Miniature guidance and navigation control (miniGNC) antibody-like protein, method for producing the same, and method for using the same

Abstract

To provide antibodies having multi-binding activity to surface molecules of both immune cells and tumor cells.SOLUTION: Provided is a multi-binding specific antibody-like protein comprising a first monomer and a second monomer, where the first monomer comprises a first binding monomer, a first CH1 domain, a first hinge, a first CH2 domain and a first CH3 domain; the second monomer comprises a second binding monomer, a CL domain, a second hinge, a second CH2 domain and a second CH3 domain; where the first monomer and the second monomer are constituted to form a dimer, the first monomer and the second monomer form a pair through at least one disulfide bond between the CH1 domain and the CL domain and at least one disulfide bond between the first hinge and the second hinge, the first monomer and the second monomer comprise a first binding domain and a second binding domain, and also a fourth binding domain and a fifth binding domain, where the multi-specific antibody-like protein is at least bispecific.SELECTED DRAWING: Figure 1

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 technology of multispecific antibodies used in cancer immunotherapy, and more specifically, to the production and use of microguidance and navigation control (miniGNC) antibodies that have multibinding activity to surface molecules of both immune cells and tumor cells. [Background technology]

[0004] Therapeutic antibodies have become a cornerstone of the treatment of diseases such as cancer, infectious diseases, and autoimmune diseases. Monoclonal, single-specific antibodies offer direct mechanisms for treating diseases, for example, through the inhibition or activation of specific signaling pathways, while multispecific antibodies can offer more complex therapeutic mechanisms. By targeting multiple different antigens or multiple epitopes within a single antigen, biological responses such as cellular co-localization and activation are elicited. This makes it possible, for example, to redirect T cells or other immune cells to specific antigen-expressing tumor cell sites. Thus, bispecific and multispecific antibodies have become important platforms in the field of immuno-oncology.

[0005] The advantages of multispecific antibody platforms have led to the development of numerous such frameworks. One such platform is known as a guidance and navigation control (GNC). GNC proteins include proteins that link multiple functionally independent binding sites to form a single entity capable of binding to both effector and target cells (Applicant's applications WO / 2019 / 005641, WO2019191120 and PCT / US20 / 59230; the entirety of which is incorporated herein). Generally, these platforms are limited to at least two specificities, hindering the exploration of complex therapeutic mechanisms requiring binding to two or more antigens. Antibody platforms with two or more specificities typically require the formation of large molecules with undesirable physical and biological properties to increase the number of binding domains. Increased molecular weight can hinder development, as larger and more complex molecules are more likely to encounter aggregation and solubility problems. Furthermore, large macromolecules may have a reduced ability to penetrate solid tumors compared to smaller-sized proteins. Therefore, a multispecific antibody platform is needed that possesses three or more specificities, although not significantly larger than that of monoclonal IgG antibodies. [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 proteins having binding specificity (e.g., multispecific protein-like antibodies including multispecific antibodies), and fragments of these binding proteins (such as scFv domains, Fab regions, Fc domains, VH, VL, light chains, heavy chains, variable regions, and complementarity-determining regions (CDRs)). The present invention further provides methods for producing and using these antibody-like proteins.

[0008] In one embodiment, the present invention provides a multispecific antibody-like protein. In one embodiment, the multispecific antibody-like protein has an N-terminus and a C-terminus and comprises a first monomer and a second monomer. The first monomer comprises a first binding monomer, a CH1 domain, a first hinge, a first CH2 domain and a first CH3 domain from the N-terminus to the C-terminus. The first monomer may optionally include a first binding domain (D1) bound to the N-terminus and / or a fourth binding domain (D4) bound to the C-terminus. The second monomer comprises a second binding monomer, a CL domain, a second hinge, a second CH2 domain and a second CH3 domain from the N-terminus to the C-terminus. The second monomer may optionally include a second binding domain (D2) bound to the N-terminus and / or a fifth binding domain (D5) bound to the C-terminus. The first and second binding monomers are configured to form a dimer. The first and second monomers are covalently paired via at least one disulfide bond between the CH1 domain and the CL domain and at least one disulfide bond between the first hinge and the second hinge. The multispecific antibody-like protein is at least bispecific.

[0009] In one embodiment, the multispecific antibody-like protein may be triplicate, quadruplicate, or quinticate. In one embodiment, the multispecific antibody-like protein may be a monoclonal antibody. In one embodiment, the multispecific antibody-like protein may be a purified monoclonal antibody. In one embodiment, the multispecific antibody-like protein may be a humanized antibody.

[0010] In one embodiment, the multispecific antibody-like protein may further contain a disulfide bond between the first CH3 domain and the second CH3 domain.

[0011] In one embodiment, the multispecific antibody-like protein may further include a second disulfide bond between the first hinge and the second hinge.

[0012] In one embodiment, the linking linker is used between various domains. In one embodiment, the linking linker is (G x S y ) n A linker may be included, where n, x, and y are each an integer from 1 to 10. In one embodiment, D1, D2, D4, or D5 are linked to the N or C terminal via a linker. In one embodiment, the linker is (G x S y ) n A linker may be included. n, x, and y can each be an integer from 1 to 10 independently. In one embodiment, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. In one embodiment, x is 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. In one embodiment, y is 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.

[0013] In one embodiment, the first CH3 domain is configured to form a hole structure, and the second CH3 domain is configured to form a knob structure. The first CH2 domain and the first CH3 domain, and the second CH2 domain and the second CH3 domain are configured to heterodimerize to form complementary Fc domains.

[0014] In one embodiment, the first CH3 domain may contain at least one “hole” mutation in T366S, L368A, or Y407V, and the second CH3 domain may contain a “knob” mutation in T366W.

[0015] In one embodiment, the Fc domain may contain a mutation in H435R / Y436F.

[0016] In one embodiment, the Fc domain is engineered to eliminate an effector cell function selected from ADCC, ADCP, or CDC.

[0017] In one embodiment, the Fc domain may include at least one mutation at L234A, L235A, G237A, 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). In one embodiment, the Fc domain includes a null mutation. In one embodiment, the IgG4 Fc domain includes the mutation S228P (Eu numbering). In one embodiment, the IgG4 Fc domain includes the mutations S228P / F234A / L234A (Eu numbering).

[0018] In one embodiment, the heavy chain constant sequence may be derived from IgG1 or IgG4.

[0019] In one embodiment, the Fc domain may include an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% identity with SEQ ID NO: 313 or 314.

[0020] In one embodiment, the first binding monomer may include a VH domain, and the second binding monomer may include a VL domain. The VH, CH1, VL, and CL domains constitute the Fab region as the third binding domain (D3). In one embodiment, the Fab region may include a disulfide bond between VH-44C and VL 100C.

[0021] In one embodiment, the first binding monomer and the second binding monomer constitute the NKG2D receptor as the third binding domain (D3).

[0022] In one embodiment, D1, D2, D4, and D5 are each independently an scFv domain, a VHH domain, a receptor, or a ligand.

[0023] In one embodiment, the scFv domain may include a VH domain bound to a VL domain. In one embodiment, the scFv domain may have a VH-VL orientation. In one embodiment, the scFv domain may have a VL-VH orientation.

[0024] In one embodiment, the scFv domain may contain a disulfide bond between VL and VH. In one embodiment, the disulfide bond is located between VL100 and VH44 of the scFv domain. In one embodiment, the scFv domain may contain the mutation R19S in VH.

[0025] In one embodiment, the VHH domain may contain VH or the R19S mutation in VHH.

[0026] In one embodiment, at least one, two, or three of D1, D2, D4, and D5 may be scFv. In one embodiment, D1, D2, D4, and D5 may all be scFv.

[0027] In one embodiment, at least one, two, or three of D1, D2, D4, and D5 may be VHH domains. In one embodiment, D1, D2, D4, and D5 may all be VHH domains.

[0028] In one embodiment, at least one, two, or three of D1, D2, D4, and D5 may be receptors. In one embodiment, D1, D2, D4, and D5 may all be receptors.

[0029] In one embodiment, at least one, two, or three of D1, D2, D4, and D5 may be ligands. In one embodiment, D1, D2, D4, and D5 may all be ligands.

[0030] In one embodiment, D1, D2, D4, and D5 may each independently have binding specificity to antigens selected from T cell activating receptors, immune cell binding receptors, immune checkpoint molecules, costimulatory factors, leukocyte receptors, tumor antigens, tumor-associated antigens (TAAs), tissue cell receptors, cancer cell receptors, or combinations thereof.

[0031] In one embodiment, the binding domain of the T cell activating receptor is adjacent to the binding domain of the tumor-associated antigen (TAA).

[0032] In one embodiment, the T cell activating receptor may include CD3.

[0033] 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.

[0034] In one embodiment, the co-stimulatory receptor may include 4-1BB, CD28, OX40, GITR, CD40L, CD40, ICOS, LIGHT, CD27, CD30, or a combination thereof.

[0035] In one embodiment, tumor-associated antigens 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 combinations thereof.

[0036] In one embodiment, D1, D2, D3, D4, and D5 are independently 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, 4-1 It may have binding specificity to antigens selected from BB, GITR, TIGIT, TIM-3, LAG-3, 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, and SIRPα CD27. The Fc domain may include a human IgG Fc domain.

[0037] In one embodiment, D1 has binding specificity to CD3, CD20, CEA, HER2, EGFR, or NKG2D ligand. In one embodiment, D2 has binding specificity to HER3, EGFR, CD3, or CD19. In one embodiment, D3 has binding specificity to HER3, EGFR, CD3, or NKG2D ligand. In one embodiment, D4 has binding specificity to 4-1BB or EGFR. In one embodiment, D5 has binding specificity to PD-L1 or HER3.

[0038] In one embodiment, D1 has binding specificity to CD3, D2 has binding specificity to HER3, D3 has binding specificity to EGFR, D4 has binding specificity to 4-1BB, and D5 has binding specificity to PD-L1.

[0039] In one embodiment, D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, D4 has binding specificity to 4-1BB, and D5 has binding specificity to PD-L1.

[0040] In one embodiment, D1 has binding specificity to EGFR, D2 has binding specificity to CD3, D3 has binding specificity to HER3, D4 has binding specificity to 4-1BB, and D5 has binding specificity to PD-L1.

[0041] In one embodiment, D1 has binding specificity to CD3 or EGFR, D2 has binding specificity to CD19, D3 has binding specificity to CD3 or EGFR, D4 has binding specificity to 4-1BB, and D5 has binding specificity to PD-L1.

[0042] In one embodiment, D1 and D4 each have binding specificity to EGFR, D2 and D5 each have binding specificity to HER3, and D3 has binding specificity to CD3.

[0043] In one embodiment, D1 has binding specificity to CD20, D2 has binding specificity to CD19, D3 has binding specificity to CD3, D4 has binding specificity to 4-1BB, and D5 has binding specificity to PD-L1.

[0044] In one embodiment, D1 may have binding specificity to the NKG2D ligand, D2 may have binding specificity to CD19, D3 may have binding specificity to CD3, D4 may have binding specificity to 4-1BB, and D5 may have binding specificity to PD-L1.

[0045] In one embodiment, D1 has binding specificity to CD3, and D3 may include the NKG2D receptor. In one embodiment, the protein may further include D2 having binding specificity to CD19. In one embodiment, the protein may further include D5 having binding specificity to PD-L1. In one embodiment, the protein may further include D4 having binding specificity to 4-1BB.

[0046] In one embodiment, the multispecific antibody-like protein is bispecific. In one embodiment, D2 has binding specificity to HER3 and D3 has binding specificity to CD3. In one embodiment, D1 has binding specificity to HER2 and D3 has binding specificity to CD3. In one embodiment, D1 has binding specificity to EGFR and D3 has binding specificity to CD3. In one embodiment, D3 has binding specificity to CD3 and D5 has binding specificity to HER3. In one embodiment, D3 has binding specificity to CD3 and D4 has binding specificity to EGFR.

[0047] In one embodiment, the bispecific antibody-like protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% identity with SEQ ID NOs: 1 and 3, 5 and 7, 9 and 11, 13 and 15, 53 and 55, 57 and 59, 113 and 115, 117 and 119, 121 and 123, 125 and 127, 157 and 159, 297 and 299, or 199 and 201.

[0048] In one embodiment, the multispecific antibody-like protein is triplicate. In one embodiment, D1 has binding specificity to EGFR, D2 has binding specificity to HER3, and D3 has binding specificity to CD3. In one embodiment, D1 has binding specificity to CEA, D2 has binding specificity to EGFR, and D3 has binding specificity to CD3. In one embodiment, D3 has binding specificity to CD3, D4 has binding specificity to EGFR, and D5 has binding specificity to HER3. In one embodiment, the antibody is a triplicate antibody having binding specificity to EGFR, HER3, and CD3. In one embodiment, the triplicate antibody-like protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% identity with SEQ ID NOs. 41 and 43, 45 and 47, 49 and 51, 101 and 103, 105 and 107, 109 and 111, 195 and 197, 137 and 139, or 161 and 163.

[0049] In one embodiment, the multispecific antibody-like protein is quadruple specific. In one embodiment, D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, and D4 has binding specificity to 4-1BB. In one embodiment, D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, and D5 has binding specificity to PD-L1. The antibody is quadruple specific, having binding specificity to EGFR, HER3, CD3, and 4-1BB. The antibody is quadruple specific, having binding specificity to EGFR, HER3, CD3, and PD-L1. In one embodiment, the quadruspecific antibody-like protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% identity with SEQ ID NOs. 33 and 35, 37 and 39, 141 and 143, 145 and 147, or 165 and 167.

[0050] In one embodiment, the antibody is quintuple specific. In one embodiment, the antibody-like protein may have binding specificity to EGFR, HER3, CD3, 4-1BB, and PD-L1. In one embodiment, the quintuple specific antibody-like protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% identity with SEQ ID NOs: 17 and 19, 21 and 23, 25 and 27, 29 and 31, 69 and 71, 73 and 75, 77 and 79, 81 and 83, 85 and 87, 89 and 91, 93 and 95, 97 and 99, 129 and 131, 133 and 135, 149 and 151, 169 and 171, 173 and 175, or 177 and 179.

[0051] In a second embodiment, the present invention provides a novel sequence of a complementarity-determining region (CDR). In one embodiment, the present invention provides a protein, an antibody-like protein, or an antibody containing the CDR.

[0052] In one embodiment, the CDR may have affinity for CEA. In one embodiment, the CDR may have an equilibrium dissociation constant (KD) for CEA. The KD is 0.1 nM, 2 nM, 5 nM, 10 nM, 20 nM, 30 nM, or 50 nM or less. In one embodiment, the CDR may contain an amino acid sequence having at least 80% sequence identity with SEQ ID NOs. 301, 302, 303, 304, 305, or 306.

[0053] In one embodiment, the present invention provides a protein having affinity for CEA. In one embodiment, the protein may have CDR H1 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 301. In one embodiment, the protein may have CDR H2 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 302. In one embodiment, the protein may have CDR H3 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 303. In one embodiment, the protein may have CDR L1 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 314. In one embodiment, the protein may have CDR L2 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 305. In one embodiment, the protein may have CDR L3 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 306. In one embodiment, the protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity with an amino acid sequence selected from SEQ ID NOs.

[0054] In one embodiment, the present invention provides a multispecific antibody-like protein having a variable region. The variable region may include an amino acid sequence selected from SEQ ID NOs. 301, 302, 303, 304, 305, or 306.

[0055] In one embodiment, the CDR may have affinity for CD3. In one embodiment, the CDR may have an equilibrium dissociation constant (KD) for CD3. The KD is 10 nM, 20 nM, 30 nM, 50 nM, 100 nM, 200 nM, 300 nM, 400 nM, or 500 nM or less. In one embodiment, the CDR may contain an amino acid sequence having at least 80% sequence identity with SEQ ID NOs. 307, 308, 309, 310, 311, or 312.

[0056] In one embodiment, the protein having affinity for CD3 has a CDR H1 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 307. In one embodiment, the protein having affinity for CD3 has a CDR H2 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 308. In one embodiment, the protein having affinity for CD3 has a CDR H3 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 309. In one embodiment, the protein having affinity for CD3 has a CDR L1 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 310. In one embodiment, the protein having affinity for CD3 has a CDR L2 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 311. In one embodiment, the protein having affinity for CD3 has a CDR L3 containing an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 312.

[0057] In one embodiment, the protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity with an amino acid sequence selected from SEQ ID NOs: 227-230, 231-234, 235-238, 239-242, and 291-294. In one embodiment, the multispecific antibody-like protein may contain an amino acid sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity with an amino acid sequence selected from SEQ ID NOs: 227-230, 231-234, 235-238, 239-242, and 291-294.

[0058] In one embodiment, the multispecific antibody-like protein may have a variable region. The variable region may include an amino acid sequence selected from SEQ ID NOs. 307, 308, 309, 310, 311, or 312.

[0059] In another embodiment, the present invention provides isolated nucleic acid sequences encoding the multispecific antibody-like proteins, fragments, domains, and regions.

[0060] In another embodiment, the present invention provides an expression vector comprising the isolated nucleic acid sequence.

[0061] In another embodiment, the present invention provides a host cell comprising the isolated nucleic acid sequence. In one embodiment, the host cell comprises the expression vector. In one embodiment, the host cell may be a prokaryotic or eukaryotic cell.

[0062] In another embodiment, the present invention provides a method for preparing the multispecific antibody-like protein. In one embodiment, the method comprises the steps of culturing host cells such that a DNA sequence encoding the multispecific antibody-like protein is expressed, and purifying the multispecific antibody. In one embodiment, the method comprises the steps of culturing host cells under conditions in which the multispecific antibody-like protein is produced, and recovering the antibody-like protein.

[0063] In another embodiment, the present invention provides an immune complex. In one embodiment, the immune complex may comprise a multispecific antibody-like protein conjugated to a contrast agent and / or a cytotoxic agent.

[0064] In another embodiment, the present invention provides a pharmaceutical composition. In one embodiment, the pharmaceutical composition may comprise a multispecific antibody-like protein and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition may further comprise a radioisotope, a radionuclide, a toxin, a therapeutic agent, a chemotherapeutic agent, or a combination thereof. In one embodiment, the pharmaceutical composition may comprise the immune complex and a pharmaceutically acceptable carrier.

[0065] In another embodiment, the present invention provides a method for treating or preventing cancer, autoimmune disease, or infection in a subject. In one embodiment, the method may include the step of administering to the subject a pharmaceutical composition, an immune complex, or the pharmaceutical composition comprising purified multispecific antibody-like proteins. In one embodiment, the method may further include the step of co-administering an effective amount of a therapeutic agent. In one embodiment, the therapeutic agent may include an antibody, a chemotherapeutic agent, an enzyme, or a combination thereof.

[0066] 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.

[0067] In another embodiment, the present invention provides a solution comprising an effective concentration of the multispecific antibody-like protein, immune complex, or pharmaceutical composition. In one embodiment, the solution is the plasma of the subject. [Brief explanation of the drawing]

[0068] 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.

[0069] [Figure 1] The heterodimer structure of a miniGNC molecule having five binding domains (D1-D5) is shown. Here, the two monomers are encoded by chain A (N-D1-D3 / VH-CH1-CH2-CH3-D4-C) and chain B (N-D2-D3 / VL-CL-CH2-CH3-D5-C).

[0070] [Figure 2] (2A) Dimerization of chains A and B of engineered miniGNCs with knockout mutations (KO) in either VH or Fc. (2B) Fractionation of the mixture into homodimer (a), desired heterodimer (b), and chain B monomer (c) by protein A purification.

[0071] [Figure 3] This study demonstrates the comparative efficacy of multispecific miniGNC molecule-mediated TDCC against BXPC3 tumor cells using penta-miniGNC (SI-75P6), tetra-miniGNC (SI-75E2), tri-miniGNC (SI-75X3), bi-miniGNC (SI-75X2), and mono-miniGNC (SI-75O2) molecules.

[0072] [Figure 4] This study demonstrates the comparative efficacy of miniGNC molecule-mediated TDCC against BXPC3 tumor cell lines with EC50 values ​​ranging from 0.1 to 5.5 pM.

[0073] [Figure 5] The survival curves for the TDCC assay, which measures comparative efficacy, are shown. (A) Killing efficacy of multispecific miniGNC molecules with a stapling domain (penta-miniGNC (SI-68P1), tetra-miniGNC (SI-68E2 and SI-68E1), and tri-miniGNC (SI-68x2)) against pancreatic cancer cells (HPAFII) (TDCC assay). (B) Efficacy of SI-68X1 against MCF-7 breast cancer cells.

[0074] [Figure 6] This study demonstrates the killing function (TDCC assay) of multispecific miniGNC molecules possessing a dimeric NKG2D receptor against breast cancer cells (MDA-MB-231), including triplicate (SI-49R25), quadruplicate (SI-49P_X), and quintuplicate (SI-49PM1 and SI-49P8). [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 discloses a microstructure multispecific guidance and navigation control (GNC) antibody (miniGNC). The miniGNC platform molecule is an assembled heterodimer of two polypeptide chains characterized by the formation of a Fab-hinge-Fc region core structure (D1 to D5) having one, two, three, or four additional binding domains (Figure 1). These two polypeptides may consist of chain A (or chain 1): N-D1-D3(VH)-CH1-hinge-CH2-CH3-D4-C, and chain B (or chain 2): N-D2-D3(VL)-CL-hinge-CH2-CH3-D5-C. The Fc domains of these two chains are engineered to include complementary mutations, also known as "knobs-into-holes," to facilitate heterodimer formation. The miniGNC platform molecule may contain variable components. For example, the VH and VL of the Fab region may be replaced by non-Fab dimers with or without binding specificity. The additional binding domain may be an antibody fragment such as scFv or VHH, or a non-antibody structure such as a ligand or receptor. The miniGNC platform antibody is bivalent, trivalent, tetravalent, or pentavalent, possessing up to five different specificities, and maintaining or slightly increasing the size of a typical bivalent IgG antibody (150kD tri-miniGNC Ab) or (175kD tetra-miniGNC Ab and 200kD penta-miniGNC Ab).

[0078] This invention relates to the production and use of miniGNC antibodies, particularly quintuple-specific miniGNC antibodies (pentaminiGNC Ab). Typically, GNC proteins, such as GNC antibodies, are characterized by containing two moieties for involvement in immune cells, such as activating T cells while targeting tumor cells. Similar to GNC antibodies, miniGNC antibodies possess multiple antigen-binding domains for involvement 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 effectiveness of antibody therapy for treating cancer, miniGNC antibodies are designed to be structurally stable and compact while retaining the characteristics of the two moieties of GNC antibodies. This improvement makes it possible to add binding specificity to a second tumor-associated antigen on the same or different tumor cells. Compared to GNC antibodies, miniGNCs contain an Fc domain that enables recycling via FcRn, extended half-life, and easy purification by protein A. Fc receptor-mediated immunity can be incorporated as needed. Because miniGNC antibodies containing Fc are highly compact, their developability can be improved, and their penetration into tumors can be facilitated. GNC antibodies are typically larger than IgG antibodies due to an increased number of antigen-binding domains (AgBDs), providing spatial flexibility to bind to both T cells and tumor cells. MiniGNC antibodies, on the other hand, maintain roughly the same size as human IgG antibodies (150kD), with bispecificity ranging from 110-130kD for bispecificity, 120-160kD for triplicity, 130-190kD for quadruplicity, and 140-220kD for quinticity. Incorporating one or two scFvs into each chain reduces the complexity of chain pairing and improves stability while navigating the tumor microenvironment. These distinctive features suggest that GNC and miniGNC antibodies, because they target the same tumor-associated antigens, may be effective alternatives to antibody therapies for treating the same cancers.The tumor-related antigens include, but are not limited to, 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.

[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 complete antibody and any antigen-binding fragment derived from the complete 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 (abbreviated as V H and the heavy chain constant domain. Each light chain is composed of a light chain variable domain (abbreviated as V L and the light chain constant domain). V H region and V LThe region can be further divided into domains of more conserved regions called hypervariable complementarity determination regions (CDRs) and framework regions (FRs). Each variable domain (V H or V L A carboxyl molecule typically consists of three CDRs and four FRs, arranged in the order FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from the amino terminus to the carboxyl terminus. The variable regions of the heavy and light chains contain binding regions that interact 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 invention, antibodies were produced by immunizing rabbits, mice, or llamas in combination with subsequent strategies such as hybridoma or display. Rabbits are known to produce antibodies with high affinity, diversity, and specificity (Weber et al.Exp.Mol.Med.49:e305). 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 hybridoma and / or phage, display in yeast or mammalian cells; or display using synthetic variable gene libraries. The general method for discovering this antibody 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 may also be even smaller subfragments, and may consist of domains as small as a single CDR domain, particularly the CDR3 region from either the VL and / or VH domains (Beiboer et al., J.Mol.Biol.296:833-49(2000)). 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 additional residues at 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 the 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. However, even a single variable domain (or half of Fv containing only the three antigen-specific CDRs) has the ability to recognize and bind to the antigen, but with lower affinity than the entire binding site.

[0088] The "light chains" of antibodies (immunoglobulins) derived from vertebrate species can be assigned to one of two distinct types, called kappa (κ) 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: Structure of a quintuplicate specific miniGNC antibody

[0104] The design of miniGNC antibodies depends on the co-expression and assembly of two polypeptide chains forming a heterodimer between chain A and chain B (Figure 1). Chain A can be the native heavy chain (HC), while chain B is a recombinant fusion peptide between the light chain and the Fc domain of the HC. The core of this antibody contains a Fab region (VH-CH1 / VL-CL), followed by a hinge and the Fc region of human IgG1 (CH2-CH3 / CH2-CH3). To destabilize the homodimer and promote heterodimer formation, a "knobs-into-holes" mutation or another complementary set of mutations can be introduced into the CH3 domain (Ridgway JB, Presta LG, Carter P., Protein Eng 1996;9:617-21). The "hole" mutations in the CH3 domain of chain A consist of T366S, L368A, and Y470V, while the "knob" mutation in the CH3 domain of chain B is T366W. The "knob" formed by the T366W mutation on chain B preferentially interacts with the "hole" formed by the three mutations on chain A. This preferential pairing can further stabilize the heterodimer, while the non-covalent pairing of Fab domain components (i.e., VH-CH1 on chain A and VL-Ck on chain B) constitutes the functional Fab region. In other words, a functional D3-binding domain (e.g., a functional Fab region or a non-Fab receptor dimer) can only be created in the chain A-chain B heterodimer. Compared to GNC antibodies, miniGNC antibodies still contain antibody fragments derived from natural IgG (Fab,Fc) and other variable sequence-based structures (e.g., scFv and VHH), but are engineered to preferentially constitute the Fab-hinge-Fc region structure after heterodimer formation. A key feature of miniGNC antibodies is the compactness of this engineered structure.

[0105] By adding one or more structurally diversified antigen-binding domains as D1, D2, D4, or D5 to the two N-terminuses and two C-terminuses of the miniGNC molecule, up to five binding specificities can be formed. Each of these added binding domains may be a structure based on a variable sequence such as scFv and VHH, or a structure based on a non-variable sequence such as a ligand and a receptor. As shown in Figure 1, D1 and D2 refer to binding domains attached to the N-terminuses of chains A and B, respectively, and D4 and D5 refer to binding domains attached to the C-terminuses of chains A and B, respectively. Therefore, the two polypeptides of a quintuple-specific miniGNC (penta-miniGNC) antibody may be constructed as follows. Chain A: N-D1-D3(VH)-CH1-Hinge-CH2-CH3-D4-C Chain B: N-D2-D3(VL)-CL-Hinge-CH2-CH3-D5-C Here, as shown in Figure 1, VL can be Vλ or Vκ, and CL can be Cλ or Cκ.

[0106] Depending on the number of binding domains and their binding specificity, the structure of the penta-miniGNC antibody shown in Figure 1 can be simplified by reducing one or more binding domains to form tetra, tri, and bi-miniGNCs. For example, Table 1 shows the generation and characterization of families of anti-CD3 miniGNC antibodies to optimize their effect in targeting EGFR and HER3. In this case, each binding domain exhibits one binding specificity. If two of the five binding domains target the same epitope of the antigen (i.e., have the same binding specificity), this penta-miniGNC antibody becomes a quadruple-specific penta-miniGNC antibody.

[0107] Example 2: Core structure of an engineered miniGNC antibody

[0108] To demonstrate that the structure of miniGNC can be stably converted into a functional heterodimer protein, a simple asymmetric format was designed to evaluate the effects of composition and mutation on heterodimerization of the miniGNC molecule. Simply put, a single scFv(D1) is fused to the N-terminus of chain A, while chain B does not contain an additional binding domain. Thus, various proportions of dimerization between chain A and chain B can be distinguished by SDS-PAGE and SEC. No chain A homodimer was observed, and the predicted sizes of the chain B homodimer, chain A heterodimer, and chain B heterodimer are 100 kDa, 150 kDa, and 125 kDa, respectively (Figure 2).

[0109] To design a strategy for selectively purifying heterodimer miniGNC molecules from a mixture, two amino acid residues in the CH3 domain (H435 and Y436) of chain B were substituted. In particular, histidine (H435) is crucial for the binding of chain B to the protein A resin during the purification of therapeutic antibodies (Tustian et al., 2016), and substitution of this amino acid or a ProA knockout mutation (ProAKO) terminates protein A binding. This strategy allows for the separation of heterodimers by selective elution from the protein A column. Since the protein A column retains heterodimers via the parent heavy chain binding site, the chain B homodimer passes through because chain B lacks protein A binding. Designing a ProAKO on chain B minimizes the potential for altering immunogenicity through amino acid substitutions of the protein A binding site with residues derived from homologous regions of the IgG3 subclass. While most miniGNC molecules primarily incorporate the structure and sequence of the IgG1 subtype, IgG3 has a structure that is overall similar to other IgG subclasses, with some specific structural perturbations in its binding to protein A, protein G, and FcRn (neonatal Fc receptor). This difference is based on previously identified differences in the Fc sequence, where the presence of R435 (H435 in other subtypes) eliminates the interaction between Fc and protein A. Therefore, in representative miniGNC molecules, the amino acids (H435 and F436) crucial for protein A binding on the miniGNC chain B are mutated to the IgG3-corresponding sequences (R435 and Y436).

[0110] In the class of multispecific miniGNC antibodies with an added scFv fused to the N-terminus of chain B, interaction with protein A binding may still be possible if the scFv originates from the VH3 family. Antibodies encoded with VH3 are known to interact with Staphylococcus protein A (SPA), and residues in FR1, CDR2, and FR3 have been confirmed to be involved in SPA binding (Roben, et al., 1995). Structural data show that protein A binding by VH3-encoded antibodies is eliminated by substituting a single relevant region with a corresponding region from an unbound immunoglobulin. The substitution of amino acid R19 in FR1 was confirmed to be important for binding to protein A and was performed using the amino acid sequence (S19) from the equivalent region in the VH4 family.

[0111] Four sets of miniGNC antibodies (SEQ ID NOs: 1-16) containing four different versions of chain B mutations (SEQ ID NOs: 3, 7, 11, and 15), including different ProAKO combinations (H435R / Y436F(Fc) and R19S(VH)), were purified and analyzed by analytical size exclusion chromatography. Only proteins containing chain B with mutations from both sets were completely free of chain B contaminants (Figure 2A). This VH3 protein A knockout mutation (R19S) and Fc protein A knockout mutation on chain B (H435R, F436Y) were incorporated into most multispecific antibody formats and used to generate bi, tri, tetra, and penta miniGNC molecules.

[0112] To demonstrate the potential to generate functional miniGNC proteins with alternative antibody isotypes, exemplary miniGNCs containing the IgG4 constant region were generated. SI-75XM9 (SEQ ID NO: 297-300) is an analogue of the SI-75X5 (SEQ ID NO: 1-4) bispecific miniGNC, except that IgG1 CH1, hinge, and Fc are substituted with IgG4 CH1, hinge, and Fc. In particular, both proteins have the same binding domains (anti-HER3 domain at D2 and anti-CD3* domain at D3), and contain the same core structure and mutations (Knobs-into-Holes Fc mutation; R19S at anti-HER3 scFv; and H435R / Y436F mutation at Fc). As shown in Table 8, SI-75XM9 has a titer comparable to SI-77X5, and the percentage of the target protein increased significantly by 19% after protein A purification, as assessed by analytical SEC (85.6% POI vs. 72.2% POI). The decrease in high molecular weight species may be related to the shorter hinge length of IgG4 (12 amino acids instead of 15), which could reduce the tendency for higher-order oligomers to aggregate. Therefore, it may be possible to generate miniGNC proteins with alternative antibody isotypes, which may also result in more desirable properties such as reduced aggregation.

[0113] Example 3: Composition of a multispecific miniGNC antibody

[0114] To generate and characterize the first group of multispecific miniGNC antibodies, three partial 1-binding domains (i.e., αCD3, αPD-L1, and α4-1BB) and two partial 2-binding domains for EGFR and HER3 were selected and compared. As shown in Table 1, this group was further subdivided into penta-miniGNC, tetra-miniGNC, tri-miniGNC, and bi-miniGNC groups. In each subgroup, at least one miniGNC antibody had CD3 binding from D3. The penta-miniGNC group includes SI-75P6 (SEQ ID NOs: 17, 19; having αEGFR from the D3 position), SI-75P4 (SEQ ID NOs: 21, 23; having 41BBL, a ligand for the 4-1BB receptor, at D4), SI-75P3 (SEQ ID NOs: 25, 27), and SI-75P9 (SEQ ID NOs: 29, 31; having αHER3 from D3). To compare the effects in the presence and absence of the α4-1BB or αPD-L1 domain, the tetra-miniGNC group contains two antibodies, namely SI-75E1 (SEQ ID NOs. 33, 35) and SI-75E2 (SEQ ID NOs. 37, 39). To compare two partial 2-binding domains on the N-terminus or C-terminus of the heterodimer, the tri-miniGNC group contains three antibodies, namely SI-75X3 (SEQ ID NOs. 41, 43), SI-75X16 (SEQ ID NOs. 45, 47), and SI-75X18 (SEQ ID NOs. 49, 51). The bi-miniGNC group contains three antibodies, namely SI-75X1 (SEQ ID NOs. 53, 55), SI-75X2 (SEQ ID NOs. 57, 59), and SI-75X5 (SEQ ID NOs. 1, 3), each having one partial 1-binding domain and one partial 2-binding domain.

[0115] The DNA encoding each member of the first group of miniGNC antibodies was cloned into the vector pTT5 and expressed at an acceptable titer for 9 days using the ExpiCHO expression system. After purifying the miniGNC antibodies with a 5 mL MabSelect Protein A column, size exclusion was performed using a high-load 16 / 600 200 pg preparative SEC column with either the Akta Avant or Purifier system. The SEC aggregates were analyzed using a Waters HPLC connected to multi-angle light scattering (MALS, Wyatt system), and the correct molecular weight was determined by the dn / dc calculation method.

[0116] Example 4: Octet analysis of binding affinity

[0117] To evaluate the function of miniGNC antibodies, the binding affinity of each domain was determined by Biolayer Interferometry (Octet 384 system). Octet analysis confirmed that the selected miniGNC antibodies retained binding specificity and affinity for all allogeneic antigens. Each miniGNC antibody was loaded into an AHC sensor at 10 ug / ml for 180 seconds, followed by a 60-second baseline step, a 180-second association step with 100 nM commercially available human antigen, and a 360-second dissociation step. Samples from all steps were contained in Octet buffer (PBS containing 0.1% Tween 20 and 1% BSA). Affinity KD values ​​were extracted by fitting using a 1:1 binding model. As shown in Table 1, the binding affinity of each binding domain varied within an acceptable range, as measured by its KD. In partial 1 binding, the KD of the aCD3 domain can range from 17.4 to 36.2 nM, the KD of αPD-L1 from 1 to 2.72 nM, and the KD of α4-1BB from 7.51 to 37.3 nM. In partial 2 binding, the KD of αEGFR can range from 5.56 to 11.1 nM, and the KD of aHER3 can range from 112.8 to 185 nM.

[0118] Example 5: Comparative efficacy of multispecific miniGNC antibodies

[0119] To measure the cancer cell-killing efficacy, the first group of multispecific miniGNC antibodies were subjected to a T cell-dependent cell-mediated cytotoxicity (TDCC) assay. Because all molecules in this group of miniGNC antibodies have an αCD3-binding domain, they can utilize T cells, redirect T cell-mediated cytolysis, and ultimately kill target cells.

[0120] The degree of antibody-induced cytotoxicity was measured by quantifying cell viability through constitutive expression of luciferase using a luminescence-based T cell-dependent cell-mediated cytotoxicity (TDCC) assay. Luciferized BXPC3 human pancreatic cancer cell line (ATCC, Manassas, VA) was cultured at 37°C and 5% CO2 in RPMI (ATCC, Manassas, VA) medium containing 10% heat-inactivated fetal bovine serum (Invitrogen, Waltham, MA). Cell viability was monitored using a Vi-CELL automated cell counter (Beckman Coulter, Pasadena, CA). Surface expression of target cells was measured by flow cytometry. Human pancreatic cancer cells, BXPC3 cells, were co-cultured with human pan-T cells in a 5:1 effector / target (E:T) ratio, and antibodies were added in a 5-fold dilution series (0-30 nM). Using a Multidrop bulk liquid dispenser (BIOTEK, Winooski, VT), target cells were sequentially inoculated at 500 cells / well (20 μL / well) and T cells at 2500 cells / well (20 μL / well) into polystyrene TC-treated microplates (384 wells, white, flat-bottomed) (Corning, Corning, NY). Antibody dilutions were added (10 μL / well), and the plates were incubated at 37°C and 5% CO2 for 72 hours. Cell viability was then quantified based on luminescence. 20 μL of Bright-Glo (Promega) was added to each well, and luminescence corresponding to tumor cell viability was measured using a CLARIOstar plate reader.

[0121] The data were fitted to a sigmoid function and calculated, and the EC50 values ​​are shown in Table 1 for comparison. Figure 3 shows dose-dependent cell viability curves for miniGNC antibodies selected from penta-miniGNC (SI-75P6), tetra-miniGNC (SI-75E2), tri-miniGNC (SI-75X3), bi-miniGNC (SI-75X2), and mono-miniGNC (SI-75O2) molecules. While all multispecific miniGNC antibodies were able to completely kill BXPC3 cells, both the penta- and tetra-miniGNC antibodies consistently showed high potency in the pM level EC50 range. In this respect, SI-75X1 was particularly potent. These data indicate that the partial 1-binding domain, especially the αPD-L1 domain, plays a crucial role as an immune checkpoint inhibitor when targeting BXPC3 cancer cells.

[0122] Example 6: Composition of the CD3-binding domain in the miniGNC antibody

[0123] By definition, miniGNC antibodies can interact with at least one immune effector cell and one target cancer cell via binding of their respective part 1 and part 2 binding domains. According to a general scheme of miniGNC antibody composition (Figure 1), when the two part 2 binding domains are assigned to D1 and D2, the efficacy may differ from when they are assigned to D1 and D4 or D2 and D5, because the relative positions of the targets on the cell surface differ vertically or bilaterally. Therefore, a second group of penta-miniGNC antibodies were constructed and shown in Table 2. These miniGNC antibodies have the same binding specificity for CD3, CD19, EGFR, 4-1BB, and PD-L1, and the same binding domains for D2, D4, and D5. SI-68P13 (SEQ ID NOs: 69, 71) has an αCD3 D3 domain and is similar to SI-75P3 in the first group except for the D2 difference (i.e., αCD19 vs. αHER3), and is similar to SI-68P17 (SEQ ID NOs: 73, 75) in the second group except that the position of the αCD3 domain has been changed to D1. The remaining miniGNC antibodies in the second group have the same binding specificity as D1 (αCD3) and D3 (αEGFR). SI-68P17 has binding specificity for CD19, 4-1BB, and PD-L1, respectively.

[0124] Anti-CD3 antibodies play a central role in T-cell activation-based immunotherapy. Humanized antibodies are preferred for the development of therapeutic antibodies. To test the site effect, CD3 domains were incorporated at sites D1 and D3 to generate SI-68P17 (SEQ ID NOs. 73, 75) and SI-68P13 (SEQ ID NOs. 69, 71). Anti-CD3 sequences 1 (CD3**), 2 (CD3***), 3 (CD****), and 4 (CD*****) of the humanized framework were cloned into expression cassettes to generate SI-68P15 (SEQ ID NOs. 77, 79), SI-68P18 (SEQ ID NOs. 81, 83), SI-68P19 (SEQ ID NOs. 85, 87), and SI-68P16 (SEQ ID NOs. 89, 91) (Table 2). Each expression cassette was transfected into 25 mL of ExpiCHO and expressed for 8 days. Protein A affinity chromatography was then performed to recover and purify each pentaminiGNC antibody. Antibodies were produced with good titers (Table 2). Octet confirmed that each pentaminiGNC antibody containing a different CD3 domain could bind to human CD3 (Table 2). Each pentaminiGNC antibody was loaded at 10 μg / ml via an AHC sensor and bound to serial dilutions (maximum 200 nM, 1:2.5 dilution) or to a single 100 nM concentration of His-tagged human CD3. Global fit to the resulting 1:1 binding model showed that the pentaminiGNC antibodies bound to CD3 with low nanomolar affinity (Table 2).

[0125] To evaluate the effect of CD3-mediated T-cell-targeting cytotoxicity on cancer cells, the BXPC3 tumor cell line was used as the target. Serial dilutions of the antibody (0–30 nM; dilution factors 1–5) were added in a total volume of 50 μl to a white 384-well plate containing luciferized target cells and activated T cells (inoculated immediately before drug administration; effector:target = 5:1). After 72 hours, 20 μl of Bright-Glo (Promega) was added to the wells, and luminescence corresponding to the viability of luciferized tumor cells was determined using a CLARIOstar plate reader. The EC50 values ​​calculated by fitting the data to a sigmoid function ranged from 0.1 to 5.5 pM, as shown in Figure 4 and Table 2. This data indicates some flexibility in the arrangement, composition, and binding affinity of anti-CD3.

[0126] Example 7: Multispecific miniGNC antibody having VHH as a binding domain

[0127] In multispecific antibody platforms such as GNC and miniGNC antibodies containing multiple scFv domains, there is a potential problem related to chain mispairing due to multiple VH and VL domains within the same molecule. Different VH and VL domains have different tendencies to interact with each other. If binding domains with different specificities have superior interaction energies, incorrect pairings may be formed when the proteins assemble. As a result, none of the binding domains may bind to the target antigen.

[0128] VHH refers to an "antibody" having a single Ig domain, i.e., "heavy chain only," and is also known as a single-domain antibody (sdAb) or nanobody. The first single-domain antibody was engineered from a heavy chain antibody found in camelids, V HAlso known as the H fragment (VHH), the VHH domain is increasingly being incorporated into antibody-based therapies due to several desirable properties. Compared to the more traditionally used scFv domain, the VHH domain offers improved stability and solubility. While the VH / VL interface of conventional antibody variable regions is hydrophobic, significant aggregation or precipitation can occur if their surfaces are temporarily exposed. On the other hand, the VHH domain has a more hydrophilic surface, resulting in superior solubility and stability. A clear advantage of the VHH domain compared to Fab or scFv domains is its smaller size. While Fab domains are approximately 50 kDa and scFv domains are approximately 25 kDa, the VHH domain is a very compact 12-15 kDa. PentaminiGNC antibodies contain five binding domains (Figure 1). Incorporating the VHH domain instead of the scFv domain significantly reduces molecular size and increases tumor penetration.

[0129] The third group of multispecific miniGNC antibodies were created and configured to have VHH binding domains for EGFR and HER3 (Gottlin et al., 2009; Eliseev et al., 2018) (Table 3). MiniGNC molecules incorporating quintuple, triplicate, and bispecific single-domain variable regions (VHH) were constructed and purified at reasonable titers. Each multispecific miniGNC (SI-75P5 (SEQ ID NOs. 93, 95), SI-75P8 (SEQ ID NOs. 97, 99), SI-75X4 (SEQ ID NOs. 101, 103), SI-75X17 (SEQ ID NOs. 105, 107), SI-75X19 (SEQ ID NOs. 109, 111), SI-75X9 (SEQ ID NOs. 113-115), SI-75X11 (SEQ ID NOs. 117, 119), SI-75X15 (SEQ ID NOs. 121, The binding activity of the domains of 123) and SI-75X13 (SEQ ID NOs. 125, 127) was confirmed by Octet. GNC antibodies were captured at a concentration of 10 ug / ml for 180 seconds using an AHC sensor. After a 60-second baseline step, a 180-second binding step was performed using single concentrations of antigen. The test antigens were 200 nM human EGFR (in-house purified) and 100 nM human CD3 (Acro). The sample contains CDD-H52W1), 20 nM human PD-L1 (Acro PD1-H5229), 400 nM human 4-1BB (proprietary purification), and 200 nM human HER3 (Acro ER3-H5223). After binding, a 420-second dissociation step was performed. KD values ​​were calculated using the one-to-one binding model of ForteBio Data Analysis software (version 11) and are shown in the table. The data indicate that all domains maintain high affinity in the miniGNC platform incorporating VHH.

[0130] T cell-targeted cytotoxicity was evaluated using the BXPC3 tumor cell line, a cancer cell line, as the target. Serial dilutions of the antibody (0-30 nM; dilution factors 1-5) were added in a total volume of 50 μl to a white 384-well plate containing luciferized target cells and activated T cells (inoculated immediately before drug administration; effector:target = 5:1). After 72 hours, 20 μl of Bright-Glo (Promega) was added to the wells, and the luminescence corresponding to the viability of the luciferized tumor cells was determined using a CLARIOstar plate reader. EC50 values ​​are shown in Table 3.

[0131] Example 8: Fab(D3) domains engineered to improve expression and protein quality

[0132] Where necessary, disulfide staples were introduced at the VH-VL interface of the fab region (Figure 5). The purpose of this engineering was to improve heterodimer pairing and stabilize the overall structure by forming a covalent disulfide bond at the core-fab interface (Weatherill et al., 2012). Cysteine ​​pairs were optionally introduced to form disulfide bonds at VLA100 of chain B and the corresponding VHA44 of the fab region of chain A.

[0133] To analyze the effect of stapled variable regions in Fab, a pair of pentaminiGNC antibodies (SI-38P11 and SI-76PM1) with identical binding specificity were created (SEQ ID NOs: 129 and 131; 133 and 135). According to the naming system in Figure 1, chain A of these two antibodies has αCD20 scFv at D1, αCD3 VH (VH Fab-CH1-Fc) at D3, and α4-1BB at D4, while chain B has αCD19 at D2 and αCD3V at D3. L (VKappa Fab CL-Fc), D5 contains αPD-L1 scFv (Table 4). SI-76PM1 was constructed by adding a disulfide to D3 (VH / VL Fab-CH1 / CL-Fc), and SI-38P11 was constructed without additional disulfide pairing to VH / VL Fab.

[0134] PentaminiGNC antibody constructs with or without a disulfide staple at the D3 position were expressed in the ExpiCHO system. The construct with stapled D3 (SI-76PM1) produced significantly higher titers than SI-38P11. Both proteins were purified using a 5 mL MabSelect Protein A column, and then size exclusion was performed using a high-load 16 / 600 200 pg preparative SEC column in an Akta Avant or Akta Pure Purifier system. SEC aggregates were analyzed using Waters HPLC connected to multi-angle light scattering (MALS, Wyatt system), and the correct molecular weight was determined by the dn / dc calculation method. As shown in Table 4, all analyses revealed that the disulfide bond, i.e., "D3 stapled Fab," and the PentaminiGNC antibody produced 5% higher target protein. Both molecules showed comparable antigen-binding kinetics (Table 4).

[0135] Example 9: Multispecific miniGNC antibody having a stapled scFv binding domain

[0136] The core structure of the multispecific miniGNC molecule was designed to acquire several features for stabilizing the heterodimer (a covalent hinge and non-covalent, preferential "knobs-into-holes" interactions via the CH3 domain of the Fc region). While stability and compactness are desirable, it remains unclear whether closer proximity between D1 and D2 or D3 and D4 affects their stability and independent function. To maintain the stability and independence of each additional binding domain, disulfide bonds can be introduced between VL100 and VH44 of each scFv domain, i.e., each scFv domain can be stapled. The entire structure can be stabilized by using disulfide bonds between VL and VH in all scFv domains. Alternatively, disulfide bonds can be introduced at any position in at least one selected scFv domain.

[0137] Four miniGNC antibodies with D1 and D2 targeting EGFR and HER3 (including tri-miniGNC (SI-68X2, SEQ ID NOs. 137, 139), tetra-miniGNC (SI-68E1, SEQ ID NOs. 141, 143; SI-68E2, SEQ ID NOs. 145, 147), and penta-miniGNC (SI-68P1, SEQ ID NOs. 149, 151) molecules) were grouped to measure the comparative efficacy of TDCC against pancreatic cancer cells (HPAF-II). While the binding specificity of part 1 to 4-1BB and PD-L1 varied, CD3 was consistent with respect to multispecificity, similar to D3 within the group. Expression constructs encoding each of these four miniGNC antibodies were modified so that all scFv domains possessed disulfide bonds. The structures were individually expressed in the ExpiCHO system, and each antibody was purified to an appropriate titer. Binding kinetics to each antigen were determined by Octet. MiniGNC antibodies were captured at a concentration of 10 ug / ml for 180 seconds using an AHC sensor. After a 60-second baseline step, a 180-second binding step was performed using single-concentration antigens. Test antigens included 200 nM human EGFR (in-house purified), 100 nM human CD3 (Acro CDD-H52W1), 20 nM human PD-L1 (Acro PD1-H5229), 400 nM human 4-1BB (in-house purified), and 200 nM human HER3 (Acro ER3-H5223). After binding, a 420-second dissociation step was performed. KD values ​​were calculated using a one-to-one binding model in ForteBio Data Analysis software (version 11) and are shown in the table. The analyzed KD values ​​(Table 5) for each miniGNC molecule with a stapled scFv domain were compared to the KD values ​​(Table 6) of monoclonal antibody controls against each antigen. The binding kinetic data shows that each stapled scFv domain has equivalent binding affinity to its respective mAb or Fc-scFv control (SI-1C3 (SEQ ID NOs. 181, 183), SI-1C7 (SEQ ID NOs. 185), SI-9C21 (SEQ ID NOs. 187, 189), SI-35SF11 (SEQ ID NOs. 191), SI-3SF11 (SEQ ID NOs. 193), and SI-20C14 (SEQ ID NOs. 287 and 289)) (Table 6).This suggests that stapling one or more scFv domains has little effect on binding affinity.

[0138] To evaluate the effect of the stapled scFv domain on the potency of the miniGNC antibody, a T-cell-targeted cytotoxicity (TDCC) assay was used, with HPAF-II, human pancreatic cancer cell lines (ATCC, Manassas, VA), as the target cells. Surface expression of the target cells was verified by flow cytometry. Serial dilutions of the antibody (0–30 nM; 1–5 dilution factors) were added in a total volume of 50 μL to a white 384-well plate containing luciferized target cells and activated T cells (inoculated immediately before drug administration; effector:target = 5:1). After 72 hours, 20 μL of Bright-Glo (Promega) was added to the wells, and luminescence corresponding to the viability of luciferized tumor cells was determined using a CLARIOstar plate reader. The data were fitted to a sigmoid function to calculate the EC50 value. As shown in Figure 6 and Table 5, the survival curves revealed that the efficacy of all four miniGNC antibodies was within the pM dose range, and that the penta-miniGNC antibody tended to exhibit higher TDCC efficacy than the tetra-miniGNC and tri-miniGNC antibodies. This observation also indicates that the use of stapled scFv domains had little effect.

[0139] Example 10: miniGNC having an NKG2D receptor dimer as a binding domain

[0140] The increased number of binding specificities allows GNC antibodies to bind not only to T cells but also to subsets of T cells, natural killer cells, and other immune cells (collectively referred to as Part 1 binding domain specificity) (Applicant's applications WO / 2019 / 005641 and WO2019191120; the whole is incorporated herein). Some of the Part 1 binding specificities may replace cellular responses or recognition of target cells. For example, NKG2D is a primary recognition receptor for detecting and eliminating transformed and infected cells, and its ligand is induced under cellular stress as a result of viral infection or genomic stress (e.g., cancer). In humans, NKG2D is expressed on NK cells and CD8+ T cells. Adding NKG2D as a binding domain / specificity to the class of miniGNC antibodies can improve the cytotoxicity and efficacy of the antibody as a single multifunctional therapeutic agent.

[0141] 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 designates NKG2D as a binding domain based on the invariant sequence of the miniGNC format, allowing for the addition of other binding domains to create a class of multispecific NKG2D-miniGNC proteins. In one miniGNC format, individual NKG2D monomers are incorporated at the D3 position of chains A and B, forming a dimeric NKG2D receptor through Fc dimerization. Thus, NKG2D functions as a receptor for multispecific miniGNC molecules to bind to its ligand. In another miniGNC format, the NKG2D tandem repeat was designed by adding a (GxSy)n spacer / linker between individual NKG2D monomers that homodimerize to form a functional dimeric receptor. This NKG2D tandem dimer structure can be positioned at D1, D2, D4, or D5.

[0142] As shown in Table 7, this class includes mono-NKG2D-miniGNC (SI-49R26, SEQ ID NOs. 153, 155), bi-miniGNC (SI-49R27, SEQ ID NOs. 157, 159), tri-miniGNC (SI-49R25, SEQ ID NOs. 161, 163), tetra-miniGNC (SI-49P_X, SEQ ID NOs. 165, 167), and penta-mini-GNC molecules (SI49P8, SI-49P9, SEQ ID NOs. 169, 171, 177, and 179). SI-49PM1 (SEQ ID NOs. 173, 175) was created by substituting the D1(αCD3) and D3 positions of SI-49P8, and the Octet binding affinity of NKG2D or CD3 was not affected by this substitution. While the binding affinity of other partial 1 binding domains remained stable in this class of NKG2D-miniGNC molecules, the binding affinity to NKG2D was within twofold. Therefore, the penta-miniGNC molecule possesses the function of binding to the NKG2D receptor for binding to the NKG2D ligand.

[0143] To evaluate and compare the efficacy of TDCCs of NKG2D-miniGNC molecules, tri, tetra, and penta-miniGNC molecules, MDA-MB-231 breast cancer cell lines were targeted using SI-49R25, SI-49P_X, SI-49P8, and SI-49PM1. Serial dilutions of miniGNC protein (0-30 nM, 1-5 dilution factors) were added 24 hours prior to adding luciferized MDA-MB-231 cells to a white 384-well plate and grown at 37°C. Activated T cells were inoculated with a total volume of 50 μl immediately before adding the miniGNC molecule (effector:target = 15:1). After a further 72-hour incubation, 20 μl of Bright-Glo (Promega) was added to the wells, and luminescence corresponding to the viability of luciferized tumor cells was determined using a CLARIOstar plate reader. The data were fitted to a sigmoid function to calculate EC50 values ​​(Figure 7). According to the dose survival curves, there were two groups, with tetra and penta-miniGNC molecules being more potent than the tri-miniGNC molecule, SI-49R25. As shown in Table 7, this difference may be due to the addition of αPD-L1. However, the EC50 value (59.3 nM) of SI-49R25 should be considered relatively potent. For the breast cancer cell line MDA-MB-231, CD19, a pan-B cell marker, is a non-involved tumor antigen. In this regard, SI-49R25 can be considered to have two binding specificities for CD3 and NKG2D ligands. Therefore, this data indicates that the incorporation of the NKG2D receptor into various miniGNC antibody forms contributes to the potency of TDCC. In a broader sense, miniGNC antibody molecules can modulate, cooperate, and direct an optimized immune response against target cells such as cancer, corresponding to multiple binding specificities.

[0144] [Table 1]

[0145] [Table 2]

[0146] Table 3

[0147] Table 4

[0148] Table 5

[0149] Table 6

[0150] Table 7

[0151] Table 8

[0152] Table 9

[0153] Match list JPEG0007854121000010.jpg12265JPEG0007854121000011.jpg12865JPEG0007854121 000012.jpg10874JPEG0007854121000013.jpg12469JPEG0007854121000014.jpg6369 >Sequence ID 1: SI-75X5 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 2: SI-75X5 Chain A Nucleotide Sequence >Sequence ID 3: SI-75X5 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 4: SI-75X5 Chain B Nucleotide Sequence >Sequence ID 5: SI-75X6 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 6: SI-75X6 Chain A Nucleotide Sequence >Sequence ID 7: SI-75X6 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 8: SI-75X6 Chain B Nucleotide Sequence >Sequence ID 9: SI-75X7 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 10: SI-75X7 Chain A Nucleotide Sequence >Sequence ID 11: SI-75X7 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 12: SI-75X7 Chain B Amino Acid Sequence >Sequence ID 13: SI-75X8 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 14: SI-75X8 Chain A Nucleotide Acid Sequence >Sequence ID 15: SI-75X8 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 16: SI-75X8 Chain B Nucleotide Sequence >Sequence ID 17: SI-75P6 Chain A Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGSGGGSGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKS CDKTHTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 18: SI-75P6 Chain A Nucleotide Sequence >Sequence ID 19: SI-75P6 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSTHVIFGGGTKVTLGGGGSGGGGSGGGGSGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYCARDRGVGYFDLWG RGTLVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNWPTTFGPGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSTTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTC PPCPAPEAAGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGPYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPSTL SASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 21: SI-75P4 Chain A Amino Acid Sequence >Sequence ID 22: SI-75P4 Chain A Nucleotide Sequence >Sequence ID 23: SI-75P4 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSTHVIFGGGTKVTLGGGGSGGGGSGGGGSGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYCARDRGVGYFDLWGRG TLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTH TCPPCPAPEAAGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 24: SI-75P4 Chain B Nucleotide Sequence >Sequence ID 25: SI-75P3 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGGSGTEFTLISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 26: SI-75P3 Chain A Nucleotide Sequence >Sequence ID 27: SI-75P3 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSTHVIFGGGTKVTLGGGGSGGGGSGGGGSGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYCARDRGVGYFDLWGRG TLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTH TCPPCPAPEAAGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 28: SI-75P3 Chain B Nucleotide Sequence >Sequence ID 29: SI-75P9 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSQVQLQESGGGLVKPGGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKT HTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 31: SI-75P9 Chain B Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGGSGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLRTPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECSGGDKT HTCPPCPAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGPYPSDIAVEWESNGQPENNYKTPPVLDSDGSFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGSDIQMTQSPS TLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 32: SI-75P9 Chain B Nucleotide Sequence >Sequence ID 33: SI-75E1 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGGSGTEFTLISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 34: SI-75E1 Chain A Nucleotide Sequence >Sequence ID 35: SI-75E1 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 36: SI-75E1 Chain B Nucleotide Sequence >Sequence ID 37: SI-75E2 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 38: SI-75E2 Chain A Nucleotide Sequence >Sequence ID 39: SI-75E2 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSTHVIFGGGTKVTLGGGGSGGGGSGGGGSGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYCARDRGVGYFDLWGRG TLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTH TCPPCPAPEAAGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 40: SI-75E2 Chain B Nucleotide Sequence >Sequence ID 41: SI-75x3 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 42: SI-75X3 Chain A Nucleotide Sequence >Sequence ID 43: SI-75X3 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 44: SI-75X3 Chain B Nucleotide Sequence >Sequence ID 45: SI-75X16 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSQVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 46: SI-75X16 Chain A Nucleotide Sequence >Sequence ID 47: SI-75X16 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 48: SI-75X16 Chain B Nucleotide Sequence >Sequence ID 49: SI-75X18 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVL >Sequence ID 50: SI-75X18 Chain A Nucleotide Sequence >Sequence ID 51: SI-75X18 Chain B Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVL >Sequence ID 52: SI-75X18 Chain B Nucleotide Sequence >Sequence ID 53: SI-75X1 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 54: SI-75X1 Chain A Nucleotide Sequence >Sequence ID 55: SI-75X1 Chain B Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 56: SI-75X1 Chain B Nucleotide Sequence >Sequence ID 57: SI-75X2 Chain A Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 58: SI-75X2 Chain A Nucleotide Sequence >Sequence ID 59: SI-75X2 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 60: SI-75X2 Chain B Nucleotide Sequence >Sequence ID 61: SI-75O2 Chain A Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 62: SI-75O2 Chain A Nucleotide Sequence >Sequence ID 63: SI-75O2 Chain B Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 64: SI-75O2 Chain B Nucleotide Sequence >Sequence ID 65: SI-75O7 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 66: SI-75O7 Chain A Nucleotide Sequence >Sequence ID 67: SI-75O7 Chain B Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 68: SI-75O7 Chain B Nucleotide Sequence >Sequence ID 69: SI-68P13 Chain A Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGGSGTEFTLISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 70: SI-68P13 Chain A Nucleotide Sequence >Sequence ID 71: SI-68P13 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAADTAVYCARMELWSYYFDYWGQGTL VTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTTH CPPCPAEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 72: SI-68P13 Chain B Nucleotide Sequence >Sequence ID 73: SI-68P17 Chain A Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGSGGGSGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKS CDKTHTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 74: SI-68P17 Chain A Nucleotide Sequence >Sequence ID 75: SI-68P17 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYCARMELWSYYFDYWGQGT LVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNWPTTFGPGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPP CAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPSTLS ASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 76: SI-68P17 Chain B Nucleotide Sequence >Sequence ID 77: SI-68P15 Chain A Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVLGGGGSGGGGSGGGGSGGGGSEGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGSGGGSGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTFPTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKS CDKTHTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 78: SI-68P15 Chain A Nucleotide Sequence >Sequence ID 79: SI-68P15 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYCARMELWSYYFDYWGQGT LVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNWPTTFGPGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPP CAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPSTLS ASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 80: SI-68P15 Chain B Nucleotide Sequence >Sequence ID 81: SI-68P18 Chain A Amino Acid Sequence DVQMTQSPSTLSATVGQRVTINCQASESISSWLAWYQQKPGQPPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQSDDFATYYCQGYFYFISRTYVNSFGGGTRVEIKGGGGSGGGGSGGGGSGGGGSQQLLESGGGRLIKPGATLRLTCKTSGFTISTNAMSWVRQPPGKGLEWIGVITGRDITYYASWAKGRFTISKTSINTVFLQMRSLRAEDTAVYYCARDGGSSAITSNNIWGRGTLVTVSSGGGSGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC DKTHTCPCPPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 82: SI-68P18 Chain A Nucleotide Sequence >Sequence ID 83: SI-68P18 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYCARMELWSYYFDYWGQGT LVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNWPTTFGPGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPP CAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPSTLS ASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 84: SI-68P18 Chain B Nucleotide Sequence >Sequence ID 85: SI-68P19 Chain A Amino Acid Sequence DVVMTQSPSSLSASVGDRVTISCQASESISSWLAWYQQKPGQAPKLLIYEASKLASGVPSRFSGSGSGTEFTLISSLEPEDFATYYCQGYFYFISRTYVNSFGGGTKVEIKGGGGSGGGSGGGSGGGSGGGSQQLVESGGGLVKPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISKTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGSGGGSGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC DKTHTCPCPPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 86: SI-68P19 Chain A Nucleotide Sequence >Sequence ID 87: SI-68P19 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYCARMELWSYYFDYWGQGT LVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNWPTTFGPGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPP CAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPSTLS ASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 88: SI-68P19 Chain B Nucleotide Sequence >Sequence ID 89: SI-68P16 Chain A Amino Acid Sequence DPVLTQSPSSLSASVGDRVTISCQSSQSVAKNNNLAWFQQKPGQAPKLLIYSASTLAAGVPSRFSGSGSGTDFTLTISSVQPEDFATYYCSARDSGNIQSFGGGTKVEIKGGGGSGGGSGGGSGGGSQQLVESGGGLVKPGGSLRLSCAASGIDLSSNAIGWVRQAPGKGLEWVGVIFGSGNTYYASWAKGRFTISRSKNTVYLQMNSLRAEDTAVYYCARGGYSSDIWGQGTLVTVSSGGGSGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 90: SI-68P16 Chain A Nucleotide Sequence >Sequence ID 91: SI-68P16 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYCARMELWSYYFDYWGQGT LVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNWPTTFGPGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPP CAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPSTLS ASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 92: SI-68P16 Chain B Nucleotide Sequence >Sequence ID 93: SI-75P5 Chain A Amino Acid Sequence EVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 94: SI-75P5 Chain A Nucleotide Sequence >Sequence ID 95: SI-75P5 Chain B Amino Acid Sequence QVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 96: SI-75P5 Chain B Nucleotide Sequence >Sequence ID 97: SI-75P8 Chain A Amino Acid Sequence EVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSSGGGGSGGGGSQVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVL >Sequence ID 98: SI-75P8 Chain A Nucleotide Sequence >Sequence ID 99: SI-75P8 Chain B Amino Acid Sequence QVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVL >Sequence ID 100: SI-75P8 Chain B Nucleotide Sequence >Sequence ID 101: SI-75X4 Chain A Amino Acid Sequence EVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMSSLRSEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 102: SI-75X4 Chain A Nucleotide Sequence >Sequence ID 103: SI-75X4 Chain B Amino Acid Sequence QVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 104: SI-75X4 Chain B Nucleotide Sequence >Sequence ID 105: SI-75X17 Chain A Amino Acid Sequence EVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSSGGGGSGGGGSQVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 106: SI-75X17 Chain A Nucleotide Sequence >Sequence ID 107: SI-75X17 Chain B Amino Acid Sequence QVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 108: SI-75X17 Chain B Nucleotide Sequence >Sequence ID 109: SI-75X19 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSS >Sequence ID 110: SI-75X19 Chain A Nucleotide Sequence >Sequence ID 111: SI-75X19 Chain B Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSQVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSS >Sequence ID 112: SI-75X19 Chain B Nucleotide Sequence >Sequence ID 113: SI-75X9 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 114: SI-75X9 Chain A Nucleotide Sequence >Sequence ID 115: SI-75X9 Chain B Amino Acid Sequence QVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 116: SI-75X9 Chain B Nucleotide Sequence >Sequence ID 117: SI-75X11 Chain A Amino Acid Sequence EVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSSGGGGSGGGGSQVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 118: SI-75X11 Chain A Nucleotide Sequence >Sequence ID 119: SI-75X11 Chain B Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 120: SI-75X11 Chain B Nucleotide Sequence >Sequence ID 121: SI-75X15 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 122: SI-75X15 Chain A Nucleotide Sequence >Sequence ID 123: SI-75X15 Chain B Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPGGGGGSGGGGSQVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSS >Sequence ID 124: SI-75X15 Chain B Amino Acid Sequence >Sequence ID 125: SI-75X13 Chain A Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSS >Sequence ID 126: SI-75X13 Chain A Nucleotide Sequence >Sequence ID 127: SI-75X13 Chain B Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLSPG >Sequence ID 128: SI-75X13 Chain B Nucleotide Sequence >Sequence ID 129: SI-38P11 Chain A Amino Acid Sequence QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDASAVYCARSTYYGGDWYFNVWGAG TTVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVREPKSCD KTHTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 130: SI-38P11 Chain A Nucleotide Sequence >Sequence ID 131: SI-38P11 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAADTAVYCARMELWSYYFDYWGQGTL VTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTTH CPPCPAEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 132: SI-38P11 Chain B Nucleotide Sequence >Sequence ID 133: SI-76PM1 Chain A Amino Acid Sequence QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDASAVYCARSTYYGGDWYFNVWGAG TTVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKCLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCD KTHTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVLGGGGSGGGSGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 134: SI-76PM1 Chain A Nucleotide Sequence >Sequence ID 135: SI-76PM1 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAADTAVYCARMELWSYYFDYWGQGTL VTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTTH CPPCPAEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 136: SI-76PM1 Chain B Nucleotide Sequence >Sequence ID 137: SI-68X2 Chain A Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGCGTKVEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKCLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 138: SI-68X2 Chain A Nucleotide Sequence >Sequence ID 139: SI-68X2 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKCLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSTGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 140: SI-68X2 Chain B Nucleotide Sequence >Sequence ID 141: SI-68E1 Chain A Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGCGTKVEIKGGGGSGGGSGGGSGGGSGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKCLEWIGHIYYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSTGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCD KTHTCPPCPAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLPGGGGGSGGGGSRSLVE SGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDATYYCQSTYLGTDYVGGAFGCGTKVEIK >Sequence ID 142: SI-68E1 Chain A Nucleotide Sequence >Sequence ID 143: SI-68E1 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKCLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSTGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 144: SI-68E1 Chain B Nucleotide Sequence >Sequence ID 145: SI-68E2 Chain A Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGCGTKVEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKCLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 146: SI-68E2 Chain A Nucleotide Sequence >Sequence ID 147: SI-68E2 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKCLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSTGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKCLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGCGTKVEIK >Sequence ID 148: SI-68E2 Chain B Nucleotide Sequence >Sequence ID 149: SI-68P1 Chain A Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGCGTKVEIKGGGGSGGGSGGGSGGGSGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKCLEWIGHIYYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSTGGGSGGGSGGGSEVQLVESGGGLVQPGGSLRLSCAASGFISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCD KTHTCPPCPAPEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLPGGGGGSGGGGSRSLVE SGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDATYYCQSTYLGTDYVGGAFGCGTKVEIK >Sequence ID 150: SI-68P1 Chain A Nucleotide Sequence >Sequence ID 151: SI-68P1 Chain B Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKCLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSTGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKCLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGCGTKVEIK >Sequence ID 152: SI-68P1 Chain B Nucleotide Sequence >Sequence ID 153: SI-49R26 Chain A Amino Acid Sequence FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 154: SI-49R26 Chain A Nucleotide Sequence >Sequence ID 155: SI-49R26 Chain B Amino Acid Sequence FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 156: SI-49R26 Chain B Nucleotide Sequence >Sequence ID 157: SI-49R27 Chain A Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKCLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 158: SI-49R27 Chain A Nucleotide Sequence >Sequence ID 159: SI-49R27 Chain B Amino Acid Sequence FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 160: SI-49R27 Chain B Nucleotide Sequences >Sequence ID 161: SI-49R25 Chain A Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKCLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 162: SI-49R25 Chain A Nucleotide Sequence >Sequence ID 163: SI-49R25 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 164: SI-49R25 Chain B Nucleotide Sequence >Sequence ID 165: SI-49P_x Chain A Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKCLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 166: SI-49P_x Chain A Nucleotide Sequence >Sequence ID 167: SI-49P_x Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKCLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGCGTKVEIK >Sequence ID 168: SI-49P_x Chain B Nucleotide Sequence >Sequence ID 169: SI-49P8 Chain A Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKCLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSTGGGSGGGSGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGGSGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGVNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGSDGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGCGTKVEIK >Sequence ID 170: SI-49P8 Chain A Nucleotide Sequence >Sequence ID 171: SI-49P8 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKCLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGCGTKVEIK >Sequence ID 172: SI-49P8 Chain B Nucleotide Sequence >Sequence ID 173: SI-49PM1 Chain A Amino Acid Sequence >Sequence ID 174: SI-49PM1 Chain A Nucleotide Sequence >Sequence ID 175: SI-49PM1 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTLGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAADTAVYCARMELWSYYFDYWGQGTL VTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTTH CPPCPAEAAGGPSVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRFTQKSLSLPGGGGGSGGGGSDIQMTQSPST LSASVGDRVTITCQASQSISSHLNWYQQKPGKAPCLLIYKASTLASGVPSRFSGSGSGTETLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARSASFDYAMDLWGQGTLVTVSS >Sequence ID 176: SI-49PM1 Chain B Nucleotide Sequence >Sequence ID 177: SI-49P9 Chain A Amino Acid >Sequence ID 178: SI-49P9 Chain A Nucleotide Sequence >Sequence ID 179: SI-49P9 Chain B Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKCLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGCGTKVEIK >Sequence ID 180: SI-49P9 Chain B Nucleotide Sequence >Sequence ID 181: SI-1C3 Heavy Chain Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 182: SI-1C3 Heavy Chain Nucleotide Sequence >Sequence ID 183: SI-1C3 Light Chain Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >Sequence ID 184: SI-1C3 Light Chain Nucleotide Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCGGAGGGACCAAGGTGGAAATTAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >Sequence ID 185: SI-1C7 Amino Acid Sequence EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVL >Sequence ID 186: SI-1C7 Nucleotide Sequence >Sequence ID 187: SI-9C21 Heavy Chain Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 188: SI-9C21 Heavy Chain Nucleotide Sequence >Sequence ID 189: SI-9C21 Light Chain Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >Sequence ID 190: SI-9C21 Light Chain Nucleotide Sequence GAAATCGTTATGACGCAGAGTCCCTCCACGCTCTCCGCTAGTGTCGGGGATCGCGTCATTATCACATGCCAGGCCTCCGAGTCAATCAGCAGCTGGCTTGCATGGTATCAACAGAAGCCGGGAAAAGCTCCTAAATTGCTGATCTATGAAGCGTCAAAATTGGCGTCTGGTGTCCCATCTAGGTTCTCCGGCTCTGGGTCTGGTGCGGAATTTACTTTGACAATCTCCAGTCTTCAACCAGACGATTTCGCTACCTACTACTGCCAAGGGTATTTCTATTTTATAAGCCGGACATATGTAAACTCCTTCGGCCAAGGAACAAAGTTGACTGTTCTTCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >Sequence ID 191: SI-35FS11 Amino Acid Sequence EPKSSDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK >Sequence ID 192: SI-35FS11 Nucleotide Sequence >Sequence ID 193: SI-3FS11 Amino Acid Sequence EPKSSDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIK >Sequence ID 194: SI-3FS11 Nucleotide Sequence >Sequence ID 195: SI-68X1 Chain A Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCQASENIYSNLAWYQQKPGKAPKLLIYDASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSTYYNNIIYGAAFGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFSFSGTQYVCWVRQAPGKCLEWIGCIYVDVANTYYATSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASHDTVCAGCGLDLWGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 196: SI-68X1 Chain A Nucleotide Sequence >Sequence ID 197: SI-68X1 Chain B Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGCGTKVEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKCLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSTGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 198: SI-68X1 Chain B Nucleotide Sequence >Sequence ID 199: SI-68X3 Chain A Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 200: SI-68X3 Chain A Nucleotide Sequence >Sequence ID 201: SI-68X3 Chain B Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >Sequence ID 202: SI-68X3 Chain B Nucleotide Sequence >Sequence ID 203: αEGFR VH Amino Acid Sequence QVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSS >Sequence ID 204: αEGFR VH Nucleotide Sequence CAAGTACAGTTGCAGCAATCCGGTCCCGGTCTCGTCAAACCGAGTGAGACGCTTAGTATAACGTGTACTGTTTCAGGCTTTAGCCTTACGAACTATGGAGTTCACTGGATTCGGCAGGCACCCGGCAAAGGTTTGGAATGGCTGGGTGTTATTTGGTCAGGTGGAAATACAGACTATAACACCCCCTTTACAAGTCGGTTCACAATTACGAAAGATAATTCCAAAAATCAAGTTTATTTCAAGTTGAGATCCGTCCGCGCGGACGACACTGCGATCTACTATTGTGCGAGGGCACTGACCTACTACGATTACGAATTTGCGTATTGGGGGCAAGGGACTCTTGTAACAGTCTCGAGC >Sequence ID 205: αEGFR VL Amino Acid Sequence EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVL >Sequence ID 206: αEGFR VL Nucleotide Sequence GAAATCGTCCTTACACAATCTCCTAGCACACTGAGTGTGAGCCCCGGCGAACGCGCGACTTTCTCTTGCAGGGCAAGTCAATCCATAGGGACTAATATACATTGGTATCAACAAAAGCCAGGTAAACCACCCAGGCTTTTGATTAAGTATGCAAGTGAGTCTATTTCCGGTATCCCTGACCGCTTCTCTGGATCAGGCAGTGGCACAGAGTTCACACTCACCATATCTAGTGTGCAATCAGAGGACTTCGCCGTGTATTACTGCCAACAGAATAATAACTGGCCGACTACCTTCGGACCCGGTACAAAGCTGACCGTTTTA >Sequence ID 207: αEGFR* VH Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSS >Sequence ID 208: αEGFR* VH Nucleotide Sequence CAAGTGCAACTCCAGGAGAGTGGGCCGGGATTGGTTAAACCGAGCGAGACCCTGAGTCTCACGTGTACAGTTTCAGGCGGGAGCGTGAGCTCAGGCGACTATTACTGGACATGGATAAGACAGAGTCCTGGAAAGGGCCTGGAGTGGATCGGTCATATTTATTATTCAGGGAACACTAACTATAATCCATCTTTGAAATCCCGATTGACAATCTCTATCGATACCAGTAAAACCCAGTTTAGCCTCAAGCTGTCCAGCGTTACTGCTGCAGACACAGCCATATACTATTGCGTACGCGATCGCGTGACTGGAGCCTTCGACATATGGGGGCAGGGAACGATGGTAACAGTCTCGAGC >Sequence ID 209: αEGFR* VL Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKVEIK >Sequence ID 210: αEGFR* VL Nucleotide Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCGGAGGGACCAAGGTGGAAATTAAA >Sequence ID 211: αEGFR* VH Stapled Amino Acid Sequence QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKCLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVST >Sequence ID 212: αEGFR* VH Stapled Nucleotide Sequence CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCGTCAGCAGTGGTGATTACTACTGGACCTGGATCCGGCAGTCCCCAGGGAAGTGCCTGGAGTGGATTGGACACATCTATTACAGTGGGAACACCAATTATAACCCCTCCCTCAAGAGCCGACTCACCATATCAATTGACACGTCCAAGACTCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGCTGCGGACACGGCCATTTATTACTGTGTGCGAGATCGAGTGACTGGTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTGTCGACA >Sequence ID 213: αEGFR* VL Stapled Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGCGTKVEIK >Sequence ID 214: αEGFR* VL Stapled Nucleotide Sequence GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCTGTGGGACCAAGGTGGAAATTAAA >Sequence ID 215: αCD19 VH Amino Acid Sequence QVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS >Sequence ID 216: αCD19 VH Nucleotide Sequence CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGCCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGC >Sequence ID 217: αCD19 VL Amino Acid Sequence ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVL >Sequence ID 218: αCD19 VL Nucleotide Sequence GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTGACCGTCCTA >Sequence ID 219: αCD3 VH Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSS >Sequence ID 220: αCD3 VH Nucleotide Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGTCATTACTGGTCGTGATATCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGTGGTTCTTCTGCTATTACTAGTAACAACATTTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA >Sequence ID 221: αCD3 VL Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIK >Sequence ID 222: αCD3 VL Nucleotide Sequence GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >Sequence ID 223: αCD3 VH stapled Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKCLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSS >Sequence ID 224: αCD3 VH stapled Nucleotide Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGTGTCTGGAGTGGATCGGAGTCATTACTGGTCGTGATATCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGTGGTTCTTCTGCTATTACTAGTAACAACATTTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCA >Sequence ID 225: αCD3 VL stapled Amino Acid Sequence DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKVEIK >Sequence ID 226: αCD3 VL stapled Nucleotide Sequence GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCTGTGGGACCAAGGTGGAGATCAAA >Sequence ID 227: αCD3* VH Amino Acid Sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSS >Sequence ID 228: αCD3* VH Nucleotide Sequence CAAGTGCAGTTGCAAGAAAGTGGTGGTAGACTGGTTCAGCCTGGTGAACCCTTGTCACTGACGTGTAAAACAAGCGGCATTGATCTGTCCTCTAACGCCATCGGATGGGTCCGACAGGCCCCAGGAAAAGGTCTGGAGTGGATCGGAGTTATCTTCGGGAGCGGCAATACATACTACGCAAGCTGGGCAAAAGGGCGATTTACGATATCACGGAGCACCTCTACAGTTTATTTGAAAATGAACTCCCTCCGGTCCGAGGATACCGCGATATATTACTGTGCCAGAGGGGGGTACTCCTCTGATATCTGGGGGCAGGGTACACTGGTTACAGTTTCATCC >Sequence ID 229: αCD3* VL Amino Acid Sequence DPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIK >Sequence ID 230: αCD3* VL Nucleotide Sequence GATCCTCAATTGACCCAGTCCCCTAGTAGCCTTTCTGCAACCGTGGGCCAGAGGGTAACAATCAATTGCCAGTCAAGCCAGTCCGTAGCGAAGAATAATAATTTGGCATGGTTCCAACAAAAACCGGGTAAACCTCCTAAACTCCTTATCTACTCAGCTTCAACCCTTGCCGCGGGTGTGCCCAGCCGGTTCTCAGGCTCAGGTTCCGGGACTCAATTTACACTTACCATCACTCGCGTCCAAAGTGAGGATTTTGCAACCTACTATTGTTCTGCACGGGATTCCGGGAACATACAGTCCTTTGGGGGTGGAACTCGGGTGGAGATAAAA >Sequence ID 231: αCD3** VH Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSS >Sequence ID 232: αCD3** VH Nucleotide Sequence GAAGTCCAATTGGTAGAAAGTGGCGGTGGTCTGGTGCAACCTGGTGGATCTCTTCGCCTCTCATGCGCCGCTAGTGGCTTTACTATTTCAACTAATGCGATGAGCTGGGTTCGCCAGGCCCCCGGCAAAGGACTTGAGTGGGTCGGCGTCATCACCGGCAGGGACATTACATACTATGCGAGTTGGGCAAAGGGCAGGTTCACGATTAGCCGCGATACTTCAAAGAATACCGTTTACCTTCAAATGAATAGCTTGAGGGCGGAAGACACAGCTGTGTATTACTGCGCGAGGGATGGAGGTAGTTCCGCCATAACTTCCAACAACATATGGGGACAAGGCACGCTGGTTACTGTCTCGAGT >Sequence ID 233: αCD3** VL Amino Acid Sequence EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVL >Sequence ID 234: αCD3** VL Nucleotide Sequence GAAATCGTTATGACGCAGAGTCCCTCCACGCTCTCCGCTAGTGTCGGGGATCGCGTCATTATCACATGCCAGGCCTCCGAGTCAATCAGCAGCTGGCTTGCATGGTATCAACAGAAGCCGGGAAAAGCTCCTAAATTGCTGATCTATGAAGCGTCAAAATTGGCGTCTGGTGTCCCATCTAGGTTCTCCGGCTCTGGGTCTGGTGCGGAATTTACTTTGACAATCTCCAGTCTTCAACCAGACGATTTCGCTACCTACTACTGCCAAGGGTATTTCTATTTTATAAGCCGGACATATGTAAACTCCTTCGGCCAAGGAACAAAGTTGACTGTTCTT >Sequence ID 235: αCD3*** VH Amino Acid Sequence QQLLESGGRLIKPGATLRLTCKTSGFTISTNAMSWVRQPPGKGLEWIGVITGRDITYYASWAKGRFTISKTSINTVFLQMRSLRAEDTAVYYCARDGGSSAITSNNIWGRGTLVTVSS >Sequence ID 236: αCD3*** VH Nucleotide Sequence CAGCAGCTGCTGGAAAGCGGCGGCCGCCTGATTAAACCGGGCGCGACCCTGCGCCTGACCTGCAAAACCAGCGGCTTTACCATTAGCACCAACGCGATGAGCTGGGTGCGCCAGCCGCCGGGCAAAGGCCTGGAATGGATTGGCGTGATTACCGGCCGCGATATTACCTATTATGCGAGCTGGGCGAAAGGCCGCTTTACCATTAGCAAAACCAGCATTAACACCGTGTTTCTGCAGATGCGCAGCCTGCGCGCGGAAGATACCGCGGTGTATTATTGCGCGCGCGATGGCGGCAGCAGCGCGATTACCAGCAACAACATTTGGGGCCGCGGCACCCTGGTGACCGTGAGCAGC >Sequence ID 237: αCD3*** VL Amino Acid Sequence DVQMTQSPSTLSATVGQRVTINCQASESISSWLAWYQQKPGQPPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQSDDFATYYCQGYFYFISRTYVNSFGGGTRVEIK >Sequence ID 238: αCD3*** VL Nucleotide Sequence GATGTGCAGATGACCCAGAGCCCGAGCACCCTGAGCGCGACCGTGGGCCAGCGCGTGACCATTAACTGCCAGGCGAGCGAAAGCATTAGCAGCTGGCTGGCGTGGTATCAGCAGAAACCGGGCCAGCCGCCGAAACTGCTGATTTATGAAGCGAGCAAACTGGCGAGCGGCGTGCCGAGCCGCTTTAGCGGCAGCGGCAGCGGCACCGAATTTACCCTGACCATTAGCAGCCTGCAGAGCGATGATTTTGCGACCTATTATTGCCAGGGCTATTTTTATTTTATTAGCCGCACCTATGTGAACAGCTTTGGCGGCGGCACCCGCGTGGAAATTAAA >Sequence ID 239: αCD3**** VH Amino Acid Sequence QQLVESGGGLVKPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISKTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSS >Sequence ID 240: αCD3**** VH Nucleotide Sequence CAGCAGCTGGTGGAAAGCGGCGGCGGCCTGGTGAAACCGGGCGGCAGCCTGCGCCTGAGCTGCGCGGCGAGCGGCTTTACCATTAGCACCAACGCGATGAGCTGGGTGCGCCAGGCGCCGGGCAAAGGCCTGGAATGGGTGGGCGTGATTACCGGCCGCGATATTACCTATTATGCGAGCTGGGCGAAAGGCCGCTTTACCATTAGCAAAACCAGCAAAAACACCGTGTATCTGCAGATGAACAGCCTGCGCGCGGAAGATACCGCGGTGTATTATTGCGCGCGCGATGGCGGCAGCAGCGCGATTACCAGCAACAACATTTGGGGCCAGGGCACCCTGGTGACCGTGAGCAGC >Sequence ID 241: αCD3**** VL Amino Acid Sequence DVVMTQSPSSLSASVGDRVTISCQASESISSWLAWYQQKPGQAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLEPEDFATYYCQGYFYFISRTYVNSFGGGTKVEIK >Sequence ID 242: αCD3**** VL Nucleotide Sequence GATGTGGTGATGACCCAGAGCCCGAGCAGCCTGAGCGCGAGCGTGGGCGATCGCGTGACCATTAGCTGCCAGGCGAGCGAAAGCATTAGCAGCTGGCTGGCGTGGTATCAGCAGAAACCGGGCCAGGCGCCGAAACTGCTGATTTATGAAGCGAGCAAACTGGCGAGCGGCGTGCCGAGCCGCTTTAGCGGCAGCGGCAGCGGCACCGAATTTACCCTGACCATTAGCAGCCTGGAACCGGAAGATTTTGCGACCTATTATTGCCAGGGCTATTTTTATTTTATTAGCCGCACCTATGTGAACAGCTTTGGCGGCGGCACCAAAGTGGAAATTAAA >Sequence ID 243: αPD-L1 VH Amino Acid Sequence EVQLLESGGGLVQPGGSLSLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 244: αPD-L1 VH Nucleotide Sequence GAAGTGCAATTGCTCGAAAGTGGTGGCGGACTTGTGCAACCTGGTGGAAGCCTCTCACTCTCTTGCGCGGCGAGTGGTTTTAGCTTCAGTAGCGGCTACGATATGTGCTGGGTAAGACAGGCTCCTGGTAAAGGCCTTGAGTGGATTGCGTGTATCGCCGCCGGGTCTGCTGGTATAACATACGATGCAAACTGGGCGAAAGGGCGCTTCACAATCTCCAGGGACAACTCAAAAAATACATTGTACCTCCAGATGAATAGCCTGAGAGCCGAAGACACCGCAGTCTACTATTGCGCAAGGTCAGCATTTAGCTTCGATTATGCAATGGATCTTTGGGGCCAGGGGACGCTCGTCACCGTCTCATCTTGA >Sequence ID 245: αPD-L1 VL Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVTVL >Sequence ID 246: αPD-L1 VL Nucleotide Sequence GACATTCAGATGACACAGTCACCGTCTACGCTCTCAGCCTCAGTAGGCGATAGGGTGACTATCACCTGCCAAGCCTCCCAATCTATAAGTTCACACCTCAACTGGTATCAACAGAAACCCGGTAAAGCACCGAAGCTGCTCATCTACAAGGCATCAACTCTTGCCTCAGGTGTGCCTAGTCGCTTCTCCGGGAGCGGCTCCGGTACTGAGTTTACTTTGACGATATCTTCCCTCCAACCCGACGACTTCGCCACATACTATTGTCAGCAGGGTTATAGTTGGGGAAATGTTGACAATGTGTTTGGAGGGGGAACGAAAGTGACTGTGTTG >Sequence ID 247: α4-1BB VH Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 248: α4-1BB VH Nucleotide Sequence GAGGTTCAGTTGGTTGAAAGTGGGGGGGGACTCGTTCAGCCTGGAGGCTCTTTGCGACTTTCTTGTACCGCTTCTGGGTTCACTATAAGTTCATATCATATGCAATGGGTAAGACAGGCGCCTGGTAAGGGACTTGAATACATAGGAACAATAAGCTCTGGTGGTAACGTCTATTACGCCTCATCCGCGCGGGGGAGGTTTACAATTTCCAGGCCTTCTAGCAAAAACACGGTAGATCTGCAAATGAACTCTCTTCGCGCTGAAGATACAGCAGTCTACTACTGCGCCAGGGATTCAGGGTATTCTGACCCCATGTGGGGGCAGGGCACATTGGTTACCGTGTCCTCT >Sequence ID 249: α4-1BB VL Amino Acid Sequence DVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKLTVL >Sequence ID 250: α4-1BB VL Nucleotide Sequence GACGTTGTGATGACGCAGTCTCCTAGTTCAGTATCAGCGTCTGTTGGGGATCGAGTCACGATTACATGCCAGGCGAGCCAAAATATTAGGACGTATCTGTCTTGGTATCAACAAAAGCCTGGTAAGGCTCCAAAACTCCTCATTTACGCCGCTGCCAACTTGGCTAGTGGAGTACCTTCACGCTTTAGTGGGTCAGGTTCTGGAACAGATTTTACGTTGACGATCTCCGATTTGGAACCAGGGGACGCTGCCACGTATTATTGCCAGTCCACCTACCTCGGGACTGACTACGTTGGTGGGGCGTTTGGCGGAGGAACAAAACTCACTGTACTT >Sequence ID 251: 41BBL Amino Acid Sequence REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >Sequence ID 252: 41BBL Nucleotide Sequence >Sequence ID 253: NKG2D dimer Amino Acid Sequence FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >Sequence ID 254: NKG2D dimer Nucleotide Sequence TTTCTTAATTCCCTTTTCAACCAAGAGGTTCAGATCCCCTTGACTGAAAGCTATTGCGGCCCTTGTCCGAAAAACTGGATATGTTACAAGAATAATTGTTACCAATTCTTCGACGAAAGCAAGAACTGGTATGAGAGTCAGGCGTCTTGTATGAGTCAGAATGCCAGCCTGCTTAAGGTTTATTCAAAAGAAGACCAGGATCTGCTTAAGTTGGTAAAGAGCT ACCACTGGATGGGGCTGGTACATATCCCAACGAATGGGTCATGGCAGTGGGAGGACGGTTCTATTCTGAGTCCAAATCTCCTGACGATCATCGAAATGCAGAAAGGGGACTGTGCCCTGTATGCATCATCCTTCAAGGGGTACATCGAGAACTGCAGTACCCCAAATACCTACATTTGTATGCAAAGAACGGTTGGAGGCGGTGGCTCAGGCGGAGGCGGCTCA GGAGGTGGCGGTTCAGGAGGCGGCGGATCTTTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTG >Sequence ID 255: αHER3 VH Amino Acid Sequence QVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >Sequence ID 256: αHER3 VH Nucleotide Sequence CAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGCCTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCGAGT >Sequence ID 257: αHER3 VL Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVL >Sequence ID 258: αHER3 VL Nucleotide Sequence CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTCTCCGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCGGAGGGACCAAGGTGACCGTCCTA >Sequence ID 259: αCD20 VH Amino Acid Sequence QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSS >Sequence ID 260: αCD20 VH Nucleotide Sequence CAGGTGCAGCTGCAGCAGCCCGGCGCCGAGCTGGTGAAGCCCGGCGCCAGCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACAACATGCACTGGGTGAAGCAGACCCCCGGCCGGGGCCTGGAGTGGATCGGCGCCATCTACCCCGGCAACGGCGACACCAGCTACAACCAGAAGTTCAAGGGCAAGGCCACCCTGACCGCCGACAAGAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACCAGCGAGGACAGCGCCGTGTACTACTGCGCCCGGAGCACCTACTACGGCGGCGACTGGTACTTCAACGTGTGGGGCGCCGGCACCACCGTGACCGTCTCGAGC >Sequence ID 261: αCD20 VL Amino Acid Sequence QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLTVL >Sequence ID 262: αCD20 VL Nucleotide Sequence CAGATCGTGCTGAGCCAGAGCCCCGCCATCCTGAGCGCCAGCCCCGGCGAGAAGGTGACCATGACCTGCCGGGCCAGCAGCAGCGTGAGCTACATCCACTGGTTCCAGCAGAAGCCCGGCAGCAGCCCCAAGCCCTGGATCTACGCCACCAGCAACCTGGCCAGCGGCGTGCCCGTGCGGTTCAGCGGCAGCGGCAGCGGCACCAGCTACAGCCTGACCATCAGCCGGGTGGAGGCCGAGGACGCCGCCACCTACTACTGCCAGCAGTGGACCAGCAACCCCCCCACCTTCGGCGGCGGCACCAAGCTGACCGTGCTG >Sequence ID 263: EGFR VHH Amino Acid Sequence EVQLQESGGGLVQAGDSLSLSCLVSGRSFNSYTMGWFRQAPGKEREFVAAILWSGPTTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAAALGVLVLAPGNVYSYWGQGTQVTVSS >Sequence ID 264: EGFR VHH Nucleotide Sequence GAGGTGCAGCTGCAGGAGTCTGGCGGCGGCCTGGTGCAGGCTGGGGACAGCCTGAGCCTGTCCTGCCTGGTGTCTGGCCGCTCCTTCAACTCCTACACCATGGGCTGGTTCCGCCAGGCCCCTGGGAAGGAGCGGGAGTTTGTGGCTGCCATCCTGTGGAGTGGCCCCACCACCTACTATGCTGACTCTGTGAAGGGCCGCTTCACCATCTCCAGAGACAATGCCAAGAACACTGTGTACCTGCAGATGAACAGCCTGAAGCCAGAGGACACAGCTGTGTACTACTGTGCTGCTGCCCTGGGAGTGCTGGTGCTGGCCCCTGGCAATGTGTACAGCTACTGGGGCCAGGGCACCCAGGTGACTGTCTCGAGC >Sequence ID 265: HER3 VHH Amino Acid Sequence QVQLVQSGGGLVQAGGSLSLSCAFSGRTFSMYTMGWFRQAPGKEREFVAANRGRGLSPDIADSVNGRFTISRDNAKNTLYLQMDSLKPEDTAVYYCAADLQYGSSWPQRSSAEYDYWGQGTTVTVSS >Sequence ID 266: HER3 VHH Nucleotide Sequence CAGGTGCAGCTGGTGCAGTCTGGCGGAGGCCTGGTGCAGGCTGGGGGCAGCCTGAGCCTGAGCTGTGCCTTCTCTGGCCGCACCTTCTCCATGTACACCATGGGCTGGTTCCGCCAGGCCCCAGGGAAGGAGAGAGAGTTTGTGGCTGCCAACAGAGGCAGAGGCCTGAGCCCAGACATTGCTGACTCTGTGAATGGCCGCTTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAGATGGACAGCCTGAAGCCAGAGGACACAGCTGTGTACTACTGTGCTGCTGACCTGCAGTATGGCAGCAGCTGGCCTCAGAGGAGCTCTGCTGAGTATGACTACTGGGGCCAGGGCACCACTGTGACTGTCTCGAGC >Sequence ID 267: αPD-L1 Stapled VH Amino Acid Sequence EVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKCLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSS >Sequence ID 268: αPD-L1 Stapled VH Nucleotide Sequence GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGTGCCTGGAGTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGTCT >Sequence ID 269: αPD-L1 Stapled VL Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGCGTKVEIK >Sequence ID 270: αPD-L1 Stapled VL Nucleotide Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCTGCGGGACCAAGGTGGAGATCAAATAG >Sequence ID 271: α4-1BB VH Stapled Amino Acid Sequence RSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >Sequence ID 272: α4-1BB VH Stapled Nucleotide Sequence CGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGGCAGGCACCTGGGAAGTGCCTGGAGTACATCGGAACCATTAGTAGTGGTGGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCA >Sequence ID 273: α4-1BB VL Stapled Amino Acid Sequence DVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGCGTKVEIK >Sequence ID 274: α4-1BB VL Stapled Nucleotide Sequence GACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACTTGGAACCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCTGTGGGACCAAGGTGGAGATCAAATGA >Sequence ID 275: αHer3 VH Stapled Amino Acid Sequence QVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKCLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVST >Sequence ID 276: αHer3 VH Stapled Nucleotide Sequence CAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGTGCCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTGTCGACA >Sequence ID 277: αHer3 VL Stapled Amino Acid Sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGCGTKVTVL >Sequence ID 278: αHer3 VL Stapled Nucleotide Sequence CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTCTCCGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCTGTGGGACCAAGGTGACCGTCCTA >Sequence ID 279: αCEA 656E11 VH Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFSFSGTQYVCWVRQAPGKGLEWIGCIYVDVANTYYATSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASHDTVCAGCGLDLWGQGTLVTVSS >Sequence ID 280: αCEA 656E11 VH Nucleotide Sequence GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTGGCACCCAGTACGTGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATGCATTTATGTGGATGTGGCTAACACTTACTACGCGACCTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGTCATGATACTGTTTGTGCTGGTTGTGGTTTGGACTTGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC >Sequence ID 281: αCEA 656E11 VL Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCQASENIYSNLAWYQQKPGKAPKLLIYDASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSTYYNNIIYGAAFGGGTKVEIK >Sequence ID 282: αCEA 656E11 VL Nucleotide Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTGAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGATGCTTCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAATCTACTTATTATAATAATATCATTTATGGGGCTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >Sequence ID 283: αHER2 VH Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVST >Sequence ID 284: αHER2 VH Nucleotide Sequence GAAGTACAGCTTGTTGAGAGTGGTGGTGGACTTGTCCAACCAGGGGGAAGTCTGCGGCTGTCATGCGCAGCCTCTGGCTTCAACATTAAGGACACCTACATTCACTGGGTTCGGCAAGCGCCGGGGAAGGGGCTGGAATGGGTCGCCAGGATATACCCTACCAACGGGTACACCAGGTATGCAGATAGCGTTAAGGGTAGATTCACTATTTCAGCTGACACTAGCAAGAACACCGCGTATCTCCAGATGAACTCCCTTCGCGCCGAGGATACGGCTGTGTACTACTGCTCTAGGTGGGGAGGAGATGGGTTTTACGCAATGGATTACTGGGGACAGGGAACACTCGTTACGGTGTCGACA >Sequence ID 285: αHER2 VL Amino Acid Sequence DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Sequence ID 286: αHER2 VL Nucleotide Sequence GACATCCAAATGACGCAGTCTCCCTCCAGTTTGAGTGCAAGTGTGGGAGACAGAGTTACGATCACATGTAGGGCAAGTCAGGACGTCAATACAGCCGTCGCATGGTACCAGCAGAAGCCTGGAAAGGCCCCGAAACTTCTGATTTACTCTGCAAGTTTCCTCTACAGTGGTGTTCCTAGTCGCTTCAGTGGGTCTCGGTCAGGCACCGATTTTACCCTGACAATTAGCAGCTTGCAACCGGAAGATTTTGCGACCTATTATTGCCAGCAACATTATACCACCCCTCCCACATTTGGACAAGGCACGAAGGTAGAGATTAAA >Sequence ID 287: SI-20C14 (anti-CEA 656E11) Heavy Chain Amino Acid Sequence EVQLVESGGGLVQPGGSLRLSCAASGFSFSGTQYVCWVRQAPGKGLEWIGCIYVDVANTYYATSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASHDTVCAGCGLDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 288: SI-20C14 (anti-CEA 656E11) Heavy Chain Nucleotide Sequence >Sequence ID 289: SI-20C14 (anti-CEA 656E11) Light Chain Amino Acid Sequence DIQMTQSPSTLSASVGDRVTITCQASENIYSNLAWYQQKPGKAPKLLIYDASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQSTYYNNIIYGAAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >Sequence ID 290: SI-20C14 (anti-CEA 656E11) Light Chain Nucleotide Sequence GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTGAGAACATTTACAGCAATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGATGCTTCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAATCTACTTATTATAATAATATCATTTATGGGGCTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >Sequence ID 291: αCD3***** VH Amino Acid Sequence QQLVESGGGLVKPGGSLRLSCAASGIDLSSNAIGWVRQAPGKGLEWVGVIFGSGNTYYASWAKGRFTISRSKNTVYLQMNSLRAEDTAVYYCARGGYSSDIWGQGTLVTVSS >Sequence ID 292: αCD3***** VH Nucleotide Sequence CAACAGTTGGTTGAGTCTGGTGGCGGTCTCGTTAAGCCTGGAGGGTCCCTTCGGCTTAGTTGTGCGGCCTCTGGGATCGACCTGTCTAGCAACGCTATAGGATGGGTACGGCAAGCTCCGGGCAAAGGCCTTGAGTGGGTCGGCGTTATTTTTGGGAGCGGTAATACGTACTACGCCAGCTGGGCAAAAGGTAGGTTCACTATCAGTCGATCAAAGAACACGGTATATCTTCAGATGAACAGTCTCCGGGCGGAGGACACCGCGGTTTATTATTGCGCAAGGGGGGGATACTCCTCAGACATATGGGGCCAAGGTACTTTGGTGACGGTCTCGAGC >Sequence ID 293: αCD3***** VL Amino Acid Sequence DPVLTQSPSSLSASVGDRVTISCQSSQSVAKNNNLAWFQQKPGQAPKLLIYSASTLAAGVPSRFSGSGSGTDFTLTISSVQPEDFATYYCSARDSGNIQSFGGGTKVEIK >Sequence ID 294: αCD3***** VL Nucleotide Sequence GATCCAGTTCTGACACAAAGTCCATCCAGCCTGTCTGCCTCAGTCGGCGACAGAGTGACCATCAGTTGCCAGAGCTCACAGTCTGTGGCTAAGAACAACAACTTGGCGTGGTTCCAACAGAAACCTGGACAGGCTCCGAAATTGCTGATCTATTCTGCTTCCACGCTTGCTGCTGGTGTTCCTTCCCGCTTTTCAGGTAGTGGTAGCGGGACAGACTTCACTTTGACTATAAGCAGCGTGCAGCCTGAAGATTTTGCGACCTACTATTGTTCTGCTAGAGACAGTGGAAATATTCAGTCCTTTGGGGGGGGAACGAAGGTCGAAATAAAG >Sequence ID 295: NKG2D Monomer Amino Acid Sequence FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >Sequence ID 296: NKG2D Monomer Nucleotide Sequence TTTCTGAATAGCCTGTTCAACCAGGAGGTGCAGATCCCACTGACCGAGAGCTATTGTGGACCTTGTCCTAAGAACTGGATCTGTTACAAGAACAACTGCTACCAGTTCTTCGACGAGAGCAAGAATTGGTATGAAAGCCAGGCCAGCTGCATGAGCCAAAACGCCTCTCTGCTGAAGGTGTACTCCAAAGAAGATCAGGACCTGCTGAAGCTGGTGAAGTCCTACCACTGGATGGGCCTGGTGCACATCCCAACCAACGGCAGCTGGCAGTGGGAAGACGGCAGCATCCTGAGCCCTAACCTGCTGACAATCATTGAGATGCAGAAAGGCGACTGCGCCCTGTACGCCAGTTCTTTTAAGGGCTACATCGAAAACTGTAGCACCCCTAACACCTACATCTGCATGCAGAGAACAGTG >Sequence ID 297: SI-75XM9 chain A amino acid sequence QVQLQESGGRLVQPGEPLSLTCKTSGIDLSSNAIGWVRQAPGKGLEWIGVIFGSGNTYYASWAKGRFTISRSTSTVYLKMNSLRSEDTAIYYCARGGYSSDIWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG >Sequence ID 298: SI-75XM9 chain A nucleotide sequence >Sequence ID 299: SI-75XM9 chain B amino acid sequence QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSSGGGGSGGGGSDPQLTQSPSSLSATVGQRVTINCQSSQSVAKNNNLAWFQQKPGKPPKLLIYSASTLAAGVPSRFSGSGSGTQFTLTITRVQSEDFATYYCSARDSGNIQSFGGGTRVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNRFTQKSLSLSLG >Sequence ID 300: SI-75XM9 chain B nucleotide sequence >Sequence ID 301: anti-CEA 656E11 CDR-H1 amino acid sequence GTQYVC >Sequence ID 302: anti-CEA 656E11 CDR-H2 amino acid sequence CIYVDVANTYYATSVKG >Sequence ID 303: anti-CEA 656E11 CDR-H3 amino acid sequence HDTVCAGCGLDL >Sequence ID 304: anti-CEA 656E11 CDR-L1 amino acid sequence QASENIYSNLA >Sequence ID 305: anti-CEA 656E11 CDR-L2 amino acid sequence DASTLAS >Sequence ID 306: anti-CEA 656E11 CDR-L3 amino acid sequence QSTYYNNIIYGAA >Sequence ID 307: anti-CD3 283E3 (BSM / FRS) CDR-H1 amino acid sequence SNAIG >Sequence ID 308: anti-CD3 283E3 (BSM / FRS) CDR-H2 amino acid sequence VIFGSGNTYYASWAKG >Sequence ID 309: anti-CD3 283E3 (BSM / FRS) CDR-H3 amino acid sequence GGYSSDI >Sequence ID 310: anti-CD3 283E3 (BSM / FRS) CDR-L1 amino acid sequence QSSQSVAKNNNLA >Sequence ID 311: anti-CD3 283E3 (BSM / FRS) CDR-L2 amino acid sequence SASTLAA >Sequence ID 312: anti-CD3 283E3 (BSM / FRS) CDR-L3 amino acid sequence SARDSGNIQS >Sequence ID 313: human IgG1 amino acid sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >Sequence ID 314: human IgG4 amino acid sequence ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG

Claims

1. A multispecific antibody-like protein having an N-terminus and a C-terminus, It comprises a first monomer and a second monomer, The first monomer comprises a first binding monomer, a CH1 domain, a first hinge, a first CH2 domain, and a first CH3 domain from the N-terminus to the C-terminus, and the first monomer comprises a first binding domain (D1) bound to the N-terminus and a fourth binding domain (D4) bound to the terminal. The second monomer comprises a second binding monomer, a CL domain, a second hinge, a second CH2 domain, and a second CH3 domain from the N-terminus to the C-terminus, and the second monomer comprises a second binding domain (D2) bound to the N-terminus and a fifth binding domain (D5) bound to the C-terminus. The first bonded monomer and the second bonded monomer are configured to form a dimer. The first monomer and the second monomer are covalently paired via at least one disulfide bond between the CH1 domain and the CL domain, and at least one disulfide bond between the first hinge and the second hinge. The first conjugated monomer includes a VH domain, the second conjugated monomer includes a VL domain, and the VH, CH1, VL, and CL domains form a Fab region as a third conjugated domain (D3). The multispecific antibody-like protein is a bispecific antibody-like protein, a triplicate antibody-like protein, or a quadruplicate antibody-like protein, wherein in the multispecific antibody-like protein, D1 has binding specificity to EGFR, and D3 has binding specificity to CD3. If the multispecific antibody-like protein is a quadruspecific antibody-like protein, then the quadruspecific antibody-like protein is The amino acid sequence includes the amino acid sequence shown in SEQ ID NO: 33 and the amino acid sequence shown in SEQ ID NO: 35, wherein D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, and D4 has binding specificity to 4-1BB, or The amino acid sequence includes the amino acid sequence shown in SEQ ID NO: 37 and the amino acid sequence shown in SEQ ID NO: 39, wherein D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, and D5 has binding specificity to PD-L1, or The amino acid sequence includes the amino acid sequence shown in SEQ ID NO: 141 and the amino acid sequence shown in SEQ ID NO: 143, wherein D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, and D4 has binding specificity to 4-1BB, or The amino acid sequence includes the amino acid sequence shown in SEQ ID NO: 145 and the amino acid sequence shown in SEQ ID NO: 147, wherein D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, and D5 has binding specificity to PD-L1; If the multispecific antibody-like protein is a triplespecific antibody-like protein, then the triplespecific antibody-like protein is The amino acid sequence includes the amino acid sequence shown in SEQ ID NO: 137 and the amino acid sequence shown in SEQ ID NO: 139, wherein D1 has binding specificity to EGFR, D2 has binding specificity to HER3, D3 has binding specificity to CD3, or The amino acid sequence includes the amino acid sequence shown in SEQ ID NO: 195 and the amino acid sequence shown in SEQ ID NO: 197, wherein D1 has binding specificity to EGFR, D2 has binding specificity to HER3, and D3 has binding specificity to CD3; If the multispecific antibody-like protein is a bispecific antibody-like protein, the bispecific antibody-like protein is A multispecific antibody-like protein comprising the amino acid sequence shown in SEQ ID NO: 53 and the amino acid sequence shown in SEQ ID NO: 55, wherein D1 has binding specificity to EGFR and D3 has binding specificity to CD3.

2. The multispecific antibody-like protein according to claim 1, wherein the first CH3 domain is configured to form a hole structure, the second CH3 domain is configured to form a knob structure, and the first CH2 domain and the first CH3 domain and the second CH2 domain and the second CH3 domain are configured to heterodimerize to form complementary Fc domains.

3. An isolated nucleic acid encoding a multispecific antibody-like protein as described in claim 1.

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.

6. An immune complex comprising the multispecific antibody-like protein described in claim 1 and a cytotoxic agent.

7. A pharmaceutical composition comprising a multispecific antibody-like protein according to claim 1 and a pharmaceutically acceptable carrier.

8. A pharmaceutical composition comprising the immune complex described in claim 6 and a pharmaceutically acceptable carrier.

9. A pharmaceutical composition for treating or preventing a subject suffering from cancer, autoimmune disease, or infectious disease, comprising a purified multispecific antibody-like protein according to claim 1.

10. A method for preparing a multispecific antibody-like protein according to claim 1, A step of culturing host cells so that a DNA sequence encoding the multispecific antibody-like protein described in claim 1 is expressed, The process of purifying the multispecific antibody-like protein, Methods that include...

11. A solution comprising a multispecific antibody-like protein according to claim 1 at an effective concentration, wherein the solution is plasma.

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