Anti-CD39 antibodies, compositions comprising Anti-CD39 antibodies and methods of using Anti-CD39 antibodies

Abstract

To provide anti-CD39 antibodies, compositions comprising anti-CD39 antibodies and methods of using anti-CD39 antibodies.SOLUTION: The disclosure provides an antibody, isoform and homolog thereof that selectively binds to CD39 as well as a composition comprising the antibody. Also provided are methods for using the antibody such as therapeutic and diagnostic methods. In one aspect, the antibody of the invention has the following characteristics: a) the antibody inhibits the binding of CD39 to ATP; b) the antibody inhibits conversion of ATP to ADP and / or ADP to AMP by CD39; c) the antibody reduces the affinity of CD39 to ATP or ADP.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 539,527, filed July 31, 2017, the entire contents of which are incorporated herein by reference.

[0002] Provided herein are antibodies having binding specificity for CD39, and compositions comprising the antibodies, including pharmaceutical compositions, diagnostic compositions, and kits. Methods of using anti-CD39 antibodies for therapeutic and diagnostic purposes are also provided. [Background technology]

[0003] CD39 is an integral membrane protein that phosphohydrolyzes the phosphate group of ATP to generate ADP and AMP. Human CD39 is a 510-amino acid protein with seven potential N-linked glycosylation sites, 11 cysteine residues, and two transmembrane regions. Structurally, it is characterized by two transmembrane domains, a small cytoplasmic domain containing the NH2- and COOH-terminal segments, and a large extracellular hydrophobic domain consisting of five highly conserved domains known as apyrase conserved regions (ACRs) 1–5, which are crucial for the enzyme's catabolic activity. CD39 is catalytically active when localized to the cell surface, and its glycosylation is important for protein folding, membrane targeting, and enzymatic activity.

[0004] CD39 is constitutively expressed in the spleen, thymus, lung, and placenta, where it is primarily associated with endothelial cells and immune cell populations, such as B cells, natural killer (NK) cells, dendritic cells, Langerhans cells, monocytes, macrophages, mesangial cells, neutrophils, and regulatory T cells (Tregs). Because CD39, in addition to other enzymes, degrades ATP, ADP, and AMP to adenosine, CD39 can be viewed as an immunological switch that shifts ATP-driven pro-inflammatory immune cell activity toward an adenosine-mediated anti-inflammatory state.

[0005] Within the neoplastic environment, cancer and immune cells interact closely and can generate an immunosuppressive environment by releasing immunomodulatory factors that support neoplastic growth. CD39 expression is increased in many solid tumors (e.g., colorectal cancer, head and neck cancer, pancreatic cancer (Kunzli et al., Am J Physiol, 2006, 292: 223-230), bladder cancer, brain cancer, breast cancer, gastric cancer, hepatocellular carcinoma, lung cancer, non-small cell lung cancer (Li et al., Oncoimmunology, 2017, 6: 6), chronic lymphocytic leukemia (Pulte et al., Clin Lymphoma Myeloma Leuk, 2011, 11(4): 367-372), lymphoma, melanoma (Dzhandzhugazyan et al., FEBS Letters, 1998, 430: 227-230), ovarian cancer, and prostate cancer, among others), suggesting that this enzyme is involved in the development and progression of malignant tumors. Modulators of CD39 may provide potential treatments for these types of cancer.

[0006] Interactions between tumor cells and their microenvironment are critical for tumor development. CD39 may mediate tumor immune evasion by inhibiting the activation, clonal expansion, and homing of tumor-specific T cells, thereby impairing tumor cell killing by effector T lymphocytes. In addition to these immunoregulatory roles, CD39 may directly contribute to modulating cancer cell growth, differentiation, invasion, migration, metastasis, and angiogenesis. CD39 is important for both the initiation of angiogenesis and the progression of neovascularization. CD39 on the vasculature mediates the angiogenic process in mouse models of melanoma, lung, and liver malignancies.

[0007] Modulators of CD39 activity may also provide potential therapeutic agents for treating CD39 conditions, including but not limited to autoimmune and infectious diseases. In particular, modulators of CD39 activity are useful in treating, but not limited to, celiac disease (Cook et al., American Academy of Allergy, Asthma & Immunology, 2017, Article in Press), colitis (Longhi et al., JCI Insight. 2017, 2(9)), thrombotic diseases (Marcus et al., Journal of Pharmacology and Experimental Therapeutics, 2003, 305, 1: 9-16), HIV infection (zur Wiesch et al., Journal of Virology, 2011, Feb: 1287-1297), HBV infection, HCV infection, and inflammatory bowel disease (Friedman et al., PNAS, 2009, 106, 39: 16788-16793) and Crohn's disease (Bai et al., J Immunol, 2014, 3366-3377), which could provide potential therapeutic agents for diseases such as [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Kunzli et al., Am J Physiol (2006) 292:223-230 [Non-patent document 2] Li et al., Oncoimmunology (2017) 6:6 [Non-patent document 2] Pulte et al., Clin Lymphoma Myeloma Leuk (2011) 11(4):367~372 Summary of the Invention [Means for solving the problem]

[0009] Provided herein are antibodies that selectively bind to CD39. In some embodiments, the antibodies bind to human CD39. In some embodiments, the antibodies also bind to homologs of human CD39.

[0010] In some embodiments, the antibody comprises at least one CDR sequence defined by the consensus sequence provided in this disclosure. In some embodiments, the antibody comprises at least one CDR sequence defined by the exemplary CDRs, V H , or V L The sequences include the heavy or light chains provided in this disclosure, or variants thereof. In some embodiments, the variants have one or more conservative amino acid substitutions.

[0011] Compositions and kits comprising the antibody are also provided. In some embodiments, the composition is a pharmaceutical composition. Any suitable pharmaceutical composition may be used. In some embodiments, the pharmaceutical composition is a composition for parenteral administration.

[0012] The present disclosure also provides methods of using the anti-CD39 antibodies provided herein. In some embodiments, the methods are methods of treatment. In some embodiments, the methods are methods of diagnosis. In some embodiments, the methods are methods of analysis. In some embodiments, the methods are methods of purifying and / or quantifying CD39.

[0013] In some embodiments, the antibody is used to treat a disease or condition, hi some aspects, the disease or condition is selected from cancer, an autoimmune disease, and an infectious disease. The present invention provides, for example, the following items. (Item 1) Specific binding to human CD39 (hCD39) and: a) inhibiting CD39 binding to ATP; b) inhibiting the conversion of ATP to ADP and / or ADP to AMP by CD39; c) decreasing the affinity of CD39 for ATP or ADP; d) inhibiting or preventing the release of ADP or AMP from CD39; e) interfering with or inhibiting the processing ability of CD39; f) inhibiting platelet aggregation; g) decreasing levels of phosphate, ADP, AMP, and / or adenosine and / or increasing levels of ATP; h) increasing T effector cell function; i) reducing the number of regulatory T cells in tissues or circulation; j) suppressing regulatory T cells or regulatory T cell activity; k) increasing B cell function; l) increasing antigen-presenting cell function; m) inhibiting CD39 function on tumor cells; n) inhibiting the processing of at least one of phosphorylated isoprenoids, phosphorylated vitamin B metabolites, and / or phosphorylated riboflavin-derived phosphoantigens; o) reducing or preventing activation of phosphoantigen-specific T cells selected from MAIT cells and γδ T cells; p) inhibiting angiogenesis; q) Stimulated CD4 + and CD8 + increasing T-cell proliferation; r) increasing the secretion of INF-γ, TNF-α, IL-2 and / or IL-1β by stimulated PBMCs

[0023] The antigen binding protein can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 of: (Item 2) The following characteristics: a) It is a monoclonal antibody; b) is a human, humanized, or chimeric antibody; c) is a bispecific, multispecific, diabody, or multivalent antibody; d) be of IgG1, IgG2, IgG3, IgG4, or IgM type; e) being an antigen-binding antibody fragment; f) is a Fab fragment, a Fab' fragment, a F(ab')2 fragment, or an Fv fragment; and / or g) be a single-chain antibody, single-domain antibody, or nanobody; 2. The antigen-binding protein of item 1, having 1, 2, 3, 4, 5, 6, or 7 of: (Item 3) Binds to hCD39 and has the following properties: a) blocking or reducing the hydrolysis of ATP to ADP and / or ADP to AMP, as determined by at least one of (i) a decrease in phosphate (Pi) release, (ii) an increase in ATP levels, and (iii) a decrease in ADP, AMP, and / or adenosine levels; b) increasing T effector cell activity; c) suppressing regulatory T cells or reducing regulatory T cell activity; d) reducing the number of regulatory T cells in tissues or in the circulation; e) increasing B cell function; f) increasing antigen-presenting cell function; g) inhibiting CD39 function on tumor cells; h) blocking or inhibiting the processing of at least one of phosphorylated isoprenoids, phosphorylated vitamin B metabolites, and phosphorylated riboflavin-derived phosphoantigens; i) reducing or preventing activation of phosphoantigen-specific T cells selected from MAIT cells and γδ T cells; k) inhibiting angiogenesis; l) decreasing affinity for ATP and / or ADP; m) inhibiting the release of ADP or AMP from CD39; n) interfering with or inhibiting the processing ability of CD39; o) inhibiting platelet aggregation; p) stimulated CD4 + and CD8 + increasing T-cell proliferation; r) increasing the secretion of INF-γ, TNF-α, IL-2, and / or IL-1β by stimulated PBMCs 10, 11, 12, 13, 14, 15, or 16 of the following: (Item 4) 10. A pharmaceutical composition comprising the antigen-binding protein of item 1 or item 2. (Item 5) An effective amount of: a) Anti-PD-1 antibody, b) anti-PD-L1 antibody, c) anti-CD73 antibody, d) anti-CD38 antibody, e) anti-A2A receptor antibodies, f) anti-A2B receptor antibodies, g) an anti-A2A / A2B dual receptor antibody, or any combination thereof; or h) small molecule inhibitors, 5. The pharmaceutical composition according to item 4, further comprising at least one of the following or a combination thereof: (Item 6) a) antibodies to inhibitory receptors or ligands, and / or b) antibodies to costimulatory receptors or ligands; 6. The pharmaceutical composition according to item 4 or 5, further comprising one or both of the following or a combination thereof: (Item 7) (i) the inhibitory receptor or ligand is at least one of CTLA-4, PD-L2, LAG-3, Tim3, neuritin, BTLA, CECAM-1, CECAM-5, VISTA, LAIR1, CD160, 2B4, TGF-R, HHLA2, ILT2, ILT3, ILT4, HLA-G, HLA-C, and / or killer cell immunoglobulin-like receptor (KIR); and / or (ii) The pharmaceutical composition of item 6, wherein the costimulatory receptor or ligand is at least one of OX40, CD2, CD27, CDS, ICAM-1, LFA-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, and / or CD83. (Item 8) 8. The pharmaceutical composition of item 7, wherein the costimulatory receptor or ligand LFA-1 further comprises the LFA-1 beta chain CD18 and / or the LFA-1 alpha chain CD11a. (Item 9) The following characteristics: a) binds to a human CD39 polypeptide or a variant thereof with a KD of less than about 20 nM; b) binds to a cynomolgus CD39 polypeptide or a variant thereof with a KD of less than about 200 nM; c) binds to a murine CD39 polypeptide or a variant thereof with a KD of less than about 200 nM; or d) A combination of at least two of a), b), and c). 2. The antigen-binding protein of item 1, having one or more of: (Item 10) 1. An antigen-binding protein that competes with, or is capable of competing with, a reference antigen-binding protein for binding to human CD39, wherein said reference antigen-binding protein is the antigen-binding protein of item 1. (Item 11) An antigen binding protein that binds to human CD39 or can compete with a reference antigen binding protein for binding to human CD39, wherein said reference antigen binding protein binds to an epitope at positions 143-158 or 274-277 of SEQ ID NO: 249 on human CD39 polypeptide, including but not limited to, D150, E153, R154 or N99 alone or in combination with D150, E153, R154 or any combination thereof. (Item 12) 12. The antigen-binding protein of item 10 or item 11, wherein the antigen-binding protein and reference antibody cross-compete or are capable of cross-competing for binding to human CD39. (Item 13) 2. The antigen-binding protein of Item 1, comprising a human heavy chain constant region or fragment, or a variant thereof, wherein the variant of the constant region comprises up to 20 conservatively modified amino acid substitutions from any of the sequences set forth in SEQ ID NOs: 179 to 218. (Item 14) 1. An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and / or VL is selected from the group consisting of: a) VHCDR1 having a sequence shown in SEQ ID NO: 1 to 45; b) VHCDR2 having a sequence shown in SEQ ID NOs: 46 to 81; c) VHCDR3 having a sequence shown in SEQ ID NOs: 82 to 109; d) VLCDR1 having the sequence shown in SEQ ID NOs: 110 to 124; e) VLCDR2 having the sequence shown in SEQ ID NOs: 125 to 140, and f) VLCDR3 having the sequence shown in SEQ ID NOs: 141 to 166 An isolated antibody molecule comprising one, two, three, four, five, or six of: (Item 15) An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), The VH is as follows: a) VHCDR1 having a sequence shown in SEQ ID NO: 1 to 45; b) VHCDR2 having the sequences set forth in SEQ ID NOs: 46 to 81, and c) VHCDR3 having the sequence shown in SEQ ID NOs: 82 to 109 Includes; The VL is: a) VLCDR1 having the sequence shown in SEQ ID NOs: 110 to 124; b) VLCDR2 having the sequence shown in SEQ ID NOs: 125 to 140, and c) VLCDR3 having the sequence shown in SEQ ID NOs: 141 to 166 1. An isolated antibody molecule comprising: (Item 16) 16. An isolated nucleic acid encoding the antigen-binding protein of claim 1, 14, or 15. (Item 17) Item 17. An expression vector comprising the nucleic acid of Item 16. (Item 18) A prokaryotic or eukaryotic host cell containing the vector described in item 17. (Item 19) 18. An oncolytic virus encoding the nucleic acid of either item 16 or item 17. (Item 20) 17. A method for producing a recombinant protein, comprising expressing the nucleic acid of item 16 in a prokaryotic or eukaryotic host cell and recovering the protein from the cell or cell culture supernatant. (Item 21) 10. A method for treating a subject suffering from cancer, a chronic infectious disease, or an inflammatory disease, comprising administering to the subject an effective amount of a pharmaceutical composition comprising the antigen-binding protein of item 1 or the pharmaceutical composition of item 3. (Item 22) 22. The method of item 21, wherein the cancer is a solid cancer. (Item 23) 22. The method of claim 21, wherein the cancer is a blood cancer. (Item 24) 1. A method for modulating immune system function in a subject in need thereof, comprising the step of contacting a population of immune cells of the subject with an effective amount of a pharmaceutical composition comprising the antigen-binding protein of item 1 under conditions such that the immune system is modulated. (Item 25) 1. A method for inducing or enhancing an immune response in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising an antigen binding protein, wherein the immune response is generated against a tumor antigen. (Item 26) 26. The method of claim 24 or 25, wherein the subject is a human subject. (Item 27) 26. The method of claim 25, wherein the antigen-binding protein comprises a bispecific antibody or a complex-forming antigen-binding protein. (Item 28) wherein the antigen binding protein, the bispecific antibody, or the complex-forming antigen binding protein induces in the subject: a) reducing CD39 ATPase activity in the target cell population; b) reducing the suppression of regulatory T cells on effector T cell activity; c) reducing the levels of regulatory T cells; d) activating effector T cells; e) inducing or enhancing the proliferation of effector T cells; f) inhibiting tumor growth; and / or g) Inducing tumor regression 28. The method of claim 27, wherein the administration is in an amount sufficient to achieve one, two, three, four, five, six, or seven of the following: (Item 29) 29. The method of claim 28, wherein the target cell population comprises T cells, B cells, monocytes, macrophages, dendritic cells, myeloid-derived suppressor cells, and / or tumor cells. (Item 30) below: a) administering chemotherapy; b) administering radiation therapy; and / or c) administering one or more additional therapeutic agents 26. The method of claim 25, further comprising one or more of: (Item 31) 31. The method of claim 30, wherein the one or more additional therapeutic agents comprise one or more immunostimulatory agents. (Item 32) 32. The method of claim 31, wherein the one or more immunostimulatory agents comprise an antagonist to an inhibitory receptor on an immune cell. (Item 33) 33. The method of claim 32, wherein the inhibitory receptor is at least one of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, Tim3, neuritin, BTLA, CECAM-1, CECAM-5, VISTA, LAIR1, CD160, 2B4, TGF-R, and / or killer cell immunoglobulin-like receptor (KIR). (Item 34) 32. The method of claim 31, wherein the one or more immunostimulatory agents comprise an agonist of a costimulatory receptor on an immune cell. (Item 35) 35. The method of claim 34, wherein the costimulatory receptor is OX40, CD2, CD27, CDS, ICAM-1, LFA-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, or CD83 ligand. (Item 36) 36. The method of claim 35, wherein the costimulatory receptor or ligand LFA-1 further comprises the LFA-1 beta chain CD18 and / or the LFA-1 alpha chain CD11a. (Item 37) 32. The method of claim 31, wherein the one or more immunostimulatory agents comprises a cytokine. (Item 38) 38. The method of claim 37, wherein the cytokine is at least one of IL-2, IL-5, IL-7, IL-12, IL-15, and / or IL-21. (Item 39) 32. The method of claim 31, wherein the one or more immunostimulatory agents comprises an oncolytic virus. (Item 40) 40. The method of claim 39, wherein the oncolytic virus is herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, or Maraba virus. (Item 41) 32. The method of claim 31, wherein the one or more immunostimulatory agents comprise chimeric antigen-engineered T cells. (Item 42) 32. The method of claim 31, wherein the one or more immunostimulatory agents comprise a bi- or multispecific T cell-directed antibody. (Item 43) 26. The method of item 25, wherein the one or more additional therapeutic agents comprises at least one trap for an immunosuppressant. (Item 44) 44. The method of claim 43, wherein the at least one trap for an immunosuppressant comprises at least one of an anti-TGF-beta antibody, a TGFb receptor trap, an anti-IL-10 antibody and / or an anti-IL-10 receptor trap, and / or an anti-IL-35 antibody trap and / or an anti-IL-35 receptor trap. (Item 45) 45. The method of any one of items 3 to 44, wherein administering the pharmaceutical composition results in the induction or enhancement of T-effector cell proliferation, or modulation of I-kappaB and / or NF-κB in T cells, or modulation of CD39 activity in T cells, or T cell receptor-induced signaling in T-effector cells, or a combination thereof. (Item 46) A method for screening a test compound comprising the antigen-binding protein of item 1 that can inhibit the activity of CD39, comprising: contacting a test sample containing CD39 with a test compound; Comparing the activity of the test sample to a control sample. Includes; The compound is identified as inhibiting the activity of CD39 by a decrease in the activity of CD39 in the test sample compared to the control sample. (Item 47) Item 47. The method of item 46, wherein the control sample comprises a sample that has not been contacted with the test compound. (Item 48) An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH is: a) VHCDR1 having an amino acid sequence that is at least 90% identical to the sequences set forth in SEQ ID NOs: 1 to 45; b) VHCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs: 46 to 81, and c) VHCDR3 having an amino acid sequence at least 90% identical to the sequences set forth in SEQ ID NOs: 82 to 109 including at least one of: VL is: a) VLCDR1 having an amino acid sequence that is at least 90% identical to the sequence shown in SEQ ID NOs: 110 to 124; b) VLCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs: 125 to 140; and c) VLCDR3 having an amino acid sequence at least 90% identical to the sequences set forth in SEQ ID NOs: 141 to 166 An isolated antibody molecule comprising at least one of: (Item 49) An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH is: a) VHCDR1 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 1 to 45; b) VHCDR2 having an amino acid sequence homologous to the sequences set forth in SEQ ID NOs: 46 to 81, and c) VHCDR3 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 82 to 109 including at least one of: VL is: a) VLCDR1 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 110 to 124; b) VLCDR2 having an amino acid sequence homologous to the sequences set forth in SEQ ID NOs: 125 to 140, and c) An isolated antibody molecule comprising at least one VLCDR3 having an amino acid sequence homologous to the sequences set forth in SEQ ID NOs: 141 to 166. (Item 50) 1. An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain and a light chain, wherein the heavy chain consists of one of SEQ ID NO:255, SEQ ID NO:257, SEQ ID NO:259, SEQ ID NO:261, SEQ ID NO:263, SEQ ID NO:265, SEQ ID NO:267, SEQ ID NO:269, SEQ ID NO:271, SEQ ID NO:273, SEQ ID NO:275, SEQ ID NO:277, SEQ ID NO:279, SEQ ID NO:281, SEQ ID NO:283, SEQ ID NO:285, SEQ ID NO:287, SEQ ID NO:289, SEQ ID NO:291, SEQ ID NO:293, or SEQ ID NO:295. 20. An isolated antibody molecule comprising one or more molecules having the sequence: SEQ ID NO:256, SEQ ID NO:258, SEQ ID NO:260, SEQ ID NO:262, SEQ ID NO:264, SEQ ID NO:266, SEQ ID NO:268, SEQ ID NO:270, SEQ ID NO:272, SEQ ID NO:274, SEQ ID NO:276, SEQ ID NO:278, SEQ ID NO:280, SEQ ID NO:282, SEQ ID NO:284, SEQ ID NO:286, SEQ ID NO:288, SEQ ID NO:290, SEQ ID NO:292, SEQ ID NO:294, or SEQ ID NO:296. (Item 51) An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain and a light chain, a) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 255, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 256; b) the heavy chain comprises one or more molecules, each having the sequence consisting of SEQ ID NO: 257, and the light chain comprises one or more molecules, each having the sequence consisting of SEQ ID NO: 258; c) the heavy chain comprises one or more molecules, each having the sequence consisting of SEQ ID NO: 259, and the light chain comprises one or more molecules, each having the sequence consisting of SEQ ID NO: 260; d) the heavy chain comprises one or more molecules, each having the sequence of SEQ ID NO: 261, and the light chain comprises one or more molecules, each having the sequence of SEQ ID NO: 262; e) the heavy chain comprises one or more molecules, each having the sequence of SEQ ID NO: 263, and the light chain comprises one or more molecules, each having the sequence of SEQ ID NO: 264; f) the heavy chain comprises one or more molecules, each having the sequence of SEQ ID NO: 265, and the light chain comprises one or more molecules, each having the sequence of SEQ ID NO: 266; g) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 267, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 268; h) the heavy chain comprises one or more molecules, each having the sequence consisting of SEQ ID NO: 269, and the light chain comprises one or more molecules, each having the sequence consisting of SEQ ID NO: 270; i) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO:271, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO:272; j) the heavy chain comprises one or more molecules, each having the sequence of SEQ ID NO: 273, and the light chain comprises one or more molecules, each having the sequence of SEQ ID NO: 274; k) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 275, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 276; l) the heavy chain comprises one or more molecules, each molecule having the sequence of SEQ ID NO: 277, and the light chain comprises one or more molecules, each molecule having the sequence of SEQ ID NO: 278; m) the heavy chain comprises one or more molecules, each having the sequence of SEQ ID NO: 279, and the light chain comprises one or more molecules, each having the sequence of SEQ ID NO: 280; n) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 281, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 282; o) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 283, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 284; p) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 285, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 286; q) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 287, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 288; r) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 289, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 290; s) the heavy chain comprises one or more molecules, each molecule having the sequence of SEQ ID NO: 291, and the light chain comprises one or more molecules, each molecule having the sequence of SEQ ID NO: 292; t) the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 293, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 294; or u) An isolated antibody molecule, wherein the heavy chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 295, and the light chain comprises one or more molecules, each molecule having the sequence consisting of SEQ ID NO: 296. (Item 52) 52. An isolated nucleic acid encoding the antigen-binding protein of any one of items 48 to 51. (Item 53) 1. An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and / or VL is selected from the group consisting of: a) (i) Kabat CDRH1 sequences defined by the consensus sequence SY-Δ3-M-Δ5 (SEQ ID NOs: 25-29 and 44-45), where Δ3 is E, F, Q, or Y, and Δ5 is H or Y; (ii) a Kabat CDR-H1 sequence defined by the consensus sequence θ1-θ2-θ3-IS (SEQ ID NOs: 30-37), where θ1 is A, H, K, L, S, or W; θ2 is L, M, N, or T; and θ3 is A or P; (iii) a Kabat CDR-H1 sequence defined by the consensus sequence η1-Y-η3-IS (SEQ ID NOs: 38-41), where η1 is S, K, N, or R, and η3 is A or G; (iv) a Chothia CDR-H1 sequence defined by the consensus sequence GYTF-Ω5-SY (SEQ ID NOs: 1-2 and 4-6), where Ω5 is T, K, Q, F, or V; (v) a Chothia CDR-H1 sequence defined by the consensus sequence GGTF-v5-v6-Y (SEQ ID NOs: 17-22 and 24), where v5 is S, G, or E and v6 is S, K, R, or S; or (vi) a Chothia CDR-H1 consensus sequence defined by the consensus sequence GGTF-κ5-κ6-κ7 (SEQ ID NOs: 7-16), where κ5 is S, Q, P, or A; κ6 is S, K, H, L, A, or W; and κ7 is Y, L, T, N, or M. a VHCDR1 sequence comprising b) (i) Consensus sequence ε1-INP-ε 5- ε6-GST-ε 10 -YAQKFQG (SEQ ID NOs: 63-66 and 68) (wherein ε1 is K, S, R, or V; ε5 is L, R, or S; ε6 is G or V; ε 10is S or W); (ii) a Kabat CDR-H2 sequence defined by the consensus sequence GI-α3-α4-α5-α6-GTANYAQKFQG (SEQ ID NOs: 69-72), where α3 is I, L, or absent; α4 is P or absent; α5 is I, G, or R; and α6 is A, F, or G; (iii) a Kabat CDR-H2 sequence defined by the consensus sequence β1-IIP-β5-β6-G-β8-ANYAQKFGQ (SEQ ID NOs: 74 and 76-79), where β1 is S or G; β5 is I, E, S, or T; β6 is F, I, or S; and β8 is I or T; (iv) consensus sequence NP-ε 5- Chothia CDR-H2 sequences defined by ε6-GST (SEQ ID NOs: 46-48) (wherein ε5 is L, R, or S and ε6 is G or V); (v) a Chothia CDR-H2 sequence defined by the consensus sequence α3-α4-α5-α6-GTA (SEQ ID NOs: 51-54), where α3 is I, L, or absent; α4 is P or absent; α5 is I, G, or R; and α6 is A, F, or G; or (vi) Chothia CDR-H2 sequence defined by the consensus sequence IP-β5-β6-G-β8-A (SEQ ID NOs: 56-60), where β5 is I, E, S, or T; β6 is F, I, or S; and β8 is I or T. a VHCDR2 sequence comprising c) (i) Consensus sequence GKREGGTEYLR-У 12 (SEQ ID NO: 82 to 86) (wherein, У 12 is H, K, S, N, or V); (ii) consensus sequence ESG-Ф4-YRDHRL-Ф 11-V (SEQ ID NOs: 94-96) (wherein Φ4 is G or T, and Φ 11 is D or G; or (iii) a VH CDR3 sequence comprising a CDR-H3 sequence defined by the consensus sequence GGAKYA-E7-E8-E9-GMDV (SEQ ID NOs: 87-93), where E7 is S, V, G, or R; E8 is T, Q, K, G, or R; and E9 is Y, H, L, or W; d) (i) a CDR-L1 sequence defined by the consensus sequence φ1-AS-φ4-φ5-V-φ7-φ8-φ9-YLA (SEQ ID NOs: 1101-114) (wherein φ1 is E, K, or R; φ4 is Q or E; φ5 is S or Y; φ7 is S or A; φ8 is S or Y; and φ9 is D or S); (ii) a CDR-L1 sequence defined by the consensus sequence β1-ASQ-β5-β6-β7-β8-β9-L-β 11 (SEQ ID NOs: 118 and 120-123) (wherein b1 is Q or R1; b5 is D or S; b6 is I or V; b7 is G or S; b8 is N, R, or S; b9 is N, Y, or W; b 11 is A or N; or (iii) consensus sequence KSS-Γ4-SVL-Γ8-S-Γ 10 -NNKNYLA (SEQ ID NOs: 115-117) (wherein Γ4 is Q, R, or K; Γ8 is F or Y; Γ 10 is S or N) a VLCDR1 sequence comprising e) (i) a CDR-L2 sequence defined by the consensus sequence ψ1-AS-ψ4-R-ψ6-ψ7 (SEQ ID NOs: 125-136), where ψ1 is G or Y, ψ4 is S or N; ψ6 is A or H; and ψ7 is T, Y, or N; (ii) a CDR-L2 sequence defined by the consensus sequence DAS-χ4-RAT (SEQ ID NOs: 138 and 139) (wherein χ4 is N or K); or (iii) a CDR-L2 sequence defined by the consensus sequence WASTR-σ6-S (SEQ ID NOs: 131 and 133-134) (wherein σ6 is A, E, or Q). and a VLCDR2 sequence comprising f) (i) a CDR-L3 sequence defined by the consensus sequence QQY-π4-π5-π6-π7-T (SEQ ID NOs: 141-147) (wherein π4 is G, H, or Y; π5 is S, N, F, G, or R; π6 is S, Y, A, G, or R; and π7 is P, I, or L); (ii) a CDR-L3 sequence defined by the consensus sequence QQ-λ3-λ4-λ5-λ6-PT (SEQ ID NOs: 148-150), where λ3 is R, F, H, S, L, D, Y, or V; λ4 is S, V, T, G, L, Y, or N; λ5 is N, L, F, K, or V; and λ6 is W, F, Y, or L; (iii) a CDR-L3 sequence defined by the consensus sequence QQY-ρ3-ρ4-WPLT (SEQ ID NOs: 151 and 152), where ρ3 is N or L and ρ4 is N or L; or (iv) a CDR-L3 sequence defined by the consensus sequence QQ-ω3-ω4-ω5-ω6-P-ω8-T (SEQ ID NOs: 153 to 156) (wherein ω3 is Y or F; ω4 is Y or W; ω5 is S, L, T, or F; ω6 is T, Y, or F; and ω8 is L or P). VLCDR3 sequence containing An isolated antibody molecule comprising one, two, three, four, five, or six of: [Brief explanation of the drawings]

[0014] [Figure 1]Figure 1 shows the monovalent affinity of anti-huCD39 antibodies for recombinant human CD39 extracellular domain. The table presents the binding kinetics of anti-CD39 antibodies interacting with soluble recombinant human CD39 (ENTDP1) extracellular domain (ECD) by biolayer interferometry (ForteBio Octet). Anti-CD39 antibodies were captured on an anti-human Fc sensor and exposed to recombinant human CD39 ECD at concentrations ranging from 10 to 300 nanomolar. The kinetic data were globally fitted to a simple 1:1 Langmuir binding model to obtain on-rate (k) and off-rate (k) values. The equilibrium dissociation constant (KD) was calculated from the k and k values.

[0015] [Figure 2-1] Figures 2A-E show the inhibition of enzymatic catabolism of ATP and ADP to Pi by the human CD39 extracellular domain (ECD). Recombinant human CD39 at a final concentration of either 10 nanomolar (A-D) or 5 nanomolar (E) was incubated with anti-CD39 IgG at a final concentration of either 1 micromolar (A-D) or 0.25 micromolar (E) in 25 mM Tris, 5 mM CaCl2, pH 7.5 at room temperature for 2 hours. ATP (500 micromolar) was added to the reaction, which was then incubated at 37°C for 60 minutes. Residual ATP levels in the reaction were measured using the CellTiter-Glo assay. Data values are the average of two replicate experiments. [Figure 2-2]Figures 2A-E show the inhibition of enzymatic catabolism of ATP and ADP to Pi by the human CD39 extracellular domain (ECD). Recombinant human CD39 at a final concentration of either 10 nanomolar (A-D) or 5 nanomolar (E) was incubated with anti-CD39 IgG at a final concentration of either 1 micromolar (A-D) or 0.25 micromolar (E) in 25 mM Tris, 5 mM CaCl2, pH 7.5 at room temperature for 2 hours. ATP (500 micromolar) was added to the reaction, which was then incubated at 37°C for 60 minutes. Residual ATP levels in the reaction were measured using the CellTiter-Glo assay. Data values are the average of two replicate experiments.

[0016] [Figure 2-3] FIG. 2F shows antibody binding to CHO cells expressing human or cynomolgus CD39.

[0017] [Figure 3] Figure 3 shows the evaluation of antibody binding to MEL-28 (A) and 721 (B) cells. Anti-CD39 antibodies (each antibody clone number indicated in the figure) were titrated from 15 μg / ml to 0.001 μg / ml. EC50 values were calculated using GraphPad Prism software. Figures represent three independent experiments.

[0018] [Figure 4] Figure 4 presents an evaluation of antibody-driven inhibition of CD39-mediated ATP hydrolysis in MEL-28 cells in a short-term ATP assay. Figure 4A shows the results comparing anti-CD39 antibodies with the nonspecific small molecule inhibitors POM-1 and ARL. Inhibition was determined by a decrease in phosphate release (Pi). Data represent at least 10 independent experiments. Anti-CD39 antibodies (each antibody clone number is indicated in the figure) were titrated from 15 μg / ml to 0.001 μg / ml. As can be seen in Figure 4B, IC50 values were calculated using GraphPad Prism software. Three independent experiments were performed.

[0019] [Figure 5] Figure 5 provides a diagram of the quantification of MEL-28 cells treated with CD39 enzyme inhibitors. Figure 5A shows the assessment of ATP levels after incubating MEL-28 cells with increasing dose titrations of an anti-CD39 antibody that inhibits enzyme activity. Figure 5B presents the IC50 values calculated using GrapPad Prism. At least three independent experiments were performed.

[0020] [Figure 6] Figure 6 shows that antibodies were evaluated for inhibition of CD39 enzymatic activity overnight on MEL-28 cells. Figure 6A shows titrations of anti-CD39 antibodies (each number represents a unique clone shown in the figure) from 100 nM to 0.000610 nM. Figure 6B presents IC50 values calculated using GraphPad Prism software. Three independent experiments are represented.

[0021] [Figure 7] Figure 7 shows the results of testing antibodies for binding to CD39 on human primary B cells and cynomolgus monkey primary B cells. In Figure 7A, anti-CD39 antibodies were titrated in B cells purified from a healthy donor and detected with an anti-human IgG-PE secondary antibody. EC50 values were calculated using GrapPad Prism software. In Figure 7B, anti-CD39 antibodies were titrated in cynomolgus monkey PBMCs and detected with an anti-human (a-human) IgG-PE secondary antibody. B cells were gated using FlowJo software, and EC50 values were calculated using GraphPad Prism.

[0022] [Figure 8] Figure 8 shows antibodies evaluated for inhibition of CD39 activity in primary human B cells. Anti-CD39 antibodies (each unique antibody clone number is indicated in the figure) were titrated from 100 nM to 0.00013 nM.

[0023] [Figure 9] Figure 9 shows the evaluation of inhibition of CD39 activity in primary human monocytes (a) and cynomolgus monkey monocytes (b). Anti-CD39 antibodies (each number represents a unique antibody clone number as shown in the figure) were titrated from 100 nM to 0.00013 nM and incubated with monocytes in the presence of ATP. Phosphate release due to processing of ATP by CD39 was quantified using the Malachite Green assay.

[0024] [Figure 10] Figure 10 shows binding of anti-CD39 antibodies to purified human CD4+CD25+CD127dim Treg cells by FACS. Anti-CD39 antibodies were titrated in purified Tregs from healthy donors and detected with an anti-human IgG secondary antibody. EC50 values were calculated using GraphPad Prism software.

[0025] [Figure 11] Figure 11 shows the results for the ability of antibodies to inhibit primary Treg CD39 activity. CD24+CD25+CD127dim regulatory T cells were incubated with serially diluted anti-CD39 antibodies and tested for ATPase activity after the addition of exogenous ATP. Free phosphate (Pi) was used as a readout for CD39 activity.

[0026] [Figure 12] FIG. 12 shows that treatment with anti-CD39 antibody increases the percentage of IFN-gamma producing CD8+ T cells that respond to CMV peptides in an antigen recall response assay.

[0027] [Figure 13]Figure 13 shows the evaluation of antibodies for inhibition of CD39 activity in MEL-28 (Figure 13A) and human monocytes (Figure 13B) compared with anti-CD39 antibodies generated based on Innate / Orega (BY-40v9) and Igenica (9-8B) and their variants. Anti-CD39 antibodies were titrated as indicated and incubated in the presence of ATP. Phosphate release due to processing of ATP by CD39 was quantified using a Malachite Green assay.

[0028] [Figure 14-1] Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-2]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-3]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-4]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-5]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-6]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-7]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues. [Figure 14-8]Figures 14A-G present examples of antibodies. Figure 14A presents an example of an antibody that binds to soluble recombinant CD39 ECD and cellular CD39 but does not inhibit ATPase activity and does not compete with cellular inhibitors for binding to the ECD inhibitor. Figure 14B presents an example of an antibody that has limited ability to inhibit the ATPase activity of both soluble recombinant CD39 and cellular CD39, placing it in a separate bin from other cellular CD39 inhibitors. Figure 14C presents an example of an antibody that inhibits the ATPase activity of soluble recombinant CD39 ECD but not cellular CD39, placing it in a separate bin from other CD39 ECD inhibitors. Figure 14D presents an example of an antibody that inhibits the ATPase activity of ECD CD39 and cellular CD39, placing it in a separate bin from other CD39 ECD and / or cellular inhibitors. Figure 14E presents an example of an inhibitory antibody that contacts CD39 separately. Figure 14E includes two tables, Table 1 and Table 2. Table 1 provides examples of inhibitory antibodies that contact CD39 separately. Table 2 provides examples of inhibitory antibodies that bind to CD39 at critical, more distinct contact residues. Figures 14F and 14G provide FACS plots highlighting the importance of certain human CD39 residues.

[0029] [Figure 15] Figure 15 shows that anti-CD39 antibodies inhibit CD39 by 75-90%. Anti-CD39 antibodies (100 nanomolar), isotype control antibodies (100 nanomolar), or ARL (200 micromolar) were incubated with MEL-28 cells, which endogenously express human CD39, for 2 hours. ATP was then added, and the rate of ATP hydrolysis to Pi by CD39 was monitored using an EnzChek kinetic Pi detection assay. The initial enzyme velocity, ν, was determined from the linear region of the Pi vs. time curve over the first 15 minutes after ATP addition. Each value is the average of three replicate experiments.

[0030] [Figure 16A] Figures 16A-B show that the CD39 inhibitor 29872 is not a competitive inhibitor due to its inhibition of Vmax suppression. [Figure 16B] Figures 16A-B show that the CD39 inhibitor 29872 is not a competitive inhibitor due to its inhibition of Vmax suppression.

[0031] [Figure 17] FIG. 17 shows that anti-CD39 antibodies can induce internalization of CD39 in cynomolgus monkey monocytes.

[0032] [Figure 18] Figure 18 presents a comparison of the Kabat and Chothia numbering systems for CDR-H1. Adapted from Martin ACR (2010). Protein Sequence and Structure Analysis of Antibody Variable Domains. In R. Kontermann & S. Duebel (Eds.), Antibody Engineering vol. 2 (pp. 33-51). Springer-Verlag, Berlin Heidelberg.

[0033] [Figure 19] FIG. 19 shows that anti-CD39 antibodies increase proliferation of stimulated CD4+ and CD8+ T cells.

[0034] [Figure 20] FIG. 20 shows that anti-CD39 antibodies increase secretion of INF-γ, TNF-α and IL-2 by stimulated PBMCs.

[0035] [Figure 21] FIG. 21 shows that anti-CD39 antibodies increase secretion of INF-γ, TNF-α, IL-2 and IL-1β by stimulated PBMCs.

[0036] [Figure 22] FIG. 22 shows that CD39 inhibition leads to ATP accumulation and blocks adenosine production. DETAILED DESCRIPTION OF THE INVENTION

[0037] 1.Definition Unless otherwise defined, all technical terms, notations and other scientific terms used herein are intended to have the meaning that is commonly understood by those skilled in the art in the field of the present invention.In some cases, terms with commonly understood meanings are defined herein for clarity and / or for easy reference, and the inclusion of such definitions herein should not necessarily be interpreted as representing the difference with what is commonly understood in the art.The techniques and procedures described or referred to herein are generally well understood, and can be found in, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 10102. Procedures involving the use of commercially available kits and reagents, as appropriate, are generally performed according to manufacturer-defined protocols and / or parameters unless otherwise specified.

[0038] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0039] The term "about" refers to and encompasses the stated value and a range above and below that value. In certain embodiments, the term "about" refers to the stated value ±10%, ±5%, or ±1% of the stated value. In certain embodiments, the term "about" refers to the stated value ±1 standard deviation of that value.

[0040] The term "combinations thereof" includes all possible combinations of the elements referred to by that term.

[0041] The terms "CD39," "CD39 antigen," and "cluster of differentiation 39" are used interchangeably herein. CD39 is also known as ectonucleoside triphosphate diphosphohydrolase-1 (gene: ENTPD1; protein: NTPDase1, see www.ncbi.nlm.nih.gov / gene / 953). CD39 has also been referred to as ATPDase and SPG64. Each of the listed terms may be used interchangeably. Unless otherwise specified, the term includes any variant, isoform, and species homolog of human CD39 naturally expressed by cells or expressed by cells transfected with the CD39 gene. In some embodiments, the CD39 protein comprises mouse CD39. In some embodiments, the CD39 protein comprises cynomolgus monkey CD39.

[0042] The term "immunoglobulin" refers to a class of structurally related proteins that generally contain two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In an "intact immunoglobulin," all four chains are interconnected by disulfide bonds. The structure of immunoglobulins is well characterized. See, e.g., Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. Briefly, each heavy chain typically contains a heavy chain variable region (V H ) and the heavy chain constant region (C H The heavy chain constant region typically comprises three domains: C H1 , C H2 , and C H3 Each light chain typically comprises a light chain variable region (V L ) and a light chain constant region. The light chain constant region typically comprises C L It contains one domain, abbreviated as .

[0043] The term "antibody" describes a type of immunoglobulin molecule and is used herein in the broadest sense. Antibodies specifically include intact antibodies (e.g., intact immunoglobulins) and antibody fragments. Antibodies contain at least one antigen-binding domain. One example of an antigen-binding domain is the V H -V L The antigen-binding domain is formed by a dimer. A "CD39 antibody," "anti-CD39 antibody," "CD39 Ab," "CD39-specific antibody," or "anti-CD39 Ab" is an antibody described herein that specifically binds to the antigen CD39. In some embodiments, the antibody binds to the extracellular domain of CD39.

[0044] V H and V L The regions can be further subdivided into regions of hypervariability ("hypervariable regions (HVRs)"; also called "complementarity determining regions" (CDRs)), interspersed with more conserved regions. The more conserved regions are called framework regions (FRs). H and V L Each CDR typically contains three CDRs and four FRs, arranged in the following order (from N-terminus to C-terminus): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. The CDRs are involved in antigen binding and confer antigen specificity and binding affinity to the antibody. See Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, MD, the entire contents of which are incorporated by reference.

[0045] Light chains from any vertebrate species can be assigned to one of two types, called kappa and lambda, based on the sequence of their constant domain.

[0046] Heavy chains from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also designated α, δ, ε, γ, and μ, respectively. The IgG and IgA classes are further divided into subclasses based on sequence and functional differences. Humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

[0047] The amino acid sequence boundaries of the CDRs can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (the "Kabat" numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (the "Chothia" numbering scheme); MacCallum et al., 1996, J. Mol. Biol. 262:732-745 (the "Contact" numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (the "IMGT" numbering scheme); and Honegge and Plueckthun, J. Mol. Biol., 2001, 309:657-70 (the "AHo" numbering scheme), each of which is incorporated by reference in its entirety.

[0048] Table 1 provides the locations of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes. Figure 1 provides a comparison of the Kabat and Chothia numbering schemes for CDR-H1. Martin (2010), see above.

[0049] Unless otherwise specified, the numbering scheme used to identify a particular CDR herein is the Kabat / Chothia numbering scheme. Where the residues encompassed by these two numbering schemes differ, the numbering scheme will be specified as either Kabat or Chothia. [Table 1]

[0050] When referring to residues in antibody heavy chain constant regions (e.g., as reported in Kabat et al., supra), the "EU numbering scheme" is generally used. Unless otherwise stated, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein.

[0051] "Antibody fragments" include portions of an intact antibody, such as the antigen-binding or variable region of the intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab')2 fragments, Fab' fragments, scFv (sFv) fragments, and scFv-Fc fragments.

[0052] An "Fv" fragment comprises a non-covalently linked dimer of one heavy- and one light-chain variable domain.

[0053] A "Fab" fragment contains the heavy and light chain variable domains as well as the constant domain of the light chain and the first constant domain of the heavy chain (C H1 Fab fragments may be generated, for example, by papain digestion of a full-length antibody.

[0054] An "F(ab')2" fragment contains two Fab' fragments joined near the hinge region by a disulfide bond. F(ab')2 fragments may be generated, for example, by pepsin digestion of an intact antibody. F(ab')2 fragments can be dissociated, for example, by treatment with β-mercaptoethanol.

[0055] "Single-chain Fv" or "sFv" or "scFv" antibody fragments contain V in a single polypeptide chain. H Domains and V L Includes domain. V H and V L are commonly linked by a peptide linker. Plueckthun A. (1994). Antibodies from Escherichia coli. In Rosenberg M. & Moore GP (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, the entire contents of which are incorporated by reference. An "scFv-Fc" fragment comprises an scFv linked to an Fc domain. For example, the Fc domain may be linked to the C-terminus of the scFv. The Fc domain may be linked to the Fc domain in a manner that reflects the orientation of the variable domains in the scFv (i.e., V H -V L or V L -V H ) depending on V H or V L Any suitable Fc domain known in the art or described herein may be used.

[0056] The term "monoclonal antibody" refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies contains antibodies that are substantially similar and bind to the same epitope, typically excluding variants that may arise during the production of the monoclonal antibody. Such variants are generally present in only minor amounts. Monoclonal antibodies are typically obtained by a process that includes selecting a single antibody from multiple antibodies. For example, the selection process can be the selection of a unique clone from multiple clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further modified, for example, to improve its affinity for the target ("affinity maturation"), to humanize the antibody, to improve its production in cell culture, and / or to reduce its immunogenicity in a subject.

[0057] The term "chimeric antibody" refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0058] "Humanized" forms of non-human antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody. Humanized antibodies are generally human immunoglobulins (recipient antibodies) in which residues from one or more CDRs have been replaced with residues from one or more CDRs of a non-human antibody (donor antibody). The donor antibody can be any suitable non-human antibody, such as a mouse, rat, rabbit, chicken, or non-human primate antibody, that has the desired specificity, affinity, or biological effect. In some cases, selected framework region residues of the recipient antibody are replaced with the corresponding framework region residues from the donor antibody. Humanized antibodies may also contain residues that are not found in either the recipient antibody or the donor antibody. Such modifications can be made to further improve antibody function. For further details, see Jones et al., Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated by reference in its entirety.

[0059] A "human antibody" is one having an amino acid sequence corresponding to that of an antibody produced by a human or human cell, or derived from a non-human source that utilizes the human antibody repertoire or human antibody-encoding sequences (e.g., obtained from a human source or designed de novo). Human antibodies specifically exclude humanized antibodies.

[0060] An "isolated antibody" is one that has been separated and / or recovered from a component of its natural environment. Components of natural environment may include enzymes, hormones, and other proteinaceous or non-proteinaceous materials. In some embodiments, an isolated antibody is purified sufficiently to obtain at least 15 residues of N-terminal or internal amino acid sequence, for example, by using a spinning cup sequencer. In some embodiments, an isolated antibody is purified to homogeneity by gel electrophoresis (e.g., SDS-PAGE) under reducing or non-reducing conditions with detection by Coomassie blue or silver staining. An isolated antibody includes an antibody in situ within recombinant cells, since at least one component of the antibody's natural environment will not be present. In some aspects, an isolated antibody is prepared by at least one purification step.

[0061] In some embodiments, the isolated antibody is at least 80%, 85%, 90%, 95%, or 99% purified by weight. In some embodiments, the isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, 99%, or 100% antibody by weight, with the remaining weight comprising the weight of other solutes dissolved in the solvent.

[0062] "Affinity" refers to the strength of the sum of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless otherwise specified, as used herein, "binding affinity" refers to the intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., an antibody and an antigen). The affinity of a molecule X for its partner Y is generally determined by the dissociation constant (K D ) Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology, such as a Biacore® instrument.

[0063] With respect to antibody binding to a target molecule, the terms "specific binding," "specifically binds," "specific for," "selectively binds," and "selective for" a particular antigen (e.g., a polypeptide target) or epitope on a particular antigen refer to binding that is measurably different from nonspecific or nonselective interactions. Specific binding can be measured, for example, by determining the binding of a molecule relative to the binding of a control molecule. Specific binding can be determined by competition with a control molecule similar to the target, such as an excess of unlabeled target. In such cases, specific binding is indicated when the binding of the labeled target to the probe is competitively inhibited by the excess of unlabeled target.

[0064] As used herein, "k" d ”(seconds -1 The term k ) refers to the dissociation rate constant of a particular antibody-antigen interaction. This value is k off Also called the value.

[0065] As used herein, "k" a " (M -1 × seconds -1 The term k ) refers to the association rate constant for a particular antibody-antigen interaction. This value is on Also called the value.

[0066] As used herein, "K" D The term "(M)" refers to the dissociation equilibrium constant for a particular antibody-antigen interaction. D =k d / k a .

[0067] As used herein, "K" A " (M -1 The term K ) refers to the association equilibrium constant for a particular antibody-antigen interaction. A =k a / k d .

[0068] An "affinity matured" antibody is one that has one or more alterations in one or more CDRs or FRs that result in an improvement in the affinity of the antibody for its antigen compared to a parent antibody that does not have the alterations. In one embodiment, the affinity matured antibody has nanomolar or picomolar affinity for the target antigen. Affinity matured antibodies may be produced using a variety of methods known in the art. For example, Marks et al. (Bio / Technology, 1992, 10:779-783, the entire contents of which are incorporated by reference) describe affinity matured antibodies. H and V L Affinity maturation by domain shuffling has been described. Random mutagenesis of CDR and / or framework residues can be performed, for example, by Barbas et al. (Proc. Nat. Acad. Sci. USA, 1994, 91:3809-3813); Schier et al., Gene, 1995, 169:147-155; Yelton et al., J. Immunol., 1995, 155:1994-2004; Jackson et al., J. Immunol., 1995, 154:3310-33199; and Hawkins et al., J. Mol. Biol., 1992, 226:889-896, each of which is incorporated by reference in its entirety.

[0069] As used herein in the context of two or more antibodies, the terms "compete with" or "cross-compete with" indicate that the two or more antibodies compete for binding to an antigen (e.g., CD39). In one exemplary assay, CD39 is coated on a plate, a first antibody is allowed to bind, and then a labeled second antibody is added. If the presence of the first antibody reduces the binding of the second antibody, the antibodies are competing. The term "compete with" also includes antibody combinations where one antibody reduces the binding of the other antibody, but no competition is observed when the antibodies are added in the reverse order. However, in some embodiments, the first and second antibodies inhibit each other's binding regardless of the order of addition. In some embodiments, one antibody reduces the binding of the other antibody to its antigen by at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.

[0070] The term "epitope" refers to a portion of an antigen that can specifically bind to an antibody. Epitopes often consist of accessible amino acid residues and / or sugar side chains on the surface and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and nonconformational epitopes are distinguished in that the binding to the former, but not the latter, is lost in the presence of denaturing solvents. An epitope may include amino acid residues directly involved in binding as well as other amino acid residues not directly involved in binding. The epitope to which an antibody binds can be determined using known techniques for determining epitopes, such as, for example, testing the binding of the antibody to CD39 variants with different point mutations.

[0071] The "identity" percentage between a polypeptide sequence and a reference sequence is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to the amino acid residues in the reference sequence, after aligning the sequence and introducing gaps as necessary to achieve the maximum percentage of sequence identity.The alignment for determining the percent amino acid sequence identity can be achieved in various ways within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW or CLUSTAL OMEGA software.Those skilled in the art can determine the appropriate parameters for sequence alignment, including any algorithms required to achieve maximum alignment over the entire length of the sequence being compared.

[0072] "Conservative substitution" or "conservative amino acid substitution" refers to the replacement of one or more amino acids with one or more chemically or functionally similar amino acids. Conservative substitution tables providing similar amino acids are well known in the art. Polypeptide sequences with such substitutions are known as "conservatively modified variants." Such conservatively modified variants include, but do not exclude, polymorphic variants, interspecies homologs, and alleles. For example, the following groups of amino acids are considered conservative substitutions for each other: [Table 2] Additional conservative substitutions can be found, for example, in Creighton, Proteins: Structures and Molecular Properties 2nd ed. (1993) W.H. Freeman & Co., New York, N.Y. Antibodies generated by making one or more conservative substitutions of amino acid residues in a parent antibody are referred to as "conservatively modified variants."

[0073] The term "amino acid" refers to the 20 common naturally occurring amino acids, including alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C), glutamic acid (Glu; E), glutamine (Gln; Q), glycine (Gly; G), histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).

[0074] "Treating" any disease or disorder or "treatment" thereof, in certain embodiments, refers to ameliorating a disease or disorder present in a subject. In another embodiment, "treating" or "treatment" includes ameliorating at least one physical parameter, which may not be discernible by the subject. In yet another embodiment, "treating" or "treatment" includes modulating the disease or disorder physically (e.g., stabilization of discernible symptoms) or physiologically (e.g., stabilization of physical parameters), or both. In yet another embodiment, "treating" or "treatment" includes delaying or preventing the onset of a disease or disorder.

[0075] As used herein, the term "therapeutically effective amount" or "effective amount" refers to an amount of an antibody or composition that, when administered to a subject, is effective in treating a disease or disorder.

[0076] As used herein, the term "subject" refers to a mammalian subject. Exemplary subjects include, but are not limited to, humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, birds, goats, and sheep. In certain embodiments, the subject is a human. In some embodiments, the subject has cancer, an autoimmune disease or condition, and / or an infectious disease that can be treated using the antibodies provided herein. In some embodiments, the subject is a human suspected of having cancer, an autoimmune disease or condition, and / or an infectious disease.

[0077] 2. Antibodies Provided herein are antibodies that selectively bind to human CD39, as well as nucleic acids encoding the antibodies. In some embodiments, the antibodies selectively bind to the extracellular domain of human CD39.

[0078] In some embodiments, the antibody binds to a homolog of human CD39. In some aspects, the antibody binds to a homolog of human CD39 from a species selected from monkey, mouse, dog, cat, rat, cow, horse, goat, and sheep. In some aspects, the homolog is a cynomolgus monkey homolog. In some aspects, the homolog is a mouse homolog.

[0079] In some embodiments, an antibody has one or more CDRs with a specific length in terms of the number of amino acid residues. In some embodiments, the Chothia CDR-H1 of the antibody is 6, 7, 8, or 9 residues in length. In some embodiments, the Kabat CDR-H1 of the antibody is 4, 5, 6, or 7 residues in length. In some embodiments, the Chothia CDR-H2 of the antibody is 5, 6, or 7 residues in length. In some embodiments, the Kabat CDR-H2 of the antibody is 15, 16, 17, or 18 residues in length. In some embodiments, the Kabat / Chothia CDR-H3 of the antibody is 5, 6, 7, 8, 9, 10, 11, or 12 residues in length.

[0080] In some embodiments, the Kabat / Chothia CDR-L1 of the antibody is 9, 10, 11, 12, 13, 14, 15, or 16 residues in length. In some embodiments, the Kabat / Chothia CDR-L2 of the antibody is 6, 7, or 8 residues in length. In some embodiments, the Kabat / Chothia CDR-L3 of the antibody is 8, 9, 10, 11, or 12 residues in length.

[0081] In some embodiments, the antibody comprises a light chain. In some aspects, the light chain is a kappa light chain. In some aspects, the light chain is a lambda light chain.

[0082] In some embodiments, the antibody comprises a heavy chain. In some aspects, the heavy chain is IgA. In some aspects, the heavy chain is IgD. In some aspects, the heavy chain is IgE. In some aspects, the heavy chain is IgG. In some aspects, the heavy chain is IgM. In some aspects, the heavy chain is IgG1. In some aspects, the heavy chain is IgG2. In some aspects, the heavy chain is IgG3. In some aspects, the heavy chain is IgG4. In some aspects, the heavy chain is IgA1. In some aspects, the heavy chain is IgA2.

[0083] In some embodiments, the antibody is an antibody fragment. In some aspects, the antibody fragment is an Fv fragment. In some aspects, the antibody fragment is a Fab fragment. In some aspects, the antibody fragment is a F(ab')2 fragment. In some aspects, the antibody fragment is a Fab' fragment. In some aspects, the antibody fragment is an scFv (sFv) fragment. In some aspects, the antibody fragment is an scFv-Fc fragment.

[0084] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a polyclonal antibody.

[0085] In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody.

[0086] In some embodiments, the antibody is an affinity matured antibody. In some aspects, the antibody is an affinity matured antibody derived from the exemplary sequences provided in this disclosure.

[0087] In some embodiments, the antibody inhibits the conversion of ATP to ADP and / or ADP to AMP by CD39. In some embodiments, the antibody decreases levels of phosphate, ADP, AMP, and / or adenosine, and / or increases levels of ATP.

[0088] In some embodiments, the antibody is a stimulated CD4 + and CD8 + Increases T cell proliferation. In some embodiments, the antibody increases secretion of INF-γ, TNF-α, IL-2, and / or IL-1β by stimulated PBMCs.

[0089] In some embodiments, the antibody increases T effector cell function. In some embodiments, the antibody reduces the number of regulatory T cells in a tissue or in the circulation. In some embodiments, the antibody suppresses regulatory T cell activity. In some embodiments, the antibody increases B cell function. In some embodiments, the antibody increases antigen-presenting cell function. In some embodiments, the antibody reduces or prevents activation of phosphoantigen-specific T cells selected from MAIT cells and gamma delta T cells.

[0090] In some embodiments, the decrease is about or less than 10%, about or less than 20%, about or less than 30%, about or less than 40%, about or less than 50%, about or less than 60%, about or less than 70%, about or less than 80%, about or less than 90%, or a near complete decrease. In some embodiments, the increase is about or more than 10%, about or more than 20%, about or more than 30%, about or more than 40%, about or more than 50%, about or more than 60%, about or more than 70%, about or more than 80%, about or more than 90%, or a complete increase.

[0091] Because CD39 degrades ATP and ADP to adenosine, it can be viewed as an immunological switch that shifts ATP-driven pro-inflammatory immune cell activity toward an adenosine-mediated anti-inflammatory state. CD39 plays a role in regulating the function of several immune cell types, including lymphocytes, neutrophils, monocytes / macrophages, dendritic cells, and endothelial cells, and shifting this switch can have significant impacts on disease. For example, CD39-mediated adenosine generation is recognized as a major mechanism for the immunosuppressive function of regulatory T cells (Tregs).

[0092] The antibody provided herein can be useful for treating various diseases and conditions, including cancer, autoimmune disease, and infectious disease.In some embodiments, the antibody inhibits the CD39 function on tumor cells.In some embodiments, the antibody inhibits angiogenesis.

[0093] CD39 + The frequency and cell surface expression of Tregs are increased in some human cancers, and CD39 plays a key role in promoting tumor growth and metastasis. +The importance of Tregs has been demonstrated using several in vivo models. Immunohistochemical staining of normal and tumor tissues has shown that CD39 expression is significantly higher in several types of human cancers than in normal tissues. In cancer specimens, CD39 is expressed by infiltrating lymphocytes, tumor stroma, and / or tumor cells. CD39 in cancer cells exhibits ATPase activity and generates adenosine. CD39 + Cancer cells inhibited CD4 and CD8 T cell proliferation and the generation of cytotoxic effector CD8 T cells (CTLs) in a CD39- and adenosine-dependent manner.

[0094] 2.1.CDR-H3 sequence In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 82-109. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 83. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 84. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 85. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 86. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 87. In some aspects, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 88. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 89. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 91. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 92. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 93. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 94. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 95. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 96. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:97.In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 98. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 99. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 100. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 101. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 102. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 103. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 104. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 105. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 106. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 107. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 108. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 109.

[0095] In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-H3 sequence provided herein. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary CDR-H3 sequences provided herein. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-H3 sequences provided herein, and has one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0096] 2.2. V with Exemplary CDRs H array In some embodiments, the antibody comprises a V or VL sequence comprising one or more CDR-H sequences that comprise, consist of, or consist essentially of one or more exemplary CDR-H sequences provided in this disclosure. H sequences, and variants thereof.

[0097] 2.2.1. V Containing Exemplary Kabat CDRs H array In some embodiments, the antibody comprises a V or VL sequence comprising one or more Kabat CDR-H sequences that comprise, consist of, or consist essentially of one or more exemplary Kabat CDR-H sequences provided in this disclosure. H sequences, and variants thereof.

[0098] 2.2.1.1. Kabat CDR-H3 In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of a Kabat CDR-H3 sequence selected from SEQ ID NOs: 82-109. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82. HIn some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 83. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 84. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 85. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 86. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:87. H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 88. H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:89. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:91. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 92. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:93. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:94. HIn some embodiments, the antibody comprises a V comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 95. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 96. H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:97. H In some embodiments, the antibody comprises a Kabat antibody comprising, consisting of, or consisting essentially of SEQ ID NO: 98. V containing the CDR-H3 sequence H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:99. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 100. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 101. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 102. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 103. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 104. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 105. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 106. HIn some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 107. H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 108. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 109. H Contains arrays.

[0099] Kabat CDR-H2 In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of a Kabat CDR-H2 sequence selected from SEQ ID NOs: 63-81. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 63. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:64. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 65. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 66. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:67. H In some embodiments, the antibody comprises the Kabat antibody sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 68. V containing the CDR-H2 sequence H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:69. HIn some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 70. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 71. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 72. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 73. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 74. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 75. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 76. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 77. H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 78. H In some embodiments, the antibody comprises a V comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 79. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 80. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:81. H Contains arrays.

[0100] Kabat CDR-H1 In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 25-45. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:25. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:26. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:27. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:28. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:29. H In some embodiments, the antibody comprises the Kabat antibody sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 30. V containing the CDR-H1 sequence H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 31. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 32. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 33. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 34. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 35. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 36. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 37. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 38. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:39. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:40. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:41. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:42. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:43. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:44. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:45. H Contains arrays.

[0101] 2.2.1.4.Kabat CDR-H3+Kabat CDR-H2 In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of a Kabat CDR-H3 sequence selected from SEQ ID NOs: 82-109, and a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 63-81. H In some embodiments, the Kabat CDR-H3 sequence and the Kabat CDR-H2 sequence both comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, the sequence is from Kabat The CDR-H3 and Kabat CDR-H2 are both a single exemplary VDR selected from SEQ ID NOs: 179-218. H It is from an array.

[0102] 2.2.1.5.Kabat CDR-H3+Kabat CDR-H1 In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of a Kabat CDR-H3 sequence selected from SEQ ID NOs: 82-109, and a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 25-45. H In some embodiments, the Kabat CDR-H3 sequence and the Kabat CDR-H1 sequence both comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, the sequence is from Kabat The CDR-H3 and Kabat CDR-H1 are both a single exemplary VDR selected from SEQ ID NOs: 179-218. H It is from an array.

[0103] 2.2.1.6.Kabat CDR-H1+Kabat CDR-H2 In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of a Kabat CDR-H1 sequence selected from SEQ ID NOs: 25-45, and a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 63-81. H In some embodiments, the Kabat CDR-H1 sequence and the Kabat CDR-H2 sequence both comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, Kabat CDR-H1 and Kabat CDR-H2 are both from a single exemplary V sequence selected from SEQ ID NOs: 179-218. H It is from an array.

[0104] 2.2.1.7.Kabat CDR-H1+Kabat CDR-H2+Kabat CDR-H3 In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of a Kabat CDR-H1 sequence selected from SEQ ID NOs: 25-45, a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 63-81, and a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 82-109. H In some embodiments, the Kabat CDR-H1 sequence, the Kabat The CDR-H2 sequence, and the Kabat CDR-H3 sequence are all from a single exemplary V H For example, in some embodiments, Kabat CDR-H1, Kabat CDR-H2, and Kabat CDR-H3 are all from a single exemplary V sequence selected from SEQ ID NOs: 179-218. H It is from an array.

[0105] In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO:25, a Kabat CDR-H2 sequence comprising SEQ ID NO:63, and a Kabat CDR-H3 sequence comprising SEQ ID NO:82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 83. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 27, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 84. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 85. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 86. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 25, a Kabat CDR-H2 sequence comprising SEQ ID NO: 66, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 27, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 82. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO:28, a Kabat CDR-H2 sequence comprising SEQ ID NO:67, and a Kabat CDR-H3 sequence comprising SEQ ID NO:82. HIn some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO:29, a Kabat CDR-H2 sequence comprising SEQ ID NO:68, and a Kabat CDR-H3 sequence comprising SEQ ID NO:82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 82. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 88. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 32, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 89. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 90. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 34, a Kabat CDR-H2 sequence comprising SEQ ID NO: 72, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 91. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 92. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 35, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 93. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 92. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 36, a Kabat CDR-H2 sequence comprising SEQ ID NO: 72, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 73, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 37, a Kabat CDR-H2 sequence comprising SEQ ID NO: 74, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 75, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 94. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 39, a Kabat CDR-H2 sequence comprising SEQ ID NO: 76, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 95. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 40, a Kabat CDR-H2 sequence comprising SEQ ID NO: 76, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 96. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 39, a Kabat CDR-H2 sequence comprising SEQ ID NO: 76, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 94. H In some embodiments, the antibody comprises a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 97. V containing the CDR-H3 sequence HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 41, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 98. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 41, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 99. H In some embodiments, the antibody comprises the Kabat A polypeptide comprising SEQ ID NO: 41. V comprising a CDR-H1 sequence, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 100 H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 75, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 101. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 42, a Kabat CDR-H2 sequence comprising SEQ ID NO: 78, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 102. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 75, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 103. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 43, a Kabat CDR-H2 sequence comprising SEQ ID NO: 79, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 104. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 103. H In some embodiments, the antibody comprises a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 106. V containing the CDR-H3 sequenceH In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 38, a Kabat CDR-H2 sequence comprising SEQ ID NO: 69, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 107. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 44, a Kabat CDR-H2 sequence comprising SEQ ID NO: 80, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 108. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 45, a Kabat CDR-H2 sequence comprising SEQ ID NO: 81, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 109. H Contains arrays.

[0106] In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO:26, a Kabat CDR-H2 sequence comprising SEQ ID NO:65, and a Kabat CDR-H3 sequence comprising SEQ ID NO:83. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 84. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 85. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO:26, a Kabat CDR-H2 sequence comprising SEQ ID NO:65, and a Kabat CDR-H3 sequence comprising SEQ ID NO:86. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 84. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 26, a Kabat CDR-H2 sequence comprising SEQ ID NO: 64, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 86. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 27, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 83. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 27, a Kabat CDR-H2 sequence comprising SEQ ID NO: 65, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 86. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 73, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 72, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 31, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. HIn some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 32, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 72, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 33, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 34, a Kabat CDR-H2 sequence comprising SEQ ID NO: 72, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 71, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 35, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 35, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 90. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 30, a Kabat CDR-H2 sequence comprising SEQ ID NO: 70, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 39, a Kabat CDR-H2 sequence comprising SEQ ID NO: 76, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 94. H Contains arrays.

[0107] 2.2.1.8. V Containing Exemplary Kabat CDRs H Array variants In some embodiments, the V provided herein H The sequences include variants of the exemplary Kabat CDR-H3, CDR-H2, and / or CDR-H1 sequences provided in this disclosure.

[0108] In some embodiments, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a variant of the exemplary Kabat CDR-H3 sequence provided herein. In some embodiments, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary Kabat CDR-H3 sequences provided herein. In some embodiments, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of any of the exemplary Kabat CDR-H3 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0109] In some embodiments, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a variant of the exemplary Kabat CDR-H2 sequences provided herein. In some embodiments, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary Kabat CDR-H2 sequences provided herein. In some embodiments, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of any of the exemplary Kabat CDR-H2 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0110] In some embodiments, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a variant of the exemplary Kabat CDR-H1 sequences provided herein. In some embodiments, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary Kabat CDR-H1 sequences provided herein. In some embodiments, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of any of the exemplary Kabat CDR-H1 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0111] 2.2.2. V Containing Exemplary Chothia CDRs H array In some embodiments, the antibody comprises a V or VL polypeptide comprising one or more Chothia CDR-H sequences that comprise, consist of, or consist essentially of one or more exemplary Chothia CDR-H sequences provided in this disclosure. H sequences, and variants thereof.

[0112] 2.2.2.1.Chothia CDR-H3 In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 82-109. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:83. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:84. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:85. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:86. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:87. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:88. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:89. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:91. HIn some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:92. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:93. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:94. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 95. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:96. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:97. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:98. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:99. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 100. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 101. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 102. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 103. HIn some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 104. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 105. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 106. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 107. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 108. H In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 109. H Contains arrays.

[0113] 2.2.2.2.Chothia CDR-H2 In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 46-62. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:46. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:47. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:48. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:49.H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:50. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:51. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:52. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:53. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:54. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:55. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:56. H In some embodiments, the antibody comprises the sequence Chothia V containing the CDR-H2 sequence H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:58. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:59. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 60. HIn some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:61. H In some embodiments, the antibody comprises a V CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:62. H Contains arrays.

[0114] Chothia CDR-H1 In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 1-24. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:1. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:2. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:3. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:4. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:5. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:6. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:7. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:8. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:9. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 10. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 11. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 12. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 13. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 14. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 15. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 16. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 17. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 18. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 19. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:20. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:21. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:22. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:23. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO:24. H Contains arrays.

[0115] 2.2.2.4.Chothia CDR-H3+Chothia CDR-H2 In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 82-109, and a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 46-62. H In some embodiments, the Chothia CDR-H3 sequence and the Chothia CDR-H2 sequence both comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, the Chothia CDR-H3 and Chothia CDR-H2 are both from a single exemplary V sequence selected from SEQ ID NOs: 179-218. H It is from an array.

[0116] 2.2.2.5.Chothia CDR-H3+Chothia CDR-H1 In some embodiments, the antibody comprises a V CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 82-109, and a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 1-24. H In some embodiments, the Chothia CDR-H3 sequence and the Chothia CDR-H1 sequence both comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, the Chothia CDR-H3 and Chothia CDR-H1 are both from a single exemplary V sequence selected from SEQ ID NOs: 179-218. H It is from an array.

[0117] 2.2.2.6.Chothia CDR-H1+Chothia CDR-H2 In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of a Chothia CDR-H1 sequence selected from SEQ ID NOs: 1-24, and a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 46-62. H In some embodiments, the Chothia CDR-H1 sequence and the Chothia CDR-H2 sequence both comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, Chothia CDR-H1 and Chothia CDR-H2 are both from a single exemplary V sequence selected from SEQ ID NOs: 179-218. H It is from an array.

[0118] 2.2.2.7.Chothia CDR-H1+Chothia CDR-H2+Chothia CDR-H3 In some embodiments, the antibody comprises a V CDR-H1 sequence comprising, consisting of, or consisting essentially of a Chothia CDR-H1 sequence selected from SEQ ID NOs: 1-24, a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 46-62, and a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 82-109. H In some embodiments, the Chothia CDR-H1 sequence, the Chothia CDR-H2 sequence, and the Chothia CDR-H3 sequence all comprise a single exemplary V sequence provided in this disclosure. H For example, in some embodiments, Chothia CDR-H1, Chothia CDR-H2, and Chothia CDR-H3 are all from a single exemplary V sequence selected from SEQ ID NOs: 179-218. H It is from an array.

[0119] In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 46, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 82. H In some embodiments, the antibody comprises a Chothia CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H1 sequence comprising SEQ ID NO:47, V comprising a CDR-H2 sequence and a Chothia CDR-H3 sequence comprising SEQ ID NO: 83 H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 46, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 84. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:47, and a Chothia CDR-H3 sequence comprising SEQ ID NO:85. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:3, a Chothia CDR-H2 sequence comprising SEQ ID NO:47, and a Chothia CDR-H3 sequence comprising SEQ ID NO:86. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:4, a Chothia CDR-H2 sequence comprising SEQ ID NO:46, and a Chothia CDR-H3 sequence comprising SEQ ID NO:82. H In some embodiments, the antibody comprises a Chothia CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H1 sequence comprising SEQ ID NO:46, V comprising a CDR-H2 sequence and a Chothia CDR-H3 sequence comprising SEQ ID NO: 82 H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:5, a Chothia CDR-H2 sequence comprising SEQ ID NO:49, and a Chothia CDR-H3 sequence comprising SEQ ID NO:82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:6, a Chothia CDR-H2 sequence comprising SEQ ID NO:50, and a Chothia CDR-H3 sequence comprising SEQ ID NO:82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:47, and a Chothia CDR-H3 sequence comprising SEQ ID NO:82. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:7, a Chothia CDR-H2 sequence comprising SEQ ID NO:51, and a Chothia CDR-H3 sequence comprising SEQ ID NO:87. H In some embodiments, the antibody comprises a Chothia CDR-H1 sequence comprising SEQ ID NO: 8, a Chothia CDR-H1 sequence comprising SEQ ID NO: 52, V comprising a CDR-H2 sequence and a Chothia CDR-H3 sequence comprising SEQ ID NO: 88 HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:9, a Chothia CDR-H2 sequence comprising SEQ ID NO:53, and a Chothia CDR-H3 sequence comprising SEQ ID NO:89. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 90. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 11, a Chothia CDR-H2 sequence comprising SEQ ID NO: 54, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 91. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 12, a Chothia CDR-H2 sequence comprising SEQ ID NO: 53, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 92. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 92. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 54, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 15, a Chothia CDR-H2 sequence comprising SEQ ID NO: 55, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 16, a Chothia CDR-H2 sequence comprising SEQ ID NO: 56, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 94. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 18, a Chothia CDR-H2 sequence comprising SEQ ID NO: 57, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 95. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 19, a Chothia CDR-H2 sequence comprising SEQ ID NO: 57, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 96. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:21, a Chothia CDR-H2 sequence comprising SEQ ID NO:57, and a Chothia CDR-H3 sequence comprising SEQ ID NO:94. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 97. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 22, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 98. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 22, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 99. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 22, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 100. H In some embodiments, the antibody comprises a Chothia CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 101. V containing the CDR-H3 sequence H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 59, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 102. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 103. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 23, a Chothia CDR-H2 sequence comprising SEQ ID NO: 60, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 104. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 105. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 106. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 51, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 107. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 61, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 108. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 17, a Chothia CDR-H2 sequence comprising SEQ ID NO: 62, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 109. H Contains arrays.

[0120] In some embodiments, the antibody comprises a V CDR-H1 sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:46, and a Chothia CDR-H3 sequence comprising SEQ ID NO:83. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:46, and a Chothia CDR-H3 sequence comprising SEQ ID NO:84. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:46, and a Chothia CDR-H3 sequence comprising SEQ ID NO:85. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:46, and a Chothia CDR-H3 sequence comprising SEQ ID NO:86. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:47, and a Chothia CDR-H3 sequence comprising SEQ ID NO:84. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:2, a Chothia CDR-H2 sequence comprising SEQ ID NO:47, and a Chothia CDR-H3 sequence comprising SEQ ID NO:86. HIn some embodiments, the antibody comprises a Chothia CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H1 sequence comprising SEQ ID NO: 46, V comprising a CDR-H2 sequence and a Chothia CDR-H3 sequence comprising SEQ ID NO: 83 H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 1, a Chothia CDR-H2 sequence comprising SEQ ID NO: 46, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 86. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 53, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 55, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 54, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:8, a Chothia CDR-H2 sequence comprising SEQ ID NO:52, and a Chothia CDR-H3 sequence comprising SEQ ID NO:87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:8, a Chothia CDR-H2 sequence comprising SEQ ID NO:53, and a Chothia CDR-H3 sequence comprising SEQ ID NO:87. HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO:9, a Chothia CDR-H2 sequence comprising SEQ ID NO:53, and a Chothia CDR-H3 sequence comprising SEQ ID NO:87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 53, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 54, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 53, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 10, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 93. H In some embodiments, the antibody comprises a Chothia V comprising a CDR-H1 sequence, a Chothia CDR-H2 sequence comprising SEQ ID NO:54, and a Chothia CDR-H3 sequence comprising SEQ ID NO:87 H In some embodiments, the antibody comprises a Chothia CDR-H1 sequence comprising SEQ ID NO: 12, a Chothia CDR-H2 sequence comprising SEQ ID NO: 53, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. V containing the CDR-H3 sequence HIn some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 90. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 15, a Chothia CDR-H2 sequence comprising SEQ ID NO: 52, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 87. H In some embodiments, the antibody comprises a V CDR-H1 sequence comprising SEQ ID NO: 18, a Chothia CDR-H2 sequence comprising SEQ ID NO: 57, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 94. H Contains arrays.

[0121] 2.2.2.8. V Containing Exemplary Chothia CDRs H Array variants In some embodiments, the V provided herein H The sequences include variants of the exemplary Chothia CDR-H3, CDR-H2, and / or CDR-H1 sequences provided in this disclosure.

[0122] In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a variant of the exemplary Chothia CDR-H3 sequence provided herein. In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary Chothia CDR-H3 sequences provided herein. In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of any of the exemplary Chothia CDR-H3 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0123] In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a variant of the exemplary Chothia CDR-H2 sequences provided herein. In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary Chothia CDR-H2 sequences provided herein. In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of any of the exemplary Chothia CDR-H2 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0124] In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a variant of the exemplary Chothia CDR-H1 sequences provided herein. In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary Chothia CDR-H1 sequences provided herein. In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of any of the exemplary Chothia CDR-H1 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0125] 2.3.V H array In some embodiments, the antibody comprises, consists of, or consists essentially of a sequence selected from SEQ ID NOs: 179-218. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 179. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 180. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 181. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 182. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 183. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 184. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 185. HIn some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 186. H In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 187. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 188. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 189. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 190. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 191. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 192. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 193. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 194. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 195. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 196. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 197. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 198. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 199. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 200. HIn some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 201. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 202. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 203. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 204. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 205. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 206. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 207. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 208. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 209. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 210. H In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 211. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 212. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 213. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 214. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 215. HIn some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 216. H In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 217. H In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 218. H Contains arrays.

[0126] 2.3.1.V H Array variants In some embodiments, the V provided herein H The sequences are the same as those of the exemplary V H It may comprise, consist of, or consist essentially of a variant of the sequence.

[0127] In some embodiments, V H The sequences are the same as those of the exemplary V H In some embodiments, the V H The sequences are the same as those of the exemplary V H The nucleic acid sequence may comprise, consist of, or consist essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity to any of the sequences.

[0128] In some embodiments, V H The sequence may be any of the exemplary V sequences provided in this disclosure with 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. HIn some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0129] 2.4.CDR-L3 Sequence In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 141-166. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 141. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 142. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 143. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 144. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 145. In some aspects, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 146. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 147. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 148. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 149. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 150. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 151. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 152. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 153. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 154. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 155. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 156.In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 157. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 158. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 159. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 160. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 161. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 162. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 163. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 164. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 165. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 166.

[0130] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-L3 sequence provided herein. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L3 sequences provided herein. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L3 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0131] 2.5. V with Exemplary CDRs L array In some embodiments, the antibody comprises a V or VL sequence comprising one or more CDR-L sequences that comprise, consist of, or consist essentially of one or more exemplary CDR-L sequences provided in this disclosure. L sequences, and variants thereof.

[0132] CDR-L3 In some embodiments, the antibody comprises a V nucleotide sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 141-166. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 141. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 142. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 143. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 144. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 145. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 146. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 147. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 148. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 149. LIn some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 150. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 151. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 152. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 153. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 154. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 155. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 156. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 157. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 158. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 159. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 160. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 161. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 162. LIn some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 163. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 164. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 165. L In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 166. L Contains arrays.

[0133] CDR-L2 In some embodiments, the antibody comprises a V nucleotide sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 125-140. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 125. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 126. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 127. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 128. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 129. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 130. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 131. LIn some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 132. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 133. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 134. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 135. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 136. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 137. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 138. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 139. L In some embodiments, the antibody comprises a V CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 140. L Contains arrays.

[0134] CDR-L1 In some embodiments, the antibody comprises a V nucleotide sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 110-124. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 110. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 111. LIn some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 112. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 113. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 114. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 115. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 116. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 117. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 118. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 119. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 120. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 121. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 122. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 123. L In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 124. L Contains arrays.

[0135] 2.5.4.CDR-L3+CDR-L2 In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 141-166, and a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 125-140. L In some embodiments, the CDR-L3 sequence and the CDR-L2 sequence both comprise a single exemplary V sequence provided in the present disclosure. L For example, in some embodiments, CDR-L3 and CDR-L2 are both from a single exemplary V sequence selected from SEQ ID NOs: 219-248. L It is from an array.

[0136] 2.5.5.CDR-L3+CDR-L1 In some embodiments, the antibody comprises a V CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 141-166, and a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 110-124. L In some embodiments, the CDR-L3 sequence and the CDR-L1 sequence both comprise a single exemplary V sequence provided in the present disclosure. L For example, in some embodiments, CDR-L3 and CDR-L1 are both from a single exemplary V sequence selected from SEQ ID NOs: 219-248. L It is from an array.

[0137] 2.5.6.CDR-L1+CDR-L2 In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 110-124, and a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 125-140. LIn some embodiments, the CDR-L1 sequence and the CDR-L2 sequence both comprise a single exemplary V sequence provided in the present disclosure. L For example, in some embodiments, CDR-L1 and CDR-L2 are both from a single exemplary V sequence selected from SEQ ID NOs: 219-248. L It is from an array.

[0138] 2.5.7.CDR-L1+CDR-L2+CDR-L3 In some embodiments, the antibody comprises a V CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 110-124, a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 125-140, and a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOs: 141-166. L In some embodiments, the CDR-L1 sequence, the CDR-L2 sequence, and the CDR-L3 sequence all comprise a single exemplary V sequence provided in the present disclosure. L For example, in some embodiments, CDR-L1, CDR-L2, and CDR-L3 are all from a single exemplary V sequence selected from SEQ ID NOs: 219-248. L It is from an array.

[0139] In some embodiments, the antibody comprises a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 125, and a CDR-L3 sequence comprising SEQ ID NO: 141. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 111, a CDR-L2 sequence comprising SEQ ID NO: 126, and a CDR-L3 sequence comprising SEQ ID NO: 142. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 127, and a CDR-L3 sequence comprising a sequence selected from SEQ ID NO: 142. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 125, and a CDR-L3 sequence comprising SEQ ID NO: 143. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 112, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence comprising SEQ ID NO: 144. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 111, a CDR-L2 sequence comprising SEQ ID NO: 126, and a CDR-L3 sequence comprising SEQ ID NO: 145. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 113, a CDR-L2 sequence comprising SEQ ID NO: 129, and a CDR-L3 sequence comprising SEQ ID NO: 146. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 114, a CDR-L2 sequence comprising SEQ ID NO: 130, and a CDR-L3 sequence comprising SEQ ID NO: 147. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 148. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 148. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 116, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 149. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 148.In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 132, and a CDR-L3 sequence comprising SEQ ID NO: 149. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 117, a CDR-L2 sequence comprising SEQ ID NO: 133, and a CDR-L3 sequence comprising SEQ ID NO: 150. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 134, and a CDR-L3 sequence comprising SEQ ID NO: 148. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence comprising SEQ ID NO: 151. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence comprising SEQ ID NO: 152. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 136, and a CDR-L3 sequence comprising SEQ ID NO: 152. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 115, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 153. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 119, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 154. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 120, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence comprising SEQ ID NO: 155. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence comprising SEQ ID NO: 156. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence comprising SEQ ID NO: 157. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 122, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence comprising SEQ ID NO: 158.In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence comprising SEQ ID NO: 159. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 118, a CDR-L2 sequence comprising SEQ ID NO: 135, and a CDR-L3 sequence comprising SEQ ID NO: 160. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 139, and a CDR-L3 sequence comprising SEQ ID NO: 161. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 123, a CDR-L2 sequence comprising SEQ ID NO: 140, and a CDR-L3 sequence comprising SEQ ID NO: 162. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 138, and a CDR-L3 sequence comprising SEQ ID NO: 163. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 121, a CDR-L2 sequence comprising SEQ ID NO: 139, and a CDR-L3 sequence comprising SEQ ID NO: 164. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 120, a CDR-L2 sequence comprising SEQ ID NO: 137, and a CDR-L3 sequence comprising SEQ ID NO: 165. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 124, a CDR-L2 sequence comprising SEQ ID NO: 125, and a CDR-L3 sequence comprising SEQ ID NO: 166.

[0140] In some embodiments, the antibody comprises a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 128, and a CDR-L3 sequence comprising SEQ ID NO: 144. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 125, and a CDR-L3 sequence comprising SEQ ID NO: 144. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 126, and a CDR-L3 sequence comprising a sequence selected from SEQ ID NO: 144. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 116, a CDR-L2 sequence comprising SEQ ID NO: 131, and a CDR-L3 sequence comprising SEQ ID NO: 150. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO:117, a CDR-L2 sequence comprising SEQ ID NO:134, and a CDR-L3 sequence comprising SEQ ID NO:150.

[0141] 2.5.8. V including example CDR-L L Array variants In some embodiments, the V provided herein L The sequences include variants of the exemplary CDR-L3, CDR-L2, and / or CDR-L1 sequences provided in this disclosure.

[0142] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-L3 sequence provided herein. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L3 sequences provided herein. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L3 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0143] In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-L2 sequences provided herein. In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary CDR-L2 sequences provided herein. In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L2 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0144] In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-L1 sequences provided herein. In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary CDR-L1 sequences provided herein. In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L1 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0145] 2.6.V L array In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of a sequence selected from SEQ ID NOs: 219-248. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 219. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 220. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 221. LIn some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 222. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 223. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 224. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 225. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 226. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 227. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 228. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 229. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 230. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 231. L In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 232. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 233. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 234. L In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 235. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 236. LIn some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 237. L In some embodiments, the antibody comprises a V that comprises, consists of, or consists essentially of SEQ ID NO: 238. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 239. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 240. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 241. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 242. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 243. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 244. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 245. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 246. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 247. L In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 248. L Contains arrays.

[0146] 2.6.1.V L Array variants In some embodiments, the V provided herein L The sequences are the same as those of the exemplary V L It may comprise, consist of, or consist essentially of a variant of the sequence.

[0147] In some embodiments, V L The sequences are the same as those of the exemplary V L In some embodiments, the V L The sequences are the same as those of the exemplary V L The nucleic acid sequence may comprise, consist of, or consist essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.05% identity to any of the sequences.

[0148] In some embodiments, V L The sequence may be any of the exemplary V sequences provided in this disclosure with 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. L In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0149] 2.7.Versus 2.7.1.CDR-H3-CDR-L3 Pair In some embodiments, the antibody comprises a CDR-H3 sequence and a CDR-L3 sequence. H and the CDR-L3 sequence is part of V L is part of.

[0150] In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of SEQ ID NOs: 82-109, and the CDR-L3 sequence comprises, consists of, or consists essentially of SEQ ID NOs: 141-166.

[0151] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 82 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0152] In some embodiments, the CDR-H3 sequence is SEQ ID NO:83 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0153] In some embodiments, the CDR-H3 sequence is SEQ ID NO:84 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0154] In some embodiments, the CDR-H3 sequence is SEQ ID NO:85 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0155] In some embodiments, the CDR-H3 sequence is SEQ ID NO:86 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0156] In some embodiments, the CDR-H3 sequence is SEQ ID NO:87 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0157] In some embodiments, the CDR-H3 sequence is SEQ ID NO:88 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0158] In some embodiments, the CDR-H3 sequence is SEQ ID NO:89 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0159] In some embodiments, the CDR-H3 sequence is SEQ ID NO:90 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0160] In some embodiments, the CDR-H3 sequence is SEQ ID NO:91 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0161] In some embodiments, the CDR-H3 sequence is SEQ ID NO:92 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0162] In some embodiments, the CDR-H3 sequence is SEQ ID NO:93 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0163] In some embodiments, the CDR-H3 sequence is SEQ ID NO:94 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0164] In some embodiments, the CDR-H3 sequence is SEQ ID NO:95 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0165] In some embodiments, the CDR-H3 sequence is SEQ ID NO:96 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0166] In some embodiments, the CDR-H3 sequence is SEQ ID NO:97 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0167] In some embodiments, the CDR-H3 sequence is SEQ ID NO:98 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0168] In some embodiments, the CDR-H3 sequence is SEQ ID NO:99 and the CDR-L3 sequence is selected from SEQ ID NOs:141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO:141. In some embodiments, the CDR-L3 sequence is SEQ ID NO:142. In some embodiments, the CDR-L3 sequence is SEQ ID NO:143. In some embodiments, the CDR-L3 sequence is SEQ ID NO:144. In some embodiments, the CDR-L3 sequence is SEQ ID NO:145. In some embodiments, the CDR-L3 sequence is SEQ ID NO:146. In some embodiments, the CDR-L3 sequence is SEQ ID NO:147. In some embodiments, the CDR-L3 sequence is SEQ ID NO:148. In some embodiments, the CDR-L3 sequence is SEQ ID NO:149. In some embodiments, the CDR-L3 sequence is SEQ ID NO:150. In some embodiments, the CDR-L3 sequence is SEQ ID NO:151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0169] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 100 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0170] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 101 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0171] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 102 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0172] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 103 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0173] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 104 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0174] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 105 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0175] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 106 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0176] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 107 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0177] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 108 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0178] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 109 and the CDR-L3 sequence is selected from SEQ ID NOs: 141-166. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 141. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 142. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 143. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 144. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 145. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 146. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 147. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 148. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 149. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 150. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 151. In some aspects, the CDR-L3 sequence is SEQ ID NO: 152. In some aspects, the CDR-L3 sequence is SEQ ID NO: 153. In some aspects, the CDR-L3 sequence is SEQ ID NO: 154. In some aspects, the CDR-L3 sequence is SEQ ID NO: 155. In some aspects, the CDR-L3 sequence is SEQ ID NO: 156. In some aspects, the CDR-L3 sequence is SEQ ID NO: 157. In some aspects, the CDR-L3 sequence is SEQ ID NO: 158. In some aspects, the CDR-L3 sequence is SEQ ID NO: 159. In some aspects, the CDR-L3 sequence is SEQ ID NO: 160. In some aspects, the CDR-L3 sequence is SEQ ID NO: 161. In some aspects, the CDR-L3 sequence is SEQ ID NO: 162. In some aspects, the CDR-L3 sequence is SEQ ID NO: 163. In some aspects, the CDR-L3 sequence is SEQ ID NO: 164. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 165. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 166.

[0179] 2.7.1.1. Variants of the CDR-H3-CDR-L3 Pair In some embodiments, the CDR-H3-CDR-L3 pairs provided herein comprise variants of the exemplary CDR-H3 and / or CDR-L1 sequences provided in this disclosure.

[0180] In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-H3 sequence provided herein. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity to any of the exemplary CDR-H3 sequences provided herein. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-H3 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0181] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-L3 sequence provided herein. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary CDR-L3 sequences provided herein. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L3 sequences provided herein, with one, two, or three amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0182] 2.7.2.V H -V L versus In some embodiments, the antibody is H Array and V L Contains arrays.

[0183] In some embodiments, V H The sequence comprises, consists of, or consists essentially of SEQ ID NOs: 179-218. H is an array, and V L The sequence comprises, consists of, or consists essentially of SEQ ID NOs: 219-248.L It is an array.

[0184] In some embodiments, V H The sequence is SEQ ID NO: 179, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V LThe sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0185] In some embodiments, V H The sequence is SEQ ID NO: 180, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V LThe sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0186] In some embodiments, V H The sequence is SEQ ID NO: 181, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V LThe sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0187] In some embodiments, V H The sequence is SEQ ID NO: 182, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V LThe sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0188] In some embodiments, V H The sequence is SEQ ID NO: 183, and V LThe sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, VL The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0189] In some embodiments, V H The sequence is SEQ ID NO: 184, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, VL The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0190] In some embodiments, V H The sequence is SEQ ID NO: 185, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, VL The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0191] In some embodiments, V H The sequence is SEQ ID NO: 186, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, VL The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0192] In some embodiments, V H The sequence is SEQ ID NO: 187, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, VL The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, VL The sequence is SEQ ID NO:248.

[0193] In some embodiments, V H The sequence is SEQ ID NO: 188, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, VL The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0194] In some embodiments, V H The sequence is SEQ ID NO: 189, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, VL The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0195] In some embodiments, V H The sequence is SEQ ID NO: 190, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, VL The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0196] In some embodiments, V H The sequence is SEQ ID NO: 191, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, VL The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0197] In some embodiments, V H The sequence is SEQ ID NO: 192, and VL The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V LThe sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0198] In some embodiments, V H The sequence is SEQ ID NO: 193, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V LThe sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0199] In some embodiments, V H The sequence is SEQ ID NO: 194, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V LThe sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0200] In some embodiments, V H The sequence is SEQ ID NO: 195, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V LThe sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0201] In some embodiments, V H The sequence is SEQ ID NO: 196, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V LThe sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V LThe sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0202] In some embodiments, V H The sequence is SEQ ID NO: 197, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V LThe sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0203] In some embodiments, V H The sequence is SEQ ID NO: 198, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V LThe sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0204] In some embodiments, V H The sequence is SEQ ID NO: 199, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V LThe sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0205] In some embodiments, V H The sequence is SEQ ID NO: 200, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V LThe sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0206] In some embodiments, V HThe sequence is SEQ ID NO: 201, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V LThe sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0207] In some embodiments, V H The sequence is SEQ ID NO: 202, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V LThe sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0208] In some embodiments, V H The sequence is SEQ ID NO: 203, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V LThe sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0209] In some embodiments, V H The sequence is SEQ ID NO: 204, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V LThe sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0210] In some embodiments, V H The sequence is SEQ ID NO: 205, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V LThe sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V LThe sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0211] In some embodiments, V H The sequence is SEQ ID NO: 206, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V LThe sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0212] In some embodiments, V H The sequence is SEQ ID NO: 207, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V LThe sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0213] In some embodiments, V H The sequence is SEQ ID NO: 208, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V LThe sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0214] In some embodiments, V H The sequence is SEQ ID NO: 209, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V LThe sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0215] In some embodiments, V HThe sequence is SEQ ID NO: 210, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V LThe sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0216] In some embodiments, V H The sequence is SEQ ID NO: 211, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V LThe sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0217] In some embodiments, V H The sequence is SEQ ID NO: 212, and V L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V LThe sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0218] In some embodiments, V H The sequence is SEQ ID NO: 213, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V LThe sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0219] In some embodiments, V H The sequence is SEQ ID NO: 214, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V LThe sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V LThe sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0220] In some embodiments, V H The sequence is SEQ ID NO: 215, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V L The sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V LThe sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodiments, V L The sequence is SEQ ID NO: 243. In some embodiments, V L The sequence is SEQ ID NO: 244. In some embodiments, V L The sequence is SEQ ID NO: 245. In some embodiments, V L The sequence is SEQ ID NO: 246. In some embodiments, V L The sequence is SEQ ID NO: 247. In some embodiments, V L The sequence is SEQ ID NO:248.

[0221] In some embodiments, V H The sequence is SEQ ID NO: 216, L The sequence is selected from SEQ ID NOs: 219-248. L The sequence is SEQ ID NO: 219. In some embodiments, V L The sequence is SEQ ID NO: 220. In some embodiments, V L The sequence is SEQ ID NO: 221. In some embodiments, V L The sequence is SEQ ID NO: 222. In some embodiments, V L The sequence is SEQ ID NO: 223. In some embodiments, V L The sequence is SEQ ID NO: 224. In some embodiments, V L The sequence is SEQ ID NO: 225. In some embodiments, V L The sequence is SEQ ID NO: 226. In some embodiments, V L The sequence is SEQ ID NO: 227. In some embodiments, V L The sequence is SEQ ID NO: 228. In some embodiments, V L The sequence is SEQ ID NO: 229. In some embodiments, V L The sequence is SEQ ID NO: 230. In some embodiments, V L The sequence is SEQ ID NO: 231. In some embodiments, V L The sequence is SEQ ID NO: 232. In some embodiments, V L The sequence is SEQ ID NO: 233. In some embodiments, V L The sequence is SEQ ID NO: 234. In some embodiments, V LThe sequence is SEQ ID NO: 235. In some embodiments, V L The sequence is SEQ ID NO: 236. In some embodiments, V L The sequence is SEQ ID NO: 237. In some embodiments, V L The sequence is SEQ ID NO: 238. In some embodiments, V L The sequence is SEQ ID NO: 239. In some embodiments, V L The sequence is SEQ ID NO: 240. In some embodiments, V L The sequence is SEQ ID NO: 241. In some embodiments, V L The sequence is SEQ ID NO: 242. In some embodim...

Claims

[Claim 1] The invention as set forth in the drawings.

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