BISPECIFIC ANTIBODIES AND METHODS OF MAKING AND USING THEREOF

Abstract
The disclosure provides bispecific antibodies having the binding specificity to at least two of human CTLA4, PD-1 or PD-L1. In one embodiment, the bispecific antibody comprises IgG domains having heavy chains and light chains, and two scFv components being connected to either C-terminal of the heavy chains or N-terminal of the light chains, wherein the IgG domains have the binding specificity to a first antigen, wherein the scFv components have the binding specificity to a second antigen, and wherein the first antigen and the second antigen are different and are independently selected from a-CTLA4, α-PD-1, and α-PD-L1.
Description
TECHNICAL FIELD

The present disclosure generally relates to the technical field of biologic therapeutics, and more particularly relates to making and using bispecific antibodies. All references are incorporated herein by its entirety.


BACKGROUND

Cancer cells develop various strategies to evade immunosurveillance. Absence of specific tumor antigens and loss of expression of major histocompatibility complex (MHC) molecules hinder the recognition of cancer cells by T lymphocytes. Immunosuppressive tumor microenvironment also contributes to the reduced recognition of tumor cells by the immune system. The tumor microenvironment is presented by immunosuppressive cellular populations composed of regulatory T cells, myeloid derived suppressor cells, tumor associated macrophages, suppressive B cells, immunosuppressive cytokines produced by tumor or stroma cells such as TGF-beta or IL-10, and immune checkpoint molecules that regulate T cell function [Marshall H T et al., Front Oncol 2018, 8:315].


Engaging a patient own immune system has been shown to be effective at controlling tumor growth and specific elimination of tumor cells while leaving normal tissue intact. Immunotherapy has provided an additional angle to treating cancer [Khalil D N et al., Adv Cancer Res 2015, 128:1-68].


Combining multiple modulators of the immune system is a new rapidly developing area of the immuno-oncology field. New therapeutic agents that can modulate immune response to tumor cells via multiple pathways can be greatly beneficial for cancer patient by increasing the patient response rate and in some cases decreasing toxicity.


Combination therapy with more than one monoclonal antibody targeting the immune system have been shown to be more efficacious in the treatment of cancer than treatments with single agents [Hellman M D et al., Adv Immunol 2016, 130: 251-77]. In addition to the increased efficacy and response rate, the combination therapy often has greater toxicity than a single agent treatment. Bispecific agents that modulate the immune system can be less toxic to patients and/or more potent, have additional mechanisms of action than treatments comprised of a combination of monoclonal antibodies with identical specificities.


SUMMARY

The current disclosure relates to the bispecific antibodies, specifically, the bispecific antibodies that contain an IgG component therefore overcome fast clearance of BiTE molecule, having an advantage over CAR-T cell therapy as an off-the-shelf therapy that does not require ex vivo expansion of patients' immune cells. Another advantage of the bispecific antibodies is the enhanced ability to overcome suppressive tumor microenvironment by simultaneous engagement of two checkpoint receptors.


The bispecific antibodies in the current disclosure can be combined with other agents, for instance T-cell engagers, and further enhance their activity.


The present disclosure relates to bispecific antibodies that bind to two distinct targets expressed on immune and tumor cells. Both targets may be checkpoint antigens. In one embodiment, both targets may be checkpoint antigens on immune cells. In one embodiment, both targets may be checkpoint antigens on tumor cells. In one embodiment, one target is a checkpoint antigen on immune cells and another target is a checkpoint antigen on tumor cells. In one embodiment, the checkpoint antigen may be selected from PD-1, PD-L1 and CTLA4. In one embodiment, the targets may include any combination of PD-1, PD-L1 and CTLA4.


The disclosure further provides the composition of the bispecific agents and their therapeutic use for treatment of cancer and autoimmune deficiencies.


In one embodiment, the application discloses a bispecific antibody comprising IgG heavy chains and light chains, and two scFv components being connected to either C terminal of the heavy chains or N terminal of the light chains, wherein the IgG has the binding specificity to a first antigen, wherein the scFv components have the binding specificity to a second antigen, and wherein the first antigen and the second antigen are different and are independently selected from α-CTLA4, α-PD-1, and α-PD-L1.


In one embodiment, the bispecific antibody has the two scFv components connected to the C terminal of the heavy chain. In one embodiment, the first antigen comprises α-CTLA4 and the second antigen comprises α-PD-1 or α-PD-L1. In another embodiment, the first antigen comprises α-PD-1 or α-PD-L1 and the second antigen comprises α-CTLA4.


In one embodiment, the bispecific antibody has the two scFv components connected to the N terminal of the light chain. In one embodiment, the first antigen comprises α-PD-1 or α-PD-L1 and the second antigen comprises α-CTLA4. In another embodiment, the first antigen comprises α-CTLA4 and the second antigen comprises α-PD-1 or α-PD-L1.


In one embodiment, the bispecific antibody is an isolated monoclonal antibody.


In one embodiment, the bispecific antibody comprises an antigenic peptide sequence having a sequence as disclosed herein. In one embodiment, the bispecific antibody may have an antigenic peptide sequence having at least 70%, 80%, 90%, 95%, 98%, or 99% similarity with the disclosed amino acid sequences.


In one embodiment, the bispecific antibody comprises an antigen-binding fragment having a sequence as disclosed herein. In one embodiment, the bispecific antibody may have an antigen-binding fragment having a sequence with at least 70%, 80%, 90%, 98%, or 99% similarity with the disclosed antibody sequences.


In one embodiment, the bispecific antibody may have a binding affinity to α-CTLA4, α-PD-1 or α-PD-L1 with a Kd not greater than 70 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, or 5 nM.


In one embodiment, the bispecific antibody may have a binding affinity to α-CTLA4 and α-PD-1 with a Kd not greater than 70 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, or 5 nM.


In one embodiment, the bispecific antibody may have a binding affinity to α-CTLA4 and α-PD-L1 with a Kd not greater than 70 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, or 5 nM.


In one embodiment, the bispecific antibody may have a binding affinity to two of α-CTLA4, α-PD-1, or α-PD-L1 with a Kd not greater than 70 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, or 5 nM.


In one embodiment, the bispecific antibody may exhibit one or more functional properties selected from high affinity binding to α-CTLA4, α-PD-1, or α-PD-L1, inhibiting binding of PD-L1 to PD-1, enhancing T cell activation, the ability to stimulate antibody responses and/or the ability to reverse the suppressive function of immunosuppressive cells, such as T regulatory cells.


In one embodiment, enhancing T-cell activation comprises T-cell proliferation, IFN-γ and/or IL-2 secretion, or a combination thereof.


In one embodiment, the bispecific antibody comprising a human framework region.


In one embodiment, the bispecific antibody may be a humanized antibody, a chimeric antibody, or a recombinant antibody.


In one embodiment, the bispecific antibody comprises an IgG1 constant region to extend the circulating half-life of the bispecific molecules. In one embodiment, the IgG1 constant region of the bispecific antibody comprises an amino acid sequence having at least 98% similarity with SEQ ID No. 136.


In one embodiment, the application discloses an isolated bispecific antibody selected from the group consisting of those clones described or having the described characteristics as disclosed herein.


In one embodiment, the application discloses an IgG1 heavy chains for the bispecific antibody, comprising an amino acid sequence selected from sequences as disclosed herein. In one embodiment, the IgG1 heavy chains may have an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 02, 06, 08, 10, 12, 14, 16, 18, 20, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 72, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, or 132.


In one embodiment, the application discloses a kappa light chain for the bispecific antibody. In one embodiment, the kappa light chain may have an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 04, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64.


In one embodiment, the application discloses a variable light chain for the bispecific antibody, comprising an amino acid sequence as disclosed herein. In one embodiment, the variable light chain may have an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, or 134.


In one embodiment, the application discloses a variable heavy chain for the bispecific antibody, comprising an amino acid sequence as disclosed herein. In one embodiment, the variable heavy chain may have an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, or 132.


In one embodiment, the application discloses an isolated nucleic acid encoding the bispecific antibody, comprising the IgG1 heavy chain disclosed herein, the kappa light chain disclosed herein, the variable light chain disclosed herein, or the variable heavy chain disclosed herein. In one embodiment, the application discloses an isolated nucleic acid encoding the bispecific antibody, comprising the IgG1 heavy chain having an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 02, 06, 08, 10, 12, 14, 16, 18, 20, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 72, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, or 132, the kappa light chain having an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 04, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64, the variable light chain having an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, or 134, or the variable heavy chain having an amino acid sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with SEQ ID NO. 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, or 132.


In one embodiment, the application discloses an expression vector comprising the isolated nucleic acid disclosed herein. In one embodiment, the expression vector comprises an isolated nucleic acid having a sequence having at least 70%, 80%, 90%, 98%, or 99% similarity with the nucleic acid sequence disclosed herein.


In one embodiment, the expression vector is expressible in a cell.


In one embodiment, the application discloses a host cell comprising the nucleic acid of disclosed herein.


In one embodiment, the application discloses a host cell comprising the expression vector.


In some embodiments, the application discloses the host cell, wherein the host cell is a prokaryotic cell or a eukaryotic cell.


In some embodiments, the application discloses a method of producing an antibody comprising culturing the host cell provided thereof so that the antibody is produced.


In some embodiments, the application discloses an immunoconjugate comprising the bispecific antibody and a cytotoxic agent. In some embodiments, the cytotoxic agent is a chemotherapeutic agent, a growth inhibitory agent, a toxin, or a radioactive isotope.


In one embodiment, the application discloses a pharmaceutical composition, comprising the bispecific antibody and a pharmaceutically acceptable carrier. In one embodiment, the application discloses a pharmaceutical composition, comprising the immunoconjugate and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition further comprises radioisotope, radionuclide, a toxin, a therapeutic agent, a chemotherapeutic agent or a combination thereof.


In one embodiment, the application discloses a method of treating a subject with a cancer, comprising administering to the subject an effective amount of the bispecific antibody disclosed herein. In one embodiment, the cancer comprises breast cancer, colorectal cancer, pancreatic cancer, head and neck cancer, melanoma, ovarian cancer, prostate cancer, non-small lung cell cancer, small cell lung cancer, glioma, esophageal cancer, nasopharyngeal cancer, kidney cancer, gastric cancer, liver cancer, bladder cancer, cervical cancer, brain cancer, lymphoma, leukaemia, myeloma.


In one embodiment, the application discloses the method of treating a subject with a cancer, wherein the cancer comprises cells expressing PD-L1.


In one embodiment, the application discloses the method of treating a subject with a cancer, further comprising co-administering an effective amount of a therapeutic agent. In some embodiments, the therapeutic agent comprises an antibody, a chemotherapy agent, an enzyme, or a combination thereof.


In some embodiments, the therapeutic agent comprises capecitabine, cisplatin, trastuzumab, fulvestrant, tamoxifen, letrozole, exemestane, anastrozole, aminoglutethimide, testolactone, vorozole, formestane, fadrozole, letrozole, erlotinib, lafatinib, dasatinib, gefitinib, imatinib, pazopinib, lapatinib, sunitinib, nilotinib, sorafenib, nab-palitaxel, a derivative or a combination thereof.


In one embodiment, the application discloses the method of treating a subject with a cancer, wherein the subject is a human.


In one embodiment, the application discloses a solution comprising an effective concentration of the bispecific antibody disclosed herein, wherein the solution is blood plasma in a subject.


Still other embodiments of the present application will become readily apparent to those skilled in the art from the following detailed description, wherein is described embodiments of the application by way of illustrating the best mode contemplated for carrying out the application. As will be realized, the application is capable of other and different embodiments and its several details are capable of modifications in various obvious respects, all without departing from the spirit and the scope of the present application. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.





BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of this disclosure may become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments arranged in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure may be described with additional specificity and detail through use of the accompanying drawings, in which:



FIG. 1 shows a diagram of example bispecific antibodies targeting CTLA4, PD-1 and PD-L1 antigens;



FIG. 2 shows binding of example anti-PD-1 antibodies to PD-1 antigen expressed on the surface of CHO cell line;



FIG. 3 depicts results from a biochemical assay assessing the ability of the representative bispecific antibodies to block the interaction between CTLA4 and CD80;



FIG. 4 shows stimulation of PBMC with super antigen SEB; FIG. 4A shows the treatment with PD224D1×CT4 IgG1 null and PL23006×CT4 IgG1 null; FIG. 4B shows the treatment with CT4×PD224D1 IgG1 null, CT4×PL221G5 IgG1 and CT4×PL221G5 IgG1 null;



FIG. 5 shows results from a signaling assay for PD-1/PDL-1 pathway;



FIG. 6 shows results from Dendritic Cell Mixed Lymphocytes Reaction study;



FIG. 7 shows results from regulatory T cell suppression assay; FIG. 7A shows the proliferation of CD8+ T cells; and FIG. 7B shows IFNg production;



FIG. 8 shows CD8 T cell degranulation in response to treatment with example bispecific antibodies;



FIG. 9 shows results from MiXeno HCC287 mouse tumor model;



FIG. 10 shows effect of example bispecific antibodies on proliferation of Flu-specific CD8 T cells;



FIG. 11 shows results from PBMC memory response to CEFT peptide pool; and



FIG. 12 shows enhancement of Redirected T Cell Cytotoxicity by example bispecific antibodies.





DETAILED DESCRIPTION

In the following detailed description of embodiments of the application, reference is made to the accompanying drawings in which like references indicates similar elements, and in which is shown by way of illustration, specific embodiments in which the application may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the application. In other instances, well-known circuits, structures, and techniques have not been shown in detail in order not to obscure the understanding of this description. The following detailed description is, therefore, not to be taken in a limiting sense, and the scoop of the application is defined only by the appended claims.


The disclosure relates to bispecific antibodies that specifically bind to human CTLA4, PD-1 or PD-L1. In some embodiments, the bispecific antibody comprises of a first arm that binds to CTLA4 and a second arm that binds to PD-1 or PD-L1. In some embodiments, the bispecific antibody comprises of a first arm that binds to PD-1 or PD-L1 and a second arm that binds to CTLA4. Examples of domains that comprise the arms include, but are not limited to, Fab and scFv domains. Each arm contains two antigen-binding domains and is connected to another arm via Fc domain. The Fc domain can be of human IgG1, IgG2, IgG3, IgG4 or an engineered isotype.


The bispecific antibodies of this application (FIG. 1) target human CTLA4, human PD-1 and human PD-L1. Each of these targeted bispecific antibodies carry an anti-CTLA4 (SEQ IDs 91, 93) and an anti-human PD-1 (SEQ IDs 95, 97, 131, 133) or PD-L1 binding domains (SEQ IDs 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129). Either one of the binding domains was converted to scFv (VH-VL orientation) for placement at the C-terminus, or scFv (VL-VH orientation) for placement at the N-terminus (FIGS. 1A and B respectively).


In some embodiments, scFv molecules described herein contain a 20-amino acid flexible gly-gly-gly-gly-ser (G4S) X4 linker that operably links the VH and VL, regardless of the V-region orientation (LH or HL). The remaining positions in the bispecific antibody may be consist of a human IgG1 Fc or IgG1 null Fc heavy chain, VH-CH1-Hinge-CH2-CH3, and its corresponding kappa light chain, VL-CL. scFv domains were genetically linked through a 10-amino acid (G4S)×2 linker to either N-terminal or C-terminal of IgG1 heavy chain, resulting in a contiguous ˜100 kDa heavy chain monomer peptide. When co-transfected with the appropriate light chain, the final symmetric bispecific molecule may be purified through the human IgG1 Fc (Protein A) and assayed to assess functional activity.


Heavy and light chain gene “cassettes” were previously constructed such that V-regions could be cloned using either restriction enzyme sites (FIG. 1A example: HindIII/NotI for the heavy chain and HindIII/BsiWI for the light chain). In one embodiment, “restriction-free cloning” NEBuilder (NEB, Ipswich, Mass.) was used.


Bispecific antibodies are produced through a process that involves design of the intact molecule, synthesis and cloning of the nucleotide sequences for each domain, expression in mammalian cells and purification of the final product. Nucleotide sequences were assembled using the Geneious 10.2.3 software package (Biomatters, Auckland, NZ) and broken up into their component domains for gene synthesis (Genewiz, South Plainsfield, N.J.). In one example (FIG. 1A), the heavy chain of CT4×PD224D1 IgG1 null bispecific antibody (SEQ ID 2) consists of the anti-CTLA4 VH domain fused to the human IgG1 null Fc domain (hinge, CH1, and CH2), followed by a 10-amino acid (G4S)×2 linker fused to the anti-PD-1 scFV domain (clone PD224D1). Using NEBuilder web-based tools, 5′ and 3′ nucleotides were appended to each of the domains so that each domain overlaps its flanking domains by 20-30 nucleotides, which direct site-specific recombination, thus genetically fusing each domain in a single gene assembly step.


The light chain of CT4×PD224D1 IgG1 null consists of the anti-CTLA4 VL domain fused to the human C kappa domain. A synthesized gene fragment was digested with the restriction enzymes HindIII and BsiWI and was then ligated in-frame with the human C kappa domain. For both constructs, a small aliquot was transformed into E. coli DH10b (Invitrogen, Carlsbad, Calif.) and plated on TB+carbenicillin 100 ug/ml plates (Teknova, Hollister, Calif.) and incubated at 37 C overnight. Resultant colonies were selected and 2 ml overnight cultures inoculated in TB+carbenicillin. DNA was prepared (Thermo-Fisher, Carlsbad, Calif.) from overnight cultures and subsequently sequenced (Genewiz, South Plainsfield, N.J.) using sequencing primers (Sigma, St. Louis, Mo.) flanking each domain. All DNA sequences were assembled and analysed in Geneious.


EXAMPLES
Example 1: Binding of Anti-PD-L1 Antibodies to PD-L1 Antigen

Binding affinities and kinetics of anti-PD-L1 antibodies to PD-L1 recombinant protein were assessed via Surface Plasmon Resonance on ForteBio Octet RED96 instrument. The antigen was immobilized on the sensor chip surface and the tested antibodies were flown over the immobilized antigens. All molecules showed strong binding to the antigen as shown in Table 1 for examples.









TABLE 1







Binding of Anti-PD-L1 Antibodies to PD-L1 Antigen











mAb
scFv-Fc
Fc-scFv
















Sample ID
KD (M)
kon (1/Ms)
kdis (1/s)
KD (M)
kon (1/Ms)
kdis (1/s)
KD (M)
kon (1/Ms)
kdis (1/s)





PL004B9
1.37E−09
5.08E+05
6.95E−04
1.42E−09
3.87E+05
5.50E−04
1.54E−09
3.07E+05
4.71E−04


PL221G5
4.83E−10
5.72E+05
2.76E−04
5.97E−10
5.08E+05
3.03E−04
4.12E−10
4.14E+05
1.71E−04


PL230C6
7.69E−10
6.09E+05
4.68E−04
9.17E−10
5.03E+05
4.61E−04
8.68E−10
4.18E+05
3.62E−04


PL231H2
7.81E−10
5.01E+05
3.91E−04
9.99E−10
4.20E+05
4.19E−04
4.62E−10
8.40E+05
3.89E−04









Example 2: Binding of Anti-PD-1 Antibodies to PD-1 Antigen

Binding of the bispecific antibodies and their components to PD-1 antigen expressed on the surface of CHO cell line was assessed using FACS method. The bispecific antibodies were incubated with CHO cell line expressing PD-1 antigen and then detected with secondary anti-human antibodies directly conjugated to Alexa Fluor 647 fluorochrome. Cellular binding of the test antibodies was analyzed on a flow cytometer BD LSRFortessa. All tested antibodies bound to the antigen with a KD in a single digit nanomolar range (FIG. 2).


Example 3: Blockade of Interaction Between CTLA4 and CD80

Ability of the bispecific antibodies to block the interaction between CTLA4 and its ligand CD80 was tested in a biochemical interaction assay (Cisbio). Briefly, a bispecific antibody was incubated with CTLA4 and CD80 proteins. Detection antibodies recognizing CTLA4 and CD80 proteins and labeled with HTRF donor/acceptor fluorescent pair then were added to the mixture. The interaction between CTLA4 and CD80 was assessed via FRET efficiency. All bispecific antibodies tested were able to block the interaction between CTLA4 and CD80 (FIG. 3).


Example 4: Stimulation of PBMC with Superantigen SEB

Ability of the bispecific antibodies to enhance cytokine release from human Peripheral Blood Mononuclear Cells (PBMC) after stimulation with superantigen SEB was assessed. All bispecific molecules were able to significantly enhance the production of IL-2 by PBMC upon stimulation with SEB, as shown in FIG. 4A and FIG. 4B.


Example 5: PD-1/PD-L1 Pathway Signaling

The bispecific antibodies were tested for their ability to block PD-1/PD-L1 pathway. Briefly, the test molecules were incubated with Jurkat reporter cell line expressing PD-1 receptor and luciferase NFAT reporter and CHO-PD-L1 cell line (Promega). The ability of the test antibodies to block the signaling through the PD-1/PD-L1 pathway was assessed via an increase in NFAT signaling. The NFAT signaling in turn was monitored via activity of luciferase reporter gene. The assay was read on a plate reader (Clariostar, BMG). All tested bispecific antibodies and monoclonal antibody controls were able to block PD-1/PD-L1 signaling (FIG. 5).


Example 6: Dendritic Cell Mixed Leukocyte Reaction

The bispecific antibodies were tested for their ability to enhance Dendritic cell Mixed Leucocyte Reaction (MLR). The test molecules were incubated for 6 days with dendritic cells from one donor and T cells isolated from another donor. Dendritic cells were differentiated in vitro from monocytes in the presence of GM-CSF and IL-4. Monocytes and T cell populations were isolated from PBMC with StemCell isolation kits. The ability of the test molecules to enhance MLR was assessed via secreted IFNγ. All tested bispecific antibodies were able to augment production of IFNγ as shown on FIG. 6.


Example 7: Suppression of CD8 T Cells by Regulatory T Cells

The bispecific antibodies were tested for their ability to block suppressive effect of regulatory T cells on effector CD8 T cell proliferation and cytokine production. CD8 T cells were isolated with StemCell isolation kit and labeled with CellTrace dye (ThermoFisher). Dendritic cells were prepared as described earlier in the MLR study. Regulatory T cells were isolated from PBMC with StemCell isolation kit and expanded in vitro. The bispecific antibody was incubated with effector CD8 T cells, dendritic cells and regulatory T cells for 4 days. The ability of the bispecific antibody to rescue effector CD8 T cell function in the presence of regulatory T cells was assessed via proliferation of effector CD8 T cells (FIG. 7A) and secreted IFNγ (FIG. 7B).


Example 8: CD8 T Cell Degranulation

Ability of bispecific molecules to have an effect on cytotoxic CD8 T cells was assessed in this study. Briefly, CD8 T cells were purified with StemCell isolation kit and stimulated with CEFT peptide pool (JPT Peptide Technologies) in the presence of the bispecific test molecules. The media was supplemented with IL-7 and IL-21. On day 11 CD8 T cells were re-stimulated with the peptides in the presence of Brefeldin and Monensin and anti-CD107a antibody directly labeled with a fluorochrome. 24 hours later CD8 T cells were stained with anti-IFNγ antibodies directly conjugated to a fluorochrome and assessed on a flow cytometer BD LSRFortessa. As shown on FIG. 8, all tested bispecific antibodies were able to increase the number of cytotoxic IFNγ positive T cells.


Example 9: MiXeno Mouse Tumor Model

Humanized mouse model was used to assess the ability of bispecific antibodies of this class to inhibit tumor growth in vivo. Briefly, NOG mice were reconstituted with human PBMC (5×106 cells per mouse). On day 3 the animals were subcutaneously inoculated with a human lung cancer cell line HCC827 (0.5E6 cells/animal) and started on a biweekly treatment with a bispecific antibody and control antibodies. Tumor volumes were measured every 2-3 days. Animal weight was monitored. The tested bispecific antibody was able to inhibit tumor growth better than the control antibodies (FIG. 9).


Example 10: Proliferation of Flu-Specific T Cells

Ability of the bispecific antibodies to augment proliferation of antigen specific CD8 T cells was assessed in this study. CD8 T cells were purified from PBMC with StemCell isolation kit, pulsed with influenza specific peptides (JPT Peptide Technologies) and incubated in the presence of the bispecific antibodies for 14 days. The media was supplemented with IL-7 and IL-21. On day 15 the cells were stained with a peptide specific MHC dextramers (Immudex) and assessed on a flow cytometer BD LSRFortessa. All tested bispecific antibodies were able to increase the number of antigen specific CD8 T cells (FIG. 10).


Example 11: PBMC Memory Response to CEFT Peptide Pool

Ability of the bispecific antibodies to augment T cell memory response was assessed. Briefly, PBMC were incubated for 4-5 days in the presence of peptides specific for CMV, EBV, Influenza and Tetanus (JPT Peptide Technologies). The amount of secreted IFNγ was quantified. The bispecific CT4×PD224D1, shown on FIG. 11, was able to enhance production of IFNγ several fold over the control treatment.


Example 12: Enhancement of Redirected T Cell Cytotoxicity

The bispecific antibodies were tested for their ability to enhance Redirected T cell Cytotoxicity (RTCC) against a tumor cell line target. The tumor cell line was stably expressing nucleus-localized Red Fluorescent Protein (RFP) delivered via lentiviral transduction (Sartorius). The tumor cells were co-cultured with PBMC and a T cell engager molecule specific for the given tumor cell line. The bispecific antibodies were added to the co-cultures. Lysis of tumor cells was assessed by counting RFP labeled tumor cell nuclei. Images were acquired on live cell imager IncuCyte (Sartorius). Activity of the antibodies were assessed after 96 hours of incubation. Four PBMC donors were tested in this study. All bispecific antibodies tested were able to enhance RTCC activity in at least one PBMC donor tested (FIG. 12).


While the present disclosure has been described with reference to particular embodiments or examples, it may be understood that the embodiments are illustrative and that the disclosure scope is not so limited. Alternative embodiments of the present disclosure may become apparent to those having ordinary skill in the art to which the present disclosure pertains. Such alternate embodiments are considered to be encompassed within the scope of the present disclosure. Accordingly, the scope of the present disclosure is defined by the appended claims and is supported by the foregoing description. All references cited or referred to in this disclosure are hereby incorporated by reference in their entireties.












SEQUENCE LISTING








SEQ ID
Description





  1
CT4 x PD224D1 nucleotide





  2
CT4 x PD224D1 amino acid





  3
CT4 Light Chain nucleotide





  4
CT4 Light Chain amino acid





  5
CT4 x PL23006 nucleotide





  6
CT4 x PL23006 amino acid





  7
CT4 x PL221G5 nucleotide





  8
CT4 x PL221G5 amino acid





  9
CT4 x PL231H2 nucleotide





 10
CT4 x PL231H2 amino acid





 11
CT4 x PL004B5 nucleotide





 12
CT4 x PL004B5 amino acid





 13
CT4 x PL004B9 nucleotide





 14
CT4 x PL004B9 amino acid





 15
CT4 x PD206F12 nucleotide





 16
CT4 x PD206F12 amino acid





 17
CT4 x PD215A1 nucleotide





 18
CT4 x PD215A1 amino acid





 19
CT4 x PD220F6 nucleotide





 20
CT4 x PD220F6 amino acid





 21
CT4 x PD225G11 nucleotide





 22
CT4 x PD225G11 amino acid





 23
Gly 4 Ser x 4 nucleotide





 24
Gly 4 Ser x 4 amino acid





 25
PL23006 x CT4 nucleotide





 26
PL23006 x CT4 amino acid





 27
PL23006 Light Chain nucleotide





 28
PL23006 Light Chain amino acid





 29
PD224D1 x CT4 nucleotide





 30
PD224D1 x CT4 amino acid





 31
PD224D1 Light Chain nucleotide





 32
PD224D1 Light Chain amino acid





 33
PL221G5 x CT4





 34
PL221G5 x CT4





 35
PL221G5 Light Chain





 36
PL221G5 Light Chain





 37
PL231H2 x CT4 nucleotide





 38
PL231H2 x CT4 amino acid





 39
PL231H2 Light Chain nucleotide





 40
PL231H2 Light Chain amino acid





 41
PL004B5 x CT4 nucleotide





 42
PL004B5 x CT4 amino acid





 43
PL004B5 Light Chain nucleotide





 44
PL004B5 Light Chain amino acid





 45
PL004B9 x CT4 nucleotide





 46
PL004B9 x CT4 amino acid





 47
PL004B9 Light Chain nucleotide





 48
PL004B9 Light Chain amino acid





 49
PD206F12 x CT4 nucleotide





 50
PD206F12 x CT4 amino acid





 51
PD206F12 Light Chain nucleotide





 52
PD206F12 Light Chain amino acid





 53
PD215A1 x CT4 nucleotide





 54
PD215A1 x CT4 amino acid





 55
PD215A1 Light Chain nucleotide





 56
PD215A1 Light Chain amino acid





 57
PD220F6 x CT4 nucleotide





 58
PD220F6 x CT4 amino acid





 59
PD220F6 Light Chain nucleotide





 60
PD220F6 Light Chain amino acid





 61
PD225G11 x CT4 nucleotide





 62
PD225G11 x CT4 amino acid





 63
PD225G11 Light Chain nucleotide





 64
PD225G11 Light Chain amino acid





 65
CT4 signal peptide nucleotide





 66
CT4 signal peptide amino acid





 67
Heavy Chain signal peptide nucleotide





 68
Heavy Chain signal peptide amino acid





 69
Light Chain signal peptide nucleotide





 70
Light Chain signal peptide amino acid





 71
CT4 scFv nucleotide





 72
CT4 scFv amino acid





 73
PD224D1 scFv nucleotide





 74
PD224D1 scFv amino acid





 75
PD206F12 scFv nucleotide





 76
PD206F12 scFv amino acid





 77
PD215A1 scFv nucleotide





 78
PD215A1 scFv amino acid





 79
PD225G11 scFv nucleotide





 80
PD225G11 scFv amino acid





 81
PL23006 scFv nucleotide





 82
PL23006 scFv amino acid





 83
PL231H2 scFv nucleotide





 84
PL231H2 scFv amino acid





 85
PL221G5 scFv nucleotide





 86
PL221G5 scFv amino acid





 87
PL004B5 scFv nucleotide





 88
PL004B5 scFv amino acid





 89
PL004B9 scFv nucleotide





 90
PL04B9 scFv amino acid





 91
CT4 VH nucleotide





 92
CT4 VH amino acid





 93
CT4 VL nucleotide





 94
CT4 VL amino acid





 95
PD224D1 VH nucleotide





 96
PD224D1 VH amino acid





 97
PD224D1 VL nucleotide





 98
PD224D1 VL amino acid





 99
PD206F12 VH nucleotide





100
PD206F12 VH amino acid





101
PD206F12 VL nucleotide





102
PD206F12 VL amino acid





103
PD215A1 VH nucleotide





104
PD215A1 VH amino acid





105
PD215A1 VL nucleotide





106
PD215A1 VL amino acid





107
PD225G11 VH nucleotide





108
PD225G11 VH amino acid





109
PD225G11 VL nucleotide





110
PD225G11 VL amino acid





111
PL23006 VH nucleotide





112
PL23006 VH amino acid





113
PL23006 VL nucleotide





114
PL23006 VL amino acid





115
PL231H2 VH nucleotide





116
PL231H2 VH amino acid





117
PL231H2 VL nucleotide





118
PL231H2 VL amino acid





119
PL221G5 VH nucleotide





120
PL221G5 VH amino acid





121
PL221G5 VL nucleotide





122
PL221G5 VL amino acid





123
PL004B5 VH nucleotide





124
PL004B5 VH amino acid





125
PL004B5 VL nucleotide





126
PL004B5 VL amino acid





127
PL004B9 VH nucleotide





128
PL004B9 VH amino acid





129
PL004B9 VL nucleotide





130
PL004B9 VL amino acid





131
PD220F6 VH nucleotide





132
PD220F6 VH amino acid





133
PD220F6 VL nucleotide





134
PD220F6 VL amino acid





135
Human IgG1 Constant Domain nucleotide





136
Human IgG1 Constant Domain amino acid





137
Human IgG1 Constant Domain null nucleotide





138
Human IgG1 Constant Domain null amino acid





139
PD220F6 scFv nucleotide





140
PD220F6 scFv amino acid










SEQ ID 01: CT4 x PD224D1 nucleotide sequence (nt)


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCA


CCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGAT


GGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT


GCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACT


GGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG


AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTC


AGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGA


CCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAG


AGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGT


CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGA


GCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAG


GAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAA


GTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCAC


AGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTAT


CCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTC


CGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCG


TGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGT


GGTGGATCCGAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGC


CTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGCTACA


TTGGTGATACTACTGGCATAGCCTACGCGAGCTGGGCGAATGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACG


GTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGCTGGTCCTACTTAGACAT


CTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCG


GTGGAGGCGGCTCTGCCCTTGTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACT


TGCCAGGCCAGTCAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTA


TCAGGCCTCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATATGGGACAGATTTCACTCTCACCATCA


GCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAGGCGGTTATTATAGTGCTGCCCTTAATACTTTCGGCGGA


GGGACCAAGGTGGAGATCAAA





SEQ ID 02: CT4 x PD224D1 amino acid sequence (aa)


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFSLSSYA



MSWVRQAPGKGLEYIGYIGDTTGIAYASWANGRFTISKDNTKNTVDLQMNSLRAEDTAVYYCARGWSYLD




IWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSALVMTQSPSSLSASVGDRVTITCQASQNIYSNLAWYQQ



KPGKVPKLLIYQASTLASGVPSRFSGSGYGTDFTLTISSLQPEDVATYYCQGGYYSAALNTFGGGTKVEI


K





SEQ ID 03: CT4 kappa light chain nt


GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCA


GGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCT


CCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACA


GACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTA


GCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA


CGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT


CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCT


CCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGC


ACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC


TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT





SEQ ID 04: CT4 kappa light chain aa


EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGT


DFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF


YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF


NRGEC





SEQ ID 05: CT4 x PL23006 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGTCGGTGGAGGAGTCTGGGGGAGGCTT


GGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGAATCGACCTTAATACCTACGACATG


ATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTGGGTTGGAATCATTACTTATAGTGGTAGTAGAT


ACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAAGACAATACCAAGAACACGGTGTATCTGCA


AATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATTATATGAGTGGTTCCCAC


TTGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCCGGTGGAGGCGGTTCAGGCGGAGGTGGAAGTGGTG


GTGGCGGCTCTGGAGGCGGCGGATCTGCCTATGATATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGT


AGGAGACAGAGTCACCATCAAGTGTCAGGCCAGTGAGGACATTTATAGCTTCTTGGCCTGGTATCAGCAG


AAACCAGGGAAAGCCCCTAAGCTCCTGATCCATTCTGCATCCTCTCTGGCATCTGGGGTCCCATCAAGGT


TCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAAC


TTACTATTGTCAACAGGGTTATGGTAAAAATAATGTTGATAATGCTTTCGGCGGAGGGACCAAGGTGGAG


ATCAAA





SEQ ID 06: CT4 x PL23006 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQSVEESGGGLVQPGGSLRLSCTASGIDLNTYDM



IWVRQAPGKGLEWVGIITYSGSRYYANWAKGRFTISKDNTKNTVYLQMNSLRAEDTAVYYCARDYMSGSH




LWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAYDMTQSPSSVSASVGDRVTIKCQASEDIYSFLAWYQQ



KPGKAPKLLIHSASSLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYGKNNVDNAFGGGTKVE


IK





SEQ ID 07: CT4 x PL221G5 null2 Fc nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGTTGGAGTCTGGGGGAGG


CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTAC


GACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTGCTGCTGGTAGTG


CTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACAC


GCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTT


TCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGAT


CTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCC


TTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCC


CACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGG


CATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCT


GCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTC


GGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 08: CT4 x PL221G5 null Fc aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGY



DMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAF




SFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISS




HLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVF



GGGTKVEIK





SEQ ID 09: CT4 x PL231H2 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCACAGGTGCAGCTGGTGGAGTCTGGGGGAGG


CCTGGTCCAGCCTGGGGGCTCCCTGAGACTCTCCTGTACAACTTCTGGAATCGACCTTAGTACCTACGAC


ATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTGGGTGGGAATCATTAGTTATGTTGGTAACA


CATACTACGCGAGCTGGGCGAAAGGCCGATTCACCCTCTCCAAAGACAATACCTCGACCACGGTGGATCT


GCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATTTTATTAGTGGTTCC


CACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCG


GCGGTGGCGGCTCCGGTGGAGGCGGTTCTGCCTATGATATGACCCAGTCTCCATCTTCCGTGTCTGCATC


TGTAGGAGACAGAGTCACCATCAATTGTCAGGCCAGTGAGAGCATTAGTAGCTTCTTATCCTGGTATCAG


CAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTTTTCTGCATCCACTCTGGCATCTGGGGTCCCATCAA


GGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGC


AACTTACTATTGTCAACAGGGTTATAGTAAAAGTAATGTGGATAATGCTTTCGGCGGAGGGACCAAGGTG


GAGATCAAA





SEQ ID 10: CT4 x PL231H2 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGLVQPGGSLRLSCTTSGIDLSTYD



MIWVRQAPGKGLEWVGIISYVGNTYYASWAKGRFTLSKDNTSTTVDLQMNSLRAEDTAVYYCARDFISGS




HLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAYDMTQSPSSVSASVGDRVTINCQASESISSFLSWYQ



QKPGKAPKLLIFSASTLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSKSNVDNAFGGGTKV


ETK





SEQ ID 11: CT4 x PL004B5 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAGGTGCAGCTGGTGGAGTCTGGGGGAGG


CTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCCTCAGTAGCTACTGG


ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGTCATTGATACTAATGTTTATA


TATACTACGCGAACTGGGCAAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT


TCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATATGTGGGTAATAATGAT


GATTATATTAACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAG


GTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCT


GTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCAGAGTGTTTATAATGGCTACTGG


TTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGGTGCATCCACTCTGGCAT


CTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCA


GCCTGATGATTTTGCAACTTATTACTGCCTAGGCAGTTATACTAGTAGTACTGAGAACTCTTTCGGCGGA


GGGACCAAGGTGGAGATCAAA





SEQ ID 12: CT4 x PL004B5 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFSLSSYW



MSWVRQAPGKGLEWIGVIDINVYIYYANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYVGNND




DYINLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQSSQSVYNGYW




LSWYQQKPGKAPKLLIYGASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCLGSYTSSTENSEGG



GTKVEIK





SEQ ID 13: CT4 x PL004B9 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAGGTGCAGCTGGTGGAGTCTGGGGGAGG


CTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGTGTCTGGAATCGACCTCAGTGTCATCAAT


ATGGGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATTACTTATGTTGGTAACA


CATATTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAAAACCTCGACCACGGTGGATCTTAAAAT


CACCAGTCCGACAACCGAGGACACGGCTGTGTATTACTGTGCGAGAGAATCTGGTACTATTTATTACAGT


TACTTTAACTTGTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTG


GTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGCATTCGAATTGACCCAGTCTCCATCCTCCCTGTC


TGCATCTGTAGGAGACAGAGTCACCATCAAGTGCCAGGCCAGTGAAAGCATTAGCAACTACTTATCCTGG


TATCAGCAGATTCCAGGGAAAGTTCCTAAGCTCCTGATCTATTATGCATCCAATCTGGCATCTGGGGTCC


CATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGA


TGTTGCAACTTATTACTGTCAAAGCTATTATGGTGGTGGTAGTGCCTATACTTTCGGCGGAGGGACCAAG


GTGGAGATCAAA





SEQ ID 14: CT4 x PL004B9 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTVSGIDLSVIN



MGWVRQAPGKGLEWIGTITYVGNTYYASWAKGRFTISKTSTTVDLKITSPTTEDTAVYYCARESGTIYYS




YFNLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAFELTQSPSSLSASVGDRVTIKCQASESISNYLSW



YQQIPGKVPKLLIYYASNLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQSYYGGGSAYTFGGGTK


VEIK





SEQ ID 15: CT4 x PD206F12 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAGGTGCAGCTGGTGGAGTCTGGGGGAGG


CTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCGACTTCAGTAGCGGCTAC


TGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTTGATCGCATGCATTTATGCTGGTACTA


GTGGTAGTACTTCCTACGCGAGCTGGGCGAGAGGCAGATTCACCATCTCCGAAACCTCCAAGAACACGGT


GACTCTTCAAATGAACAGCCTGAGAGCCGAGGACTCGGCTGTGTATTACTGTGCGAGAAATCTTTACACT


TACAATAGCTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTG


GTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTC


TGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCAGAGTGTTTATGATAACAACTGGTTA


GCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATACAGTATCCACTCTGGCATCTG


GGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCC


TGATGATTTTGCAACTTATTACTGCCAAGGCACTTATTATAGTAGTGGTTGGAACTTTGCTTTCGGCGGA


GGGACCAAGGTGGAGATCAAA





SEQ ID 16: CT4 x PD206F12 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFDFSSGY



WICWVRQAPGKGLELIACIYAGTSGSTSYASWARGRFTISETSKNIVTLQMNSLRAEDSAVYYCARNLYT




YNSLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQSSQSVYDNNWL




AWYQQKPGKAPKLLIYTVSTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGTYYSSGWNFAFGG



GTKVEIK





SEQ ID 17: CT4 x PD215A1 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCACAGGAGCAGCTGTTGGAGTCTGGGGGAGG


CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGATTCTCCTTTAGCAGCTACTGG


ATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATGCATTACGACTGGTAGTGGTA


GCACTTACTACGCGAGCTGGGCGAAGCGCCGGTTCACCATCTCCAAAGACAATTCCAAGAACACGGTGAC


TCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTACGAGAGCATTTGACTTGTGG


GGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCG


GCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGA


CAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTTACAGCTACTTAAACTGGTATCAGCAGAAACCA


GGGAAAGCCCCTAAGCTCCTGATCTATGGTGCATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGTG


GCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTA


CTGTCAAAGCAGTTGGTTGAGTGGTGCTGTTGGTAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 18: CT4 x PD215A1 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQEQLLESGGGLVQPGGSLRLSCTASGFSFSSYW



MCWVRQAPGKGLEWIGCITTGSGSTYYASWAKRRFTISKDNSKNTVTLQMNSLRAEDTAVYYCTRAFDLW



GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQSIYSYLNWYQQKP


GKAPKLLIYGASNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQSSWLSGAVGNAFGGGTKVEIK





SEQ ID 19: CT4 x PD220F6 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCACAGGAGCAGGTGAAGGAGACCGGGGGAGG


CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGCAGCTATGGA


GTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCGCATTGATTTTTCCCGGGATTGGTT


TCAAAGACTACGCGAGCTGGGTGAATGGCCGGTTCACCCTCTCCAGCGACAACGCCCAGAACACTGTGGA


ACTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAGATTTGGACTTGTGG


GGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCG


GCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGA


CAGAGTCACCATCACTTGCCAGTCCAGTCCGAGTGTTTATAGTAACTACTTATCCTGGTATCAGCAGAAA


CCAGGGAAAGTTCCTAAGCTCCTGATCTATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCA


GTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTA


TTACTGTGCAGGCGGTTATAGTAGTAGTACTCGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 20: CT4 x PD220F6 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQEQVKETGGGLVQPGGSLRLSCAASGFTISSYG



VSWVRQAPGKGLEWVALIFPGIGFKDYASWVNGRFTLSSDNAQNTVELQMNSLRAEDTAVYYCARDLDLW



GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQSSPSVYSNYLSWYQQK


PGKVPKLLIYYASTLASGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCAGGYSSSTRAFGGGTKVEIK





SEQ ID 21: CT4 x PD225G11 nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


CTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAGGTGCAGCTGTTGGAGTCTGGGGGAGG


CTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCAGCCAC


TGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTTATACTGGTAGTA


TTGATGTCTTTTACTACGCGAGCTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACAC


GCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAGCCGCTAAT


ACTGATACTACCTACTTTAACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGAT


CTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGCCTATGATATGACCCAGTCTCC


ATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAGGCCAGTCAGAGCATTAACAAC


CAACTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATGGTGCATCCACTCTGG


CATCTGGGGTCCCATCTCGGTTCACCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCT


GCAGCCTGAAGATGTTGCAACTTATTACTGTCATGTTCATTATTGCAGTGGTGGTAGTTGTTTTTGGGCT


TTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 22: CT4 x PD225G11 aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSSH



WICWVRQAPGKGLEWIACIYIGSIDVFYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARAAN




TDTTYFNLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAYDMTQSPSSLSASVGDRVTINCQASQSINN




QLSWYQQKPGKVPKLLIYGASTLASGVPSRFTGSGSGTDFTLTISSLQPEDVATYYCHVHYCSGGSCFWA



FGGGTKVEIK





SEQ ID 23: G4S x 4 nt


GGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCT





SEQ ID 24: G4S x 4 aa


GGGGSGGGGSGGGGSGGGGS





SEQ ID 25: PL23006 x CT4 nt


CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCT


CTGGAATCGACCTTAATACCTACGACATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTGGGT


TGGAATCATTACTTATAGTGGTAGTAGATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAA


GACAATACCAAGAACACGGTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACT


GTGCGAGAGATTATATGAGTGGTTCCCACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAG


CACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTG


GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCG


GCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC


CTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC


AAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGG


GGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGT


CACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG


GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCC


TCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCC


AGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCC


CCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG


ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGA


CTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTC


TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGG


GTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGGCGTGGTCCA


GCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGG


GTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACAATAAATACT


ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAAT


GAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGAC


TACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGTTCAGGCGGAGGTGGAAGTGGTG


GTGGCGGCTCTGGAGGCGGCGGATCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC


AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAG


CAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACA


GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGC


AGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA





SEQ ID 26: PL23006 x CT4 aa


QSVEESGGGLVQPGGSLRLSCTASGIDLNTYDMIWVRQAPGKGLEWVGIITYSGSRYYANWAKGRFTISK


DNIKNITYLQMNSLRAEDTAVYYCARDYMSGSHLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL


GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD


KRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV


EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLP


PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV


FSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHW


VRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFD



YWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQ



QKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK





SEQ ID 27: PL23006 kappa light chain nt


GCCTATGATATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCAAGTGTC


AGGCCAGTGAGGACATTTATAGCTTCTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCCATTCTGCATCCTCTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGGTTATGGTA


AAAATAATGTTGATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA


CGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT


CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCT


CCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGC


ACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC


TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT





SEQ ID 28: PL23006 kappa light chain aa


AYDMTQSPSSVSASVGDRVTIKCQASEDIYSFLAWYQQKPGKAPKLLIHSASSLASGVPSRFSGSGSGTD


FTLTISSLQPEDFATYYCQQGYGKNNVDNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN


NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK


SFNRGEC





SEQ ID 29: PD224D1 x CT4 nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


CCTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTA


CATCGGCTACATTGGTGATACTACTGGCATAGCCTACGCGAGCTGGGCGAATGGCAGATTCACCATCTCC


AAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATT


ACTGTGCGAGAGGCTGGTCCTACTTAGACATCTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGCGCTAG


CACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTG


GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCG


GCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC


CTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC


AAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGG


GGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGT


CACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG


GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCC


TCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCC


AGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCC


CCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG


ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGA


CTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTC


TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGG


GTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGGCGTGGTCCA


GCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGG


GTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACAATAAATACT


ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAAT


GAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGAC


TACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCG


GTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCC


AGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAG


CAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACA


GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGC


AGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA





SEQ ID 30: PD224D1 x CT4 aa


EVQLVESGGGLVQPGGSLRLSCIASGESLSSYAMSWVRQAPGKGLEYIGYIGDTTGIAYASWANGRFTIS


KDNTKNTVDLQMNSLRAEDTAVYYCARGWSYLDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL


GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD


KRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV


EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLP


PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV


FSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHW


VRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFD



YWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQ



QKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK





SEQ ID 31: PD224 light chain nt


GCCCTTGTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGGCCAGTCAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCT


GATCTATCAGGCCTCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATATGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAGGCGGTTATTATA


GTGCTGCCCTTAATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA


CGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCT


CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCT


CCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGC


ACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC


TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT





SEQ ID 32: PD224 light chain aa


ALVMTQSPSSLSASVGDRVTITCQASQNIYSNLAWYQQKPGKVPKLLIYQASTLASGVPSRFSGSGYGTD


FTLTISSLQPEDVATYYCQGGYYSAALNTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN


FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS


FNRGEC





SEQ ID 33: PL221G5 x CT4 null Fc nt


GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTC


ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGG


CCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCT


GGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC


TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGA


ACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT


CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAG


CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGT


GCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCAT


GATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTC


AACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCA


CGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGC


GGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAA


CCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGG


TCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAA


GACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC


AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGA


AGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGA


GTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTC


AGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCAT


ATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAA


GAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACC


GGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGAT


CTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCC


AGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGC


AGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCA


GGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAG


ACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAA


GGGACCAAGGTGGAAATCAAA





SEQ ID 34: PL221G5 x CT4 null Fc aa


EVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRF


TISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSASTKGPSVFPLAPSSKST


SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK


PSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF


NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPRE


PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS


RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTF



SSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCART




GWLGPFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGS




SYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQ



GTKVEIK





SEQ ID 35: PL221G5 Light Chain nt


GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAA


TTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTT


GGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATC


TGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAAT


AACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG


AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGC


AGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG


AGCTTCAACAGGGGAGAGTGT





SEQ ID 36: PL221G5 Light Chain aa


DIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTE


FTLTISSLQPDDFATYYCQQGYSWGNVDNVEGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN


NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK


SFNRGEC





SEQ ID 37: PL231H2 x CT4 null Fc nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCCAGCCTGGGGGCTCCCTGAGACTCTCCTGTACAA


CTTCTGGAATCGACCTTAGTACCTACGACATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTG


GGTGGGAATCATTAGTTATGTTGGTAACACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCCTCTCC


AAAGACAATACCTCGACCACGGTGGATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATT


ACTGTGCGAGAGATTTTATTAGTGGTTCCCACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGC


TAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC


CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA


GCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGT


GCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTG


GACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCG


CGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGA


GGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGC


GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG


TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCT


CCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTG


CCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCA


GCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCT


GGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAAC


GTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTC


CGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGGCGTGGT


CCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACTATGCAC


TGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACAATAAAT


ACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCA


AATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTT


GACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCG


GCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTC


TCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTAC


CAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAG


ACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTT


TGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATC


AAA





SEQ ID 38: PL231H2 x CT4 null Fc aa


QVQLVESGGGLVQPGGSLRLSCTTSGIDLSTYDMIWVRQAPGKGLEWVGIISYVGNTYYASWAKGRFTLS


KDNTSTTVDLQMNSLRAEDTAVYYCARDFISGSHLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAA


LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKV


DKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG


VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTL


PPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN


VFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMH


WVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPF



DYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWY



QQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEI


K





SEQ ID 39: PL231H2 Light Chain nt


GCCTATGATATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGTC


AGGCCAGTGAGAGCATTAGTAGCTTCTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTTTTCTGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGGTTATAGTA


AAAGTAATGTGGATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATC


TGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAAT


AACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG


AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGC


AGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG


AGCTTCAACAGGGGAGAGTGT





SEQ ID 40: PL231H2 Light Chain aa


AYDMTQSPSSVSASVGDRVTINCQASESISSFLSWYQQKPGKAPKLLIFSASTLASGVPSRFSGSGSGTD


FTLTISSLQPEDFATYYCQQGYSKSNVDNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN


NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK


SFNRGEC





SEQ ID 41: PL004B5 x CT4 nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCTCCCTCAGTAGCTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGAGTCATTGATACTAATGTTTATATATACTACGCGAACTGGGCAAAAGGCAGATTCACCATCTCC


AGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATT


ACTGTGCGAGATATGTGGGTAATAATGATGATTATATTAACTTGTGGGGCCAGGGAACCCTGGTCACCGT


CTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGC


ACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCG


CCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGT


GGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAAC


ACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCAC


CTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCG


GACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTAC


GTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTG


TGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAA


CAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTG


TACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCT


TCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCC


TCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAG


CAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCT


CCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGG


AGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTAT


ACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAA


ACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCT


GTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTG


GGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAG


GTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCT


GTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTA


GCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTG


GCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCC


TGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAG


GTGGAAATCAAA





SEQ ID 42: PL004B5 x CT4 aa


EVQLVESGGGLVQPGGSLRLSCAASGFSLSSYWMSWVRQAPGKGLEWIGVIDTNVYIYYANWAKGRFTIS


RDNSKNTLYLQMNSLRAEDTAVYYCARYVGNNDDYINLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGG


TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN


TKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY


VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQV


YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ


QGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSY



TMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWL




GPFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYL




AWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTK



VEIK





SEQ ID 43: PL004B5 Light Chain nt


GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGTCCAGTCAGAGTGTTTATAATGGCTACTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAA


GCTCCTGATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGG


ACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCTAGGCAGTT


ATACTAGTAGTACTGAGAACTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACC


ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG


AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCC


AGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAA


AGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACA


AAGAGCTTCAACAGGGGAGAGTGT





SEQ ID 44: PL004B5 Light Chain aa


DIQMTQSPSTLSASVGDRVTITCQSSQSVYNGYWLSWYQQKPGKAPKLLIYGASTLASGVPSRFSGSGSG


TEFTLTISSLQPDDFATYYCLGSYTSSTENSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL


NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT


KSFNRGEC





SEQ ID 45: PL004B9 x CT4 nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


TGTCTGGAATCGACCTCAGTGTCATCAATATGGGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGAACCATTACTTATGTTGGTAACACATATTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCC


AAAACCTCGACCACGGTGGATCTTAAAATCACCAGTCCGACAACCGAGGACACGGCTGTGTATTACTGTG


CGAGAGAATCTGGTACTATTTATTACAGTTACTTTAACTTGTGGGGCCAAGGGACCCTGGTCACCGTCTC


GAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGG


CGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACT


ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACA


ATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTA


TCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGG


CCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTG


GTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTC


TTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCC


TGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCA


TCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA


AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTG


GAAATCAAA





SEQ ID 46: PL004B9 x CT4 aa


EVQLVESGGGLVQPGGSLRLSCTVSGIDLSVINMGWVRQAPGKGLEWIGTITYVGNTYYASWAKGRFTIS


KTSTTVDLKITSPTTEDTAVYYCARESGTIYYSYFNLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYT



MHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLG




PFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLA



WYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKV


EIK





SEQ ID 47: PL004B9 Light Chain nt


GCATTCGAATTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAAGTGCC


AGGCCAGTGAAAGCATTAGCAACTACTTATCCTGGTATCAGCAGATTCCAGGGAAAGTTCCTAAGCTCCT


GATCTATTATGCATCCAATCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCTATTATGGTG


GTGGTAGTGCCTATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGT


CTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC


TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGA


GTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGA


CTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGC


TTCAACAGGGGAGAGTGT





SEQ ID 48: PL004B9 Light Chain aa


AFELTQSPSSLSASVGDRVTIKCQASESISNYLSWYQQIPGKVPKLLIYYASNLASGVPSRFSGSGSGTD


FTLTISSLQPEDVATYYCQSYYGGGSAYTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN


FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS


FNRGEC





SEQ ID 49: PD206F12 x CT4 nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCGACTTCAGTAGCGGCTACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTTGATCGCATGCATTTATGCTGGTACTAGTGGTAGTACTTCCTACGCGAGCTGGGCGAGAGGCAGATTC


ACCATCTCCGAAACCTCCAAGAACACGGTGACTCTTCAAATGAACAGCCTGAGAGCCGAGGACTCGGCTG


TGTATTACTGTGCGAGAAATCTTTACACTTACAATAGCTTGTGGGGCCAGGGAACCCTGGTCACCGTCTC


GAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACA


GCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCC


TGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGT


GACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACC


AAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG


AAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC


CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG


GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG


TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAA


AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC


ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT


ATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC


CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG


GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC


TGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGG


CGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACT


ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACA


ATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTA


TCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGG


CCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTG


GTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTC


TTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCC


TGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCA


TCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA


AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTG


GAAATCAAA





SEQ ID 50: PD206F12 x CT4 aa


EVQLVESGGGLVQPGGSLRLSCAASGFDFSSGYWICWVRQAPGKGLELIACIYAGTSGSTSYASWARGRF


TISETSKNTVTLQMNSLRAEDSAVYYCARNLYTYNSLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGT


AALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT


KVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV


DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY


TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ


GNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYT



MHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLG




PFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLA



WYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKV


EIK





SEQ ID 51: PD206F12 Light Chain nt


GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGTCCAGTCAGAGTGTTTATGATAACAACTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAA


GCTCCTGATCTATACAGTATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGG


ACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCACTT


ATTATAGTAGTGGTTGGAACTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGC


ACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTG


CTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT


CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAG


CAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTC


ACAAAGAGCTTCAACAGGGGAGAGTGT





SEQ ID 52: PD206F12 Light Chain aa


DIQMTQSPSTLSASVGDRVTITCQSSQSVYDNNWLAWYQQKPGKAPKLLIYTVSTLASGVPSRFSGSGSG


TEFTLTISSLQPDDFATYYCQGTYYSSGWNFAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL


LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV


TKSFNRGEC





SEQ ID 53: PD215A1 x CT4 nt


CAGGAGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


CCTCTGGATTCTCCTTTAGCAGCTACTGGATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGATGCATTACGACTGGTAGTGGTAGCACTTACTACGCGAGCTGGGCGAAGCGCCGGTTCACCATC


TCCAAAGACAATTCCAAGAACACGGTGACTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT


ATTACTGTACGAGAGCATTTGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAA


GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGC


CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGC


ACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAG


CAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGA


GTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCAC


CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG


CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG


CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG


TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCC


CATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCC


CGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCG


CCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA


CGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA


TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCG


GTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGG


GAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGC


CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAG


ACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAG


CCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGG


GGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCG


GCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGA


AAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAA


CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCA


GTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTA


TTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA





SEQ ID 54: PD215A1 x CT4 aa


QEQLLESGGGLVQPGGSLRLSCTASGFSFSSYWMCWVRQAPGKGLEWIGCITTGSGSTYYASWAKRRFTI


SKDNSKNTVTLQMNSLRAEDTAVYYCTRAFDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC


LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR


VEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV


HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPS


RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS


CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVR


QAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYW


GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQK


PGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK





SEQ ID 55: PD215A1 Light Chain nt


GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGGCCAGTCAGAGCATTTACAGCTACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTATGGTGCATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAAAGCAGTTGGTTGA


GTGGTGCTGTTGGTAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATC


TGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAAT


AACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG


AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGC


AGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAG


AGCTTCAACAGGGGAGAGTGT





SEQ IF 56: PD215A1 Light Chain aa


DIQMTQSPSSLSASVGDRVTITCQASQSIYSYLNWYQQKPGKAPKLLIYGASNLASGVPSRFSGSGSGTD


FTLTISSLQPEDFATYYCQSSWLSGAVGNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN


NFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK


SFNRGEC





SEQ ID 57: PD220F6 x CT4 nt


CAGGAGCAGGTGAAGGAGACCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCATCAGCAGCTATGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GGTCGCATTGATTTTTCCCGGGATTGGTTTCAAAGACTACGCGAGCTGGGTGAATGGCCGGTTCACCCTC


TCCAGCGACAACGCCCAGAACACTGTGGAACTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT


ATTACTGTGCGAGAGATTTGGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAA


GGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGC


CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGC


ACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAG


CAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGA


GTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCAC


CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATG


CGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG


CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG


TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCC


CATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCC


CGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCG


CCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA


CGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA


TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCG


GTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGG


GAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGC


CAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAG


ACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAG


CCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGG


GGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCG


GCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGA


AAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAA


CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCA


GTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTA


TTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA





SEQ ID 58: PD220F6 x CT4 aa


QEQVKETGGGLVQPGGSLRLSCAASGFTISSYGVSWVRQAPGKGLEWVALIFPGIGFKDYASWVNGRFTL


SSDNAQNTVELQMNSLRAEDTAVYYCARDLDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC


LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR


VEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV


HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPS


RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS


CSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVR


QAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYW


GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQK


PGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK





SEQ ID 59: PD220F6 Light Chain nt


GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGTCCAGTCCGAGTGTTTATAGTAACTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCT


CCTGATCTATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACA


GATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATA


GTAGTAGTACTCGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGT


CTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAAC


TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGA


GTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGA


CTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGC


TTCAACAGGGGAGAGTGT





SEQ ID 60: PD220F6 Light Chain aa


DIQMTQSPSSLSASVGDRVTITCQSSPSVYSNYLSWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGT


DFTLTISSLQPEDVATYYCAGGYSSSTRAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN


FYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS


FNRGEC





SEQ ID 61: PD225G11 x CT4 nt


GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTTAGCAGCAGCCACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTGGATCGCATGCATTTATACTGGTAGTATTGATGTCTTTTACTACGCGAGCTGGGCGAAAGGCCGGTTC


ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGG


CCGTATATTACTGTGCGAGAGCCGCTAATACTGATACTACCTACTTTAACTTGTGGGGCCAGGGAACCCT


GGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC


TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGA


ACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCT


CAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAG


CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGT


GCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCAT


GATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTC


AACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCA


CGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGC


GGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAA


CCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGG


TCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAA


GACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGC


AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGA


AGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCAGGTGCAATTGGTGGA


GTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTC


AGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCAT


ATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAA


GAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACC


GGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGAT


CTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATTGTGTTGACGCAGTCTCC


AGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGC


AGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATTCAGCA


GGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAG


ACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCGTGGACGTTCGGCCAA


GGGACCAAGGTGGAAATCAAA





SEQ ID 62: PD225G11 x CT4 aa


EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSHWICWVRQAPGKGLEWIACIYTGSIDVFYYASWAKGRF


TISRDNSKNTLYLQMNSLRAEDTAVYYCARAANTDTTYFNLWGQGTLVTVSSASTKGPSVFPLAPSSKST


SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK


PSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF


NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPRE


PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS


RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTF



SSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCART




GWLGPFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGS




SYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQ



GTKVEIK





SEQ ID 63: PD225G11 Light Chain nt


GCCTATGATATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCC


AGGCCAGTCAGAGCATTAACAACCAACTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCT


GATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCACCGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCATGTTCATTATTGCA


GTGGTGGTAGTTGTTTTTGGGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACC


ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG


AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCC


AGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAA


AGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACA


AAGAGCTTCAACAGGGGAGAGTGT





SEQ ID 64: PD225G11 Light Chain aa


AYDMTQSPSSLSASVGDRVTINCQASQSINNQLSWYQQKPGKVPKLLIYGASTLASGVPSRFTGSGSGTD


FTLTISSLQPEDVATYYCHVHYCSGGSCFWAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL


NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT


KSFNRGEC





SEQ ID 65: CT4 heavy chain signal peptide nucleotide sequence nt


ATGAAACACCTGTGGTTCTTCCTCCTCCTGGTGGCAGCTCCCAGATGGGTCCTGTCC





SEQ ID 66: CT4 heavy chain signal peptide nucleotide sequence aa


MKHLWFFLLLVAAPRWVLS





SEQ ID 67: PL230/PD224 Heavy chain signal peptide nt


ATGGCTGTCTTGGGGCTGCTCTTCTGCCTGGTGACATTCCCAAGCTGTGTCCTATCC





SEQ ID 68: PL230/PD224 Heavy chain signal peptide aa


MAVLGLLFCLVTFPSCVLS





SEQ ID 69: PL230/PD224 Light chain signal peptide nt


ATGAGGGCCCCTGCTCAGTTTCTTGGCTTCTTGCTTTTCTGGATTCCAGCCTCCAGAAGT





SEQ ID 70: PL230/PD224 Light chain signal peptide aa


MRAPAQFLGFLLFWIPASRS





SEQ ID 71: CT4 scFv nt


CAGGTGCAATTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTG


GGTGACATTTATATCATATGATGGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATC


TCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATAT


ATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTC


GAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGAAATT


GTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCA


GTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCAT


CTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTC


ACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCAC


CGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA





SEQ ID 72: CT4 scFv aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEI


VLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGTDF


TLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK





SEQ ID73: PD224D1 scFv nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGC


CTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGCTACA


TTGGTGATACTACTGGCATAGCCTACGCGAGCTGGGCGAATGGCAGATTCACCATCTCCAAAGACAATACCAAGAACACG


GTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGCTGGTCCTACTTAGACAT


CTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCG


GTGGAGGCGGCTCTGCCCTTGTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACT


TGCCAGGCCAGTCAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTA


TCAGGCCTCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATATGGGACAGATTTCACTCTCACCATCA


GCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAGGCGGTTATTATAGTGCTGCCCTTAATACTTTCGGCGGA


GGGACCAAGGTGGAGATCAAA





SEQ ID 74: PD224D1 scFv aa


EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYAMSWVRQAPGKGLEYIGYIGDTTGIAYASWANGRFTISKDNTKNTVDLQMNS


LRAEDTAVYYCARGWSYLDIWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSALVMTQSPSSLSASVGDRVTITCQASQNIYSN



LAWYQQKPGKVPKLLIYQASTLASGVPSRFSGSGYGTDFTLTISSLQPEDVATYYCQGGYYSAALNTFGGGTKVEIK






SEQ ID 75: PD206F12 scFv nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCGACTTCAGTAGCGGCTACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTTGATCGCATGCATTTATGCTGGTACTAGTGGTAGTACTTCCTACGCGAGCTGGGCGAGAGGCAGATTC


ACCATCTCCGAAACCTCCAAGAACACGGTGACTCTTCAAATGAACAGCCTGAGAGCCGAGGACTCGGCTG


TGTATTACTGTGCGAGAAATCTTTACACTTACAATAGCTTGTGGGGCCAGGGAACCCTGGTCACCGTCTC


GAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATC


CAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCA


GTCAGAGTGTTTATGATAACAACTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTATACAGTATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAA


TTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCACTTATTATA


GTAGTGGTTGGAACTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 76: PD206F12 scFv aa


EVQLVESGGGLVQPGGSLRLSCAASGFDFSSGYWICWVRQAPGKGLELIACIYAGTSGSTSYASWARGRF


TISETSKNTVTLQMNSLRAEDSAVYYCARNLYTYNSLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDI


QMTQSPSTLSASVGDRVTITCQSSQSVYDNNWLAWYQQKPGKAPKLLIYTVSTLASGVPSRFSGSGSGTE


FTLTISSLQPDDFATYYCQGTYYSSGWNFAFGGGTKVEIK





SEQ ID 77: PD215A1 scFv nt


CAGGAGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


CCTCTGGATTCTCCTTTAGCAGCTACTGGATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGATGCATTACGACTGGTAGTGGTAGCACTTACTACGCGAGCTGGGCGAAGCGCCGGTTCACCATC


TCCAAAGACAATTCCAAGAACACGGTGACTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT


ATTACTGTACGAGAGCATTTGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGG


ATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCT


CCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTTACA


GCTACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGGTGCATCCAATCT


GGCATCTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGT


CTGCAACCTGAAGATTTTGCAACTTACTACTGTCAAAGCAGTTGGTTGAGTGGTGCTGTTGGTAATGCTT


TCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 78: PD215A1 scFv aa


QEQLLESGGGLVQPGGSLRLSCTASGFSFSSYWMCWVRQAPGKGLEWIGCITTGSGSTYYASWAKRRFTI


SKDNSKNTVTLQMNSLRAEDTAVYYCTRAFDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMIQS


PSSLSASVGDRVTITCQASQSIYSYLNWYQQKPGKAPKLLIYGASNLASGVPSRFSGSGSGTDFTLTISS


LQPEDFATYYCQSSWLSGAVGNAFGGGTKVEIK





SEQ ID 79: PD225G11 scFv nt


GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTTAGCAGCAGCCACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTGGATCGCATGCATTTATACTGGTAGTATTGATGTCTTTTACTACGCGAGCTGGGCGAAAGGCCGGTTC


ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGG


CCGTATATTACTGTGCGAGAGCCGCTAATACTGATACTACCTACTTTAACTTGTGGGGCCAGGGAACCCT


GGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGC


GGCTCTGCCTATGATATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCA


ATTGCCAGGCCAGTCAGAGCATTAACAACCAACTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAA


GCTCCTGATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCACCGGCAGTGGATCTGGG


ACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCATGTTCATT


ATTGCAGTGGTGGTAGTTGTTTTTGGGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 80: PD225G11 scFv aa


EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSHWICWVRQAPGKGLEWIACIYTGSIDVFYYASWAKGRF


TISRDNSKNTLYLQMNSLRAEDTAVYYCARAANTDTTYFNLWGQGTLVTVSSGGGGSGGGGSGGGGSGGG


GSAYDMTQSPSSLSASVGDRVTINCQASQSINNQLSWYQQKPGKVPKLLIYGASTLASGVPSRFTGSGSG


TDFTLTISSLQPEDVATYYCHVHYCSGGSCFWAFGGGTKVEIK





SEQ ID 81: PL23006 scFv nt


CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCT


CTGGAATCGACCTTAATACCTACGACATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTGGGT


TGGAATCATTACTTATAGTGGTAGTAGATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAA


GACAATACCAAGAACACGGTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACT


GTGCGAGAGATTATATGAGTGGTTCCCACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCCGGTGG


AGGCGGTTCAGGCGGAGGTGGAAGTGGTGGTGGCGGCTCTGGAGGCGGCGGATCTGCCTATGATATGACC


CAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCAAGTGTCAGGCCAGTGAGGACA


TTTATAGCTTCTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCCATTCTGCATC


CTCTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATC


AGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGGTTATGGTAAAAATAATGTTGATA


ATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 82: PL23006 scFv aa


QSVEESGGGLVQPGGSLRLSCTASGIDLNTYDMIWVRQAPGKGLEWVGIITYSGSRYYANWAKGRFTISK


DNTKNTVYLQMNSLRAEDTAVYYCARDYMSGSHLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAYDMT


QSPSSVSASVGDRVTIKCQASEDIYSFLAWYQQKPGKAPKLLIHSASSLASGVPSRFSGSGSGTDFTLTI


SSLQPEDFATYYCQQGYGKNNVDNAFGGGTKVEIK





SEQ ID 83: PL231H2 scFv nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCCAGCCTGGGGGCTCCCTGAGACTCTCCTGTACAA


CTTCTGGAATCGACCTTAGTACCTACGACATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTG


GGTGGGAATCATTAGTTATGTTGGTAACACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCCTCTCC


AAAGACAATACCTCGACCACGGTGGATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATT


ACTGTGCGAGAGATTTTATTAGTGGTTCCCACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGG


TGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGTTCTGCCTATGATATG


ACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGTCAGGCCAGTGAGA


GCATTAGTAGCTTCTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTTTTCTGC


ATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACC


ATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGGTTATAGTAAAAGTAATGTGG


ATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 84: PL231H2 scFv aa


QVQLVESGGGLVQPGGSLRLSCTTSGIDLSTYDMIWVRQAPGKGLEWVGIISYVGNTYYASWAKGRFTLS


KDNTSTTVDLQMNSLRAEDTAVYYCARDFISGSHLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAYDM


TQSPSSVSASVGDRVTINCQASESISSFLSWYQQKPGKAPKLLIFSASTLASGVPSRFSGSGSGTDFTLT


ISSLQPEDFATYYCQQGYSKSNVDNAFGGGTKVEIK





SEQ ID 85: PL221G5 scFv nt


GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTC


ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGG


CCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCT


GGTCACCGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGC


GGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCA


CTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAA


GCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGG


ACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTT


ATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 86: PL221G5 scFv aa


EVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRF


TISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGG


GSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSG


TEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIK





SEQ ID 87: PL004B5 scFv nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCTCCCTCAGTAGCTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGAGTCATTGATACTAATGTTTATATATACTACGCGAACTGGGCAAAAGGCAGATTCACCATCTCC


AGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATT


ACTGTGCGAGATATGTGGGTAATAATGATGATTATATTAACTTGTGGGGCCAGGGAACCCTGGTCACCGT


CTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGAC


ATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGT


CCAGTCAGAGTGTTTATAATGGCTACTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCT


CCTGATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACA


GAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCTAGGCAGTTATA


CTAGTAGTACTGAGAACTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 88: PL004B5 scFv aa


EVQLVESGGGLVQPGGSLRLSCAASGFSLSSYWMSWVRQAPGKGLEWIGVIDTNVYIYYANWAKGRFTIS


RDNSKNTLYLQMNSLRAEDTAVYYCARYVGNNDDYINLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSD


IQMTQSPSTLSASVGDRVTITCQSSQSVYNGYWLSWYQQKPGKAPKLLIYGASTLASGVPSRFSGSGSGT


EFTLTISSLQPDDFATYYCLGSYTSSTENSFGGGTKVEIK





SEQ ID 89: PL004B9 scFv nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


TGTCTGGAATCGACCTCAGTGTCATCAATATGGGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGAACCATTACTTATGTTGGTAACACATATTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCC


AAAACCTCGACCACGGTGGATCTTAAAATCACCAGTCCGACAACCGAGGACACGGCTGTGTATTACTGTG


CGAGAGAATCTGGTACTATTTATTACAGTTACTTTAACTTGTGGGGCCAAGGGACCCTGGTCACCGTCTC


GAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGCATTC


GAATTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAAGTGCCAGGCCA


GTGAAAGCATTAGCAACTACTTATCCTGGTATCAGCAGATTCCAGGGAAAGTTCCTAAGCTCCTGATCTA


TTATGCATCCAATCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACT


CTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCTATTATGGTGGTGGTA


GTGCCTATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 90: PL004B9 scFv aa


EVQLVESGGGLVQPGGSLRLSCTVSGIDLSVINMGWVRQAPGKGLEWIGTITYVGNTYYASWAKGRFTIS


KTSTTVDLKITSPTTEDTAVYYCARESGTIYYSYFNLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAF


ELTQSPSSLSASVGDRVTIKCQASESISNYLSWYQQIPGKVPKLLIYYASNLASGVPSRFSGSGSGTDFT


LTISSLQPEDVATYYCQSYYGGGSAYTFGGGTKVEIK





SEQ ID 91: CT4 VH nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCA


CCTTCAGTAGCTATACTATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACATTTATATCATATGAT


GGAAACAATAAATACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCT


GCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATATATTACTGTGCGAGGACCGGCTGGCTGGGGCCCTTTGACTACT


GGGGCCAGGGAACCCTGGTCACCGTCTCCTCA





SEQ ID 92: CT4 VH aa


QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYYADSVKGRFTI


SRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSS





SEQ ID 93: CT4 VL nt


GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCA


GGGCCAGTCAGAGTGTTGGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCT


CCTCATCTATGGTGCATTCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACA


GACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTA


GCTCACCGTGGACGTTCGGCCAAGGGACCAAGGTGGAAATCAAA





SEQ ID 94: CT4 VL aa


EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIPDRFSGSGSGT


DFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIK





SEQ ID 95: PD224D1 VH nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


CCTCTGGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTA


CATCGGCTACATTGGTGATACTACTGGCATAGCCTACGCGAGCTGGGCGAATGGCAGATTCACCATCTCC


AAAGACAATACCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATT


ACTGTGCGAGAGGCTGGTCCTACTTAGACATCTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGC





SEQ ID 96: PD224D1 VH aa


EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYAMSWVRQAPGKGLEYIGYIGDTTGIAYASWANGRFTIS


KDNTKNTVDL


QMNSLRAEDTAVYYCARGWSYLDIWGQGTLVTSS





SEQ ID 97: PD224D1 VL nt


GCCCTTGTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGGCCAGTCAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCT


GATCTATCAGGCCTCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATATGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAGGCGGTTATTATA


GTGCTGCCCTTAATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 98: PD224D1 VL aa


ALVMTQSPSSLSASVGDRVTITCQASQNIYSNLAWYQQKPGKVPKLLIYQASTLASGVPSRFSGSGYGTD


FTLTISSLQP


EDVATYYCQGGYYSAALNTFGGGTKVEIK





SEQ ID 99: PD206F12 VH nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCGACTTCAGTAGCGGCTACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTTGATCGCATGCATTTATGCTGGTACTAGTGGTAGTACTTCCTACGCGAGCTGGGCGAGAGGCAGATTC


ACCATCTCCGAAACCTCCAAGAACACGGTGACTCTTCAAATGAACAGCCTGAGAGCCGAGGACTCGGCTG


TGTATTACTGTGCGAGAAATCTTTACACTTACAATAGCTTGTGGGGCCAGGGAACCCTGGTCACCGTCTC


GAGC





SEQ ID 100: PD206F12 VH aa


EVQLVESGGGLVQPGGSLRLSCAASGFDFSSGYWICWVRQAPGKGLELIACIYAGTSGSTSYASWARGRF


TISETSKNTVTLQMNSLRAEDSAVYYCARNLYTYNSLWGQGTLVTVSS





SEQ ID 101: PD206F12 VL nt


GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGTCCAGTCAGAGTGTTTATGATAACAACTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAA


GCTCCTGATCTATACAGTATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGG


ACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCACTT


ATTATAGTAGTGGTTGGAACTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 102: PD206F12 VL aa


DIQMIQSPSTLSASVGDRVTITCQSSQSVYDNNWLAWYQQKPGKAPKLLIYTVSTLASGVPSRFSGSGSG


TEFTLTISSLQPDDFATYYCQGTYYSSGWNFAFGGGTKVEIK





SEQ ID 103: PD215A1 VH nt


CAGGAGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


CCTCTGGATTCTCCTTTAGCAGCTACTGGATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGATGCATTACGACTGGTAGTGGTAGCACTTACTACGCGAGCTGGGCGAAGCGCCGGTTCACCATC


TCCAAAGACAATTCCAAGAACACGGTGACTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT


ATTACTGTACGAGAGCATTTGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC





SEQ ID 104: PD215A1 VH aa


QEQLLESGGGLVQPGGSLRLSCTASGFSFSSYWMCWVRQAPGKGLEWIGCITTGSGSTYYASWAKRRFTI


SKDNSKNIVTLQMNSLRAEDTAVYYCTRAFDLWGQGTLVTVSS





SEQ ID 105: PD215A1 VL nt


GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGGCCAGTCAGAGCATTTACAGCTACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTATGGTGCATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAAAGCAGTTGGTTGA


GTGGTGCTGTTGGTAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 106: PD215A1 VL aa


DIQMTQSPSSLSASVGDRVTITCQASQSIYSYLNWYQQKPGKAPKLLIYGASNLASGVPSRFSGSGSGTD


FTLTISSLQPEDFATYYCQSSWLSGAVGNAFGGGTKVEIK





SEQ ID 107: PD225G11 VH nt


GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCTTTAGCAGCAGCCACTGGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTGGATCGCATGCATTTATACTGGTAGTATTGATGTCTTTTACTACGCGAGCTGGGCGAAAGGCCGGTTC


ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGG


CCGTATATTACTGTGCGAGAGCCGCTAATACTGATACTACCTACTTTAACTTGTGGGGCCAGGGAACCCT


GGTCACCGTCTCGAGC





SEQ ID 108: PD225G11 VH aa


EVQLLESGGGLVQPGGSLRLSCAASGFTFSSSHWICWVRQAPGKGLEWIACIYTGSIDVFYYASWAKGRF


TISRDNSKNTLYLQMNSLRAEDTAVYYCARAANTDITYFNLWGQGTLVTVSS





SEQ ID 109: PD225G11 VL nt


GCCTATGATATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCC


AGGCCAGTCAGAGCATTAACAACCAACTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCT


GATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCACCGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCATGTTCATTATTGCA


GTGGTGGTAGTTGTTTTTGGGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 110: PD225G11 VL aa


AYDMTQSPSSLSASVGDRVTINCQASQSINNQLSWYQQKPGKVPKLLIYGASTLASGVPSRFTGSGSGTD


FTLTISSLQPEDVATYYCHVHYCSGGSCFWAFGGGTKVEIK





SEQ ID 111: PL23006 VH nt


CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCT


CTGGAATCGACCTTAATACCTACGACATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTGGGT


TGGAATCATTACTTATAGTGGTAGTAGATACTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAAA


GACAATACCAAGAACACGGTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACT


GTGCGAGAGATTATATGAGTGGTTCCCACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCC





SEQ ID 112: PL23006 VH aa


QSVEESGGGLVQPGGSLRLSCTASGIDLNTYDMIWVRQAPGKGLEWVGIITYSGSRYYANWAKGRFTISK


DNTKNTVYLQMNSLRAEDTAVYYCARDYMSGSHLWGQGTLVTVSS





SEQ ID 113: PL23006 VL nt


GCCTATGATATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCAAGTGTC


AGGCCAGTGAGGACATTTATAGCTTCTTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCCATTCTGCATCCTCTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGGTTATGGTA


AAAATAATGTTGATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 114: PL23006 VL aa


AYDMTQSPSSVSASVGDRVTIKCQASEDIYSFLAWYQQKPGKAPKLLIHSASSLASGVPSRFSGSGSGTD


FTLTISSLQP


EDFATYYCQQGYGKNNVDNAFGGGTKVEIK





SEQ ID 115: PL231H2 VH nt


CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCCTGGTCCAGCCTGGGGGCTCCCTGAGACTCTCCTGTACAA


CTTCTGGAATCGACCTTAGTACCTACGACATGATCTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTG


GGTGGGAATCATTAGTTATGTTGGTAACACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCCTCTCC


AAAGACAATACCTCGACCACGGTGGATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATT


ACTGTGCGAGAGATTTTATTAGTGGTTCCCACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC





SEQ ID 116: PL231H2 VH aa


QVQLVESGGGLVQPGGSLRLSCTTSGIDLSTYDMIWVRQAPGKGLEWVGIISYVGNTYYASWAKGRFTLS


KDNTSTTVDLQMNSLRAEDTAVYYCARDFISGSHLWGQGTLVTVSS





SEA ID 117: PL231H2 VL nt


GCCTATGATATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGTC


AGGCCAGTGAGAGCATTAGTAGCTTCTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTTTTCTGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAACAGGGTTATAGTA


AAAGTAATGTGGATAATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 118: PL231H2 VL aa


AYDMTQSPSSVSASVGDRVTINCQASESISSFLSWYQQKPGKAPKLLIFSASTLASGVPSRFSGSGSGTD


FTLTISSLQPEDFATYYCQQGYSKSNVDNAFGGGTKVEIK





SEQ ID 119: PL221G5 VH nt


GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA


GTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTC


ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGG


CCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCT


GGTCACCGTCTCGAGC





SEA ID 120: PL221G5 VH aa


EVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRF


TISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSS





SEQ ID 121: PL221G5 VL nt


GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCT


GATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAA


TTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTT


GGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEA ID 122: PL221G5 VL aa


DIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTE


FTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIK





SEA ID 123: PL004B5 VH nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCTCCCTCAGTAGCTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGAGTCATTGATACTAATGTTTATATATACTACGCGAACTGGGCAAAAGGCAGATTCACCATCTCC


AGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATT


ACTGTGCGAGATATGTGGGTAATAATGATGATTATATTAACTTGTGGGGCCAGGGAACCCTGGTCACCGT


CTCGAGC





SEQ ID 124: PL004B5 VH aa


EVQLVESGGGLVQPGGSLRLSCAASGFSLSSYWMSWVRQAPGKGLEWIGVIDTNVYIYYANWAKGRFTIS


RDNSKNTLYLQMNSLRAEDTAVYYCARYVGNNDDYINLWGQGTLVTVSS





SEQ ID 125: PL004B5 VL nt


GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGTCCAGTCAGAGTGTTTATAATGGCTACTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAA


GCTCCTGATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGG


ACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCTAGGCAGTT


ATACTAGTAGTACTGAGAACTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 126: PL004B5 VL aa


DIQMTQSPSTLSASVGDRVTITCQSSQSVYNGYWLSWYQQKPGKAPKLLIYGASTLASGVPSRFSGSGSG


TEFTLTISSLQPDDFATYYCLGSYTSSTENSFGGGTKVEIK





SEA ID 127: PL004B9 VH nt


GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAG


TGTCTGGAATCGACCTCAGTGTCATCAATATGGGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GATCGGAACCATTACTTATGTTGGTAACACATATTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCC


AAAACCTCGACCACGGTGGATCTTAAAATCACCAGTCCGACAACCGAGGACACGGCTGTGTATTACTGTG


CGAGAGAATCTGGTACTATTTATTACAGTTACTTTAACTTGTGGGGCCAAGGGACCCTGGTCACCGTCTC


GAGC





SEQ ID 128: PL004B9 VH aa


EVQLVESGGGLVQPGGSLRLSCTVSGIDLSVINMGWVRQAPGKGLEWIGTITYVGNTYYASWAKGRFTIS


KTSTTVDLKITSPTTEDTAVYYCARESGTIYYSYFNLWGQGTLVTVSS





SEQ ID 129: PL004B9 VL nt


GCATTCGAATTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAAGTGCC


AGGCCAGTGAAAGCATTAGCAACTACTTATCCTGGTATCAGCAGATTCCAGGGAAAGTTCCTAAGCTCCT


GATCTATTATGCATCCAATCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGAT


TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCTATTATGGTG


GTGGTAGTGCCTATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 130: PL004B9 VL aa


AFELTQSPSSLSASVGDRVTIKCQASESISNYLSWYQQIPGKVPKLLIYYASNLASGVPSRFSGSGSGTD


FTLTISSLQPEDVATYYCQSYYGGGSAYTFGGGTKVEIK





SEQ ID 131: PD220F6 VH nt


CAGGAGCAGGTGAAGGAGACCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCATCAGCAGCTATGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GGTCGCATTGATTTTTCCCGGGATTGGTTTCAAAGACTACGCGAGCTGGGTGAATGGCCGGTTCACCCTC


TCCAGCGACAACGCCCAGAACACTGTGGAACTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT


ATTACTGTGCGAGAGATTTGGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC





SEQ ID 132: PD220F6 VH aa


QEQVKETGGGLVQPGGSLRLSCAASGFTISSYGVSWVRQAPGKGLEWVALIFPGIGFKDYASWVNGRFTL


SSDNAQNTVELQMNSLRAEDTAVYYCARDLDLWGQGTLVTVSS





SEQ ID 133: PD220F6 VL nt


GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCC


AGTCCAGTCCGAGTGTTTATAGTAACTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCT


CCTGATCTATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACA


GATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATA


GTAGTAGTACTCGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 134: PD220F6 VL aa


DIQMTQSPSSLSASVGDRVTITCQSSPSVYSNYLSWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGT


DFTLTISSLQPEDVATYYCAGGYSSSTRAFGGGTKVEIK





SEQ ID 135: human IgG1 constant region nt


GCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG


CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGAC


CAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC


GTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG


TGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACT


CCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCT


GAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACG


GCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAG


CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC


CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCC


TGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCC


CAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG


CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGA


ACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTC


TCCGGGT





SEQ ID 136: human IgG1 constant region aa


ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT


VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP


EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA


LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV


LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG





SEQ ID 137: human IgG1 effector null nt


GCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG


CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGAC


CAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACC


GTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGG


TGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGC


CGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCT


GAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACG


GCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAG


CGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCC


CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCC


TGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCC


CAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG


CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGA


ACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTC


TCCGGGT





SEQ ID 138: human IgG1 effector null aa


ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT


VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTP


EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKA


LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV


LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG





SEQ ID 139: PD220F6 scFv nt


CAGGAGCAGGTGAAGGAGACCGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAG


CCTCTGGATTCACCATCAGCAGCTATGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTG


GGTCGCATTGATTTTTCCCGGGATTGGTTTCAAAGACTACGCGAGCTGGGTGAATGGCCGGTTCACCCTC


TCCAGCGACAACGCCCAGAACACTGTGGAACTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTAT


ATTACTGTGCGAGAGATTTGGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTGGAGGCGG


ATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCT


CCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCCAGTCCGAGTGTTTATA


GTAACTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATTATGCATCCAC


TCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGC


AGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATAGTAGTAGTACTCGTGCTTTCG


GCGGAGGGACCAAGGTGGAGATCAAA





SEQ ID 140: PD220F6 scFv aa


QEQVKETGGGLVQPGGSLRLSCAASGFTISSYGVSWVRQAPGKGLEWVALIFPGIGFKDYASWVNGRFTL


SSDNAQNTVELQMNSLRAEDTAVYYCARDLDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQS


PSSLSASVGDRVTITCQSSPSVYSNYLSWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGTDFTLTIS


SLQPEDVATYYCAGGYSSSTRAFGGGTKVEIK





SEQ ID 141: CT4 VH CDR1 aa


SSYTMH





SEQ ID 142: CT4 VH CDR2 aa


FISYDGNNKYYADSVKG





SEQ ID 143: CT4 VH CDR3 aa


TGWLGPFDY





SEQ ID 144: CT4 VL CDR1 aa


RASQSVGSSYLA





SEQ ID 145: CT4 VL CDR2 aa


GAFSRAT





SEQ ID 146: CT4 VL CDR3 aa


QQYGSSPWT





SEQ ID 147: PL23006 VH CDR1 aa


NTYDMI





SEQ ID 148: PL230C6 VH CDR2 aa


IITYSGSRYYANWAKG





SEQ ID 149: PL230C6 VH CDR3 aa


DYMSGSHL





SEQ ID 150: PL230C6 VL CDR1 aa


QASEDIYSFLA





SEQ ID 151: PL230C6 VL CDR2 aa


SASSLAS





SEQ ID 152: PL230C6 VL CDR3 aa


QQGYGKNNVDNA





SEQ ID 153: PD224D1 VH CDR1 aa


NTYDMT





SEQ ID 154: PD224D1 CDR2 aa


IITYSGSRYYANWAKG





SEQ ID 155: PD224D1 CDR3 aa


DYMSGSHL





SEQ ID 156: PD224D1 CDR1 aa


QASEDIYSFLA





SEQ ID 157: PD224D1 CDR2 aa


SASSLAS





SEQ ID 158: PD224D1 CDR3 aa


QQGYGKNNVDNA





SEQ ID 159: PL221G5 VH CDR1 aa


SGYDMC





SEQ ID 160: PL221G5 CDR2 aa


CIAAGSAGITYDANWAKG





SEQ ID 161: PL221G5 CDR3 aa


SAFSFDYAMDL





SEQ ID 162: PL221G5 CDR1 aa


QASQSISSHLN





SEQ ID 163: PL221G5 CDR2 aa


KASTLAS





SEQ ID 164: PL221G5 CDR3 aa


QQGYSWGNVDNV





SEQ ID 165: PL231H2 VH CDR1 aa


STYDMI





SEQ ID 166: PL231H2 VH CDR2 aa


IISYVGNTYYASWAKG





SEQ ID 167: PL231H2 VH CDR3 aa


DFISGSHL





SEQ ID 168: PL231H2 VL CDR1 aa


QASESISSFLS





SEQ ID 169: PL231H2 VL CDR2 aa


SASTLAS





SEQ ID 170: PL231H2 VL CDR3 aa


QQGYSKSNVDNA





SEQ ID 171: PL004B5 VH CDR1 aa


SSYWMS





SEQ ID 172: PL004B5 VH CDR2 aa


VIDTNVYIYYANWAKG





SEQ ID 173: PL004B5 VH CDR3 aa


YVGNNDDYINL





SEQ ID 174: PL004B5 VL CDR1 aa


QSSQSVYNGWLS





SEQ ID 175: PL004B5 VL CDR2 aa


GASTLAS





SEQ ID 176: PL004B5 VL CDR3 aa


LGSYTSSTENS





SEQ ID 177: PL004B9 VH CDR1 aa


SVINMG





SEQ ID 178: PL004B9 VH CDR2 aa


TITYVGNTYYASWAKG





SEQ ID 179: PL004B9 VH CDR3 aa


ESGTIYYSYFNL





SEQ ID 180: PL004B9 VL CDR1 aa


QASESISNYLS





SEQ ID 181: PL004B9 VL CDR2 aa


YASNLAS





SEQ ID 182: PL004B9 VL CDR3 aa


QSYYGGGSAYT





SEQ ID 183: PD206F12 VH CDR1 aa


SGYWIC





SEQ ID 184: PD206F12 VH CDR2 aa


CIYAGTSGSTSYASWARG





SEQ ID 185: PD206F12 VH CDR3 aa


NLYTYNSL





SEQ ID 186: PD206F12 VL CDR1 aa


QSSQSVYDNNWLA





SEQ ID 187: PD206F12 VL CDR2 aa


TVSTLAS





SEQ ID 188: PD206F12 VL CDR3 aa


QGTYYSSGWNFA





SEQ ID 189: PD215A1 VH CDR1 aa


SSYWMC





SEQ ID 190: PD215A1 VH CDR2 aa


CITTGSGSTYYASWAKR





SEQ ID 191: PD215A1 VH CDR3 aa


AFDL





SEQ ID 192: PD215A1 VL CDR1 aa


QASQSIYSYLN





SEQ ID 193: PD215A1 VL CDR2 aa


GASNLAS





SEQ ID 194: PD215A1 VL CDR3 aa


QSSWLSGAVGNA





SEQ ID 195: PD220F6 VH CDR1 aa


SSYGVS





SEQ ID 196: PD220F6 VH CDR2 aa


LIFPGIGFKDYASWVNG





SEQ ID 197: PD220F6 VH CDR3 aa


DLDL





SEQ ID 198: PD220F6 VL CDR1 aa


QSSPSVYSNYLS





SEQ ID 199: PD220F6 VL CDR2 aa


YASTLAS





SEQ ID 200: PD220F6 VL CDR3 aa


AGGYSSSTRA





SEQ ID 201: PD225G11 VH CDR1 aa


SSHWIC





SEQ ID 202: PD225G11 VH CDR2 aa


CIYTGSIDVFYYASWAKG





SEQ ID 203: PD225G11 VH CDR3 aa


AANTDTTYFNL





SEQ ID 204: PD225G11 VL CDR1 aa


QASQSINNQLS





SEQ ID 205: PD225G11 VL CDR2 aa


GASTLAS





SEQ ID 206: PD225G11 VL CDR3 aa


HVHYCSGGSCFWA



















CDR Sequences for anti-CTLA4, anti-PD-1 and anti-PD-L1












VH
VL














mAb
Target
CDR 1
CDR 2
CDR 3
CDR 1
CDR 2
CDR 3





CT4
CTLA4
SSYTMH
FISYDGNNKYYADSVKG
TGWLGPFDY
RASQSVGSSYLA
GAFSRAT
QQYGSSPWT




Seq ID
Seq ID 142
Seq ID 143
Seq ID 144
Seq ID
Seq ID 146




141



145






PL230C6
PD-L1
NTYDMI
IITYSGSRYYANWAKG
DYMSGSHL
QASEDIYSFLA
SASSLAS
QQGYGKNNVDNA




Seq ID
Seq ID 148
Seq ID 149
Seq ID 150
Seq ID
Seq ID 152




147



151






PD224D1
PD-1
SSYAMS
YIGDTTGIAYASWANG
GWSYLDI
QASQNIYSNLA
QASTLAS
QGGYYSAALNT




Seq ID
Seq ID 154
Seq ID 155
Seq ID 156
Seq ID
Seq ID 158




153



157






PL221G5
PD-L1
SGYDMC
CIAAGSAGITYDANWAKG
SAFSFDYAMDL
QASQSISSHLN
KASTLAS
QQGYSWGNVDNV




Seq ID
Seq ID 160
Seq ID 161
Seq ID 162
Seq ID
Seq ID 164




159



163






PL231H2
PD-L1
STYDMI
IISYVGNTYYASWAKG
DFISGSHL
QASESISSFLS
SASTLAS
QQGYSKSNVDNA




Seq ID
Seq ID 166
Seq ID 167
Seq ID 168
Seq ID
Seq ID 170




165



169






PL004B5
PD-L1
SSYWMS
VIDTNVYIYYANWAKG
YVGNNDDYINL
QSSQSVYNGWLS
GASTLAS
LGSYTSSTENS




Seq ID
Seq ID 172
Seq ID 173
Seq ID 174
Seq ID
Seq ID 176




171



175






PL004B9
PD-L1
SVINMG
TITYVGNTYYASWAKG
ESGTIYYSYFNL
QASESISNYLS
YASNLAS
QSYYGGGSAYT




Seq ID
Seq ID 178
Seq ID 179
Seq ID 180
Seq ID
Seq ID 182




177



181






PD206F12
PD-1
SGYWIC
CIYAGTSGSTSYASWARG
NLYTYNSL
QSSQSVYDNNWLA
TVSTLAS
QGTYYSSGWNFA




Seq ID
Seq ID 184
Seq ID 185
Seq ID 186
Seq ID
Seq ID 188




183



187






PD215A1
PD-1
SSYWMC
CITTGSGSTYYASWAKR
AFDL
QASQSIYSYLN
GASNLAS
QSSWLSGAVGNA




Seq ID
Seq ID 190
Seq ID 191
Seq ID 192
Seq ID
Seq ID 194




189



193






PD220F6
PD-1
SSYGVS
LIFPGIGFKDYASWVNG
DLDL
QSSPSVYSNYLS
YASTLAS
AGGYSSSTRA




Seq ID
Seq ID 196
Seq ID 197
Seq ID 198
Seq ID
Seq ID 200




195



199






PD225G11
PD-1
SSHWIC
CIYTGSIDVFYYASWAKG
AANTDTTYFNL
QASQSINNQLS
GASTLAS
HVHYCSGGSCFWA




Seq ID
Seq ID 202
Seq ID 203
Seq ID 204
Seq ID
Seq ID 206




201



205








Claims
  • 1. A bispecific antibody comprising IgG domains having heavy chains and light chains, and two scFv components being connected to either C terminal of the heavy chains or N terminal of the light chains, wherein the IgG domains have the binding specificity to a first antigen, wherein the scFv components have the binding specificity to a second antigen, and wherein the first antigen and the second antigen are different and are independently selected from α-CTLA4, α-PD-1, and α-PD-L1.
  • 2. The bispecific antibody of claim 1, wherein the two scFv components are connected to the C terminal of the heavy chain.
  • 3. The bispecific antibody of claim 2, wherein the first antigen comprises α-CTLA4 and the second antigen comprises α-PD-1 or α-PD-L1.
  • 4. The bispecific antibody of claim 2, wherein the first antigen comprises α-PD-1 or α-PD-L1 and the second antigen comprises α-CTLA4.
  • 5. The bispecific antibody of claim 1, wherein the two scFv components are connected to the N terminal of the light chain.
  • 6. The bispecific antibody of claim 5, wherein the first antigen comprises α-PD-1 or α-PD-L1 and the second antigen comprises α-CTLA4.
  • 7. The bispecific antibody of claim 5, wherein the first antigen comprises α-CTLA4 and the second antigen comprises α-PD-1 or α-PD-L1.
  • 8. (canceled)
  • 9. The bispecific antibody of claim 1, comprising an antigen-binding fragment having a sequence having at least 98% similarity with SEQ ID No. 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, or 134.
  • 10-12. (canceled)
  • 13. The bispecific antibody of claim 1, having a binding affinity to two of α-CTLA4, α-PD-1, or α-PD-L1 with a Kd not greater than 70 nM.
  • 14. (canceled)
  • 15. The bispecific antibody of claim 1, wherein the antibody is a humanized antibody, a chimeric antibody, or a recombinant antibody, or an isolated monoclonal antibody.
  • 16. An IgG1 heavy chain for the bispecific antibody of claim 1, comprising an amino acid sequence having at least 98% similarity with SEQ ID No. 02, 06, 08, 10, 12, 14, 16, 18, 20, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 72, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, or 132.
  • 17. A kappa light chain for the bispecific antibody of claim 1, comprising an amino acid sequence having at least 98% similarity with SEQ ID No. 04, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64.
  • 18. A variable light chain for the bispecific antibody of claim 1, comprising an amino acid sequence having at least 98% similarity with SEQ ID No. 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, or 134.
  • 19. A variable heavy chain for the bispecific antibody of claim 1, comprising an amino acid sequence having at least 98% similarity with SEQ ID No. 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, or 132.
  • 20. An isolated nucleic acid encoding the bispecific antibody of claim 1.
  • 21. An expression vector comprising the isolated nucleic acid of claim 20.
  • 22-23. (canceled)
  • 24. A host cell comprising the expression vector of claim 21, wherein the host cell is a prokaryotic cell or a eukaryotic cell.
  • 25. (canceled)
  • 26. A method of producing a bispecific antibody, comprising culturing the host cell of claim 24 so that the bispecific antibody is produced.
  • 27-28. (canceled)
  • 29. A pharmaceutical composition, comprising the bispecific antibody of claim 1 and a pharmaceutically acceptable carrier.
  • 30-31. (canceled)
  • 32. A method of treating a subject with a cancer, comprising administering to the subject an effective amount of the bispecific antibody of claim 1, wherein the cancer comprises cells expressing PD-L1.
  • 33-39. (canceled)
CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application No. 62/580,845 filed on Nov. 2, 2017, titled “BISPECIFIC ANTIBODIES AND METHODS OF MAKING AND USING THEREOF”, which are expressly incorporated herein by reference in its entirety.

PCT Information
Filing Document Filing Date Country Kind
PCT/US2018/058810 11/2/2018 WO 00
Provisional Applications (1)
Number Date Country
62580845 Nov 2017 US