Guidance and navigation control (GNC) antibody-like protein, method for producing the same, and method for using the same

Abstract

To provide: multi-specific antibody-like proteins; immuno-conjugates comprising a cytotoxic or imaging agent linked to the multi-specific antibody-like proteins; and pharmaceutical compositions.SOLUTION: The invention provides multi-specific antibody-like proteins with one or more binding domains including a first binding domain (D1), a second binding domain (D2), a third binding domain (D3), a fourth binding domain (D4), a fifth binding domain (D5) or a sixth binding domain (D6). The multi-specific antibody-like proteins may be mono-specific, bi-specific, tri-specific, tetra-specific, penta-specific or hexa-specific. Such binding domains as D1, D2, D3, D4, D5 and D6 each independently have a specific binding affinity to a T cell activating receptor, an immune cell receptor, an immune checkpoint molecule, a co-stimulation factor, a receptor of a leukocyte, a tumor antigen, a tumor associated antigen (TAA), a receptor of a tissue cell, a receptor of a cancer cell, or a combination thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Cross-reference of related applications

[0002] This application claims priority to U.S. Provisional Application No. 62 / 991,042, filed on 17 March 2020 (35 U.S. SC 119(e)), the entire disclosure of which is incorporated herein by reference.

[0003] This application relates to the technical field of multispecific antibodies used in cancer immunotherapy, and more specifically, to methods for producing and using guidance and navigation control (GNC) antibodies that have multi-binding activity to surface molecules of both immune cells and tumor cells. [Background technology]

[0004] Cancer cells employ a variety of strategies to evade destruction and elimination by the host's immune system. There is an urgent need to improve the function, specificity, potency, and effectiveness of biological therapies. The success of targeted therapies in cancer treatment has also been hampered by various resistance mechanisms. Tumor plasticity has emerged as a mode of targeted therapy evasion in a variety of cancers, from prostate and lung adenocarcinoma to melanoma and basal cell carcinoma. Mechanisms that hinder the formation of a robust anti-tumor immune response are thought to include at least some of the following categories: 1) defects in tumor antigen processing or presentation; 2) lack of activation mechanisms; 3) inhibitory mechanisms and immunosuppressive states; and 4) resistant tumor cells (4). To overcome these evasion and resistance mechanisms, novel therapeutic strategies are being designed that facilitate combination immunotherapy strategies using multiple immune effectors (including, but not limited to, T-cell engagers, checkpoint inhibitors, and innate immunity). However, such combination therapy strategies often mean two or more independent biologics, requiring not only approval of the clinical safety and efficacy of each product but also the manufacture of independent biologics. Combination therapies may target either immune cells, tumor cells, or both. Examples include antibody therapies using bispecific antibodies targeting both CD3 and CD19, or CAR-T cell therapies containing modified T cells expressing anti-CD19 chimeric antibodies. One common side effect of these immunotherapies is cytokine release syndrome, indicating insufficient immunomodulation. In this context, new strategies are needed to overcome tumor plasticity, i.e., the heterogeneous and dynamic expression of tumor antigens and / or resistant tumor cells, while acquiring additional immunomodulation.

[0005] To this end, a platform of multispecific antibodies, also known as guidance and navigation controls (GNCs), has been established to facilitate multiple targeting of T cell engagers, costimulators, checkpoint inhibitors, and tumor antigens (Applicant's applications WO / 2019 / 005641, WO2019191120, and PCT / US20 / 59230; the entirety of which is incorporated herein). Furthermore, quadruplespecific GNC (tetra-GNC) antibodies can be used to construct GNC-T cell therapies for treating both liquid and solid tumors. Despite the multifunctional GNC molecules, epitope-negative tumor cells remain untargeted, thus avoiding immunotherapy. For example, NKG2D ligand expression is tightly regulated to prevent damage to autoimmune tissues, and therefore, normal tissues typically do not express NKG2D ligand. Thus, using the NKG2D receptor could be an effective targeting mechanism for cancer immunotherapy via innate immune recognition processes. Thus, there is a clear need to further develop multispecific antibodies relevant to cell therapy. While multispecific monotherapies remain highly desirable and cost-effective, designing, expressing, and manufacturing potent and stable multispecific antibodies superior to tetra-GNC antibodies remains technically challenging. [Overview of the Initiative]

[0006] The following summary is illustrative and not intended to be limiting. Further embodiments, features, and characteristics beyond those described above will become apparent by reference to the drawings and the detailed description below.

[0007] The present invention provides a protein having binding specificity (e.g., a multispecific antibody-like protein and its fragments), a method for producing and using a multispecific antibody-like protein and its fragments. The multispecific antibody-like protein may include a multispecific antibody. These binding protein fragments may include, but are not limited to, an scFv domain, a Fab region, an Fc domain, VH, VL, a light chain, a heavy chain, a variable region, and a complementarity-determining region (CDR).

[0008] In one embodiment, the multispecific antibody-like protein may be a multispecific antibody, a monoclonal antibody, an isolated monoclonal antibody, or a humanized antibody.

[0009] In one embodiment, the protein may include various domains and regions, such as binding domains. In one embodiment, the multispecific antibody-like protein may have one or more binding domains, including a first binding domain (D1), a second binding domain (D2), a third binding domain (D3), a fourth binding domain (D4), a fifth binding domain (D5), or a sixth binding domain (D6). The multispecific antibody-like protein of the present invention may be monospecific, bispecific, triplicate, quadruplespecific, quintuple, or hexaspecific.

[0010] In one embodiment, the binding domains such as D1, D2, D3, D4, D5, and D6 may each independently have specific binding affinity to T cell activating receptors, immune cell receptors, immune checkpoint molecules, costimulatory factors, leukocyte receptors, tumor antigens, tumor-associated antigens (TAAs), tissue cell receptors, cancer cell receptors, or combinations thereof.

[0011] In one embodiment, the T cell activating receptor may include CD3. In one embodiment, the immune checkpoint receptor may include PD-L1, PD-1, TIGIT, TIM-3, LAG-3, CTLA4, BTLA, VISTA, PD-L2, CD160, LOX-1, Siglec 15, CD47, HVEM SIRPα, CSF1R, CD73, Siglec 15, CD47, or a combination thereof. In one embodiment, the costimulatory receptor may include 4-1BB, CD28, OX40, GITR, CD40L, CD40, ICOS, LIGHT, CD27, CD30, or a combination thereof. In one embodiment, the tumor-associated antigen may include EGFR, HER2, HER3, EGRFVIII, CD19, BCMA, CD20, CD33, CD123, CD22, CD30, ROR1, CEA, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, TROP2, NKG2D ligand, CD39, CLDN18.2, DLL3, HLA-G, FcRH5, GPRC5D, LIV-1, MUC1, CD138, CD70, uPAR, CD38, or a combination thereof.

[0012] In one embodiment, the binding domain for the T cell activating receptor is adjacent to the binding domain for the tumor-associated antigen (TAA).

[0013] In one embodiment, D1, D3, D4, D5, and D6 may each be independently an scFv domain, a receptor, or a ligand. In one embodiment, at least one, two, three, four, or five of D1, D3, D4, D5, and D6 in the hexaspecific antibody-like protein contain scFv domains. In one embodiment, D1, D3, D4, D5, and D6 are all scFv domains.

[0014] In one embodiment, at least one, two, three, four, or five of D1, D3, D4, D5, and D6 in the hexaspecific antibody-like protein include receptors. In one embodiment, D1, D3, D4, D5, and D6 are all receptors.

[0015] In one embodiment, at least one, two, three, four, or five of D1, D3, D4, D5, and D6 in the hexavalent antibody-like protein contain a ligand. In one embodiment, D1, D3, D4, D5, and D6 all contain a ligand.

[0016] In one embodiment, the scFv domain can include VH bound to VL in the VH-VL or VL-VH orientation. In one embodiment, the scFv domain can include a disulfide bond between VL and VH. In one embodiment, the disulfide bond is between VL100 and VH44 of the scFv domain. In one embodiment, the scFv domain can include substitution R19S (Kabat) in VH.

[0017] In one embodiment, the multispecific antibody-like protein can include an Fc region. In one embodiment, the Fc region is engineered to eliminate effector cell functions including, but not limited to, ADCC, ADCP, or CDC. In one embodiment, the Fc region includes at least one mutation at L234A, L235A, G237A, or K322A (Eu numbering). In one embodiment, the Fc region includes mutations at L234A / L235A / G237A / K322A. In one embodiment, the Fc region includes mutations at L234A / L235A / K322A (Eu numbering).

[0018] Domains and regions can be connected via a linker. In one embodiment, the linker can include (G x S y ) n [[ID=—20]]where n, x, and y are each independently an integer from 1 to 10. In one embodiment, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In one embodiment, x is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In one embodiment, y is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0019] In one embodiment, the present invention provides a hexaspecific antibody-like protein. In one embodiment, the hexaspecific antibody-like protein has an N-terminus and a C-terminus and comprises a Fab region which may include a light chain as a second binding domain (D2), a Fab region which may include a light chain as a second binding domain (D2), an Fc region which includes a third binding domain (D3) which has binding affinity to PD-L1, and a fourth binding domain (D4) which has binding affinity to 4-1BB at the C-terminus, wherein the light chain may include a fifth binding domain (D5) covalently bonded to the C-terminus and a sixth binding domain (D6) covalently bonded to the N-terminus. D1, D2, D5, and D6 may each independently have binding affinity to a tumor-associated antigen (TAA) or CD3.

[0020] In one embodiment, the hexaspecific antibody-like protein may contain D1 or D2 having a binding affinity to CD3. In one embodiment, the hexaspecific antibody-like protein may contain D1 having a binding affinity to CD3. In one embodiment, the hexaspecific antibody-like protein may contain D2 having a binding affinity to CD3.

[0021] In one embodiment, the hexaspecific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to EGFR, EGFRvIII, CD20, mesothelin, claudin 18.2, HER2, CD33, or a combination thereof; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5 and D6, which independently have binding specificity to tumor-associated antigens.

[0022] In one embodiment, the hexaspecific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to tumor-associated antigens; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5 and D6, which independently have binding specificity to NKG2D ligand, HER3, CD19, or a combination thereof.

[0023] In one embodiment, the hexaspecific antibody-like protein may include D1 having binding specificity to EGFR; D2 having binding specificity to CD3; D3 potentially having binding specificity to PD-L1; D4 having binding specificity to 4-1BB; D5 having binding specificity to CD19; and D6 having binding specificity to HER3.

[0024] In one embodiment, the hexaspecific antibody-like protein may include D1 having binding specificity to EGFR; D2 having binding specificity to CD3; D3 having binding specificity to PD-L1; D4 having binding specificity to 4-1BB; D5 having binding specificity to HER3; and D6 having binding specificity to CD19.

[0025] In one embodiment, the hexaspecific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to EGFR; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; D5, which has binding specificity to HER3; and D6, which has binding specificity to CD19.

[0026] In one embodiment, the hexaspecific antibody-like protein may contain an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity with SEQ ID NOs: 176, 178, 106, 108, 332, 334, 324, 326, 328, or 330.

[0027] In one embodiment, the present invention provides a quadruple-specific or quintuple-specific antibody-like protein. In one embodiment, the antibody-like protein includes an N-terminus and a C-terminus, and may include a first binding domain (D1) at the N-terminus, a Fab region which may include a light chain as a second binding domain (D2) (which may optionally include a fifth binding domain (D5) covalently bonded to the C-terminus or a sixth binding domain (D6) covalently bonded to the N-terminus), an Fc region, a third binding domain (D3), and a fourth binding domain (D4) at the C-terminus. In one embodiment, the multispecific antibody-like proteins are sequence numbers 110, 112, 116, 118, 122, 124, 128, 130, 134, 136, 140, 142, 146, 148, 152, 154, 158, 160, 164, 166, 170, 172, 112, 114, 118, 120, 124, 126, 130, 132, 136, 138, 142, It contains an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity with 144, 148, 150, 154, 156, 160, 162, 166, 168, 172, 174, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 302, 304, 306, or 308.

[0028] In one embodiment, the multispecific antibody-like protein may be quadruplespecific. In one embodiment, the multispecific antibody-like protein may be quintuple specific. In one embodiment, D2, D5, and D6 may each independently have binding affinity to tumor-associated antigens (TAAs).

[0029] In one embodiment, the quadruple-specific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to tumor-associated antigens; D3, which has binding specificity to PD-L1; and D4, which has binding specificity to 4-1BB.

[0030] In one embodiment, the quadruple-specific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to an antigen selected from the group consisting of EGFR, HER2, CD19, CD20, CD22, CD30, CD22, mesothelin, GD2, and claudin 18.2; D3, which has binding specificity to PD-L1; and D4, which has binding specificity to 4-1BB.

[0031] In one embodiment, the quintuple-specific antibody-like protein may include D1, which has binding specificity to CD3; D2 and D5, which independently have binding specificity to tumor-associated antigens; D3, which has binding specificity to PD-L1; and D4, which has binding specificity to 4-1BB.

[0032] In one embodiment, the quintuple-specific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to tumor-associated antigens; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5, which has binding specificity to HER3.

[0033] In one embodiment, the quintuple-specific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to EGFR or EGFRvIII; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5, which has binding specificity to HER3.

[0034] In one embodiment, the quintuple-specific antibody-like protein may include D1, which has binding specificity to CD3; D2, which has binding specificity to CD20; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5, which has binding specificity to CD19.

[0035] In one embodiment, the quintuple-specific antibody-like protein may include D1 and D6, each independently having binding specificity to tumor-associated antigens; D2, having binding specificity to CD3; D3, having binding specificity to PD-L1; and D4, having binding specificity to 4-1BB.

[0036] In one embodiment, the quintuple-specific antibody-like protein may include D1, which has binding specificity to EGFR; D2, which has binding specificity to CD3; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D6, which has binding specificity to CD19.

[0037] In one embodiment, the present invention provides a multispecific antibody-like protein having at least one binding domain as a receptor. In one embodiment, the receptor is NKG2D.

[0038] In one embodiment, the multispecific antibody-like protein comprises an N-terminus and a C-terminus, and optionally includes a first binding domain (D1) located at the N-terminus, a second binding domain (D2) which may include a light chain (which optionally includes a fifth binding domain (D5) covalently bonded to the C-terminus and / or a sixth binding domain (D6) covalently bonded to the N-terminus), an Fc region, optionally a third binding domain (D3), and optionally a fourth binding domain (D4) located at the C-terminus, wherein at least one of D1, D2, D3, D4, D5, and D6 is NKG2D, and each of D1, D2, D3, D4, D5, and D6 may independently have binding affinity specifically to a T cell activating receptor, an immune cell receptor, an immune checkpoint molecule, a costimulatory factor, a leukocyte receptor, a tumor antigen, a tumor-associated antigen (TAA), a tissue cell receptor, a cancer cell receptor, or a combination thereof.

[0039] In one embodiment, the multispecific antibody-like protein containing NKG2D may be monospecific, bispecific, triplicate, quadruplespecific, or quintic specific.

[0040] In one embodiment, a multispecific antibody-like protein containing NKG2D may contain D2, which includes a dimer bound to CL and CH1. The dimer is NKG2D. In one embodiment, a monospecific antibody-like protein containing NKG2D may contain an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity with SEQ ID NO: 196 or 198.

[0041] In one embodiment, the multispecific antibody-like proteins containing NKG2D are, independently of each other, EGFR, HER2, HER3, EGFRvIII, ROR1, CD3, CD28, CEA, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, TROP2, NKG2D, NKG2D ligand, BCMA, CD19, CD20, CD33, CD123, CD22, CD30, PD-L1, PD1, OX40, 4-1BB, GITR, TIGIT, TIM-3, and LAG-3. It may contain D1, D2, D3, D4, D5, and D6, which have binding specificity to antigens selected from the group consisting of CTLA4, CD40, CD40L, VISTA, ICOS, BTLA, LIGHT, HVEM, CSF1R, CD73, CD39, CLDN18.2, DLL3, HLA-G, FcRH5, GPRC5D, LIV-1, MUC1, CD138, CD70, CD16, uPAR, Siglec 15, CD47, CD38, NKp46, PD-L2, CD160, LOX-1, SIRPα, and CD27. The Fc domain may contain human IgG Fc domains.

[0042] In one embodiment, the multispecific antibody-like protein containing NKG2D may include D2, D5, and D6, each independently having binding specificity to a tumor-associated antigen. In one embodiment, the multispecific antibody-like protein containing NKG2D may include D2, which has binding specificity to a tumor-associated antigen. In one embodiment, the multispecific antibody-like protein containing NKG2D may include D1, D2, D3, and D4, each independently having binding specificity to the NKG2D ligand, CD3, PD-L1, 4-1BB, or a combination thereof.

[0043] In one embodiment, a multispecific antibody-like protein containing NKG2D may contain an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity with SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 78, 80, 82, 84, 86, 88, 30, or 32.

[0044] In one embodiment, the multispecific antibody-like protein containing NKG2D may include D1, which has binding specificity to the NKG2D ligand; D2, which has binding specificity to CD3; D3, which has binding specificity to PD-L1; and D4, which has binding specificity to 4-1BB.

[0045] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to the NKG2D ligand; D2, which has binding specificity to CD3; D3, which has binding specificity to 4-1BB; and D4, which has binding specificity to PD-L1.

[0046] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to 4-1BB; D2, which has binding specificity to PD-L1; D3, which has binding specificity to CD3; and D4, which has binding specificity to the NKG2D ligand.

[0047] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to PD-L1; D2, which has binding specificity to 4-1BB; D3, which has binding specificity to CD3; and D4, which has binding specificity to the NKG2D ligand.

[0048] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to tumor-associated antigens; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5, which has binding specificity to the NKG2D ligand.

[0049] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to an antigen selected from the group consisting of mesothelin, claudin 18.2, HER2, EGFRvIII, and CD33; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D5, which has binding specificity to the NKG2D ligand.

[0050] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; and D2, which has binding specificity to the NKG2D ligand.

[0051] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to the NKG2D ligand; and D6, which has binding specificity to tumor-associated antigens.

[0052] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to the NKG2D ligand; and D6, which has binding specificity to CD19.

[0053] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to the NKG2D ligand; D3, which has binding specificity to PD-L1; and D4, which has binding specificity to 4-1BB.

[0054] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to the NKG2D ligand; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D6, which has binding specificity to tumor-associated antigens.

[0055] In one embodiment, the multispecific antibody-like protein containing NKG2D includes D1, which has binding specificity to CD3; D2, which has binding specificity to the NKG2D ligand; D3, which has binding specificity to PD-L1; D4, which has binding specificity to 4-1BB; and D6, which has binding specificity to CD19.

[0056] In a second aspect, the present invention provides an isolated nucleic acid sequence encoding the amino acid sequence of the multispecific antibody-like protein of the present invention.

[0057] In a third embodiment, the present invention provides an expression vector. In one embodiment, the expression vector comprises an isolated nucleic acid sequence of the present invention.

[0058] In another embodiment, the present invention provides a host cell comprising the isolated nucleic acid sequence. In one embodiment, the host cell is a prokaryotic cell. In one embodiment, the host cell is a eukaryotic cell.

[0059] In another embodiment, the present invention provides multispecific antibody-like proteins and fragments thereof. In one embodiment, the method comprises the steps of: culturing a host cell containing an isolated nucleic acid sequence such that a DNA sequence encoding a multispecific antibody or monomer is expressed; and purifying the multispecific antibody. The isolated nucleic acid sequence encodes amino acids of a multispecific antibody-like protein or fragment thereof.

[0060] In another embodiment, the present invention provides an immune complex. In one embodiment, the immune complex may comprise a cytotoxic agent or contrast agent conjugated to a multispecific antibody via a linker. The linker may comprise an ester bond, an ether bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphate ester bond, a peptide bond, a hydrophobic poly(ethylene glycol) linker, or a combination thereof. In one embodiment, the cytotoxic agent or contrast agent may comprise a chemotherapeutic agent, a growth inhibitor, a cytotoxic agent from the calicheamicin class, a mitotic inhibitor, a radioisotope, a toxin, a therapeutic agent, or a combination thereof.

[0061] In another embodiment, the present invention provides pharmaceutical compositions. In one embodiment, the pharmaceutical composition may comprise a pharmaceutically acceptable carrier and a multispecific antibody protein or fragment thereof, and / or an immune complex. In one embodiment, the pharmaceutical composition may comprise a therapeutic agent selected from radioisotopes, radionuclides, toxins, chemotherapeutic agents, or combinations thereof.

[0062] In another embodiment, the present invention provides a method for treating or preventing a target cancer, autoimmune disease, or infection. In one embodiment, the method comprises the step of administering a pharmaceutical composition which may comprise purified multispecific antibody-like proteins or fragments thereof. In one embodiment, the method may comprise the step of administering an effective amount of purified multispecific antibody-like proteins, immune complexes, or pharmaceutical compositions to the target.

[0063] In one embodiment, the above method may further include the step of co-administering an effective amount of therapeutic agent. The therapeutic agent includes antibodies, chemotherapeutic agents, enzymes, anti-estrogen agents, receptor tyrosine kinase inhibitors, kinase inhibitors, cell cycle inhibitors, checkpoint inhibitors, DNA, RNA or protein synthesis inhibitors, RAS inhibitors, inhibitors of PD1, PD-L1, CTLA4, 4-1BB, OX40, GITR, ICOS, LIGHT, TIM3, LAG3, TIGIT, CD40, CD27, HVEM, BTLA, VISTA, B7H4, CSF1R, NKG2D, CD73, or combinations thereof.

[0064] In one embodiment, the subject is a human. In one embodiment, the subject is a mammal. In one embodiment, the subject is a chimpanzee. In one embodiment, the subject is a pet animal.

[0065] In another embodiment, the present invention provides a solution comprising an effective concentration of purified multispecific antibody-like proteins or their fragments, immune complexes, or pharmaceutical compositions. In one embodiment, the solution is human plasma. [Brief explanation of the drawing]

[0066] The aforementioned and other features of the disclosure herein will become more fully apparent from the following description and the appended claims, together with the accompanying drawings. The drawings show only a few embodiments prepared in accordance with the disclosure herein and should therefore not be considered limiting, and further specificities and details of the disclosure herein may be illustrated through the use of the accompanying drawings.

[0067] [Figure 1] This paper describes a hexa-GNC antibody that has a Fab region or a dimeric receptor as the D2 binding domain, and is configured to have five antigen-binding domains in the heavy chain (D1, D3, and D4) and light chain (D5 and D6), and exhibits diverse structures selected from antibody fragments based on variable sequences, receptors encoded by non-variable sequences, and ligands.

[0068] [Figure 2] The results of analytical SEC demonstrate the stability and high quality of purified tetra-GNC antibodies (A-C) containing NKG2D receptor and 41BBL, as well as purified NKG2D penta-GNC (D).

[0069] [Figure 3] This paper describes a TDCC assay that measures the comparative efficacy of four tetra-GNC antibodies (SI-49E1, SI-49E2, SI-49E3, SI-49E4) and two bispecific control antibodies (SI-49X1, SI-49X2) lacking both the αPD-L1 and α41BB domains, targeting MICA expressing the MDA-MB-231 cell line.

[0070] [Figure 4] This paper describes a TDCC assay that measures the comparative efficacy of one NKG2D-MSLN penta-GNC (SI-49P1), two MSLN tetra-GNCs (SI-51E4 and SI-51E1), and one NKG2D-MSLN tri-GNC (SI-51X1, control) when targeting MICA and mesothelin-expressing MDA-MB-231 cells.

[0071] [Figure 5] This paper presents a TDCC assay to measure the comparative efficacy of a tetra-GNC antibody when targeting a group of cervical cancer cells (Hela) having three part 1 binding domains and a single part 2 that specifically binds to a tumor antigen.

[0072] [Figure 6] This paper describes a TDCC assay to measure the comparative efficacy of multispecific GNC antibodies that have the same binding specificity to EGFR in all molecules and the same binding specificity to HER3 in SI-1 and SI-1P2 molecules, both in the presence and absence of partial 1-binding specificity (SI-1) (SI-1P2, SI-55E1, and SI-55E2), when targeting EGFR-expressing MDA-MB-231 breast cancer cells.

[0073] [Figure 7] This paper presents a TDCC assay to measure the comparative efficacy of tetra-GNC antibodies (SI-50E6, stapled) and those without additional disulfide bonds in all scFv domains (SI-50E1) against bi-GNC antibody (SI-50X1) when targeting EGFR-expressing MDA-MB-231 breast cancer cells.

[0074] [Figure 8] This demonstrates the production of a class of multispecific GNC antibodies with any combination of three partial 1-binding specificities for CD3, PD-L1, and 4-1BB from D1, D3, and D4, and three partial 2-binding specificities for tumor antigens from D2, D5, and D6, using a modular cloning system. [Modes for carrying out the invention]

[0075] The following detailed description refers to the accompanying drawings, which constitute part of it. In the drawings, unless otherwise indicated in the context, similar symbols generally identify similar components. The exemplary embodiments described in the detailed description, drawings, and claims are not intended to be limiting. Other embodiments may be utilized and other modifications may be made without departing from the spirit or scope of the subject matter presented herein. As described herein and shown in the figures, it will be readily apparent that aspects of this disclosure can be arranged, substituted, combined, separated, and designed in the various configurations expressly considered herein.

[0076] The present invention provides, in particular, isolated antibodies; methods for producing such antibodies; bispecific or multispecific molecules, antibody-drug conjugates and / or immune conjugates composed of such antibodies or antigen-binding fragments; pharmaceutical compositions comprising such antibodies, bispecific or multispecific molecules, antibody-drug conjugates and / or immune conjugates; methods for producing such molecules and compositions; and methods for treating cancer using the molecules and compositions of the present invention.

[0077] This invention relates to methods for producing and using multispecific GNC antibodies, particularly quadruple-specific, quintuple-specific and hexa-specific GNC (tetra-GNC, penta-GNC, hexa-GNC) antibodies. Generally, GNC proteins, such as GNC antibodies, are characterized by being composed of two parts: part 1, which is involved in immune cells such as T cell activation, and part 2, which targets tumor cells. GNC antibodies possess multiple antigen-binding domains involved in immune cells, such as anti-CD3 for T cell activation, anti-4-1BB for co-stimulation, and anti-PD-L1 for inhibiting immune checkpoints. To improve the efficacy of antibody therapy for cancer treatment, GNC antibodies are designed to be structurally stable and compact while retaining the characteristics of the two parts of the GNC antibody. This improvement may add binding specificity to a second tumor-associated antigen on the same or different tumor cells. GNC antibodies contain an Fc domain that allows for recycling via FcRn, extension of half-life, and easy purification based on protein A. If necessary, Fc receptor-mediated immunity can be incorporated. GNC antibodies are typically larger than IgG antibodies due to their increased antigen-binding domain (AgBD), which provides spatial flexibility for binding to both T cells and tumor cells. GNC antibodies have the potential to be effective antibody therapies for treating cancer by targeting one or more tumor antigens (including, but not limited to, BCMA, CD19, CD20, CD33, CD123, CD22, CD30, ROR1, CEA, HER2, HER3, EGFR, EGFRvIII, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, and TROP2). Multispecific T-cell engaging antibodies, such as tetra-GNC antibodies and penta-GNC antibodies, offer significant advantages over conventional immunotherapies. These antibodies exhibit CD3 crosslinking functionality on T cells possessing tumor-associated antigens (TAAs). This functionality redirects and induces these antibodies to kill tumor cells without the need to remove T cells from the patient or to genetically modify them to be specific to tumor cells before reintroducing them into the patient (also known as chimeric antigen receptor T cells or CAR-T therapy).GNC protein-mediated antibody therapy or T-cell therapy does not involve genetic modification of T cells. The latter carries the risk of clonal proliferation of modified T cells, i.e., conversion into T-cell leukemia.

[0078] The present invention provides quadruple, quintuple, and hexa-specific GNC (tetra-GNC, penta-GNC, hexa-GNC) antibodies comprising heavy chains (HC) and light chains (LC) (Figure 1). Hexa-GNC antibodies can be configured to have a Fab region or a dimeric receptor as the D2 binding domain, and five antigen-binding domains in the heavy chain (D1, D3, and D4) and light chain (D5 and D6), and feature diverse structures selected from antibody fragments based on variable sequences (e.g., scFv), receptors and ligands encoded by non-variable sequences. The VH and VL of the Fab region may be replaced with non-Fab dimers that have or do not have binding specificity. In one embodiment, the Fc domains of the two chains are engineered to include complementary mutations, also known as "knobs-into-holes," to promote heterodimer formation. Hexa-GNC antibodies have six independent binding specificities for at least six antigens expressed by immunoeffector cells or target cancer cells. Compared to conventional combination therapies, the hexa-GNC antibody class is designed to treat cancer as a single agent to improve efficacy and reduce manufacturing costs. In this way, the treatment simplifies the standard operating procedures (SOPs) for clinical management, alleviates logistical concerns regarding multivariate dosing, and becomes more affordable for patients.

[0079] The term "antibody" is used in the broadest sense and covers, as long as it exhibits the desired biological activity, specifically, a single monoclonal antibody (agonist antibody and antagonist antibody), an antibody composition having polyepitope specificity, and antibody fragments (e.g., Fab, F(ab′)2, and Fv). In some embodiments, the antibody may be monoclonal, polyclonal, chimeric, scFv, bispecific, bifunctional, human, and humanized antibodies. Examples of active fragments of molecules that bind to known antigens include Fab, F(ab′)2, scFv, and Fv fragments, as well as products of Fab immunoglobulin expression libraries, epitope-binding fragments of any of the antibodies and fragments described above. In some embodiments, the antibody may include an immunoglobulin molecule and an immunologically active portion of the immunoglobulin molecule, i.e., a molecule containing a binding site that binds immunologically specifically to an antigen. The immunoglobulin may be an immunoglobulin molecule of any type (IgG, IgM, IgD, IgE, IgA, and IgY), class (IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. In one embodiment, the antibody may be a full antibody and any antigen-binding fragment derived from the full antibody. A typical antibody usually refers to a heterotetrameric protein consisting of two heavy (H) chains and two light (L) chains. Each heavy chain is composed of a heavy chain variable domain (V H abbreviated as) and a heavy chain constant domain. Each light chain is composed of a light chain variable domain (V L abbreviated as) and a light chain constant domain. The V H region and the V L region can be further divided into domains of more conserved regions called hypervariable complementarity-determining regions s (CDRs) and framework regions (FRs). Each variable domain (V H or V L ) is usually composed of three CDRs and four FRs arranged in the order of FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from the amino terminus to the carboxy terminus. The variable regions of the heavy and light chains have a binding region that interacts with the antigen.

[0080] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a substantially homogeneous population of antibodies. That is, individual antibodies within the population are identical except for any spontaneous mutations that may be present in small amounts. Monoclonal antibodies are highly specific and directed to a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations, which typically contain different antibodies against different determinants (epitopes), each monoclonal antibody is directed to a single determinant on the antigen. In addition to their specificity, monoclonal antibodies have the advantage of being synthesized by hybridoma culture and not contaminated with other immunoglobulins. The modifier “monoclonal” indicates the characteristic of the antibody that it is obtained from a substantially homogeneous population of antibodies, and should not be interpreted as requiring antibody production by a specific method. For example, monoclonal antibodies used in accordance with the disclosure herein may be prepared by the hybridoma method first described by Kohler & Milstein, Nature, 256:495 (1975), or by the recombinant DNA method (see, for example, USPat. No. 4, 816, 567).

[0081] Monoclonal antibodies may contain “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and / or light chain is identical or homologous to the corresponding sequence of an antibody derived from a particular species or belonging to a particular antibody class or subclass, while the rest of the chain is identical or homologous to the corresponding sequence of an antibody derived from a different species or belonging to a different antibody class or subclass, and of a fragment of such an antibody, insofar as it exhibits the desired biological activity (USPat. No. 4, 816, 567, and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855

[1984] ).

[0082] Monoclonal antibodies can be produced using a variety of methods, including mouse hybridoma or phage display (see review Siegel.Transfus.Clin.Biol.9:15-22 (2002)), or by molecular cloning of antibodies directly from primary B cells (see Tiller.New Biotechnol.28:453-7 (2011)). In this disclosure, antibodies were produced by immunizing rabbits with both human PD-L1 protein and cells transiently expressing human PD-L1 on the cell surface. Rabbits are known to produce antibodies with high affinity, diversity, and specificity (Weber et al.Exp.Mol.Med.49:e305). B cells from immunized animals were cultured in vitro and screened for the production of anti-PD-L1 antibodies. In addition to rabbit immunization and subsequent B cell culture, other common strategies for antibody generation and discovery include immunization of other animals (such as mice), subsequent display in hybridomas and / or phages, yeast or mammalian cells; or display using synthetic variable gene libraries. Antibody variable genes are isolated using recombinant DNA technology, and the resulting antibodies are expressed recombinantly and further screened for desired features such as the ability to inhibit the binding of PD-1 and PD-L1, the ability to bind to non-human primate PD-L1, and the ability to enhance human T cell activation. This general method of antibody discovery is similar to the method described in Seeber et al. PLOS One.9:e86184 (2014).

[0083] The term “antigen or epitope binding portion or fragment” refers to a fragment of an antibody that can bind to an antigen. These fragments may possess the antigen-binding function and additional function capabilities of an intact antibody. Examples of binding fragments include, but are not limited to, single-chain Fv fragments (scFv) consisting of the VL and VH domains of a single arm of an antibody linked to a single polypeptide chain by a synthetic linker, or Fab fragments, which are monovalent fragments consisting of the VL, constant light chain (CL), VH, and constant heavy chain 1 (CH1) domains. Antibody fragments are produced using conventional methods known to those skilled in the art. Antibody fragments can be screened for utility using the same techniques used for intact antibodies.

[0084] The "antigen or epitope-binding fragments" may be derived from the antibodies disclosed herein by many techniques known in the art. For example, purified monoclonal antibodies can be cleaved with an enzyme such as pepsin and subjected to HPLC gel filtration. A suitable fraction containing the Fab fragments can then be collected and concentrated by membrane filtration or the like. For further descriptions of general techniques for isolating active fragments of antibodies, see, for example, Khaw, BA et al. J. Nucl. Med. 23:1011-1019 (1982) and Rousseaux et al. Methods Enzymology, 121:663-69, Academic Press, 1986.

[0085] Papain digestion of antibodies produces two identical antigen-binding fragments called "Fab" fragments, each with a single antigen-binding site, and the remaining "Fc" fragment, whose name reflects its ability to easily crystallize. Pepsin treatment produces an F(ab′)2 fragment with two antigen-binding sites that can crosslink antigens.

[0086] The Fab fragment may contain the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. The Fab' fragment differs from the Fab fragment by having several residues added to the carboxyl terminus of the heavy chain CH1 domain, which contains one or more cysteines from the antibody hinge region. Fab'-SH is the herein designation for Fab' having a free thiol group in the cysteine ​​residue of the constant domain. The F(ab')2 antibody fragment was originally generated as a pair of Fab' fragments with a hinge cysteine ​​in between. Other chemical combinations of antibody fragments are also known.

[0087] "Fv" is the smallest antibody fragment containing a complete antigen recognition and binding site. This region consists of a dimer of one heavy chain variable domain and one light chain variable domain, tightly bound together by non-covalent bonds. In this configuration, the three CDRs of each variable domain interact to define the antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody.

[0088] The "light chains" of antibodies (immunoglobulins) derived from vertebrate species can be assigned to one of two distinct types, called kappa and lambda (λ), based on the amino acid sequence of the constant domain.

[0089] Depending on the amino acid sequence of the heavy chain constant domain, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, IgM, and some of these can be further divided into subclasses (isotypes), such as IgG-1, IgG-2, IgG-3, IgG-4, IgA-1, and IgA-2. The heavy chain constant domains corresponding to different classes of immunoglobulins are called α, delta, epsilon, γ, and μ, respectively. The subunit structures and three-dimensional arrangements of different classes of immunoglobulins are well known.

[0090] A “humanized antibody” refers to a type of modified antibody that has a CDR derived from a non-human donor immunoglobulin, with the remaining immunoglobulin-derived portion of the molecule derived from one (or more) human immunoglobulins. Furthermore, framework support residues may be modified to maintain binding affinity. Methods for obtaining “humanized antibodies” are well known to those skilled in the art (see, for example, Queen et al., Proc. Natl Acad Sci USA, 86:10029-10032 (1989), Hodgson et al., Bio / Technology, 9:421 (1991)).

[0091] As used herein, the terms “polypeptide,” “peptide,” and “protein” are interchangeable and are defined to mean biomolecules composed of amino acids linked by peptide bonds.

[0092] As used herein, the terms “a,” “an,” and “the” are defined as meaning “one or more,” and include the plural form unless the context is appropriate.

[0093] "Isolated" means a biomolecule that does not contain at least some of its naturally occurring components. When used to describe the various polypeptides disclosed herein, "isolated" means a polypeptide identified, separated, and / or recovered from the cells or cell cultures from which it expresses. Typically, isolated polypeptides are prepared by at least one purification step. "Isolated antibody" means an antibody that substantially does not contain other antibodies with different antigen-binding specificities.

[0094] "Recombination" means that antibodies are produced in exogenous host cells using recombinant nucleic acid technology.

[0095] The term "antigen" refers to an entity or fragment thereof that can elicit an immune response in living organisms, particularly animals, and more specifically mammals, including humans. This term includes immunogens and their regions involved in antigenicity or antigenic determinants.

[0096] Furthermore, as used herein, the term “immunogenic” refers to a substance that induces or enhances the production of antibodies, T cells, or other reactive immune cells against an immunogenic agent, thereby contributing to the immune response in a human or animal. An immune response occurs when an individual produces sufficient antibodies, T cells, and other reactive immune cells in response to an immunogenic composition disclosed herein in order to alleviate or reduce a disorder being treated.

[0097] "Specific binding" or "specific" to a particular antigen or epitope means a binding that is clearly different from nonspecific interactions. Specific binding can be measured, for example, by determining the binding of a molecule by comparing it to the binding of a control molecule, which is a similarly structured molecule that generally does not exhibit binding activity. For example, specific binding can be determined by competition with a regulatory molecule similar to the target.

[0098] The term "affinity" refers to a measure of the attractiveness between two polypeptides, such as antibody / antigen or receptor / ligand. The inherent attractiveness between two polypeptides can be expressed as the binding affinity equilibrium dissociation constant (KD) for a particular interaction. The KD binding affinity constant can be measured, for example, by biolayer interferometry. Here, KD is the ratio of kdis (dissociation rate constant) to kon (binding rate constant), i.e., KD = kdis / kon.

[0099] Specific binding to a particular antigen or epitope is, for example, at least about 10 -4 M, at least about 10 -5 M, at least about 10 -6 M, at least about 10 -7 M, at least about 10 -8 M, at least about 10 -9 M, at least about 10 -10 M, at least about 10 -11 M, at least about 10 -12This can be represented by antibodies having a KD of M or higher against an antigen or epitope, where KD refers to the equilibrium dissociation constant of a particular antibody-antigen interaction. Typically, antibodies that specifically bind to an antigen may have a KD of 20, 50, 100, 500, 1000, 5000, 10000, or greater than that of the control molecule against the antigen or epitope.

[0100] Furthermore, specific binding to a particular antigen or epitope can be demonstrated, for example, by antibodies having a KA or Ka ratio of at least 20, 50, 100, 500, 1000, 5000, or greater than 20-, 50-, 10000-, or greater than the epitope relative to the control. Here, KA or Ka refers to the association rate of a particular antibody-antigen interaction.

[0101] The "homology" between two sequences is determined by sequence identity. If the two sequences being compared are of different lengths, sequence identity preferably relates to the proportion of nucleotide residues in the shorter sequence that are identical to the nucleotide residues in the longer sequence. Sequence identity can conventionally be determined using a computer program. Deviations that appear in the comparison of a given sequence with the sequences disclosed herein may be caused, for example, by additions, deletions, substitutions, insertions, or recombinations.

[0102] The disclosures herein may be more readily understood by referring to the following detailed descriptions of the specific embodiments and examples contained herein. Although the disclosures herein have been described with reference to specific details of the specific embodiments thereof, such detailed descriptions should not be considered as limitations on the scope of the disclosure.

[0103] Examples Example 1: Method and Assay Expression and Purification

[0104] Restriction cloning and / or Gibson-A-Sembri were used to clone heavy and light chain encoding DNA sequences from custom gene fragments into a pTT5 vector. Plasmid DNA was transiently transfected into ExpiCHO cells (Thermo A29133) according to the manufacturer's instructions to produce multispecific GNC protein. Titer was measured 7–9 days later using a ForteBio Octet instrument equipped with a protein A sensor.

[0105] GNC proteins were purified by protein A chromatography (Cytiva, 17549853), washed with phosphate-buffered saline (PBS), eluted with 50 mM sodium acetate (pH 3.6), and immediately neutralized with 1 / 5 of 1 M sodium acetate (pH 7.0). After affinity purification, protein quality was evaluated by analytical size exclusion chromatography (aSEC). aSEC was performed using Acquity Arc Waters with an XBridge BEH SEC 300A, 7.8 x 300 mm, 3.5 μm column. Proteins were further purified by a preparative SEC step using a Superdex200Increase10 / 300GL column. All subsequent assays were performed by aSEC using at least 90% of the target protein.

[0106] T cell-dependent cytotoxicity assay

[0107] The T cell-dependent cytotoxicity (TDCC) assay was performed according to the method described by Nazarian et al. (2014). Target cells from an established cancer cell line (ADCC) were first transduced with a luciferase expression gene to produce luciferase-positive target cells. These target cells were then grown in cell culture flasks. After expanding to an appropriate number, these target cells were lifted, counted, and re-inoculated into 384 wells (Corning 3570) at an appropriate density according to the previous growth characteristics using a BioTek EL406 liquid dispenser. For adherent cell lines, the cells were adhered to plates overnight in a tissue culture incubator with a CO2-controlled jacket. Either PBMCs or previously expanded T cells (dynabeads) were then plated at an appropriate effector / target ratio (typically 5:1), and the plates were administered a diluted series of the test T cell target agent. The test substance was subjected to four quadruplicate experiments, and a 96-well dilution block was stamped into a 384-well quadrant using a robot (Opentrons OT-2 liquid handling robot). The TDCC assay plate was incubated for 72–96 hours. Cell viability curves were read using the Promega Bright-glo luciferase assay kit. In short, 20 μL was added to the TDCC assay plate, incubated for approximately 15 minutes, and then luminescence was measured using a BMG Clariostar plate reader. The cell death curve and EC50 values ​​were analyzed and plotted using GraphPad software.

[0108] SEC-MALS Analytical size exclusion chromatography (SEC) was performed in combination with multi-angle light scattering (MALS), absorbance (UV), and / or refractive index (RI) concentration detectors. SEC-MALS is typically used for antibody analytical characterization and early-stage clinical trials to support FDA IND submissions. Size exclusion is performed using Acquity Arc Waters and XBridge BEH SEC300A, 7.8x300mm, 3.5μm columns. The MALS component uses a Wyatt miniDAWN TREOS / OPtillab T-rEX system. Molecular weight can be determined from the measured change in solution refractive index n Δn with respect to the change in molecular concentration Δc (measured using an Optilab T-rEX differential refractometer to obtain the dn / dc (=Δn / Δc) value). The intensity of light scattered by molecules, as measured by the miniDAWN TREOS multi-angle light scattering (MALS) detector, is directly proportional to the molar mass.

[0109] OCTET The ForteBio Octet platform employs Biolayer Interference (BLI) as a label-free technique for measuring protein-protein interactions. This is an optical analysis technique that analyzes the interference pattern of white light reflected from two surfaces on a biosensor chip: an immobilized protein layer and an internal reference layer. As the number of molecules bound to the tip of the biosensor changes, the interference pattern changes and can be measured in real time. In this method, the binding of an antibody immobilized on the tip surface of an anti-human IgG Fc capture (AHC) biosensor to an antigen in solution increases the optical thickness of the biosensor tip, resulting in a wavelength shift Δλ that directly reflects the change in the thickness of the biological layer. The interaction between these two molecules can be measured in real time, allowing for accurate and precise monitoring of binding specificity, binding and dissociation rates, or concentrations. Unbound molecules, changes in the refractive index of the surrounding medium, or changes in flow rate do not affect the interference pattern. The Octet system allows for the immobilization of GNC proteins using an AHC chip, and the binding of GNC proteins to target antigens can be easily analyzed using purified antigens as analytes at a single concentration (e.g., 100 nM) or a series of concentrations (e.g., seven 1:2 serial dilutions starting from 200 nM).

[0110] Tm by dynamic light scattering (DLS) The hydrodynamic radius (Rh) of antibody samples (1 mg / ml) was measured using a DynaPro plate reader at a rate of 0.26 °C / min, in 1 °C increments from 25 °C to 75 °C. A total of three acquisitions were collected at each temperature for 5 seconds. The radius at which Rh began to change significantly, the starting temperature, and the midpoint (Tm) of the transition curve were calculated using DYNAMICS 7.8.1.3 software (Wyatt Technologies).

[0111] Quantitative flow cytometry (qFACS) Using CountBright absolute counting beads (Thermo C36950) for calibration, the number of corresponding receptors in various tumor cell lines was quantified using the primary antibody panitumumab (EGFR), MM111-derived anti-HER3 (HER3), PL221G5 (PD-L1), TF 3H8-1 (CEA), and trastuzumab (HER2) (Wang L et al. Curr Protoc. Cytom. 2016).

[0112] Example 2: GNC antibody having NKG2D as one of its binding domains NKG2D is a primary recognition receptor for the detection and elimination of transformed and infected cells, and its ligand is induced during cellular stress as a result of genomic stress such as infection or cancer. In humans, NKG2D is encoded by the KLRK1 gene located in the NK gene complex (NKC), and is recognized by NK cells, γδT cells, and CD8 cells. + It is expressed by αβT cells. The human NKG2D receptor complex assembles into a hexameric structure, while NKG2D itself forms a homodimer, and its external domain is involved in ligand binding. In NK cells, NKG2D functions as an activating receptor and can itself induce cytotoxicity. CD8 + The function of NKG2D on T cells is to send co-stimulatory signals to activate them. The major histocompatibility complex class I polypeptide-associated sequence A gene (MICA) is essentially all human natural killer (NK), γδT, and CD8 + It encodes a membrane-bound protein that acts as a ligand stimulating the activating receptor NKG2D, which is expressed on the surface of αβ T cells. While the MICA protein is absent in most cells, it can be induced by infection or oncogenic transformation and is frequently expressed in epithelial tumors. When NKG2D binds to MICA, it activates cytolytic responses of NK cells and γδ T cells against infected and tumor cells expressing MICA. Therefore, membrane-bound MICA functions as a signal for the initial immune response to infection and spontaneously occurring tumors. Conversely, human tumor cells spontaneously release soluble MICA, leading to downregulation of NKG2D and NK and CD8+ It causes severe impairment of the T-cell antitumor immune response. This is thought to promote immune evasion of tumors and weaken the host's resistance to infections that may be neutralized by free NKG2D. In this context, and by definition of GNC proteins, NKG2D is one of the cytotoxic cell-binding moieties (see applicant's application PCT / US2018 / 039160; the whole is incorporated herein).

[0113] GNC antibodies exhibiting NKG2D ligand-binding specificity contain a common core antibody domain whose Fc region may or may not have effector function. Tetra-GNC antibodies with an NKG2D dimer as one of the binding domains on the heavy chain (HC) were generated (Table 1). These antibodies had two additional scFv domains (including a binding domain to 4-1BB, which is a TNF superfamily receptor typically expressed on activated T cells (SI-49E1, SI-49E2, SI-49E3, SI-49E4; Table 1)), or one additional scFv and 41BBL (trimeric form) (typically found on antigen-presenting cells (APCs) and binding to 4-1BB (SI-49E11, SI-49E12, SI-49E13; Table 1)). These four binding domains (D1 to D4) were fused via the G / S linker region and expressed as a single heavy chain (HC, chain A or chain 1). By definition shown in Figure 1, these types of tetra-GNC antibodies are characterized by having one scFv (D1) located at the N-terminus of the VH domain (D2 or Fab) and two scFvs (D3 and D4) contiguously bound to the Fc region, whereas the light chain (LC) contains only the VL domain (D2 or Fab) in its native composition. One strategy for producing penta-GNC antibodies with NKG2D binding specificity is to design an additional NKG2D tandem repeat homodimer at the N(D6) or C(D5) terminus of the LC (Figure 1). Five D5-pentaGNC antibodies were generated, each possessing an NKG2D dimer as the binding domain from LC (SI-49P1, SI-49P2, SI-49P3, SI-49P4, and SI-49P5; Table 2). These D5-pentaGNC antibodies are characterized by a single cancer target moiety (D2) combined with four cytotoxic binding moieties: anti-CD3, anti-PD-L1, anti-4-1BB, and NKG2D. Table 3 shows information on both exemplary cancer target moieties and cytotoxic binding moieties as independent binding domains. According to this definition, PD-L1 is expressed in cancer cells as an immune checkpoint marker, but is not classified as a cancer-targeting moiety.These D5-pentaGNC antibodies consist of a core antibody-binding domain (a total of five different specificities) having three additional scFv-binding regions in the HC and one NKG2D tandem repeat homodimer in the LC, although the composition can be diverse. For example, the pentaGNC antibody may include a core antibody-binding domain (a total of five different specificities) having two additional scFv-binding regions, one TNF superfamily (trimeric) domain, and one NKG2D tandem repeat homodimer. Since NKG2D and 41BBL are not typical antigen-binding domain structures, i.e., neither Fab nor scFv, GNC antibodies having Fab in the core may elsewhere be called GNC molecules or GNC proteins in the same sense. Furthermore, the domain structures may be engineered to stabilize these multispecific GNC proteins. For example, each scFv domain may have both stapled and unstapled variants by disulfide bonds at vL100 and vH44, selected to stabilize the overall structure.

[0114] Analysis of SEC demonstrates the stability and high quality of purified tetra-GNC antibodies containing the NKG2D receptor and 41BBL, as well as multiple D5-penta-GNCs (including SI-49E1, SI-49E2, SI-49E3, SI-49E4, SI-49E11, SI-49E12, SI-49E13, SI-49P1, SI-49P2, SI-49P3, and SI-49P4) (2D) from LC that exhibit NKG2D binding specificity (Figures 2A-2C). This result demonstrates that these atypical GNC antibodies can be easily purified and maintained in a stable state.

[0115] Example 3: Comparison of the efficacy of GNC antibodies containing NKG2D as one of the binding domains. In NK cells, NKG2D functions as an activating receptor and can itself cause cytotoxicity, while CD8 +In T cells, the function of NKG2D is to activate them by sending co-stimulatory signals. NKG2D forms homodimers, and its external domain facilitates ligand binding. This function allows NKG2D to become a non-variable sequence-based binding domain in the GNC format, and other binding domains can be added to create a class of multispecific NKG2D-GNC proteins. In one GNC format, individual NKG2D monomers are incorporated into the D2 position of the heavy and light chains, forming a dimeric NKG2D receptor through HC / LC dimerization. Thus, NKG2D can function as a receptor for the multispecific antibody-like protein GNC molecule to bind to its ligand. In other GNC formats, the NKG2D tandem repeat is designed by adding a (GxSy)n linker between individual NKG2D monomers that homodimerize to form a functional dimeric receptor. This NKG2D tandem dimer structure can be located at D1, D3, D4, D5, or D6.

[0116] To evaluate the effect of NKG2D position in tetra-GNC antibodies, SI-49E1, SI-49E2, SI-49E3, and SI-49E4 were used in a TDCC assay (Figure 3). Using the MICA-expressing MDA-MB-231 cell line, all four NKG2D tetra-GNC antibodies showed higher potency than the control antibodies SI-49X1 (bispecific NKG2D-αCD3-Fc antibody) and SI-49X2 (bispecific Fc-αCD3-NKG2D antibody). Both control antibodies SI-49X1 and SI-49X2 lack anti-PD-L1 and anti-4-1BBscFv. This result suggests that binding specificity to PD-L1 and / or 4-1BB contributes to toxicity. Small differences among the four NKG2D tetra-GNC antibodies may largely reflect differences in their composition and accessibility to immune cells.

[0117] The effect of NKG2D position in penta-GNC antibodies was evaluated using TDCC assays with SI-49P1, SI-49P2, SI-49P3, SI-49P4, and SI-49P5 (Table 2) (Figure 4). The NKG2D-αMSLN penta-GNC antibody SI-49P1 killed cells with higher efficacy than the tetra-GNC control antibodies SI-51E4 and SI-51E1, and the NKG2D-α-mesothelin (αMSLN) control antibody SI-51X1. This observation suggests that the addition and position of NKG2D to tetra-GNC antibodies tend to improve efficacy. The control antibody SI-51X1, a trispecific αNKG2D-LC / αCD3-αMSLN-Fc without αPD-L1 and α4-1BB, showed lower efficacy, indicating that both the αPD-L1 and α4-1BB domains can enhance toxicity. The cell-killing efficacy is in the order of Penta-GNC > Tetra-GNC > Penta-GNC control antibody.

[0118] To quantify the ability of NKG2D receptor domain dimers to redirect T cells and kill tumor cells possessing MICA in the context of tetra-GNC or penta-GNC antibodies, a TDCC assay was performed using MDA-MB-231 target cells. The test materials included a control tetra-GNC antibody (SI-38E72, αCD3xαFITCxαPD-L1xα4-1BB) with a negative control anti-FITC domain at D2, tetra-GNC antibodies (SI-49E1, SI-49E2, SI-49E3, SI-49E4, NKG2DxαCD3xαPD-L1xα4-1BB) with binding domains at different GNC positions, and penta-GNC (SI-49P1, αCD3xαMSLNxαPD-L1xα4-1BBxNKG2D) with an additional αMSLN binding domain. The effector cell:target cell ratio (E:T) was 5:1, and after incubation of purified T cells, target cells, and drug dilutions for 96 hours, luminescence representing the remaining tumor cells was read. Note that absolute values ​​of EC50 may differ because some experiments were performed on different days. Nevertheless, the results in Table 4 show that all tetra-GNC antibodies containing the NKG2D domain have significantly higher TDCC efficacy, ranging from approximately 10-fold (SI-49E2) to over 130-fold (SI-49E4) compared to the corresponding tetra-GNC antibody (SI-38E72) that does not contain NKG2D. While the differences among these tetra-GNC antibodies may be due to the composition of the four binding domains in the same group, the addition of an anti-TAA moiety significantly increased the efficacy of the penta-GNC antibody SI-49P1 by more than 600-fold. Therefore, efficacy can be improved by adding one cytotoxic binding moiety such as NKG2D, and the efficacy of T cell-mediated tumor cell death can be specifically increased by adding an anti-TAA binding moiety.

[0119] Example 4: Mutation to remove light chain impurities Antibody-based proteins are almost always purified by protein A affinity chromatography. In this case, the protein A resin is purified by the C of the Fc domain. H2 -C H3 It captures the antibody at the binding site at the interface. However, protein A is VH3 Family Fv's V H It also binds to the domain. In most antibody-based platforms, V H This is not a problem because domains are generally on heavy chains. However, V H3 When scFv containing V is bound to the light chain, V is produced during purification. H The domain binds to the protein A resin, and there is a risk that monomers and dimers of the light chain may be mixed into the desired heavy-light heterotetramer. Therefore, the light chain may contain any V H3 A potential obstacle in producing multispecific antibodies containing a specific domain is the presence of additional contaminants during protein A elution. This is particularly problematic when the light chain is expressed more efficiently than the heavy chain, resulting in a large amount of light chain contaminants being purified along with the target protein assembly.

[0120] To rationally disrupt protein A binding of VH3 family members, a structural approach that disrupts the binding interface was employed. Crystal structure 1DEE (Graille M. et al. Proc. Nat. Acad. Sci. 2000.) showed that residue R19 (Kabat numbering) of VH3 directly contacts two side chains of protein A domain D. In particular, contact with Q32 and D36 can be eliminated, significantly weakening the interaction. Therefore, R19 was mutated to a serine that does not form these interactions due to the shortness of its side chain. Furthermore, it is suggested that S19 is naturally present in other VH family members and may be less immunogenic than other substitutions.

[0121] V on GNC light chain H3The R19S mutation (Kabat numbering) was incorporated into the FR1 region of the VH domain of the contained scFv. Specifically, the hexa-GNC antibody SI-55-H11 contained the R19S mutation in the light chain sequences encoding the anti-HER3 scFv domain at D5 and the anti-CD19 scFv domain at 6. Since the target residue is located at the protein A binding interface, the R-to-S mutation disrupts the interaction with protein A. By removing protein A binding in the light chain scFv, binding of light chain monomers and dimers to protein A during purification is prevented. As a result, a more homogeneous product free of light chain impurities is obtained. Up to two V per light chain. H3 In the case of hexa-GNCs that can contain scFv, this mutation is particularly important for the efficient purification of the target product.

[0122] Example 5: Comparison of the efficacy of multispecific GNC antibodies with different binding domain structures.

[0123] In a general scheme of multispecific GNC proteins (Figure 1), each binding domain of a multispecific GNC antibody can be a Fab, scFv based on a variable sequence, or a ligand, receptor, or other binding structure based on a non-variable sequence. To evaluate how the structural diversity of each binding domain affects the overall function of multispecific GNC antibodies, a TDCC assay was performed to induce T cell-mediated death of pancreatic cancer cells (BxPC3). As shown in Table 5, changes in binding specificity to EGFR, HER3, CD19, CD3, and 4-1BB were evaluated using three penta-GNC antibodies (SI-1P1, SI-55P9, and SI-55P10) and one hexa-GNC antibody (SI-55H11). All test substances contained αPD-L1scFv at position D3, and there were no changes in its position or structure. For binding specificity to EGFR, the changes included position (D1 vs D2). Regarding binding, the changes included both structural (stapled vs. unstapled) and positional (D1 vs. D2). For binding specificity to 4-1BB, the changes included both structural and binding mechanism (scFv based on the variable sequence via 41BBL and ligand-receptor interaction based on the non-variable sequence, i.e., interaction from the 4-1BB ligand trimer to the 4-1BB receptor). For binding specificity to CD19, the changes were related to the humanized variable sequence. For binding specificity to HER3, since HER3 was not detected on the surface of BXPC3 cells, this difference accounted for this group as either tetra-GNC, penta-GNC, or hexa-GNC antibodies (see Table 9).

[0124] The TDCC assay was performed under the same conditions (e.g., effector:target cell ratio (E:T) 5:1), and purified T cells, target cells, and drug dilutions were incubated for 72 hours, after which luminescence representing the remaining tumor cells was read. Note that EC50 values ​​may vary between experiments within the margin of error, as some experiments were performed on different days. Nevertheless, the potency of these penta-GNC and hexa-GNC antibodies is less than 1 pM and within a 10-fold range, indicating that structural modifications could significantly improve manufacturing cost and feasibility rather than their effect on killing BXPC3 cells. In this context, the composition of binding specificity remains a determinant for creating multispecific GNC antibodies that target specific forms of cancer.

[0125] Example 6: Composition of part 1 and part 2 of a multispecific GNC antibody Multispecific GNC antibodies with up to six binding specificities can be applied to antibody therapies with the highest ability to kill cancer cells. For example, the EC50 value can be reduced from nM to pM or fM levels. Successful, highly effective multispecific GNC antibodies depend on the composition of both part 1 and part 2 antigens. Table 4 established the comparative efficacy of four part 1 binding specificities (i.e., αCD3, αPD-L1, α4-1BB, and NKG2D) in tetra-GNC antibodies by a TDCC assay using MDA-MB-231 cells as target breast cancer cells. Compared to a control antibody (SI-38E72) containing three part 1 binding domains (i.e., αCD3, αPD-L1, and α4-1BB as D1, D3, and D4 of HC, respectively), the addition of a fourth part 1 binding domain improved the potency of the non-variable sequence-based NKG2D dimer receptor by approximately 10- to 130-fold, depending on the composition. However, by adding the anti-TAA portion, the potency of the pentaGNC antibody (SI-55H11) was significantly increased by up to 600 times.

[0126] To evaluate the partial-1 binding specificity in combination with three partial-1 binding domains, a TDCC assay was performed using the breast cancer cell line MDA-MB-231 as the target cell line. All test substances contained αCD3, αPD-L1, and α-4-1BBscFv at positions D1, D3, and D4, respectively. Tetra-GNC antibody (SI-38E72) (which lacks a partial-1 binding domain and has an α-FITC domain at D2 that is not specific to any tumor antigen) was used as a control. Other tetra-GNC test substances had various binding domains at D2 (SI-55E: αEGFR cetuximab; SI-55E2: αEGFR panitumumab; SI-50E1: αHER2 trastuzumab; and SI-51E1: α-mesothelin amatsuximab), while the penta-GNC antibody (SI-1P1) had αEGFR cetuximab at D2 and αHER3 MM111scFv at D5. The effector:target cell ratio (E:T) was 5:1 or 10:1, and luminescence representing the remaining tumor cells was read after incubation of purified T cells, target cells, and drug dilutions for 96 hours. Note that EC50 values ​​may differ as some experiments were performed on different days, but should be considered within the margin of error. Nevertheless, the results show that all GNC antibodies containing the αTAA domain in D2 induced significantly more potent TDCC (20-100 times) than controls containing αFITC in D2 (Table 6). The EC50 of the penta-GNC antibody (SI-1P1) was similar to that of tetra-GNC, indicating that adding a domain can improve TAA selectivity while maintaining potent TDCC.

[0127] Example 7: Screening of TAA using a tetra-GNC configuration with three partial 1-bonds The configuration of three partial 1 binding domains fixed to D1, D3, and D4 (Table 6) can be used as the backbone HC to accurately identify novel and / or effective partial 2 binding domains of TAA. To evaluate the ability of multispecific GNC antibodies targeting different tumor antigens to induce T cell-mediated killing, a TDCC assay was performed using the cervical cancer cell line HeLa as the target cell. All test substances had αCD3, αPD-L1, and α4-1BBscFv at D1, D3, and D4, respectively. The tetra-GNC antibody (SI-38E72) was used as a control because it has an αFITC domain at D2 that is not specific to any tumor antigen. Other tetra-GNC test substances have various binding domains at D2 (Table 7). The effector cell:target cell ratio (E:T) was 10:1, and after incubation of purified T cells, target cells, and drug dilutions for 96 hours, luminescence representing the remaining tumor cells was read. Note that some experiments were conducted on different days, so EC50 values ​​may differ, but these are within the margin of error. Nevertheless, the results from experiments conducted on the same day show that the two anti-EGFR tetra-GNC antibodies (SI-55E1 (Cet) and SI-55E2 (Pan)) killed more than 50% of cancer cells at potencies of 13 pM and 9 pM, respectively (Figure 5). The other test substances (SI-51E1, SI-52E1, SI-50E2, SI-54E1, SI-55E3, SI-56E1, SI-57E1, and SI-38E17) killed less than 20% of inoculated cells, showing weaker killing power. Therefore, their EC50 values ​​were not as high as those of SI-55E1 and SI-55E2. SI-55E3 possesses an anti-EGFR binding domain in a Fab derived from D2 or nimotuzumab, and its binding affinity to EGFR is lower than that of panitumumab (SI-55E1) and cetuximab (SI-55E2) (Applicant's application PCT / US2020 / 059230; the entire application is incorporated herein). Surprisingly, SI-55E3 was one of the few to exhibit weak killing activity. This finding suggests that both binding specificity and affinity play a role in multispecific GNC antibody-mediated TDCC.

[0128] Example 8: Comparison of the efficacy of the same multispecific GNC antibody in killing different cancer cells.

[0129] To further characterize the comparative potency of SI-55E1 and SI-55E2, which have the same partial 1 binding domain structure and target EGFR, the MDA-MB-231 cell line was used in the TDCC assay. In the same-day experiment, two additional antibodies targeting both EGFR and HER3 were used. SI-1P2 is a penta-GNC antibody that has the same partial 1 binding domain structure as SI-55E1 and SI-55E2, plus an additional partial 2 domain that binds to HER3, while SI-1 is a bispecific antibody against both EGFR and HER3 in the absence of the partial 1 binding domain. The materials and methods for this TDCC assay were the same as those described in Example 1. As shown in Figure 6, SI-55E1, SI-55E2, and SI-1P2 exhibited comparable potency, as indicated by overlapping dose survival curves, with their EC50 values ​​ranging from 17 to 29 fM (Table 6). In contrast, SI-1 did not respond at doses of less than nM units in the same-day experiment. These results support the concept that three partial 1-binding domains (CD3, PD-L1, and 4-1BB) significantly contribute to the efficacy of multispecific GNC antibodies.

[0130] To measure the additional effects of partial 1 binding domains, such as anti-CD3, two tetra-GNC antibodies (SI-50E1 and SI-50E6) and one bi-GNC antibody (SI-50X1) were analyzed using a TDCC assay with the MDA-MB-231 cell line as the target cell line. All three antibodies exhibited the same binding specificity to trastuzumab-derived HER2 (Table 6). SI-50E1 and SI-50E6 had identical partial 1 and partial 2 binding domain configurations; however, the scFv domain of SI-50E6 was engineered (i.e., stapled) with additional disulfide bonds to enhance stability, whereas the scFv domain of SI-50E1 was not stapled. SI-50X1 is a bispecific antibody targeting both CD3 and HER2. The TDCC dose-response curves clearly show that all three GNC antibodies were potent and their EC50 values ​​were in the fM range (Figure 7). The differences in the curves and EC values ​​were due to the presence or absence of partial 2-binding domains for PD-L1 and 4-1BB among the three antibodies.

[0131] Example 9: Selection of TAAs and assembly of partial 2-binding domains for multispecific GNC antibodies

[0132] Antibody therapies employ various strategies to kill cancer cells directly or indirectly, and both mechanisms of action depend on binding to surface antigens. Meanwhile, cancer cells acquire the ability to evade recognition by antibodies and / or immune cells through evolution. Multispecific GNC antibodies with the capability of up to six binding specificities showed maximum potency when measured by in vitro EC50 in the pM and fM ranges. Highly effective multispecific GNC antibodies depend on the composition of both part 1 and part 2 antigens. Here, the three part 1 binding domains (CD3, PD-L1, and 4-1BB) in the composition (D1, D3, and D4 of HC respectively) provide the backbone of the multispecific GNC antibody. GNC antibodies formatted in this way enable the selection, screening, and optimization of TAAs for target cancer cells (Figure 8).

[0133] To demonstrate the importance of TAA surface expression profiles, quantitative flow cytometry (qFACS) was performed to quantify the approximate number of receptors per cell for various tumor targets. EGFR, HER2, and HER3 are members of the EGFR family, and their expression is typically upregulated by solid tumors, while PD-L1 is a target for inhibiting immune checkpoint signaling utilized in some human cancers. Nevertheless, surface expression of HER3 and PD-L1 could not be detected in MDA-MB-232 cells and HeLa cells, respectively (Table 8). This observation may explain the lack of synthetic lethality when targeting both EGFR and HER3 with SI-1P1 compared to SI-55E1, SI-55E2, and SI-50E1 targeting EGFR or HER2, respectively (Table 6). Furthermore, the failure to induce TDCC with the control antibody (SI-38E72) can likely be interpreted as being due to the absence of PD-L1 in HeLa cells (Table 7). In light of the evolution and dynamic expression profiles of cancer cells, any candidate antibody can be tested for TDCC using the various types of cancer cells shown in Table 9.

[0134] To screen for TAAs, a modular cloning platform can be used to efficiently identify TAAs or TAA epitopes for assembling partial 2-binding domains of multispecific GNC antibodies. For example, TAA-Fc tetra-GNC-1 and TAA-Fc tetra-GNC-2 are two groups of tetra-GNC antibodies with the same pairwise binding specificity. The only difference is that all TAA-Fc tetra-GNC-2 antibodies have stapled scFv domains D1, D3, and D4 of the HC (VH44→C and VL100→C mutations). In this case, the HC was swapped to generate two groups of tetra-GNC antibodies. In other examples, the LC can be swapped to generate multispecific GNC antibodies with added TAA-binding domains (e.g., SI-55P10 to SI-55H11, and SI-55E1 to SI-1P1). This modular cloning platform allows for the efficient assembly of multispecific GNC antibodies containing up to three TAAs, starting from a single anti-TAA monoclonal antibody.

[0135] Example 10: Function of a multispecific GNC protein with a receptor at the D2 position

[0136] To further validate the flexibility of the GNC platform in accommodating diverse binding domains at various molecular positions, a group of proteins with an NKG2D receptor at the D2 position were produced (Table 10). It was predicted that when monomeric NKG2D is incorporated at the D2 position on both GNC chains, the NKG2D monomer would dimerize upon interchain association. SI-49R21 is a monospecific GNC (antibody-like protein) with an NKG2D receptor instead of an antibody VH / VL domain. SI-49R22 contains the same format except its Fc domain also contains knobs-into-holes mutations for heterodimerization (chain A: T366S / L368A / Y407V; and chain B: T366W). SI-49R23 is a monospecific protein with NKG2D directly fused to the antibody's Fc domain, and SI-49R24 has the same structure but further contains knobs-into-holes mutations in the Fc. SI-49R19 is a bispecific GNC with anti-CD3 scFv at D1 and NKG2D at D2, while SI-49R18 is a triplicate GNC with an additional anti-CD19 at D6. SI-49E15 has anti-CD3 scFv at D1, NKG2D at D2, anti-PD-L1 scFv at D3, and anti-4-1BB scFv at D4. SI-49P6 has the same domain as SI-49E15, plus an additional anti-CD19 scFv at D6. SI-49P7 has the same structure as SI-49P6, except that it contains a 4-1BB ligand trimer at D4 instead of anti-4-1BB scFv.

[0137] All proteins possessing NKG2D at the D2 position were successfully expressed and purified. To verify the function of the NKG2D receptor at the D2 position, octet binding was performed. After loading GNC proteins into an AHC sensor at 5 ug / ml, they were conjugated to a 1:2 serial dilution of human MICA (Acro, MIA-H5221) (maximum concentration 100 nM). The binding affinity (KD value) obtained from a global fit to a 1:1 binding model is shown in Table 11. Mono, bi, tri, tetra, and penta GNC proteins possessing NKG2D at the D2 position have been shown to retain strong binding to the NKG2D ligand MICA, as evidenced by KD values ​​of less than 20 nM.

[0138] Example 11: Antigen binding independent of GNC site, humanization, or domain format.

[0139] To further demonstrate the adaptability of the GNC platform, we produced a group of hexaspecific GNC proteins targeting the same antigen (CD3xEGFRxPD-L1x4-1BBxCD19xHER3). This group as a whole included anti-PD-L1scFv in D3, anti-4-1BBscFv in D4, anti-HER3scFv in D5, and anti-CD19scFv in D6. Two molecules (SI-77H4 and SI-77H5) contained anti-CD3scFv in D1 and anti-EGFR Fab in D2, the difference being that the anti-EGFR domain of SI-77H4 was humanized, while the anti-EGFR domain of SI-77H5 retained the mouse sequence. The two molecules (SI-55H11 and SI-55H12) contain anti-EGFR scFv in D1 and anti-CD3 Fab in D2, the difference being that D2VH / VL contains a disulfide staple in SI-55H11 (VH-44C, VL-100C) rather than in SI-55H12. Therefore, this group was able to determine whether the D1 / D2 configuration affects either protein expression characteristics or binding affinity to target tumor-associated antigens.

[0140] The protein was transiently expressed in ExpiCHO cells as described in Example 1. Approximately 8 days later, GNC titer was measured using a Protein A sensor on the Octet platform (Table 12). The results showed good expression of the hexaspecific GNC protein regardless of the position and format of the anti-EGFR and anti-CD3 domains (≥30 μg / ml). After the initial Protein A purification step, all proteins showed similarly low aggregation levels, and the percentage of target protein ranged from 72 to 85% (Table 12). Next, the affinity of the anti-EGFR domain to human EGFR was evaluated by loading the GNC protein onto an AHC sensor and using a single concentration (100 nM) of His-tagged human EGFR (expressed in-house) as the analyte. As shown in Table 12, the position and format of the anti-EGFR and anti-CD3 domains did not significantly affect the EGFR binding affinity (KD values ​​within approximately 2x). Therefore, the GNC protein retains full function regardless of the position of the anti-TAA and anti-CD3 domains between D1 and D2.

[0141] [Table 1] JPEG0007880406000002.jpg16125

[0142] [Table 2]

[0143] [Table 3]

[0144] [Table 4]

[0145] [Table 5] a 284A10: Refer to applicant's application PCT / US2018 / 039143. b SI-huBU12: Refer to applicant's application PCT / US2020 / 059230.

[0146] [Table 6]

[0147] [Table 7]

[0148] [Table 8]

[0149] [Table 9]

[0150] [Table 10] *SI-49R22 contains heterodimerized Fc with knobs-into-holes mutations (chain A: T366S / L368A / Y407V; chain B: T366W). **SI-49R23 lacks the CH1 / CL domain.** ***SI-49R24 contains a heterodimerized Fc with a knobs-into-holes mutation (chain A: T366S / L368A / Y407V; chain B: T366W) and lacks the CH1 / CL domain.

[0151] [Table 11]

[0152] [Table 12] *SI-55H11 D2 contains a disulfide staple between VH and VL (VH-44C, VL-100C).

[0153] JPEG0007880406000014.jpg221160 JPEG0007880406000015.jpg136160 JPEG0007880406000016.jpg157126 CDR's underlined in amino acid sequences Chain A: HC or Chain 1 Chain B: LC or Chain 2 >SEQ ID 1 SI-49E1 chain A nt >SEQ ID 2 SI-49E1 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 3 SI-49E1 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 4 SI-49E1 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 5 SI-49E2 chain A nt >SEQ ID 6 SI-49E2 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIKGGGGSGGGGSGEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIK >SEQ ID 7 SI-49E2 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT > SEQ ID 8 SI-49E2 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 9 SI-49E3 chain A nt >SEQ ID 10 SI-49E3 chain A aa DVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSTGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 11 SI-49E3 chain B nt GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 12 SI-49E3 chain B aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 13 SI-49E4 chain A nt >SEQ ID 14 SI-49E4 chain A aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSTGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 15 SI-49E4 chain B nt GACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 16 SI-49E4 chain B aa DVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 17 SI-49E11 chain A nt >SEQ ID 18 SI-49E11 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >SEQ ID 19 SI-49E11 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 20 SI-49E11 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 21 SI-49E12 chain A nt >SEQ ID 22 SI-49E12 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSA FGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSKPGSGEGSTGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGSGEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIK >SEQ ID 23 SI-49E12 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 24 SI-49E12 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 25 SI-49E13 chain A nt >SEQ ID 26 SI-49E13 chain A aa REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLSTGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 27 SI-49E13 chain B nt GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 28 SI-49E13 chain B aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 29 SI-49E14 chain A nt >SEQ ID 30 SI-49E14 chain A aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSTGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNIWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 31 SI-49E14 chain B nt >SEQ ID 32 SI-49E14 chain B aa REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 33 SI-1P1 chain A nt >SEQ ID 34 SI-1P1 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 35 SI-1P1 chain B nt >SEQ ID 36 SI-1P1 chain B aa DILLTQSPVILSVSPGERVSFSC RASQSIGTNIH WYQQRTNGSPRLLIK YES GIPSRFSGSGSGTDFTLSINSVESEDIADYYC QQNNNWPTT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKGLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 37 SI-1P2 chain A nt >SEQ ID 38 SI-1P2 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 39 SI-1P2 chain B nt >SEQ ID 40 SI-1P2 chain B aa DILLTQSPVILSVSPGERVSFSC RASQSIGTNIH WYQQRTNGSPRLLIK YES GIPSRFSGSGSGTDFTLSINSVESEDIADYYC QQNNNWPTT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKCLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 41 SI-1P4 chain A nt >SEQ ID 42 SI-1P4 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 43 SI-1P4 chain B nt >SEQ ID 44 SI-1P4 chain B aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKCLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 45 SI-39P1 chain A nt >SEQ ID 46 SI-39P1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSDVQLQESGPSLVKPSQSLSLTCTVTGYSIT SDFAWN WIRQFPGNKLEWMG YISYSGNTRYNPSLKS RISITRDTSKNQFFLQLNSVTIEDTATYYCVT AGRGFPY WGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSQSLVESGGGLVQPGGSLRLSCAASGFSFS SNYWIC WVRQAPGKGLEWIA CIYVGSSGDTYYASSAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DSSSYYMFNL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSALVMTQSPSTLSASVGDRVTINC QASEDIDTYLA WYQQKPGKAPKLLIF YASDLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGGYYTSSADTRGA FGGGTKVEIK >SEQ ID 47 SI-39P1 chain B nt >SEQ ID 48 SI-39P1 chain B aa DILMTQSPSSMSVSLGDTVSITC HSSQDINSNIG WLQQRPGKSFKGLIY HGTNLDD EVPSRFSGSGSGADYSLTISSLESEDFADYYC VQYAQFPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKGLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 49 SI-38P5 chain A nt >SEQ ID 50 SI-38P5 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFT SYNMH WVKQTPGRGLEWIG AIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR STYYGGDWYFNV WGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 51 SI-38P5 chain B nt >SEQ ID 52 SI-38P5 chain B aa QIVLSQSPAILSASPGEKVTMTC RASSSVSYIH WFQQKPGSSPKPWIY ATSNLAS GVPVRFSGSGSGTSYSLTISRVEAEDAATYYC QQWTSNPPT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFS SSWIG WVRQAPGKGLEWMG IIYPDDSDTRYSPSFQG QVTISADKSIRTAYLQWSSLKASDTAMYYCAR HVTMIWGVIIDF WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAIQLTQSPSSLSASVGDRVTITC RASQGISSALA WYQQKPGKAPKLLIY DASSLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQFNSYPFT FGPGTKVDIK >SEQ ID 53 SI-38P6 chain A nt >SEQ ID 54 SI-38P6 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFT SYNMH WVKQTPGRGLEWIG AIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR STYYGGDWYFNV WGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 55 SI-38P6 chain B nt >SEQ ID 56 SI-38P6 chain B aa QIVLSQSPAILSASPGEKVTMTC RASSSVSYIH WFQQKPGSSPKPWIY ATSNLAS GVPVRFSGSGSGTSYSLTISRVEAEDAATYYC QQWTSNPPT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFS SSWIG WVRQAPGKCLEWMG IIYPDDSDTRYSPSFQG QVTISADKSIRTAYLQWSSLKASDTAMYYCAR HVTMIWGVIIDF WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAIQLTQSPSSLSASVGDRVTITC QUESTIONS WYQQKPGKAPKLLIY DASSLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQFNSYPFT FGCGTKVDIK >SEQ ID 57 SI-49P1 chain A nt >SEQ ID 58 SI-49P1 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSQVQLQQSGPELEKPGASVKISCKASGYSFT GYTMN WVKQSHGKSLEWIG COLOR SYNQKFRG KATLTVDKSSSTAYMDLLSLTSEDSAVYFCAR GGYDGRGFDY WGSGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY LISTEN GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC STYLE DOVE FGCGTKVEIK >SEQ ID 59 SI-49P1 chain B nt >SEQ ID 60 SI-49P1 chain B aa DIELTQSPAIMSASPGEKVTMTC SASSSVSYMH WYQQKSGTSPKRWIY DTSKLAS GVPGRFSGSGSGNSYSLTISSVEAEDDATYYC QQWSKHPLT FGSGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 61 SI-49P2 chain A nt >SEQ ID 62 SI-49P2 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVRPGASVKLSCKASGYTFT SYWIN WVKQRPGQGLEWIG NIYPSDSYTNYNQKFKD KATLTVDKSSSTAYMQLSSPTSEDSAVYYCTR SWRGNSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY LISTEN GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC STYLE DOVE FGCGTKVEIK >SEQ ID 63 SI-49P2 chain B nt >SEQ ID 64 SI-49P2 chain B aa DIVMTQSPSSLTVTAGEKVTMSC KSSQSLLNSGNQKNYLT WYQQKPGQPPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVQAEDLAVYYC QNDYSYPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRT >SEQ ID 65 SI-49P3 chain A nt >SEQ ID 66 SI-49P3 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIK DTYIH WVRQAPGKGLEWVA RIYPTNGYTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCSR WGGD GFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY LISTEN GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC STYLE DOVE FGCGTKVEIK >SEQ ID 67 SI-49P3 chain B nt >SEQ ID 68 SI-49P3 chain B aa DIQMTQSPSSLSASVGDRVTITC RASQDVNTAVA WYQQKPGKAPKLLIY SASFLYSGVPS RFSGSRSGTDFTLTISSLQPEDFATYYC QQHYTTPPT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 69 SI-49P4 chain A nt >SEQ ID 70 SI-49P4 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSDVQLQESGPSLVKPSQSLSLTCTVTGYSIT SDFA WNWIRQFPGNKLEWMG YISYSGNTRINPSLKS RISITRDTSKNQFFLQLNSVTIEDTATYYCVT AGRGFP YWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 71 SI-49P4 chain B nt >SEQ ID 72 SI-49P4 chain B aa DILMTQSPSSMSVSLGDTVSITC HSSQDINSNIG WLQQRPGKSFKGLIY HGTNLDD EVPSRFSGSGSGADYSLTISSLESEDFADYYC VQYAQFPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 73 SI-49P5 chain A nt >SEQ ID 74 SI-49P5 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVQSGAEVKKPGSSVKVSCKASGYTIT DSNIH WVRQAPGQSLEWIG YIYPYNGGTDYNQKFKN RATLTVDNPTNTAYMELSSLRSEDTAFYYCVN GNPWLA YWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 75 SI-49P5 chain B nt >SEQ ID 76 SI-49P5 chain B aa DIQLTQSPSTLSASVGDRVTITC RASESLDNYGIRFLT WFQQKPGKAPKLLMY AASNQGS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQTKEVPWS FGQGTKVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 77 SI-49P6 chain A nt >SEQ ID 78 SI-49P6 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 79 SI-49P6 chain B nt >SEQ ID 80 SI-49P6 chain B aa ENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLS TSGMGVG WIRQPPGKGLEWLA HIWWDDDKRYNPALKS RLTISKDTSKNQVYLQMNSLDAEDTAVYYCAR MELWSYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 81 SI-49P7 chain A nt >SEQ ID 82 SI-49P7 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >SEQ ID 83 SI-49P7 chain B nt >SEQ ID 84 SI-49P7 chain B aa ENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLS TSGMGVG WIRQPPGKGLEWLA HIWWDDDKRYNPALKS RLTISKDTSKNQVYLQMNSLDAEDTAVYYCAR MELWSYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 85 SI-49P10 chain A nt >SEQ ID 86 SI-49P10 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 87 SI-49P10 chain B nt >SEQ ID 88 SI-49P10 chain B aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKGSTGSGSKPGSGEGSTKGQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 97 SI-38E17 chain A nt >SEQ ID 98 SI-38E17 chain A aa >SEQ ID 99 SI-38E17 chain B nt GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTTTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 100 SI-38E17 chain B aa AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 105 SI-55H11 chain A nt >SEQ ID 106 SI-55H11 chain A aa >SEQ ID 107 SI-55H11 chain B nt >SEQ ID 108 SI-55H11 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 109 SI-50E1 chain A nt >SEQ ID 110 SI-50E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIK DTYIH WVRQAPGKGLEWVA RIYPTNGYTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCSR WGGDGFYAMD YWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 111 SI-50E1 and SI-50E6 chain B nt GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGATAGGGTCACCATCACCTGCCGTGCCAGTCAGGATGTGAATACTGCTGTAGCCTGGTATCAACAGAAACCAGGAAAAGCTCCGAAACTACTGATTTACTCGGCATCCTTCCTCTACTCTGGAGTCCCTTCTCGCTTCTCTGGCTCCAGATCTGGGACGGATTTCACTCTGACCATCAGCAGTCTGCAGCCGGAAGACTTCGCAACTTATTACTGTCAGCAACATTATACTACTCCTCCCACGTTCGGACAGGGTACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 112 SI-50E1 and SI-50E6 chain B aa DIQMTQSPSSLSASVGDRVTITC RASQDVNTAVA WYQQKPGKAPKLLIY SASFLYS GVPSRFSGSRSGTDFTLTISSLQPEDFATYYC QQHYTTPPT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 113 SI-50E6 chain A nt >SEQ ID 114 SI-50E6 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIK DTYIH WVRQAPGKGLEWVA RIYPTNGYTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCSR WGGDGFYAMDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 115 SI-50E2 chain A nt >SEQ ID 116 SI-50E2 chain A aa >SEQ ID 117 SI-50E2 and SI-50E7 chain B nt GACATCCAGATGACACAATCTCCTAGCAGTCTGAGCGCAAGTGTTGGAGATCGTGTCACCATCACATGCAAGGCCAGCCAGGATGTGAGCATTGGAGTCGCCTGGTATCAGCAGAAACCCGGCAAGGCACCCAAGCTGCTGATCTACTCGGCCAGTTACAGATACACTGGCGTACCTTCGAGGTTTAGTGGTAGCGGTTCTGGAACCGATTTCACCCTCACCATTAGCTCCCTCCAACCCGAGGACTTCGCCACCTACTACTGCCAGCAATACTACATCTACCCTTACACGTTCGGCCAAGGCACTAAGGTCGAGATTAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 118 SI-50E2 and SI-50E7 chain B aa DIQMTQSPSSLSASVGDRVTITC KASQDVSIGVA WYQQKPGKAPKLLIY SASYRYT GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYYIYPYT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 119 SI-50E7 chain A nt >SEQ ID 120 SI-50E7 chain A aa >SEQ ID 122 SI-51E1 chain A aa >SEQ ID 123 SI-51E1 and SI-51E4 chain B nt GACATCGAGCTCACTCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGGAGAAGGTCACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTTACATGCACTGGTACCAGCAGAAGTCAGGCACCTCCCCCAAAAGATGGATTTATGACACATCCAAACTGGCTTCTGGAGTCCCAGGTCGCTTCAGTGGCAGTGGGTCTGGAAACTCTTACTCTCTCACAATCAGCAGCGTGGAGGCTGAAGATGATGCAACTTATTACTGCCAGCAGTGGAGTAAGCACCCTCTCACGTTCGGATCCGGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 124 SI-51E1 and SI-51E4 chain B aa DIELTQSPAIMSASPGEKVTMTC SASSSVSYMH WYQQKSGTSPKRWIY DTSKLAS GVPGRFSGSGSGNSYSLTISSVEAEDDATYYC QQWSKHPLT FGSGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 125 SI-51E4 chain A nt >SEQ ID 126 SI-51E4 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQSGPELEKPGASVKISCKASGYSFT GYTMN WVKQSHGKSLEWIG LITPYNGASSYNQKFRG KATLTVDKSSSTAYMDLLSLTSEDSAVYFCAR GGYDGRGFDY WGSGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 128 SI-52E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLLQSGPELEKPGASVMISCKASGSSFT GYNMN WVRQNIGKSLEWIG AIDPYYGGTSYNQKFKG RATLTVDKSSSTAYMHLKSLTSEDSAVYYCVS GMEY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 129 SI-52E1 and SI-52E4 chain B nt GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGATCTAGTCAGAGTCTTGTACACCGTAATGGAAACACCTATTTACATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATTCACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGTTCTCAAAGTACACATGTTCCTCCGCTCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 130 SI-52E1 and SI-52E4 chain B aa EIVMTQSPATLSVSPGERATLSC RSSQSLVH RNGNTYLHWYLQKPGQSPKLLIH KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDLGVYFC SQSTHVPPLT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 131 SI-52E4 chain A nt >SEQ ID 132 SI-52E4 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLLQSGPELEKPGASVMISCKASGSSFT GYNMN WVRQNIGKSLEWIG AIDPYYGGTSYNQKFKG RATLTVDKSSSTAYMHLKSLTSEDSAVYYCVS GMEY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 133 SI-53E1 chain A nt >SEQ ID 134 SI-53E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVRPGASVKLSCKASGYTFT SYWIN WVKQRPGQGLEWIG NIYPSDSYTNYNQKFKD KATLTVDKSSSTAYMQLSSPTSEDSAVYYCTR SWRGNSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 135 SI-53E1 and SI-53E3 chain B nt GACATTGTGATGACACAGTCTCCATCCTCCCTGACTGTGACAGCAGGAGAGAAGGTCACTATGAGCTGCAAGTCCAGTCAGAGTCTGTTAAACAGTGGAAATCAAAAGAACTACTTGACCTGGTACCAGCAGAAACCAGGGCAGCCTCCTAAACTGTTGATCTACTGGGCATCCACTAGGGAATCTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGTGCAGGCTGAAGACCTGGCAGTTTATTACTGTCAGAATGATTATAGTTATCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 136 SI-53E1 and SI-53E3 chain B aa DIVMTQSPSSLTVTAGEKVTMSC KSSQSLLNSGNQKNYLT WYQQKPGQPPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVQAEDLAVYYC QNDYSYPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 137 SI-53E3 chain A nt >SEQ ID 138 SI-53E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVRPGASVKLSCKASGYTFT SYWIN WVKQRPGQGLEWIG NIYPSDSYTNYNQKFKD KATLTVDKSSSTAYMQLSSPTSEDSAVYYCTR SWRGNSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 139 SI-54E1 chain A nt >SEQ ID 140 SI-54E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFT SYNMH WVKQTPGRGLEWIG AIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR STYYGGDWYFNV WGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 141 SI-54E1 and SI-54E3 chain B nt CAGATCGTGCTGAGCCAGAGCCCCGCCATCCTGAGCGCCAGCCCCGGCGAGAAGGTGACCATGACCTGCCGGGCCAGCAGCAGCGTGAGCTACATCCACTGGTTCCAGCAGAAGCCCGGCAGCAGCCCCAAGCCCTGGATCTACGCCACCAGCAACCTGGCCAGCGGCGTGCCCGTGCGGTTCAGCGGCAGCGGCAGCGGCACCAGCTACAGCCTGACCATCAGCCGGGTGGAGGCCGAGGACGCCGCCACCTACTACTGCCAGCAGTGGACCAGCAACCCCCCCACCTTCGGCGGCGGCACCAAGCTGGAGATCAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 142 SI-54E1 and SI-54E3 chain B aa QIVLSQ SPAILSASPG EKVTMTC RASSSVSYIH WFQQKPGSSPKPWIY ATSNLAS GVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 143 SI-54E3 chain A nt >SEQ ID 144 SI-54E3 chain A aa >SEQ ID 145 SI-55E1 chain A nt >SEQ ID 146 SI-55E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 147 SI-55E1 and SI-55E8 chain B nt GACATCTTGCTGACTCAGTCTCCAGTCATCCTGTCTGTGAGTCCAGGAGAAAGAGTCAGTTTCTCCTGCAGGGCCAGTCAGAGTATTGGCACAAACATACACTGGTATCAGCAAAGAACAAATGGTTCTCCAAGGCTTCTCATAAAGTATGCTTCTGAGTCTATCTCTGGGATTCCTTCCAGGTTTAGTGGCAGTGGATCAGGGACAGATTTTACTCTTAGCATCAACAGTGTGGAGTCTGAAGATATTGCAGATTATTACTGTCAACAAAATAATAACTGGCCAACCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 148 SI-55E1 and SI-55E8 chain B aa DILLTQSPVILSVSPGERVSFSC RASQSIGTNIH WYQQRTNGSPRLLIK YES GIPSRFSGSGSGTDFTLSINSVESEDIADYYC QQNNNWPTT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 149 SI-55E8 chain A nt >SEQ ID 150 SI-55E8 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 151 SI-55E2 chain A nt >SEQ ID 152 SI-55E2 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 153 SI-55E2 and SI-55E9 chain B nt GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCGGAGGGACCAAGGTGGAAATTAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 154 SI-55E2 and SI-55E9 chain B aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 155 SI-55E9 chain A nt >SEQ ID 156 SI-55E9 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 157 SI-55E3 chain A nt >SEQ ID 158 SI-55E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFT NYYYYY WVRQAPGQGLEWIG GINPTSGGSNFNEKFKT RVTITADESSTTAYMELSSLRSEDTAFYFCTR QGLWFDSDGRGFDF WGQGTTVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 159 SI-55E3 and SI-55E10 chain B nt GATATTCAAATGACTCAATCTCCTTCTTCTCTTTCTGCTTCTGTTGGTGATCGTGTTACTATTACTTGTCGTTCTTCTCAAAATATTGTTCATTCTAATGGTAATACTTATCTTGATTGGTATCAACAAACTCCTGGTAAAGCTCCTAAACTTCTTATTTATAAAGTTTCTAATCGTTTTTCTGGTGTTCCTTCTCGTTTTTCTGGTTCTGGTTCTGGTACTGATTTTACTTTTACTATTTCTTCTCTTCAACCTGAAGATATTGCTACTTATTATTGTTTTCAATATTCTCATGTTCCTTGGACTTTTGGTCAAGGTACTAAACTTCAAATTACTCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 160 SI-55E3 and SI-55E10 chain B aa DIQMTQSPSSLSASVGDRVTITC RSSQNIVHSNGNTYLD WYQQTPGKAPKLLIY KVSNRFS GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC FQYSHVPWT FGQGTKLQITRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 161 SI-55E10 chain A nt >SEQ ID 162 SI-55E10 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFT NYYIY WVRQAPGQGLEWIG GINPTSGGSNFNEKFKT RVTITADESSTTAYMELSSLRSEDTAFYFCTR QGLWFDSDSDGRGFDF WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 163 SI-56E1 chain A nt >SEQ ID 164 SI-56E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVQSGAEVKKPGASVKVSCKASGYRFT NYWIH WVRQAPGQGLEWIG GINPGNNYATYRRKFQG RVTMTADTSTSTVYMELSSLRSEDTAVYYCTR EGYGNYGAWFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 165 SI-56E1 and SI-56E3 chain B nt GACGTTCAAGTGACCCAGAGCCCATCCAGCCTGAGCGCATCTGTAGGAGACCGGGTCACCATCACTTGTAGATCCAGTCAGAGTCTTGCAAACAGTTATGGGAACACCTTTTTGTCTTGGTATCTGCACAAACCAGGTAAAGCCCCACAATTGCTCATCTACGGAATCTCTAACAGATTTAGTGGTGTACCAGACAGGTTCAGCGGTTCCGGAAGTGGTACTGATTTCACCCTCACGATCTCGTCTCTCCAGCCAGAAGATTTCGCCACTTATTACTGTTTACAAGGTACACATCAGCCGTACACATTCGGTCAGGGTACTAAAGTAGAAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 166 SI-56E1 and SI-56E3 chain B aa DVQVTQSPSSLSASVGDRVTITC RSSQSLANSYGNTFLS WYLHKPGKAPQLLIY GISNRFS GVPDRFSGSGSGTDFTLTISS LQPEDFATYYCLQGTHQPYT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 167 SI-56E3 chain A nt >SEQ ID 168 SI-56E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVQSGAEVKKPGASVKVSCKASGYRFT NYWIH WVRQAPGQGLEWIG GINPGNNYATYRRKFQG RVTMTADTSTSTVYMELSSLRSEDTAVYYCTR EGYGNYGAWFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 169 SI-57E1 chain A nt >SEQ ID 170 SI-57E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQIQLQQSGPEVVKPGASVKISCKASGYTFT DYYIT WVKQKPGQGLE WIGWIYPGSGNTKYNEKFKG KATLTVDTSSSTAFMQLSSLTSEDTAVYFCAN YGNYWFAY WGQGTQVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 171 SI-57E1 and SI-57E3 chain B nt GACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCATCTCCTGCAAGGCCAGCCAAAGTGTTGATTTTGATGGTGATAGTTATATGAACTGGTACCAACAGAAACCAGGACAGCCACCCAAAGTCCTCATCTATGCTGCATCCAATCTAGAATCTGGGATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACAGACTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATTACTGTCAGCAAAGTAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 172 SI-57E1 and SI-57E3 chain B aa DIVLTQSPASLAVSLGQRATISC KASQSVDFDGDSYM NWYQQKPGQPPKVLIY AASNLES GIPARFSGSGSGTDFTLNIHPVEEEDAATYYC QQSNEDPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 173 SI-57E3 chain A nt >SEQ ID 174 SI-57E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQIQLQQSGPEVVKPGASVKISCKASGYTFT DYYIT WVKQKPGQGLE WIGWIYPGSGNTKYNEKFKG KATLTVDTSSSTAFMQLSSLTSEDTAVYFCAN YGNYWFAY WGQGTQVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 175 SI-1H1 chain A nt >SEQ ID 176 SI-1H1 chain A aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 177 SI-1H1 chain B nt >SEQ ID 178 SI-1H1 chain B aa QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGS SSTHVI FGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKGLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLS TSGMGVG WIRQPPGKGLEWLA HIWWDDDKRYNPALKS RLTISKDTSKNQVYLQMNSLDAEDTAVYYCAR MELWSYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIK >SEQ ID 183 SI-49R19 chain A nt >SEQ ID 184 SI-49R19 chain A aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >SEQ ID 185 SI-49R19 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 186 SI-49R19 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 187 SI-49R18 chain A nt >SEQ ID 188 SI-49R18 chain A aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >SEQ ID 189 SI-49R18 chain B nt >SEQ ID 190 SI-49R18 chain B aa ENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 191 SI-49E15 chain A nt >SEQ ID 192 SI-49E15 chain A aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 193 SI-49E15 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 194 SI-49E15 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 195 SI-49R21 chain A nt >SEQ ID 196 SI-49R21 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 197 SI-49R21 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 198 SI-49R21 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 199 SI-49R22 chain A nt >SEQ ID 200 SI-49R22 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 201 SI-49R22 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 202 SI-49R22 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 203 SI-49R22 chain C nt >SEQ ID 204 SI-49R22 chain C aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 205 SI-49R23 chain A nt >SEQ ID 206 SI-49R23 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 207 SI-49R24 chain A nt >SEQ ID 208 SI-49R24 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 209 SI-49R24 chain B nt >SEQ ID 210 SI-49R24 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 217 anti-claudin zolbetuximab VH nt CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTGGTGAGGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATAAACTGGGTGAAGCAGAGGCCTGGACAAGGCCTTGAGTGGATCGGAAATATTTATCCTTCTGATAGTTATACTAACTACAATCAAAAGTTCAAGGACAAGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAGCAGCCCGACATCTGAGGACTCTGCGGTCTATTACTGTACAAGATCGTGGAGGGGTAACTCCTTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA >SEQ ID 218 anti-claudin zolbetuximab VH aa QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWINWVKQRPGQGLEWIGNIYPSDSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRSWRGNSFDYWGQGTTLTVSS >SEQ ID 219 anti-claudin zolbetuximab VL nt GACATTGTGATGACACAGTCTCCATCCTCCCTGACTGTGACAGCAGGAGAGAAGGTCACTATGAGCTGCAAGTCCAGTCAGAGTCTGTTAAACAGTGGAAATCAAAAGAACTACTTGACCTGGTACCAGCAGAAACCAGGGCAGCCTCCTAAACTGTTGATCTACTGGGCATCCACTAGGGAATCTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGTGCAGGCTGAAGACCTGGCAGTTTATTACTGTCAGAATGATTATAGTTATCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAA >SEQ ID 220 anti-claudin zolbetuximab VL aa DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSYPFTFGSGTKLEIK >SEQ ID 221 anti-HER2 trastuzumab VH nt GAGGTTCAGCTGGTGGAGTCTGGCGGTGGCCTGGTGCAGCCAGGGGGCTCACTCCGTTTGTCCTGTGCAGCTTCTGGCTTCAACATTAAAGACACCTATATACACTGGGTGCGTCAGGCCCCGGGTAAGGGCCTGGAATGGGTTGCAAGGATTTATCCTACGAATGGTTATACTAGATATGCCGATAGCGTCAAGGGCCGTTTCACTATAAGCGCAGACACATCCAAAAACACAGCCTACCTGCAGATGAACAGCCTGCGTGCTGAGGACACTGCCGTCTATTATTGTTCTAGATGGGGAGGGGACGGCTTCTATGCTATGGACTACTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCG >SEQ ID 222 anti-HER2 trastuzumab VH aa EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS >SEQ ID 223 anti-HER2 trastuzumab VL nt GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGATAGGGTCACCATCACCTGCCGTGCCAGTCAGGATGTGAATACTGCTGTAGCCTGGTATCAACAGAAACCAGGAAAAGCTCCGAAACTACTGATTTACTCGGCATCCTTCCTCTACTCTGGAGTCCCTTCTCGCTTCTCTGGCTCCAGATCTGGGACGGATTTCACTCTGACCATCAGCAGTCTGCAGCCGGAAGACTTCGCAACTTATTACTGTCAGCAACATTATACTACTCCTCCCACGTTCGGACAGGGTACCAAGGTGGAGATCAAA >SEQ ID 224 anti-HER2 trastuzumab VL aa DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >SEQ ID 225 anti-HER2 pertuzumab VH nt GAAGTGCAGCTCGTCGAAAGCGGTGGCGGACTGGTTCAGCCCGGTGGTTCTCTGCGGCTGTCTTGTGCTGCCTCGGGTTTCACGTTCACTGACTACACAATGGACTGGGTGCGTCAGGCTCCTGGAAAGGGATTGGAGTGGGTAGCCGACGTTAATCCAAACTCCGGCGGGAGCATCTACAACCAGAGGTTCAAGGGGAGGTTCACTCTGAGCGTGGATCGCTCCAAGAACACGCTGTACCTCCAGATGAACTCTCTCAGGGCCGAGGACACGGCTGTTTACTATTGCGCGAGGAACCTGGGTCCTTCCTTCTACTTCGACTACTGGGGACAGGGAACCCTGGTGACCGTCAGCTCC >SEQ ID 226 anti-HER2 pertuzumab VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSS >SEQ ID 227 anti-HER2 pertuzumab VL nt GACATCCAGATGACACAATCTCCTAGCAGTCTGAGCGCAAGTGTTGGAGATCGTGTCACCATCACATGCAAGGCCAGCCAGGATGTGAGCATTGGAGTCGCCTGGTATCAGCAGAAACCCGGCAAGGCACCCAAGCTGCTGATCTACTCGGCCAGTTACAGATACACTGGCGTACCTTCGAGGTTTAGTGGTAGCGGTTCTGGAACCGATTTCACCCTCACCATTAGCTCCCTCCAACCCGAGGACTTCGCCACCTACTACTGCCAGCAATACTACATCTACCCTTACACGTTCGGCCAAGGCACTAAGGTCGAGATTAAA >SEQ ID 228 anti-HER2 pertuzumab VL aa DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKVEIK >SEQ ID 229 anti-mesothelin amatuximab VH nt CAGGTACAACTGCAGCAGTCTGGGCCTGAGCTGGAGAAGCCTGGCGCTTCAGTGAAGATATCCTGCAAGGCTTCTGGTTACTCATTCACTGGCTACACCATGAACTGGGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGACTTATTACTCCTTACAATGGTGCTTCTAGCTACAACCAGAAGTTCAGGGGCAAGGCCACATTAACTGTAGACAAGTCATCCAGCACAGCCTACATGGACCTCCTCAGTCTGACATCTGAAGACTCTGCAGTCTATTTCTGTGCAAGGGGGGGTTACGACGGGAGGGGTTTTGACTACTGGGGATCTGGGACCCCGGTCACCGTCTCCTCA >SEQ ID 230 anti-mesothelin amatuximab VH aa QVQLQQSGPELEKPGASVKISCKASGYSFTGYTMNWVKQSHGKSLEWIGLITPYNGASSYNQKFRGKATLTVDKSSSTAYMDLLSLTSEDSAVYFCARGGYDGRGFDYWGSGTPVTVSS >SEQ ID 231 anti-mesothelin amatuximab VL nt GACATCGAGCTCACTCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGGAGAAGGTCACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTTACATGCACTGGTACCAGCAGAAGTCAGGCACCTCCCCCAAAAGATGGATTTATGACACATCCAAACTGGCTTCTGGAGTCCCAGGTCGCTTCAGTGGCAGTGGGTCTGGAAACTCTTACTCTCTCACAATCAGCAGCGTGGAGGCTGAAGATGATGCAACTTATTACTGCCAGCAGTGGAGTAAGCACCCTCTCACGTTCGGATCCGGGACCAAGGTGGAAATCAAA >SEQ ID 232 anti-mesothelin amatuximab VL aa DIELTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASGVPGRFSGSGSGNSYSLTISSVEAEDDATYYCQQWSKHPLTFGSGTKVEIK >SEQ ID 233 anti-GD2 dinutuximab VH nt GAGGTCCAACTGCTGCAGTCTGGACCTGAGCTGGAGAAGCCTGGCGCTTCAGTGATGATATCCTGCAAGGCTTCTGGTTCCTCATTCACTGGCTACAACATGAACTGGGTGAGGCAGAACATTGGAAAGAGCCTTGAATGGATTGGAGCTATTGATCCTTACTATGGTG GAACTAGCTACAACCAGAAGTTCAAGGGCAGGGCCACATTGACTGTAGACAAATCGTCCAGCAGCCTACATGCACCTCAAGAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGTAAGCGGAATGGAGTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCCA >SEQ ID 234 anti-GD2 dinutuximab VH aa EVQLLQSGPELEKPGASSVMISCKASGSSFTGYNMNWVRQNIGKSLEWIGAIDPYYGGTSYNQKFKGRATLTVDKSSSTAYMHLKSLTSEDSAVYYCVSGMEYWGQGTSVTVSS >SEQ ID 235 anti-GD2 dinutuximab VL nt GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTGTGTCTCCAGGGGAAAGCCACCCTCTCCTGCAGATCTAGTCAGAGTCTTGTACACCGTAATGGAAACACCTATTTATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATTCACAAAGTTT CCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATCTGTTCTCAAAGTACACATGTTCCTCCGCTCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAA >SEQ ID 236 anti-GD2 dinutuximab VL aa EIVMTQSPATLSVSPGERATLSCRSSQSLVHRNGNTYLHWYLQKPGQSPKLLIHKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPPLTFGAGTKLELK >SEQ ID 237 anti-CD20 rituximab VH nt CAGGGTGCAGCTGCAGCAGCCCGGCGCCGAGCTGGTGAAGCCCGGCGCCAGCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACAACATGCACTGGGTGAAGCAGACCCCCGGCCGGGGCCTGGAGTGGATCGGGCCATCTACCCCGGCAACGGCGACACCAGCTACA ACCAGAAGTTCAAGGGCAAGGCCACCCTGACCGCCGACAAGAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACCAGCGAGGACAGCGCCGTGTACTACTGCGCCCGGGAGCACCTACTACGGCGGCGACTGGTACTTCAACGTGTGGGGCGCCGGCACCACCGTGACCGTGAGCGCC >SEQ ID 238 anti-CD20 rituximab VH aa QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSA >SEQ ID 239 anti-CD20 rituximab VL nt CAGATCGTGCTGAGCCAGAGCCCCGCCATCCTGAGCGCCAGCCCCGGCGAGAAGGTGACCATGACCTGCCGGGCCAGCAGCAGCGTGAGCTACATCCACTGGTTCCAGCAGAAGCCCGGCAGCAGCCCCAAGCCCTGGATCTACGCCACCAGCAACCTGGCCAGCGGCGTGCCCGTGCGGTTCAGCGGCAGCGGCAGCGGCACCAGCTACAGCCTGACCATCAGCCGGGTGGAGGCCGAGGACGCCGCCACCTACTACTGCCAGCAGTGGACCAGCAACCCCCCCACCTTCGGCGGCGGCACCAAGCTGGAGATCAAG >SEQ ID 240 anti-CD20 rituximab VL aa QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIK >SEQ ID 241 anti-EGFR cetuximab VH nt CAGGTGCAGCTGAAGCAGTCAGGACCTGGCCTAGTGCAGCCCTCACAGAGCCTGTCCATCACCTGCACAGTCTCTGGTTTCTCATTAACTAACTATGGTGTACACTGGGTTCGCCAGTCTCCAGGAAAGGGTCTGGAGTGGCTGGGAGTGATATGGAGTGGTGGAAACACAGACTATAATACACCTTTCACATCCAGACTGAGCATCAACAAGGACAATTCCAAGAGCCAAGTTTTCTTTAAAATGAACAGTCTGCAATCTAATGACACAGCCATATATTACTGTGCCAGAGCCCTCACCTACTATGATTACGAGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTAGC >SEQ ID 242 anti-EGFR cetuximab VH aa QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSS >SEQ ID 243 anti-EGFR cetuximab VL nt GACATCTTGCTGACTCAGTCTCCAGTCATCCTGTCTGTGAGTCCAGGAGAAAGAGTCAGTTTCTCCTGCAGGGCCAGTCAGAGTATTGGCACAAACATACACTGGTATCAGCAAAGAACAAATGGTTCTCCAAGGCTTCTCATAAAGTATGCTTCTGAGTCTATCTCTGGGATTCCTTCCAGGTTTAGTGGCAGTGGATCAGGGACAGATTTTACTCTTAGCATCAACAGTGTGGAGTCTGAAGATATTGCAGATTATTACTGTCAACAAAATAATAACTGGCCAACCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAA >SEQ ID 244 anti-EGFR cetuximab VL aa DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK >SEQ ID 245 anti-EGFR panitumumab VH nt CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCGTCAGCAGTGGTGATTACTACTGGACCTGGATCCGGCAGTCCCCAGGGAAGGGACTGGAGTGGATTGGACACATCTATTACAGTGGGAACACCAATTATAACCCCTCCCTCAAGAGCCGACTCACCATATCAATTGACACGTCCAAGACTCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGCTGCGGACACGGCCATTTATTACTGTGTGCGAGATCGAGTGACTGGTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCGAGC >SEQ ID 246 anti-EGFR panitumumab VH aa QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSS >SEQ ID 247 anti-EGFR panitumumab VL nt GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCGGAGGGACCAAGGTGGAAATTAAA >SEQ ID 248 anti-EGFR panitumumab VL aa DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKVEIK SEQ ID 249 anti-EGFR nimotuzumab VH nt CAGGGTGCAGCTGCAGCAGAGCGGCGCCGAGGTGAAGAAGCCCGGCAGCAGCGTGAAGGTGAGCTGCAAGGCCAGCGGCTACACCTTCACCAACTACATCTACTGGGTGCGGCAGGCCCCGGCAGGGCCTGGAGTGGATCGGCGCATCAACCCCACCAGCGGCGGCAGCAACTTCAACG AGAAGTTCAAGACCCGGGTGACCATCACCGCCGACGAGAGCAGCACCACCGCCTACATGGAGCTGAGCAGCCTGCGGAGCGAGGACACCGCCTTCTACTTCTGCACCCGGCAGGGCCTGTGGTTCGACAGCGACGGCCGGGGCTTCGACTTCTGGGGCCAGGGCACCACCGTGACCGTGAGCAGC >SEQ ID 250 anti-EGFR nimotuzumab VH aa QVQLQQSGAEVKKPGSSVKVSCKASGYTFTNYYIYWVRQAPGQGLEWIGGINPTSGGSNFNEKFKTRVTITADESSTTAYMELSSLRSEDTAFYFCTRQGLWFDSDGRGFDFWGQGTTVTVSS SEQ ID 251 anti-EGFR nimotuzumab VL nt GATATTCAAATGACTCAATCTCCTTCTTCTCTTTCTGCTTCTGTTGGTGATCGTGTTACTATTACTTGTCGTTCTTCTCAAAATATTGTTCATTCTAATGGTAATACTTATCTTGATTGGTATCAACAAACTCCTGGTAAAGCTCCTAAACTTCTTATTTATAAAGTTTCTAATCGTTTTTCTGGTGTTCCTTCTCGTTTTTCTGGTTCTGGTTCTGGTACTGATTTTACTTTTACTATTTCTTCTCTTCAACCTGAAGATATTGCTACTTATTATTGTTTTCAATATTCTCATGTTCCTTGGACTTTTGGTCAAGGTACTAAACTTCAAATTACT >SEQ ID 252 anti-EGFR nimotuzumab VL aa DIQMTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPGKAPKLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQYSHVPWTFGQGTKLQIT >SEQ ID 253 anti-CD22 inotuzumab VH nt GAGGTGCAATTGGTCCAGTCAGGAGCAGAGGTTAAGAAGCCTGGTGCTTCCGTCAAAGTTTCGTGTAAGGCCAGCGGCTACAGGTTCACAAATTATTGGATTCATTGGGTCAGGCAGGCTCCGGGACAAGGCCTGGAATGGATCGGTGGCATTAATCCCGGGAATAACTACGCTACATATAGGAGAAAATTCCAGGGCAGAGTTACGATGACCGCGGACACCTCCACAAGCACTGTCTACATGGAGCTGTCATCTCTGAGATCCGAGGACACCGCAGTGTACTATTGTACTAGAGAAGGCTACGGTAATTACGGAGCCTGGTTCGCCTACTGGGGCCAGGGTACCCTAGTCACAGTCTCCTCA >SEQ ID 254 anti-CD22 inotuzumab VH aa EVQLVQSGAEVKKPGASVKVSCKASGYRFTNYWIHWVRQAPGQGLEWIGGINPGNNYATYRRKFQGRVTMTADTSTSTVYMELSSLRSEDTAVYYCTREGYGNYGAWFAYWGQGTLVTVSS >SEQ ID 255 anti-CD22 inotuzumab VL nt GACGTTCAAGTGACCCAGAGCCCATCCAGCCTGAGCGCATCTGTAGGAGACCGGGTCACCATCACTTGTAGATCCAGTCAGAGTCTTGCAAACAGTTATGGGAACACCTTTTTGTCTTGGTATCTGCACAAACCAGGTAAAGCCCCACAATTGCTCATCTACGGAATCTCTAACAGATTTAGTGGTGTACCAGACAGGTTCAGCGGTTCCGGAAGTGGTACTGATTTCACCCTCACGATCTCGTCTCTCCAGCCAGAAGATTTCGCCACTTATTACTGTTTACAAGGTACACATCAGCCGTACACATTCGGTCAGGGTACTAAAGTAGAAATCAAA >SEQ ID 256 anti-CD22 inotuzumab VL aa DVQVTQSPSSLSASVGDRVTITCRSSQSLANSYGNTFLSWYLHKPGKAPQLLIYGISNRFSGVPDRFSGSGSGTDFTLTISSLQPEDFATYYCLQGTHQPYTFGQGTKVEIK >SEQ ID 257 anti-CD30 brentuximab VH nt CAGATCCAGCTGCAGCAGTCTGGACCTGAGGTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCTGCAAGGCTTCTGGCTACACCTTCACTGACTACTATATAACCTGGGTGAAGCAGAAGCCTGGACAGGGACTTGAGTGGATTGGATGGATTTATCCTGGAAGCGGTAATACTAAGTACAATGAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACACATCCTCCAGCACAGCCTTCATGCAGCTCAGCAGCCTGACATCTGAGGACACTGCTGTCTATTTCTGTGCGAACTATGGTAACTACTGGTTTGCTTACTGGGGCCAAGGGACTCAGGTCACTGTCTCTGCA >SEQ ID 258 anti-CD30 brentuximab VH aa QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWIYPGSGNTKYNEKFKGKATLTVDTSSSTAFMQLSSLTSEDTAVYFCANYGNYWFAYWGQGTQVTVSA >SEQ ID 259 anti-CD30 brentuximab VL nt GACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCATCTCCTGCAAGGCCAGCCAAAGTGTTGATTTTGATGGTGATAGTTATATGAACTGGTACCAACAGAAACCAGGACAGCCACCCAAAGTCCTCATCTATGCTGCATCCAATCTAGAATCTGGGATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACAGACTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATTACTGTCAGCAAAGTAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA >SEQ ID 260 anti-CD30 brentuximab VL aa DIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSYMNWYQQKPGQPPKVLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK >SEQ ID 261 anti-HER3 MM-111 VH nt CAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCGAGC >SEQ ID 262 anti-HER3 MM-111 VH aa QVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 263 anti-HER3 MM-111 VL nt CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTCTCCGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCGGAGGGACCAAGGTGACCGTCCTA >SEQ ID 264 anti-HER3 MM-111 VL aa QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVL >SEQ ID 265 anti-EGFRvIII ABT-806 VH nt GATGTGCAGCTTCAGGAGTCGGGACCTAGCCTGGTGAAACCTTCTCAGTCTCTGTCCCTCACCTGCACTGTCACTGGCTACTCAATCACCAGTGATTTTGCCTGGAACTGGATTCGGCAGTTTCCAGGAAACAAGCTGGAGTGGATGGGCTACATAAGTTATAGTGGTAACACTAGGTACAACCCATCTCTCAAAAGTCGAATCTCTATCACTCGCGACACATCCAAGAACCAATTCTTCCTGCAGTTGAACTCTGTGACTATTGAGGACACAGCCACATATTACTGTGTAACGGCGGGACGCGGGTTTCCTTATTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA >SEQ ID 266 anti-EGFRvIII ABT-806 VH aa DVQLQESGPSLVKPSQSLSLTCTVTGYSITSDFAWNWIRQFPGNKLEWMGYISYSGNTRYNPSLKSRISITRDTSKNQFFLQLNSVTIEDTATYYCVTAGRGFPYWGQGTLVTVSA >SEQ ID 267 anti-EGFRvIII ABT-806 VL nt GACATCCTGATGACCCAATCTCCATCCTCCATGTCTGTATCTCTGGGAGACACAGTCAGCATCACTTGCCATTCAAGTCAGGACATTAACAGTAATATAGGGTGGTTGCAGCAGAGACCAGGGAAATCATTTAAGGGCCTGATCTATCATGGAACCAACTTGGACGATGAAGTTCCATCAAGGTTCAGTGGCAGTGGATCTGGAGCCGATTATTCTCTCACCATCAGCAGCCTGGAATCTGAAGATTTTGCAGACTATTACTGTGTACAGTATGCTCAGTTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA >SEQ ID 268 anti-EGFRvIII ABT-806 VL aa DILMTQSPSSMSVSLGDTVSITCHSSQDINSNIGWLQQRPGKSFKGLIYHGTNLDDEVPSRFSGSGSGADYSLTISSLESEDFADYYCVQYAQFPWTFGGGTKLEIK >SEQ ID 269 anti-CD19 21D4 VH nt GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAGAAACCAGGAGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTAGCAGTTCATGGATCGGCTGGGTGCGCCAGGCACCTGGGAAAGGCCTGGAATGGATGGGGATCATCTATCCTGATGACTCTGATACCAGATACAGTCCATCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGGACTGCCTACCTGCAGTGGAGTAGCCTGAAGGCCTCGGACACCGCTATGTATTACTGTGCGAGACATGTTACTATGATTTGGGGAGTTATTATTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA >SEQ ID 270 anti-CD19 21D4 VH aa EVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQAPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSS >SEQ ID 271 anti-CD19 21D4 VL nt GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTTTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAA >SEQ ID 272 anti-CD19 21D4 VL aa AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIK >SEQ ID 273 anti-CD33 gemtuzumab VH nt GAGGTCCAATTGGTACAATCCGGCGCTGAGGTTAAGAAACCGGGTTCCTCAGTCAAAGTTAGTTGTAAGGCATCAGGTTACACGATCACTGATAGTAACATACATTGGGTGAGACAGGCTCCTGGGCAGTCCCTTGAGTGGATTGGATACATTTATCCATATAATGGCGGCACGGATTACAACCAGAAATTTAAGAATAGAGCGACACTGACCGTTGACAACCCCACCAATACCGCGTATATGGAATTGTCAAGCCTGAGGTCTGAGGACACGGCCTTCTACTATTGCGTAAACGGTAACCCGTGGCTGGCCTACTGGGGGCAGGGGACACTCGTAACCGTCTCTTCT >SEQ ID 274 anti-CD33 gemtuzumab VH aa EVQLVQSGAEVKKPGSSVKVSCKASGYTITDSNIHWVRQAPGQSLEWIGYIYPYNGGTDYNQKFKNRATLTVDNPTNTAYMELSSLRSEDTAFYYCVNGNPWLAYWGQGTLVTVSS >SEQ ID 275 anti-CD33 gemtuzumab VL nt GATATACAACTTACGCAGTCTCCCTCCACTCTGTCAGCGTCCGTAGGGGACAGAGTAACGATAACATGCAGGGCCTCAGAAAGTCTTGACAACTACGGCATAAGGTTCCTCACATGGTTTCAACAGAAGCCGGGTAAAGCACCAAAACTCCTGATGTATGCTGCGTCTAACCAGGGGTCCGGTGTTCCTAGTCGGTTTTCAGGCAGCGGTAGCGGTACCGAGTTCACTCTCACAATTTCCAGTCTTCAGCCTGACGATTTCGCAACGTATTATTGCCAACAAACTAAGGAAGTGCCTTGGAGCTTTGGGCAAGGCACCAAGGTCGAGGTGAAG >SEQ ID 276 anti-CD33 gemtuzumab VL aa DIQLTQSPSTLSASVGDRVTITCRASESLDNYGIRFLTWFQQKPGKAPKLLMYAASNQGSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQTKEVPWSFGQGTKVEVK >SEQ ID 277 anti-CD3 284A10 VH nt GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGTCATTACTGGTCGTGATATCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGTGGTTCTTCTGCTATTACTAGTAACAACATTTGGGGCCAGGGAACCCTGGTCACCGTGTCGACA >SEQ ID 278 anti-CD3 284A10 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVST >SEQ ID 279 anti-CD3 284A10 VL nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >SEQ ID 280 anti-CD3 284A10 VL aa DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIK >SEQ ID 281 anti-PD-L1 PL221G5 VH nt GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC >SEQ ID 282 anti-PD-L1 PL221G5 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSS >SEQ ID 283 anti-PD-L1 PL221G5 VL nt GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >SEQ ID 284 anti-PD-L1 PL221G5 VL aa DIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIK >SEQ ID 285 anti-4-1BB 466F6 VH nt CGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGTGGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCA >SEQ ID 286 anti-4-1BB 466F6 VH aa RSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >SEQ ID 287 anti-4-1BB 466F6 VL nt GACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >SEQ ID 288 anti-4-1BB 466F6 VL aa DVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK >SEQ ID 289 anti-CD19 SI-BU12 VH nt CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGCCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT >SEQ ID 290 anti-CD19 SI-BU12 VH aa QVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS >SEQ ID 291 anti-CD19 SI-BU12 VL nt GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTGACCGTCCTA >SEQ ID 292 anti-CD19 SI-BU12 VL aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVL >SEQ ID 293 NKG2D nt TTTCTTAATTCCCTTTTCAACCAAGAGGTTCAGATCCCCTTGACTGAAAGCTATTGCGGCCCTTGTCCGAAAAACTGGATATGTTACAAGAATAATTGTTACCAATTCTTCGACGAAAGCAAGAACTGGTATGAGAGTCAGGCGTCTTGTATGAGTCAGAATGCCAGCCTGCTTAAGGTTTATTCAAAAGAAGACCAGGATCTGCTTAAGTTGGTAAAGAGCTACCACTGGATGGGGCTGGTACATATCCCAACGAATGGGTCATGGCAGTGGGAGGACGGTTCTATTCTGAGTCCAAATCTCCTGACGATCATCGAAATGCAGAAAGGGGACTGTGCCCTGTATGCATCATCCTTCAAGGGGTACATCGAGAACTGCAGTACCCCAAATACCTACATTTGTATGCAAAGAACGGTT >SEQ ID 294 NKG2D aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 295 4-1BB ligand nt >SEQ ID 296 4-1BB ligand aa REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >SEQ ID 301 SI-55P9 chain A nt >SEQ ID 302 SI-55P9 chain A aa >SEQ ID 303 SI-55P9 chain B nt >SEQ ID 304 SI-55P9 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 305 SI-55P10 chain A nt >SEQ ID 306 SI-55P10 chain A aa >SEQ ID 307 SI-55P10 chain B nt >SEQ ID 308 SI-55P10 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 309 NKG2D dimer nt TTTCTTAATTCCCTTTTCAACCAAGAGGTTCAGATCCCCTTGACTGAAAGCTATTGCGGCCCTTGTCCGAAAAACTGGATATGTTACAAGAATAATTGTTACCAATTCTTCGACGAAAGCAAGAACTGGTATGAGAGTCAGGCGTCTTGTATGAGTCAGAATGCCAGCCTGCTTAAGGTTTATTCAAAAGAAGACCAGGATCTGCTTAAGTTGGTAAAGAGCT ACCACTGGATGGGGCTGGTACATATCCCAACGAATGGGTCATGGCAGTGGGAGGACGGTTCTATTCTGAGTCCAAATCTCCTGACGATCATCGAAATGCAGAAAGGGGACTGTGCCCTGTATGCATCATCCTTCAAGGGGTACATCGAGAACTGCAGTACCCCAAATACCTACATTTGTATGCAAAGAACGGTTGGAGGCGGTGGCTCAGGCGGAGGCGGCTCA GGAGGTGGCGGTTCAGGAGGCGGCGGATCTTTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTG >SEQ ID 310 NKG2D dimer aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 311 anti-FITC 4-4-20 VH nt GAGGTGAAGCTGGATGAGACTGGAGGAGGCTTGGTGCAACCTGGGAGGCCCATGAAACTCTCCTGTGTTGCCTCTGGATTCACTTTTAGTGACTACTGGATGAACTGGGTCCGCCAGTCTCCAGAGAAAGGACTGGAGTGGGTAGCACAAATTAGAAACAAACCTTATAATTATGAAACATATTATTCAGATTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGTAGTGTCTACCTGCAAATGAACAACTTAAGAGTTGAAGACATGGGTATCTATTACTGTACGGGTTCTTACTATGGTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA >SEQ ID 312 anti-FITC 4-4-20 VH aa EVKLDETGGGLVQPGRPMKLSCVASGFTFSDYWMNWVRQSPEKGLEWVAQIRNKPYNYETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVEDMGIYYCTGSYYGMDYWGQGTSVTVSS >SEQ ID 313 anti-FITC 4-4-20 VL nt GATGTCGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTATTTACGTTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGGTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCTCTCAAAGTACACATGTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA >SEQ ID 314 anti-FITC 4-4-20 VL aa DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLRWYLQKPGQSPKVLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPWTFGGGTKLEIK >SEQ ID 315 anti-CD3 284A10 FR 1 VH nt GAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCTTCACCATCAGCACCAACGCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGGGCGTGATCACCGGCAGGGACATCACCTACTACGCCAGCTGGGCCAAGGGCAGGTTCACCATCAGCAGGGACACCAGCAAGAACACCGTGTACCTGCAGATGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGGGACGGCGGCAGCAGCGCCATCACCAGCAACAACATCTGGGGCCAGGGCACCCTGGTGACCGTGAGCAGC >SEQ ID 316 anti-CD3 284A10 FR 1 VH aa EVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSS >SEQ ID 317 anti-CD3 284A10 FR 1 VL nt GAGATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCAGCGTGGGCGACAGGGTGATCATCACCTGCCAGGCCAGCGAGAGCATCAGCAGCTGGCTGGCCTGGTACCAGCAGAAGCCCGGCAAGGCCCCCAAGCTGCTGATCTACGAGGCCAGCAAGCTGGCCAGCGGCGTGCCCAGCAGGTTCAGCGGCAGCGGCAGCGGCGCCGAGTTCACCCTGACCATCAGCAGCCTGCAGCCCGACGACTTCGCCACCTACTACTGCCAGGGCTACTTCTACTTCATCAGCAGGACCTACGTGAACAGCTTCGGCCAGGGCACCAAGCTGACCGTGCTG >SEQ ID 318 anti-CD3 284A10 FR 1 VL aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVL >SEQ ID 319 anti-EGFR H7 VH nt CAAGTACAGTTGCAGCAATCCGGTCCCGGTCTCGTCAAACCGAGTGAGACGCTTAGTATAACGTGTACTGTTTCAGGCTTTAGCCTTACGAACTATGGAGTTCACTGGATTCGGCAGGCACCCGGCAAAGGTTTGGAATGGCTGGGTGTTATTTGGTCAGGTGGAAATACAGACTATAACACCCCCTTTACAAGTCGGTTCACAATTACGAAAGATAATTCCAAAAATCAAGTTTATTTCAAGTTGAGATCCGTCCGCGCGGACGACACTGCGATCTACTATTGTGCGAGGGCACTGACCTACTACGATTACGAATTTGCGTATTGGGGGCAAGGGACTCTTGTAACAGTCTCGAGC >SEQ ID 320 anti-EGFR H7 VH aa QVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSS >SEQ ID 321 anti-EGFR H7 VL nt GAAATCGTCCTTACACAATCTCCTAGCACACTGAGTGTGAGCCCCGGCGAACGCGCGACTTTCTCTTGCAGGGCAAGTCAATCCATAGGGACTAATATACATTGGTATCAACAAAAGCCAGGTAAACCACCCAGGCTTTTGATTAAGTATGCAAGTGAGTCTATTTCCGGTATCCCTGACCGCTTCTCTGGATCAGGCAGTGGCACAGAGTTCACACTCACCATATCTAGTGTGCAATCAGAGGACTTCGCCGTGTATTACTGCCAACAGAATAATAACTGGCCGACTACCTTCGGACCCGGTACAAAGCTGACCGTTTTA >SEQ ID 322 anti-EGFR H7 VL aa EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVL >SEQ ID 323 SI-77H4 chain A nt >SEQ ID 324 SI-77H4 chain A aa >SEQ ID 325 SI-77H4 chain B nt >SEQ ID 326 SI-77H4 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGCGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 327 SI-77H5 chain A nt >SEQ ID 328 SI-77H5 chain A aa >SEQ ID 329 SI-77H5 chain B nt >SEQ ID 330 SI-77H5 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGCGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 331 SI-55H12 chain A nt >SEQ ID 332 SI-55H12 chain A aa >SEQ ID 333 SI-55H12 chain B nt >SEQ ID 334 SI-55H12 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS

Claims

1. It is a multispecific antibody protein, Having an N-terminus and a C-terminus, and in series from the N-terminus to the C-terminus, The first binding domain (D1) at the N-terminus has binding affinity to CD3. The second binding domain (D2) is a Fab region containing the heavy chain and light chain portions. Fc region, A third binding domain (D3) having binding affinity to PD-L1, and A fourth binding domain (D4) located at the C-terminus that has binding affinity to 4-1BB, Includes, D1, D3, and D4 are each scFv domains. D2 has binding affinity to tumor-associated antigens (TAAs), The aforementioned multispecific antibody protein is The amino acid sequences shown in SEQ ID NOs: 110 and 112, SEQ ID NOs: 112 and 114, SEQ ID NOs: 116 and 118, or SEQ ID NOs: 118 and 120, wherein D2 has binding affinity to HER2, or The amino acid sequence is represented by the sequence numbers 122 and 124, or the amino acid sequence is represented by the sequence numbers 124 and 126, wherein D2 has binding affinity to MSLN, or The amino acid sequence is represented by the sequence numbers 128 and 130, or the amino acid sequence is represented by the sequence numbers 130 and 132, wherein D2 has binding affinity to GD2, or The amino acid sequence is represented by the amino acid sequences shown in SEQ ID NOs: 134 and 136, or the amino acid sequences shown in SEQ ID NOs: 136 and 138, wherein D2 has binding affinity to claudin 18.2, or The amino acid sequence is represented by the sequence numbers 140 and 142, or the amino acid sequence is represented by the sequence numbers 142 and 144, wherein D2 has binding affinity to CD20, or The amino acid sequences shown in SEQ ID NOs: 146 and 148, 148 and 150, 152 and 154, 154 and 156, 158 and 160, or 160 and 162, wherein D2 has binding affinity to EGFR, or The amino acid sequence is represented by the sequence numbers 164 and 166, or the amino acid sequence is represented by the sequence numbers 166 and 168, wherein D2 has binding affinity to CD22, or The amino acid sequence is represented by the sequence numbers 170 and 172, or the amino acid sequence is represented by the sequence numbers 172 and 174, wherein D2 has binding affinity to CD30, or The amino acid sequences shown in SEQ ID NOs: 98 and 100 are present, and D2 has binding affinity to CD19, or A multispecific antibody protein comprising the amino acid sequences shown in SEQ ID NOs. 192 and 194, wherein D2 has binding affinity to NKG2D.

2. It is a multispecific antibody protein, Having an N-terminus and a C-terminus, and in series from the N-terminus to the C-terminus, The first binding domain (D1) at the N-terminus has binding affinity to CD3. The second binding domain (D2) is a Fab region containing the heavy chain and light chain portions. Fc region, A third binding domain (D3) having binding affinity to PD-L1, and A fourth binding domain (D4) located at the C-terminus that has binding affinity to 4-1BB, Includes, In D2, the fifth binding domain (D5) is covalently bonded to the C-terminus of the light chain portion, D1 is bonded to the N-terminus of the heavy chain portion, and the Fc region is bonded to the C-terminus of the heavy chain portion. D1, D3, D4, and D5 are each scFv domains. D2 and D5 each independently possess binding affinity to tumor-associated antigens (TAAs). The aforementioned multispecific antibody protein is The amino acid sequences include those shown in SEQ ID NOs: 34 and 36, SEQ ID NOs: 38 and 40, or SEQ ID NOs: 42 and 44, wherein D2 has binding affinity to EGFR and D5 has binding affinity to HER3, or The amino acid sequences shown in SEQ ID NOs. 46 and 48 are included, wherein D2 has binding affinity to EGFRvIII and D5 has binding affinity to HER3, or The amino acid sequence is represented by the amino acid sequences shown in SEQ ID NOs. 50 and 52, or the amino acid sequence is represented by SEQ ID NOs. 54 and 56, wherein D2 has binding affinity to CD20 and D5 has binding affinity to CD19, or The amino acid sequence is represented by the sequence numbers 58 and 60, wherein D2 has binding affinity to MESO and D5 has binding affinity to NKG2D ligand, or The amino acid sequences shown in SEQ ID NOs. 62 and 64 are present, wherein D2 has binding affinity to claudin 18.2, and D5 has binding affinity to NKG2D ligand, or The amino acid sequence includes the sequences shown in SEQ ID NOs. 66 and 68, wherein D2 has binding affinity to HER2 and D5 has binding affinity to NKG2D ligand, or The amino acid sequence includes the sequences shown in SEQ ID NOs. 70 and 72, wherein D2 has binding affinity to EGFRvIII and D5 has binding affinity to NKG2D ligand, or A multispecific antibody protein comprising the amino acid sequences shown in SEQ ID NOs. 74 and 76, wherein D2 has binding affinity to CD33 and D5 has binding affinity to NKG2D ligand.

3. An isolated nucleic acid encoding the amino acid sequence of a multispecific antibody protein according to claim 1 or 2.

4. An expression vector comprising the isolated nucleic acid described in claim 3.

5. A host cell comprising the isolated nucleic acid described in claim 3, The host cell is a host cell that is either a prokaryotic cell or a eukaryotic cell.

6. An immune complex comprising a cytotoxic agent or contrast agent conjugated to a multispecific antibody protein according to claim 1 or 2 via a linker, The linker comprises an ester bond, an ether bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphate ester bond, a peptide bond, a hydrophobic poly(ethylene glycol) linker, or a combination thereof, in an immunocomplex.

7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a multispecific antibody protein according to claim 1 or 2 and / or an immune complex according to claim 6.

8. A pharmaceutical composition for treating a subject suffering from cancer, autoimmune disease, or infectious disease, A pharmaceutical composition comprising an effective amount of the multispecific antibody protein described in claim 1 or 2 and / or the immune complex described in claim 6.

9. A solution comprising the multispecific antibody protein according to claim 1 or 2 in an effective concentration, The aforementioned solution is plasma.

Images