO: 193)



METGLRWLLLVAVLKGVQCQSLEESGGGLVQPEGSLTLAC






TASGFSFSSYYYICWVRQAPGTGLEWIGCINTGSDDTHYA






SWLKGRFTFSKASSTTLTLQMTSLTAADTATYFCARSSGS






SDDAYDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSST






VTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGL






YSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSK






PMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDV






SQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTL






PIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEP






KVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNGK






AEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCS






VMHEALHNHYTQKSISRSPGK*






A11B1_5A7 Light Chain



(SEQ ID NO: 194)



MDTRAPTQLLGLLLLWLPGARCDVVMTQTPASVSEPVGGA






VTIKCQASQSIGSNLAWYQHKPGQPPKLLIYFASSLASGV






SSRFKGGRSGTQFTLTISDLECADAATYYCHCTYYPLSYV






TFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCVA






NKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLSS






TLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_4E1 Heavy Chain



(SEQ ID NO: 195)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGTSLTLSC






TASGFSFGSYYYMCWVRQAPGKGLEWIACIDVGSSGDTYY






ASWVNGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDT






AAGGFGNLELWGPGTLVTVSSGQPKAPSVFPLAPCCGDTP






SSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQS






SGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPST






CSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVV






VDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVV






STLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQP






LEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEK






NGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVF






TCSVMHEALHNHYTQKSISRSPGK*






A11B1_4E1 Light Chain



(SEQ ID NO: 196)



MDTRAPTQLLGLLLLWLPGARCAFELTQTPSSVSEPVGGT






VTIKCQASQSIYSYFSWYQQKPGQPPKRLIYQASTLASGV






PSRFKGSGSGTDFTLTISDLECADAATYYCQNNYGRGSGS






YFFGFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIV






CVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYN






LSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_3H9 Heavy Chain



(SEQ ID NO: 197)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






KASGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGSGSTYYA






NWAKGRFTISKTSSTMVTLQMTSLTVADTATYFCAKGGAI






DLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGC






LVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSS






VVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPP






PELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDP






EVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQ






DWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTM






GPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNY






KTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEA






LHNHYTQKSISRSPGK*






A11B1_3H9 Light Chain



(SEQ ID NO: 198)



MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVEAAVGG






TVTIKCQASQSISSYLAWYQQKPGQRPKLLIYRASTLASG






VPSRFKGSGSGTDYTLTISDLECADAATYYCHTYYLSSSI






SYGNTFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_3G2 Heavy Chain



(SEQ ID NO: 199)



METGLRWLLLVAVLKGVQCQEQLEESGGDLVKPEGSLTLT






CKASGFSFSSIYWICWVRQAPGKGLEWIACTTVVKSGRTY






YANWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCAREF






VDGGGSSGRDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDT






PSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQ






SSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPS






TCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCV






VVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRV






VSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQ






PLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWE






KNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDV






FTCSVMHEALHNHYTQKSISRSPGK*






A11B1_3G2 Light Chain



(SEQ ID NO: 200)



MDTRAPTQLLGLLLLWLPGARCAYDMTQTPASVEAAVGGT






VTIKCQASQSISRDLSWYQQKPGQPPKRLIYKASTLASGV






PSRFKGSGSGTDFTLTISDLECADAATYYCQQGYSSIDVD






NDFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIVCV






ANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYNLS






STLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_3B1 Heavy Chain



(SEQ ID NO: 201)



METGLRWLLLVAVLKGVQCQEQLEESGGGLVKPEGSLTLT






CKASGFDLSSGYDMCWVRQAPGKGLEWIACIYADYSGSTY






YASWVNGRFTISSSTSLNTVDLKMTSLTAADTATYFCARG






ATGNGGYGYYFNLWGPGTLVTVSSGQPKAPSVFPLAPCCG






DTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSV






RQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVA






PSTCSKPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVT






CVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTI






RVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKAR






GQPLEPKVYTMGPPREELSSRSVSLTCMINGFYPSDISVE






WEKNGKAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRG






DVFTCSVMHEALHNHYTQKSISRSPGK*






A11B1_3B1 Light Chain



(SEQ ID NO: 202)



MDTRAPTQLLGLLLLWLPGARCADIVMTQTPASVSEPVGG






TVTIKCQASQNINSGLAWYQQKPGQPPKLLIYKASTLASG






VSSRFKGSGSGTEFTLTISDLECADAATYYCQTYYYSSSS






SDNAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIV






CVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYN






LSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_2D3 Heavy Chain



(SEQ ID NO: 203)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






TASGFSFSSSYWICWVRQAPGKGLEWIACIYGGSSGNIAY






ASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDIP






SDAFTLDLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSS






TVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSG






LYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCS






KPMCPPPELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVD






VSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRVVST






LPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLE






PKVYTMGPPREELSSRSVSLTCMINGFYPSDISVEWEKNG






KAEDNYKTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTC






SVMHEALHNHYTQKSISRSPGK*






A11B1_2D3 Light Chain



(SEQ ID NO: 204)



MDTRAPTQLLGLLLLWLPGATFAQVLTQTPSSVSAAVGST






VTINCQASQSVYKDNNLAWYQQKPGQPPKLLIYKASTLAS






GVPSRFKGSGSGTQFTLTISGVQCEDAATYYCQGEFSCGS






ADCIAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTI






VCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTY






NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






A11B1_2A7 Heavy Chain



(SEQ ID NO: 205)



METGLRWLLLVAVLKGVQCQSLEESGGDLVKPGASLTLTC






KGSGIDFSSGYGMWWVRQAPGKGLEYIGYIDTGYGSTYYA






SWAKGRFTISKTSSTTVTLQMTSLTVADTATYFCAKGGAI






DLWGPGTLVTVSSGQPKAPSVFPLAPCCGDTPSSTVTLGC






LVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGLYSLSS






VVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPMCPP






PELPGGPSVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDP






EVQFTWYINNEQVRTARPPLREQQFNSTIRVVSTLPIAHQ






DWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTM






GPPREELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNY






KTTPTVLDSDGSYFLYSKLSVPTSEWQRGDVFTCSVMHEA






LHNHYTQKSISRSPGK*






A11B1_2A7 Light Chain



(SEQ ID NO: 206)



MDTRAPTQLLGLLLLWLPGATFAAVLTQTPASTSAAVGGT






VTINCQSSQSVYRSNWLAWYQQKPGQPPKLLIYDVFNLAS






GVPSRFKGSGSGTQFTLTISGVQCADAATYYCQGSYYSGN






WYSAFGGGTEVVVKGDPVAPTVLIFPPAADQVATGTVTIV






CVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNSADCTYN






LSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC*






Human mAb Sequences












Heavy Chain and Light Chain Variable Region Sequences







2004_04B03








Heavy Chain FR1
QVQLVESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 208)





Heavy Chain CDR1
GFTFSNYG (SEQ ID NO: 209)





Heavy Chain FR2
MNWVRQAPGKGLEWVSY (SEQ ID NO: 210)





Heavy Chain CDR2
ISSSGSTV (SEQ ID NO: 211)





Heavy Chain FR3
YYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAS



(SEQ ID NO: 212)





Heavy Chain CDR3
GQLDTSDAFDI (SEQ ID NO: 213)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Heavy Chain V Gene
IGHV3-48


Segment






Light Chain FR1
DIEMTQSPSSPSASVGDRVTITCRAS (SEQ ID NO: 215)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC



(SEQ ID NO: 219)





Light Chain CDR3
QQSYSTPLT (SEQ ID NO: 220)





Light Chain FR4
FGGGTKVEIK (SEQ ID NO: 221)





Light Chain V Gene
 IGKV1-39;  IGKV1D-39


Segment






Light Chain Locus
kappa










2004_05_A06








Heavy Chain FR1
EVQLLESGGGVVQSGRSLRVSCAAS (SEQ ID NO: 222)





Heavy Chain CDR1
GFSFSSYG (SEQ ID NO: 223)





Heavy Chain FR2
MHWVRQAPGKGLEWVSY (SEQ ID NO: 224)





Heavy Chain CDR2
ISSSGSTI (SEQ ID NO: 225)





Heavy Chain FR3
YYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 226)





Heavy Chain CDR3
DLGHFDSGSSYFDY (SEQ ID NO: 442)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Heavy Chain V Gene
IGHV3-48


Segment






Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QGISNY (SEQ ID NO: 228)





Light Chain FR2
LAWYQQKPGKVPKLLIY (SEQ ID NO: 229)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
TLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC



(SEQ ID NO: 230)





Light Chain CDR3
QQSYSTPLT (SEQ ID NO: 220)





Light Chain FR4
FGGGTKVEVK (SEQ ID NO: 231)





Light Chain V Gene
IGKV1-27


Segment






Light Chain Locus
kappa










2004_04_C12








Heavy Chain FR1
EVQLLESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 232)





Heavy Chain CDR1
GFTFSNYG (SEQ ID NO: 209)





Heavy Chain FR2
MNWVRQAPGKGLEWVSY (SEQ ID NO: 210)





Heavy Chain CDR2
ISSSSSTI (SEQ ID NO: 233)





Heavy Chain FR3
YYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAS



(SEQ ID NO: 212)





Heavy Chain CDR3
GQXDXSDAFDI (SEQ ID NO: 234)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Heavy Chain V Gene
IGHV3OR16-8


Segment






Light Chain FR1
DIEMTQSPSSPSASVGDRVTITCRAS (SEQ ID NO: 215)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNXYQQKPGKAPKLLXY (SEQ ID NO: 235)





Light Chain CDR2
XAS (SEQ ID NO: 236)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDXATYYC



(SEQ ID NO: 237)





Light Chain CDR3
QQSYSTPLT (SEQ ID NO: 220)





Light Chain FR4
FGGGXKXEIK (SEQ ID NO: 238)





Light Chain V Gene
IGKV1-39; IGKV1D-39


Segment






Light Chain Locus
kappa










2002_02_B07








Heavy Chain FR1
EVQLLESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 232)





Heavy Chain CDR1
GFTFSTYG (SEQ ID NO: 436)





Heavy Chain FR2
MHWVRQAPGKGLEWVSY (SEQ ID NO: 224)





Heavy Chain CDR2
ISSSGSTI (SEQ ID NO: 225)





Heavy Chain FR3
YYADSVKGRFAISRDNAKNTLYLQMNSLRAEDTALYYCAK



(SEQ ID NO: 239)





Heavy Chain CDR3
ATRYDILTGYSDGVDYFDY (SEQ ID NO: 240)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Heavy Chain V Gene
IGHV3-48


Segment






Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC



(SEQ ID NO: 219)





Light Chain CDR3
HQSYSTPYT (SEQ ID NO: 241)





Light Chain FR4
FGQGTKLEIK (SEQ ID NO: 242)





Light Chain V Gene
IGKV1-39; IGKV1D-39


Segment






Light Chain Locus
kappa










2004_05_B04








Heavy Chain FR1
QVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 243)





Heavy Chain CDR1
GFTFSSYW (SEQ ID NO: 437)





Heavy Chain FR2
MSWVRQAPGKGLEWVAN (SEQ ID NO: 244)





Heavy Chain CDR2
IKQDGSEK (SEQ ID NO: 245)





Heavy Chain FR3
YYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 246)





Heavy Chain CDR3
VTSPHAFDI (SEQ ID NO: 247)





Heavy Chain FR4
WGRGTLVTVSS (SEQ ID NO: 248)





Heavy Chain V Gene
IGHV3-7


Segment






Light Chain FR1
DIQMTQSPSAMSASVGDRVTITCRAS (SEQ ID NO: 249)





Light Chain CDR1
QGISNY (SEQ ID NO: 228)





Light Chain FR2
LAWFQQKPGKVPKRLIY (SEQ ID NO: 250)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC



(SEQ ID NO: 219)





Light Chain CDR3
QQSYSTPLT (SEQ ID NO: 220)





Light Chain FR4
FGGGTKVEVK (SEQ ID NO: 231)





Light Chain V Gene
IGKV1-39; IGKV1D-17; IGKV1D-39


Segment






Light Chain Locus
kappa










2003_03_E12








Heavy Chain FR1
QVQLVESGGGVVRPGGSLRLSCAAS (SEQ ID NO: 251)





Heavy Chain CDR1
GFTFDDYG (SEQ ID NO: 438)





Heavy Chain FR2
MSWVRQAPGKGLEWVSG (SEQ ID NO: 252)





Heavy Chain CDR2
INWNGGST (SEQ ID NO: 253)





Heavy Chain FR3
GYADSVKGRFTISRDNSKNTLYLQMNSLRGEDTAVYYCVT



(SEQ ID NO: 254)





Heavy Chain CDR3
QGSAFDI (SEQ ID NO: 255)





Heavy Chain FR4
WGRGTLVTVSS (SEQ ID NO: 248)





Heavy Chain V Gene
IGHV3-20


Segment






Light Chain FR1
SYELTQPPSLSVSPGQTARITCSGD (SEQ ID NO: 256)





Light Chain CDR1
ALAKQY (SEQ ID NO: 257)





Light Chain FR2
AYWYQQTPGQAPVLVIY (SEQ ID NO: 258)





Light Chain CDR2
KDT (SEQ ID NO: 259)





Light Chain FR3
ERPSGIPERFSGSSSGTTVTLTISGVQAEDEVDYYC



(SEQ ID NO: 260)





Light Chain CDR3
QSTDSSGTYQV (SEQ ID NO: 261)





Light Chain FR4
FGGGTKLTVL (SEQ ID NO: 262)





Light Chain V Gene
IGLV3-25


Segment






Light Chain Locus
lambda










1994_01_C07








Heavy Chain FR1
QVQLVQSGAEVKKPGASVKVSCKAS (SEQ ID NO: 263)





Heavy Chain CDR1
GYTFTSYG (SEQ ID NO: 439)





Heavy Chain FR2
ISWVRQAPGQGLEWMGW (SEQ ID NO: 264)





Heavy Chain CDR2
ISAYNGNT (SEQ ID NO: 265)





Heavy Chain FR3
NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAAYYCAR



(SEQ ID NO: 266)





Heavy Chain CDR3
VTGITGTTIDP (SEQ ID NO: 267)





Heavy Chain FR4
WGQGTMVTVSS (SEQ ID NO: 268)





Heavy Chain V Gene
IGHV1-18


Segment






Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
DAS (SEQ ID NO: 269)





Light Chain FR3
SLESGVPSRFSGSGSGTEFTLTISSLQPDDFAVYYC



(SEQ ID NO: 270)





Light Chain CDR3
QQYNNWPQT (SEQ ID NO: 271)





Light Chain FR4
FGQGTKVEIK (SEQ ID NO: 272)





Light Chain V Gene
IGKV1-13; IGKV1D-13


Segment






Light Chain Locus
kappa










1995_01_G07








Heavy Chain FR1
QVQLVESGGGLVKPGGSLRLSCAAS (SEQ ID NO: 273)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MSWVRQAPGKGLEWVSA (SEQ ID NO: 274)





Heavy Chain CDR2
ISGSGGST (SEQ ID NO: 275)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 276)





Heavy Chain CDR3
DYGGYDGVYFDY (SEQ ID NO: 277)





Heavy Chain FR4
WGRGTLVTVSS (SEQ ID NO: 248)





Heavy Chain V Gene
IGHV3-23


Segment






Light Chain FR1
SYELTQDPAVSVALGQTVRITCQGD (SEQ ID NO: 278)





Light Chain CDR1
SLRSYY (SEQ ID NO: 279)





Light Chain FR2
ASWYQQKPGQAPVLVIY (SEQ ID NO: 280)





Light Chain CDR2
GKN (SEQ ID NO: 281)





Light Chain FR3
NRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYC



(SEQ ID NO: 282)





Light Chain CDR3
NSRDSSGNHVV (SEQ ID NO: 283)





Light Chain FR4
FGGGTKVTVL (SEQ ID NO: 284)





Light Chain V Gene
IGLV3-19


Segment






Light Chain Locus
lamdba










1995_01_G05








Heavy Chain FR1
EVQLLESGGGLVKPGGSLRLSCAAS (SEQ ID NO: 285)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MHWVRQAPGKGLEWVAV (SEQ ID NO: 286)





Heavy Chain CDR2
ISYDGSNK (SEQ ID NO: 287)





Heavy Chain FR3
YYADSVKGRFAISRDNSKNTLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 288)





Heavy Chain CDR3
DRDVGPTYYYYGMDV (SEQ ID NO: 289)





Heavy Chain FR4
WGQGTMVTVSS (SEQ ID NO: 268)





Heavy Chain V Gene
IGHV3-30


Segment






Light Chain FR1
SYELTQPPSLSVSPGQTARITCSGH (SEQ ID NO: 290)





Light Chain CDR1
ALPKQY (SEQ ID NO: 291)





Light Chain FR2
AYWYQQTPGQAPVLVIY (SEQ ID NO: 258)





Light Chain CDR2
KDT (SEQ ID NO: 259)





Light Chain FR3
ERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYC



(SEQ ID NO: 292)





Light Chain CDR3
QSADSSGPYQV (SEQ ID NO: 293)





Light Chain FR4
FGGGTQLTVL (SEQ ID NO: 294)





Light Chain V Gene
IGLV3-25


Segment






Light Chain Locus
lamdba










2004_03_G10








Heavy Chain FR1
EVQLLESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 232)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MSWVRQAPGKGLEWVSA (SEQ ID NO: 274)





Heavy Chain CDR2
ISGSGGST (SEQ ID NO: 275)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK



(SEQ ID NO: 295)





Heavy Chain CDR3
DREYIAVAADY (SEQ ID NO: 296)





Heavy Chain FR4
WGQGTTVTVSS (SEQ ID NO: 297)





Heavy Chain V Gene
IGHV3-23


Segment






Light Chain FR1
DIQMTQSPSSLSASVGDTISITCRAS (SEQ ID NO: 298)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSRTDFTLTISSVQPEDFATYYC



(SEQ ID NO: 299)





Light Chain CDR3
QQSYSTPFT (SEQ ID NO: 300)





Light Chain FR4
FGPGTKVEIK (SEQ ID NO: 301)





Light Chain V Gene
IGKV1-39; IGKV1D-39


Segment






Light Chain Locus
kappa










2002_02_B05








Heavy Chain FR1
EVQLLESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 232)





Heavy Chain CDR1
GFTFSTYG (SEQ ID NO: 436)





Heavy Chain FR2
MHWVRQAPGKGLEWVSY (SEQ ID NO: 224)





Heavy Chain CDR2
ISSSGSTI (SEQ ID NO: 225)





Heavy Chain FR3
YYADSVKGRFAISRDNAKNTLYLQMNSLRAEDTALYYCAK



(SEQ ID NO: 239)





Heavy Chain CDR3
ATRYDILTGYSDGVDYFDY (SEQ ID NO: 240)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Heavy Chain V Gene
IGHV3-48


Segment






Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC



(SEQ ID NO: 219)





Light Chain CDR3
QQSYSTPFT (SEQ ID NO: 300)





Light Chain FR4
FGPGTKVEIK (SEQ ID NO: 301)





Light Chain V Gene
IGKV1-39; IGKV1D-39


Segment






Light Chain Locus
kappa










2003_03_F05








Heavy Chain FR1
EVQLVESGAEVKKPGASVKVSCKAS (SEQ ID NO: 302)





Heavy Chain CDR1
GYTFTRYY (SEQ ID NO: 441)





Heavy Chain FR2
MHWVRQAPGQGLEWMGI (SEQ ID NO: 303)





Heavy Chain CDR2
INPSGGST (SEQ ID NO: 304)





Heavy Chain FR3
IYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR



(SEQ ID NO: 305)





Heavy Chain CDR3
SLRDGYNYIGSLGY (SEQ ID NO: 306)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Heavy Chain V Gene
IGHV1-46


Segment






Light Chain FR1
QSELTQPPSASGTPGQRVTISCSGS (SEQ ID NO: 307)





Light Chain CDR1
SSNIGSNY (SEQ ID NO: 308)





Light Chain FR2
VYWYQQLPGTAPKLLIY (SEQ ID NO: 309)





Light Chain CDR2
RNN (SEQ ID NO: 310)





Light Chain FR3
QRPSGVPDRFSGSKSGTSASLAIRGLQSEDEAGYYC



(SEQ ID NO: 311)





Light Chain CDR3
AAWDDSLNGLNWV (SEQ ID NO: 207)





Light Chain FR4
FGGGTQLTVL (SEQ ID NO: 294)





Light Chain V Gene
IGLV1-44; IGLV1-47


Segment






Light Chain Locus
lambda










1994_01_A07








Heavy Chain FR1
QVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 243)





Heavy Chain CDR1
GFTFDDYA (SEQ ID NO: 312)





Heavy Chain FR2
MHWVRQAPGKGLEWVSG (SEQ ID NO: 313)





Heavy Chain CDR2
ISWNSGST (SEQ ID NO: 314)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAG



(SEQ ID NO: 315)





Heavy Chain CDR3
GSRRYDSSGYYYESFDY (SEQ ID NO: 316)





Heavy Chain FR4
WGQGTTVTVSS (SEQ ID NO: 297)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
DAS (SEQ ID NO: 269)





Light Chain FR3
NLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID



NO: 317)





Light Chain CDR3
QQSYHTPYT (SEQ ID NO: 318)





Light Chain FR4
FGQGTKVEIK (SEQ ID NO: 272)





Light Chain Locus
kappa










1994_01_A09








Heavy Chain FR1
QMQLVQSGAEVKKPGSSVKVSCKAS (SEQ ID NO: 319)





Heavy Chain CDR1
GGTFSSYA (SEQ ID NO: 320)





Heavy Chain FR2
ISWVRQAPGQGLEWMGR (SEQ ID NO: 321)





Heavy Chain CDR2
IIPILGIA (SEQ ID NO: 322)





Heavy Chain FR3
NYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAR



(SEQ ID NO: 323)





Heavy Chain CDR3
DINRYNWNFRAFDI (SEQ ID NO: 324)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
DIVMTQSPDSLAVSLGERATINCKSS (SEQ ID NO: 435)





Light Chain CDR1
QSVLYSSNNKNY (SEQ ID NO: 325)





Light Chain FR2
LAWYQQKPRQPPKLLIY (SEQ ID NO: 326)





Light Chain CDR2
WAS (SEQ ID NO: 327)





Light Chain FR3
TRESGVPDRFSGNGSGTDFTLTISSLQAEDVAAYYC (SEQ ID



NO: 328)





Light Chain CDR3
QQHYSTPLT (SEQ ID NO: 329)





Light Chain FR4
FGPGTKVEIK (SEQ ID NO: 301)





Light Chain Locus
kappa










1994_01_D12








Heavy Chain FR1
QVQLVQSGAEVKKPGSSVKVSCKAS (SEQ ID NO: 330)





Heavy Chain CDR1
GYTFTSYG (SEQ ID NO: 439)





Heavy Chain FR2
ISWVRQAPGQGLEWMGW (SEQ ID NO: 264)





Heavy Chain CDR2
ISAYNGNT (SEQ ID NO: 265)





Heavy Chain FR3
NYAQKLQGRVTMTTNTSTSTAYMELRSLRSDDTAVYYCAR



(SEQ ID NO: 331)





Heavy Chain CDR3
VTGITGTTIDP (SEQ ID NO: 267)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYRQKPGKAPKLLIY (SEQ ID NO: 332)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDAATYYC (SEQ ID



NO: 333)





Light Chain CDR3
QQYDSQSGT (SEQ ID NO: 334)





Light Chain FR4
FGQGTKLEIK (SEQ ID NO: 242)





Light Chain Locus
kappa










1995_01_F05








Heavy Chain FR1
EVQLVESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 335)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MHWVRQAPGKGLEWVAV (SEQ ID NO: 286)





Heavy Chain CDR2
ISYDGVKK (SEQ ID NO: 336)





Heavy Chain FR3
YYADSVKGRFTISRDNSKSTLYLQMNSLRVDDTAVYYCAK



(SEQ ID NO: 337)





Heavy Chain CDR3
DLGWQNDY (SEQ ID NO: 338)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
QSVLTQPASVSGSPGQSITISCTGT DLGWQNDY (SEQ ID NO:



339)





Light Chain CDR1
SSDVGGHNY (SEQ ID NO: 340)





Light Chain FR2
VSWYQQHPGKAPKLMIY (SEQ ID NO: 341)





Light Chain CDR2
DVS (SEQ ID NO: 342)





Light Chain FR3
NRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC (SEQ ID



NO: 343)





Light Chain CDR3
SSYTSSSPWV (SEQ ID NO: 344)





Light Chain FR4
FGGGTKLTVLG (SEQ ID NO: 345)





Light Chain Locus
lambda










1995_01_F09








Heavy Chain FR1
EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 346)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MSWVRQAPGKGLEWVSA (SEQ ID NO: 274)





Heavy Chain CDR2
ISGSGGST (SEQ ID NO: 275)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNALYLQMNSLRAEDTAVYYCRG



(SEQ ID NO: 347)





Heavy Chain CDR3
YCSSTSCYGRRGAFDI (SEQ ID NO: 348)





Heavy Chain FR4
SGQGTLVTVSS (SEQ ID NO: 349)





Light Chain FR1
QAVLTQPPSASGTPGQRVTISCSGR (SEQ ID NO: 350)





Light Chain CDR1
NSNIGSNN (SEQ ID NO: 351)





Light Chain FR2
VNWYQHLPGTAPKLLIY (SEQ ID NO: 352)





Light Chain CDR2
SNN (SEQ ID NO: 353)





Light Chain FR3
QRPSGVPDRFSASKSGTSASLAISGLQSEDEADYYC (SEQ ID



NO: 354)





Light Chain CDR3
AAWDDRMNGPV (SEQ ID NO: 355)





Light Chain FR4
IGGGTKVTVLG (SEQ ID NO: 356)





Light Chain Locus
lambda










1996_01_H07








Heavy Chain FR1
QVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 243)





Heavy Chain CDR1
GFTFSSYW (SEQ ID NO: 437)





Heavy Chain FR2
MHWVRQAPAKGLVWVSR (SEQ ID NO: 357)





Heavy Chain CDR2
INSDGSST (SEQ ID NO: 358)





Heavy Chain FR3
SYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 359)





Heavy Chain CDR3
DFWSGRPYYYYMDV (SEQ ID NO: 360)





Heavy Chain FR4
WGQGTTVTVSS (SEQ ID NO: 297)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QDIGDD (SEQ ID NO: 361)





Light Chain FR2
LAWFQQKPGKAPKRLIY (SEQ ID NO: 362)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
TLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID



NO: 363)





Light Chain CDR3
QQSYSTPRT (SEQ ID NO: 364)





Light Chain FR4
FGPGTKVEIK (SEQ ID NO: 301)





Light Chain Locus
kappa










1997_02_B01








Heavy Chain FR1
EVQLVESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 335)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MHWVRQAPGKGLEWVAV (SEQ ID NO: 286)





Heavy Chain CDR2
ISYDGSNK (SEQ ID NO: 287)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSRRAEDTAVYYCAR



(SEQ ID NO: 365)





Heavy Chain CDR3
WGIVAARPNYYYGMDV (SEQ ID NO: 366)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
QSALTQPRSVSGSPGQSVTISCTGT (SEQ ID NO: 367)





Light Chain CDR1
SSDVGGYNY (SEQ ID NO: 368)





Light Chain FR2
VSWYQQHPGKAPKLMIY (SEQ ID NO: 341)





Light Chain CDR2
DVS (SEQ ID NO: 342)





Light Chain FR3
KRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYHC (SEQ ID



NO: 443)





Light Chain CDR3
SSYANNSPWV (SEQ ID NO: 369)





Light Chain FR4
FGGGTKVTVLG (SEQ ID NO: 370)





Light Chain Locus
lambda










2002_02_E01








Heavy Chain FR1
QVQLVQSGAEVRKPGASVKVSCKAS (SEQ ID NO: 371)





Heavy Chain CDR1
GYTFTSYG (SEQ ID NO: 439)





Heavy Chain FR2
ISWVRQAPGQGLEWMGW (SEQ ID NO: 264)





Heavy Chain CDR2
ISAYNGNT (SEQ ID NO: 265)





Heavy Chain FR3
NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR



(SEQ ID NO: 372)





Heavy Chain CDR3
VTGITGTTIDP (SEQ ID NO: 267)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCQAS (SEQ ID NO: 373)





Light Chain CDR1
QDISNY (SEQ ID NO: 374)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
DAS (SEQ ID NO: 269)





Light Chain FR3
NLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYC (SEQ ID NO:



375)





Light Chain CDR3
QQYANLPLT (SEQ ID NO: 376)





Light Chain FR4
FGGGTKVEIK (SEQ ID NO: 221)





Light Chain Locus
kappa










2002_02_G11








Heavy Chain FR1
EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 346)





Heavy Chain CDR1
GFTVSSNY (SEQ ID NO: 377)





Heavy Chain FR2
MSWVRQAPGKGLEWVSV (SEQ ID NO: 378)





Heavy Chain CDR2
IYSGGST (SEQ ID NO: 379)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 276)





Heavy Chain CDR3
GGLTGDDAFDI (SEQ ID NO: 380)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSF (SEQ ID NO: 381)





Light Chain FR2
LNWYQQKPGTAPKLLIY (SEQ ID NO: 382)





Light Chain CDR2
TTS (SEQ ID NO: 383)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID



NO: 219)





Light Chain CDR3
QQGNSLPLT (SEQ ID NO: 384)





Light Chain FR4
FGGGTKVEIK (SEQ ID NO: 221)





Light Chain Locus
kappa










2003_03_A09








Heavy Chain FR1
QVQLVESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 208)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MHWVRQAPGKGLEWVAV (SEQ ID NO: 286)





Heavy Chain CDR2
ISYDGSNK (SEQ ID NO: 287)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR



(SEQ ID NO: 276)





Heavy Chain CDR3
DKELSY (SEQ ID NO: 385)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
QSGLTQPASVSGSPGQSITISCTGT (SEQ ID NO: 386)





Light Chain CDR1
SSDVGGYNY (SEQ ID NO: 368)





Light Chain FR2
VSWYQQHPGKAPKLMIY (SEQ ID NO: 341)





Light Chain CDR2
EVS (SEQ ID NO: 387)





Light Chain FR3
NRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYC (SEQ ID



NO: 388)





Light Chain CDR3
SSYTSSSPWV (SEQ ID NO: 344)





Light Chain FR4
FGGGTKLTVLG (SEQ ID NO: 345)





Light Chain Locus
lambda










2004_04_D03








Heavy Chain FR1
QVQLVESGGGVVQPGRSLRLSCAAS (SEQ ID NO: 208)





Heavy Chain CDR1
GFTFSNYG (SEQ ID NO: 209)





Heavy Chain FR2
MNWVRQAPGKGLEWVSY (SEQ ID NO: 210)





Heavy Chain CDR2
ISSSSSTI (SEQ ID NO: 233)





Heavy Chain FR3
YYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAS



(SEQ ID NO: 212)





Heavy Chain CDR3
GQLDTSDAFDI (SEQ ID NO: 213)





Heavy Chain FR4
WGQGTTVTVSS (SEQ ID NO: 297)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 227)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
KTS (SEQ ID NO: 389)





Light Chain FR3
NLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID



NO: 390)





Light Chain CDR3
QQSYSTPLT (SEQ ID NO: 220)





Light Chain FR4
FGGGTKVEIK (SEQ ID NO: 221)





Light Chain Locus
kappa










2004_04_F01








Heavy Chain FR1
EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO: 346)





Heavy Chain CDR1
GFTFSSYA (SEQ ID NO: 440)





Heavy Chain FR2
MSWVRQAPAKGLEWVSA (SEQ ID NO: 391)





Heavy Chain CDR2
ISGSGGST (SEQ ID NO: 275)





Heavy Chain FR3
YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK



(SEQ ID NO: 295)





Heavy Chain CDR3
DRPYSYGKNDAFDI (SEQ ID NO: 392)





Heavy Chain FR4
WGQGTTVTVSS (SEQ ID NO: 297)





Light Chain FR1
DIQMTQSPSSLSASVGDRVTITCQAS (SEQ ID NO: 373)





Light Chain CDR1
QDVSNY (SEQ ID NO: 393)





Light Chain FR2
LNWYRQKPGKAPKLLIY (SEQ ID NO: 332)





Light Chain CDR2
AAS (SEQ ID NO: 218)





Light Chain FR3
SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID



NO: 219)





Light Chain CDR3
QQSYSTPLT (SEQ ID NO: 220)





Light Chain FR4
FGGGTKLEIK (SEQ ID NO: 394)





Light Chain Locus
kappa










2005_05_E05








Heavy Chain FR1
EVQLVQSGAEVKKPGASVKVSCKAS (SEQ ID NO: 395)





Heavy Chain CDR1
GYTFTSYY (SEQ ID NO: 396)





Heavy Chain FR2
MHWVRQAPGQGLEWMGI (SEQ ID NO: 303)





Heavy Chain CDR2
INPSGGST (SEQ ID NO: 304)





Heavy Chain FR3
SYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR



(SEQ ID NO: 397)





Heavy Chain CDR3
SPWLITFGGVIAMGY (SEQ ID NO: 402)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
QSVLTQPPSASGTPGQRVTISCSGS (SEQ ID NO: 403)





Light Chain CDR1
SSNIGSNY (SEQ ID NO: 308)





Light Chain FR2
VYWYQQLPGTAPKLLIY (SEQ ID NO: 309)





Light Chain CDR2
RNN (SEQ ID NO: 310)





Light Chain FR3
QRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYC (SEQ ID



NO: 404)





Light Chain CDR3
AAWDDSLSGVV (SEQ ID NO: 405)





Light Chain FR4
FGGGTQLTVLG (SEQ ID NO: 406)





Light Chain Locus
lambda










1994_01_D04








Heavy Chain FR1
QVQLVQSGAEVRKPGASVKVSCKAS (SEQ ID NO: 371)





Heavy Chain CDR1
GYTFTSYG (SEQ ID NO: 439)





Heavy Chain FR2
ISWVRQAPGQGLEWMGW (SEQ ID NO: 264)





Heavy Chain CDR2
ISAYNGNT (SEQ ID NO: 265)





Heavy Chain FR3
NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR



(SEQ ID NO: 372)





Heavy Chain CDR3
VTGITGTTIDP (SEQ ID NO: 267)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
DIVMTQSPSSLSASVGDRVTITCRAS (SEQ ID NO: 407)





Light Chain CDR1
QSISSY (SEQ ID NO: 216)





Light Chain FR2
LNWYQQKPGKAPKLLIY (SEQ ID NO: 217)





Light Chain CDR2
DAS (SEQ ID NO: 269)





Light Chain FR3
NLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID



NO: 317)





Light Chain CDR3
QQFNNYPLT (SEQ ID NO: 408)





Light Chain FR4
FGGGTKLEIK (SEQ ID NO: 394)





Light Chain Locus
kappa










1997_02_B03








Heavy Chain FR1
QVQLVESGAEVKKPGASVKVSCKAS (SEQ ID NO: 409)





Heavy Chain CDR1
GYTFTSYY (SEQ ID NO: 396)





Heavy Chain FR2
MHWVRQAPGQGLEWMGI (SEQ ID NO: 303)





Heavy Chain CDR2
INPSGGST (SEQ ID NO: 304)





Heavy Chain FR3
SYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR



(SEQ ID NO: 397)





Heavy Chain CDR3
AGGYYYYYMDV (SEQ ID NO: 398)





Heavy Chain FR4
WGQGTLVTVSS (SEQ ID NO: 214)





Light Chain FR1
QSGLTQPPSASGTPGQRVTISCSGS (SEQ ID NO: 399)





Light Chain CDR1
GPNIGNNY (SEQ ID NO: 400)





Light Chain FR2
VYWYQQLPGTAPKLLMY (SEQ ID NO: 401)





Light Chain CDR2
RNN (SEQ ID NO: 310)





Light Chain FR3
QRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYC (SEQ ID



NO: 410)





Light Chain CDR3
AAWDDSLNGYV (SEQ ID NO: 411)





Light Chain FR4
FGTGTKLTVLG (SEQ ID NO: 412)





Light Chain Locus
lambda









Humanized mAb Sequences










Humanized 79E3E3 Heavy Chain Variable Region



(SEQ ID NO: 413)



QIQLVQSGAEVKKPGESLKISCKASGYTFTDYAIGWVRQMPGKGLEWMGIINTQTGKPK






YSPSFQGQFIFSLDTSINTTYLQWSSLKASDTAIYFCTRLGTGNTKGFAYWGQGTTVTV





SS





Humanized 79E3E3 Light Chain Variable Region


(SEQ ID NO: 414)



DIQITQSPSSLSASLGDKVTITCRSSQSLLYSENNQDYLAWYQQKPGKAPKLLIYGAS






NLQSGVPSRFSGRGSGTDFTLTISSLQPEDFATYYCEQTYRYPFTFGPGTKVDIKR





Humanized 9-G05 Heavy Chain VH_1


Leader sequence-VH-hIgG1CH-Stop codon*


(SEQ ID NO: 415)




custom-character
custom-character QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVR







QAPGQRLEWMGYINPDNGGTIYNQKFKGRVTLTVDTSASTAYMELSSLRSEDTAVYYC





ARLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD






YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK







PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV







WDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNG







KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF







YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM







HEALHNHYTQKSLSLSPGK*






Humanized 9-G05 Heavy Chain VH_2


Leader sequence-VH-hIgG1CH-Stop codon*


(SEQ ID NO: 416)




custom-character
custom-character QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVR







QAPGQRLEWIGYINPDNGGTIYNQKFKGRVTLTVDTSASTAYMELSSLRSEDTAVYYCA





RLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY






FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS







NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV







VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGK







EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP







SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE







ALHNHYTQKSLSLSPGK*






Humanized 9-G05 Heavy Chain VH_3


Leader sequence-VH-hIgG1CH-Stop codon*


(SEQ ID NO: 417)




custom-character
custom-character QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVR







QAPGQRLEWMGYINPDNGGTIYNQKFKGRATLTVDTSASTAYMELSSLRSEDTAVYYC





ARLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD






YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK







PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV







WDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNG







KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF







YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM







HEALHNHYTQKSLSLSPGK*






Humanized 9-G05 Heavy Chain VH_4


Leader sequence-VH-hIgG1CH-Stop codon*


(SEQ ID NO: 418)




custom-character
custom-character QVQLVQSGAEVKKPGASVKVSCKASGYTFPDYNMDWVR







QAPGQSLEWIGYINPDNGGTIYNQKFKGRATLTVDTSASTAYMELSSLRSEDTAVYYCA





RLDSSGYGYYAMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY






FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS







NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV







VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGK







EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP







SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE







ALHNHYTQKSLSLSPGK*






Humanized 9-G05 Light Chain VL_1


Leader sequence-VL-hIgKCL-Stop codon*


(SEQ ID NO: 419)




custom-character
custom-character SDIVMTQSPDSLAVSLGERATINCRASESVDNYGISFMHWY







QQKPGQPPKLLIYRASNLDSGVPDRFSGSGSGTDFTLTISSLQAEDVATYYCQQSYKDPR





TFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA






LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN







RGEC*






Humanized 9-G05 Light Chain VL_2


Leader sequence-VL-hIgKCL-Stop codon*


(SEQ ID NO: 420)




custom-character
custom-character SDIVLTQSPASLAVSPGQRATITCRASESVDNYGISFMHWYQ







QKPGQPPKLLIYRASNLDSEVPARFSGSGSRTDFTLTINPVEANDTATYYCQQSYKDPRT





FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL






QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR







GEC*






16E10 Heavy Chain Variable Region


(SEQ ID NO: 421)



QSLEESGGDLVKPGASLTLTCRVSGFSFSSSYYMCWVRQAPGKGLEWIACIGTTRGSTY






YATWAKGRFTISKISSTTVTLQMTSLTDADTATYFCARDATGYRINTIGLYFNLWGPGTL





VTVSS





Humanized 16E10 Heavy Chain Variable Region VH_1


(SEQ ID NO: 422)



QSLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTY






YADSAKGRFTISKISKNTVYLQMTSLRAEDTAVYFCARDATGYRINTIGLYFNLWGPGT





LVTVSS





Humanized 16E10 Heavy Chain Variable Region VH_2


(SEQ ID NO: 423)



EVQLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGST






YYADSAKGRFTISKDNSKNTVYLQMTSLRAEDTAVYFCARDATGYRINTIGLYFNLWG





QGTLVTVSS





Humanized 16E10 Heavy Chain Variable Region VH_3


(SEQ ID NO: 424)



QSLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTY






YADSAKGRFTISKESKNTVYLQMSSLRAEDTAVYFCARDATGYRINTIGLYFNLWGPGT





LVTVSS





Humanized 16E10 Heavy Chain Variable Region VH_4


(SEQ ID NO: 425)



EVQLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGST






YYADSAKGRFTISKDNSKNTVYLQMSSLRAEDTAVYFCARDATGYRINTIGLYFNLWG





QGTLVTVSS





Humanized 16E10 Heavy Chain Variable Region VH_5


(SEQ ID NO: 426)



QSLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGSTY






YADSAKGRFTISKESKNTVYLQMSSLRAEDTAVYFCARDATGYRIQTIGLYFNLWGPGT





LVTVSS





Humanized 16E10 Heavy Chain Variable Region VH_6


(SEQ ID NO: 427)



EVQLLESGGGLVKPGGSLRLSCAVSGFSFSSSYYMCWVRQAPGKGLEWVSCIGTTRGST






YYADSAKGRFTISKDNSKNTVYLQMSSLRAEDTAVYFCARDATGYRIQTIGLYFNLWG





QGTLVTVSS





16E10 Light Chain Variable Region


(SEQ ID NO: 428)



ELTQTPSSVEAAVGGTPTIKCQASQTIYSYLSWYQQKPGQPPKLLIYEASKLASGVPSRFS






GSGSGTDYTLTISDLECADAATYYCQSYHGTASTEYNTFGGGTEVVVK





Humanized 16E10 Light Chain Variable Region VL_1


(SEQ ID NO: 429)



QLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFS






GSGSGTDYTLTISSLQPEDFATYYCQSYHGTASTEYNTFGGGTKVEIK





Humanized 16E10 Light Chain Variable Region VL_2


(SEQ ID NO: 430)



DIQLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSR






FSGSGSGTDYTLTISSLQPEDFATYYCQSYHGTASTEYNTFGGGTKVEIK





Humanized 16E10 Light Chain Variable Region VL_3


(SEQ ID NO: 431)



QLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFS






GSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYNTFGGGTKVEIK





Humanized 16E10 Light Chain Variable Region VL_4


(SEQ ID NO: 432)



DIQLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSR






FSGSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYNTFGGGTKVEIK





Humanized 16E10 Light Chain Variable Region VL_5


(SEQ ID NO: 433)



QLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSRFS






GSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYQTFGGGTKVEIK





Humanized 16E10 Light Chain Variable Region VL_6


(SEQ ID NO: 434)



DIQLTQSPSSLSASVGDRVTITCQASQTIYSYLSWYQQKPGKPPKLLIYEASKLASGVPSR






FSGSGSGTDYTLTISSLQPEDTATYYCQSYHGTASTEYQTFGGGTKVEIK






EQUIVALENTS

It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims
  • 1. An anti-integrin alpha 11 beta 1 (α11β1) antibody, or antigen-binding fragment thereof, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-443.
  • 2. An anti-α11β1 antibody, or antigen-binding fragment thereof, comprising a CDR sequence encompassed within any one of SEQ ID NO: 103-207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443.
  • 3. An anti-α11β1 antibody, or antigen-binding fragment thereof, comprising CDR1, CDR2, and CDR3 encompassed within any one of SEQ ID NO: 103-206, or 413-435.
  • 4. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 1, comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 103-114, 207-311 or 436-442, and 312-435 or 443.
  • 5. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 2, comprising a CDR sequence encompassed within any one of SEQ ID NO: 103-114, 207, 209, 211, 213, 216, 218, 220, 223, 225, 228, 233, 234, 236, 240, 241, 245, 247, 253, 255, 257, 259, 261, 265, 267, 269, 271, 275, 277, 279, 281, 283, 287, 289, 291, 293, 296, 300, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 325, 327, 329, 334, 336, 338, 340, 342, 344, 348, 351, 353, 355, 358, 360, 361, 364, 366, 368, 369, 374, 376, 377, 379, 380, 381, 383, 384, 385, 387, 389, 392, 393, 396, 398, 400, 402, 405, 408, 411, 413-435, or 436-443.
  • 6. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 2, comprising one or more CDR sequences encompassed within any one of SEQ ID NO: 103-114, or 413-434.
  • 7. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 3, comprising CDR1, CDR2, and CDR3 encompassed within any one of SEQ ID NO: 103-114 or 413-434.
  • 8. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody, or antigen-binding fragment thereof, is a monoclonal antibody, or antigen-binding fragment thereof.
  • 9. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody, or antigen-binding fragment thereof, is a humanized antibody, or antigen-binding fragment thereof.
  • 10. The anti-α11β1 antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody, or antigen-binding fragment thereof, reduces interaction of α11β1 with collagen in human α11β1-expressing cells.
  • 11. An anti-α11β1 antibody, or antigen-binding fragment thereof, that competes with the antibody, or antigen-binding fragment thereof, of claim 1.
  • 12. A nucleic acid, comprising a nucleic acid sequence encoding an antibody, or antigen-binding fragment thereof, of claim 1.
  • 13. The nucleic acid of claim 11, wherein the nucleic acid sequence comprises a sequence selected from a group consisting of SEQ ID NO: 1-102.
  • 14. A vector comprising the nucleic acid of claim 12.
  • 15. A host cell comprising the vector of claim 14.
  • 16. A method of producing an antibody, or antigen-binding fragment thereof, comprising culturing the host cell of claim 14 under conditions suitable for expression of the antibody or antigen-binding fragment thereof.
  • 17. A method of treating a subject having or at risk of a fibrotic disorder, the method comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of claim 1.
  • 18. The method of claim 17, wherein the fibrotic disorder is idiopathic pulmonary fibrosis (IPF), chronic kidney disease, diabetic cardiomyopathy, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD/NASH), Crohn's disease, ulcerative colitis, or systemic sclerosis.
  • 19. A method of treating a subject having or at risk of cancer, the method comprising administering to the subject a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of claim 1.
  • 20. The method of claim 19, wherein the cancer is a head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma, non-small cell lung cancer, adrenocortical carcinoma, acute myeloid leukemia, bladder urothelial carcinoma, invasive breast carcinoma, cervical squamous cell carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, glioblastoma multiforme, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, skin cutaneous melanoma, mesothelioma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, sarcoma, stomach adenocarcinoma, testicular germ cell tumors, thymoma, thyroid carcinoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, uveal melanoma, kidney renal clear cell carcinoma, kidney chromophobe, kidney renal papillary cell carcinoma, or a combination thereof.
  • 21. The method of claim 19, further comprising administering to the subject an effective amount of a chemotherapeutic agent or an oncolytic therapeutic agent.
CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a 35 U.S.C. § 371 national stage application of International Application Number PCT/US2020/066107, filed Dec. 18, 2020, which claims priority to U.S. Provisional Application No. 62/951,723, filed Dec. 20, 2019; U.S. Provisional Application No. 62/983,155, filed Feb. 28, 2020; and U.S. Provisional Application No. 63/054,717, filed Jul. 21, 2020, each of which is incorporated herein in its entirety.

PCT Information
Filing Document Filing Date Country Kind
PCT/US2020/066107 12/18/2020 WO
Provisional Applications (3)
Number Date Country
63054717 Jul 2020 US
62983155 Feb 2020 US
62951723 Dec 2019 US