Anti-CD39 antibody, composition containing the anti-CD39 antibody, and method of using the anti-CD39 antibody

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 Jul. 31, 2017, the entire disclosure of which is hereby incorporated by reference herein.

[0002] Provided herein are antibodies having binding specificity for CD39, and compositions comprising such antibodies, including pharmaceutical compositions, diagnostic compositions, and kits. Also provided are methods of using anti-CD39 antibodies for therapeutic and diagnostic purposes.

Background Art

[0003] CD39 is an endogenous membrane protein that phosphohydrolyzes the phosphate group of ATP to generate ADP and AMP. Human CD39 is a 510 amino acid protein with 7 potential N-linked glycosylation sites, 11 cysteine residues, and 2 transmembrane regions. Structurally, it is characterized by two transmembrane domains, with a small cytoplasmic domain containing NH 2 - 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 extremely important for the catabolic activity of the enzyme. CD39 becomes catalytically active when localized to the cell surface, and its glycosylation is important for protein folding, membrane targeting, and enzyme activity.

[0004] CD39 is constitutively expressed in the spleen, thymus, lung, and placenta, and in these tissues it is mainly 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). In addition to other enzymes, since CD39 degrades ATP, ADP, and AMP to adenosine, CD39 can be considered an immunological switch that shifts ATP-driven pro-inflammatory immune cell activity towards an anti-inflammatory state mediated by adenosine.

[0005] In the neoplastic environment, cancer and immune cells can interact closely and generate an immunosuppressive environment by releasing immunomodulatory factors that assist in the growth of the neoplasm. Expression of CD39 is increased in a number of solid tumors (e.g., in particular, 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) and lymphoma, melanoma (Dzhandzhugazyan et al., FEBS Letters, 1998, 430: 227 - 230), ovarian cancer, and prostate cancer), suggesting that this enzyme is involved in the development and progression of malignant tumors. Modulators of CD39 can lead to potential treatments for these types of cancer.

[0006] The interaction between tumor cells and their microenvironment is important for tumorigenesis. CD39 is involved in tumor immune escape by inhibiting the activation, clonal expansion, and homing of tumor-specific T cells, and may weaken the killing of tumor cells by effector T lymphocytes. In addition to these immunomodulatory roles, CD39 may directly contribute to the modulation of cancer cell growth, differentiation, invasion, migration, metastasis, and angiogenesis. CD39 is important for both the initiation and progression of angiogenesis. CD39 on the vasculature mediates the angiogenesis process in mouse models of melanoma, lung, and liver malignancies.

[0007] Modulators of CD39 activity can also lead to potential therapeutic agents for treating the status of CD39, including but not limited to autoimmune diseases and infectious diseases. In particular, modulators of CD39 activity can lead to potential therapeutic agents for diseases such as, for example, 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, as well as inflammatory bowel disease (Friedman et al., PNAS, 2009, 106, 39: 16788-16793) and Crohn's disease (Bai et al., J Immunol, 2014, 3366-3377).

Prior Art Documents

Non-Patent Documents

[0008]

Non-Patent Document 1

[0009] Antibodies that selectively bind to CD39 are provided herein. In some embodiments, the antibody binds to human CD39. In some embodiments, the antibody also binds to homologs of human CD39.

[0010] In some embodiments, the antibody comprises at least one CDR sequence defined by the consensus sequences provided in this disclosure. In some embodiments, the antibody comprises the exemplary CDRs, V H , or V L sequences, the heavy or light chains provided in this disclosure, or variants thereof. In some aspects, the variant is a variant having 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] This disclosure also provides methods of using the anti - CD39 antibodies provided herein. In some embodiments, the method is a method of treatment. In some embodiments, the method is a diagnostic method. In some embodiments, the method is an analytical method. In some embodiments, the method is a method of purifying and / or quantifying CD39.

[0013] In some embodiments, the antibody is used to treat a disease or condition. In some aspects, the disease or condition is selected from cancer, autoimmune diseases, and infectious diseases. The present invention provides, for example, the following items. (Item 1) Specifically binds to human CD39 (hCD39) and has the following properties: a) inhibiting the binding of CD39 to ATP; b) inhibiting the conversion of ATP to ADP and / or ADP to AMP by CD39; c) reducing 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) reducing the levels of phosphate, ADP, AMP, and / or adenosine, and / or increasing the level of ATP; h) increasing T effector cell function; i) reducing the number of regulatory T cells in tissues or in 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 against tumor cells; n) inhibiting the processing of at least one phosphoantigen derived from phosphorylated isoprenoids, phosphorylated vitamin B metabolites, and / or phosphorylated riboflavin; o) decreasing or preventing the activation of phosphoantigen-specific T cells selected from MAIT cells and γδ T cells; p) inhibiting angiogenesis; q) increasing the proliferation of stimulated CD4 + and CD8 + T cells; r) Increasing the secretion by stimulated PBMC of INF-γ, TNF-α, IL-2 and / or IL-1β An antigen-binding protein, of which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 may be possible. (Item 2) The following characteristics: a) Being a monoclonal antibody; b) Being a human antibody, a humanized antibody, or a chimeric antibody; c) Being a bispecific antibody, a multispecific antibody, a diabody, or a multivalent antibody; d) Being of the IgG1, IgG2, IgG3, IgG4, or IgM type; e) Being an antigen-binding antibody fragment; f) Being a Fab fragment, a Fab’ fragment, an F(ab’)2 fragment, or an Fv fragment; and / or g) Being a single-chain antibody, a single-domain antibody, or a nanobody The antigen-binding protein according to item 1, having 1, 2, 3, 4, 5, 6, or 7 of the above. (Item 3) Binding to hCD39 and having the following characteristics: a) Blocking or reducing the hydrolysis of ATP to ADP and / or ADP to AMP, determined by at least one of (i) a decrease in the release of phosphate (Pi), (ii) an increase in the ATP level, and (iii) a decrease in the 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 circulation; e) Increasing B cell function; f) Increasing antigen-presenting cell function; g) Inhibiting CD39 function against tumor cells; h) blocking or inhibiting the processing of at least one of phosphorylated isoprenoids, phosphorylated vitamin B metabolites, and phosphoantigens derived from phosphorylated riboflavin; i) reducing or preventing the activation of phosphoantigen-specific T cells selected from MAIT cells and γδ T cells; k) inhibiting angiogenesis; l) reducing the 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 the proliferation of T cells; r) increasing the secretion by stimulated PBMC of INF-γ, TNF-α, IL-2, and / or IL-1β A pharmaceutical composition comprising an effective amount of an antibody having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 of the above. (Item 4) A pharmaceutical composition comprising the antigen-binding protein according to Item 1 or Item 2. (Item 5) An effective amount of the following: a) an anti-PD-1 antibody, b) an anti-PD-L1 antibody, c) an anti-CD73 antibody, d) an anti-CD38 antibody, e) an anti-A2A receptor antibody, f) an anti-A2B receptor antibody, g) an anti-A2A / A2B dual receptor antibody, or any combination thereof, or h) a small molecule inhibitor, The pharmaceutical composition according to Item 4, further comprising at least one or a combination of these. (Item 6) a) an antibody against an inhibitory receptor or ligand, and / or b) an antibody against a costimulatory receptor or ligand, The pharmaceutical composition according to item 4 or item 5, further comprising one or both of these 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 costimulatory receptor or ligand is at least one of OX40, CD2, CD27, CD8, 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, the pharmaceutical composition according to item 6. (Item 8) The pharmaceutical composition according to item 7, wherein the costimulatory receptor or ligand LFA-1 further comprises LFA-1 β chain CD18 and / or LFA-1 α chain CD11a. (Item 9) The following characteristics: a) binding to a human CD39 polypeptide or a variant thereof with a KD of less than about 20 nM; b) binding to a cynomolgus CD39 polypeptide or a variant thereof with a KD of less than about 200 nM; c) binding to a mouse CD39 polypeptide or a variant thereof with a KD of less than about 200 nM; or d) at least two combinations of a), b), and c) The antigen-binding protein according to item 1, having one or more of these. (Item 10) An antigen-binding protein that competes with or can compete with a reference antigen-binding protein with respect to binding to human CD39, wherein the reference antigen-binding protein is the antigen-binding protein described in item 1. (Item 11) An antigen-binding protein that binds to human CD39 or can compete with a reference antigen-binding protein with respect to binding to human CD39, wherein the reference antigen-binding protein binds to an epitope at positions 143-158 or 274-277 of SEQ ID NO: 249 on a human CD39 polypeptide, including but not limited to D150, E153, R154 or N99 alone, or a combination of D150, E153, R154 or any combination thereof. (Item 12) The antigen-binding protein according to item 10 or item 11, wherein the antigen-binding protein and the reference antibody cross-compete or can cross-compete with respect to binding to human CD39. (Item 13) The antigen-binding protein according to item 1, comprising a human heavy chain constant region or fragment or variants thereof, wherein the variant of the constant region comprises up to 20 conservatively modified amino acid substitutions from any of the sequences shown in SEQ ID NOs: 179-218. (Item 14) 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 VH and / or VL are as follows: a) VHCDR1 having the sequence shown in SEQ ID NOs: 1-45, b) VHCDR2 having the sequence shown in SEQ ID NOs: 46-81, c) VHCDR3 having the sequence shown in SEQ ID NOs: 82-109, d) VLCDR1 having the sequence shown in SEQ ID NOs: 110-124, e) VLCDR2 having the sequence shown in SEQ ID NOs: 125-140, and f) VLCDR3 having the sequence shown in SEQ ID NOs: 141-166 An isolated antibody molecule comprising 1, 2, 3, 4, 5, or 6 thereof. (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), wherein said VH is as follows: a) VHCDR1 having the sequence shown in SEQ ID NOs: 1 to 45, b) VHCDR2 having the sequence shown in SEQ ID NOs: 46 to 81, and c) VHCDR3 having the sequence shown in SEQ ID NOs: 82 to 109 and comprising; wherein said VL is as follows: 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 An isolated antibody molecule comprising. (Item 16) An isolated nucleic acid encoding the antigen-binding protein according to Item 1, Item 14, or Item 15. (Item 17) An expression vector comprising the nucleic acid according to Item 16. (Item 18) A prokaryotic or eukaryotic host cell comprising the vector according to Item 17. (Item 19) An oncolytic virus encoding the nucleic acid according to either Item 16 or Item 17. (Item 20) A method for producing a recombinant protein, comprising the steps of expressing the nucleic acid according to Item 16 in a prokaryotic or eukaryotic host cell, and recovering the protein from said cell or cell culture supernatant. (Item 21) A method for treating a subject suffering from cancer, a chronic infectious disease, or an inflammatory disease, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the antigen-binding protein according to item 1 or the pharmaceutical composition according to item 3. (Item 22) The method according to item 21, wherein the cancer is a solid cancer. (Item 23) The method according to item 21, wherein the cancer is a hematological cancer. (Item 24) A method for modulating immune system function in a subject in need thereof, the method comprising contacting a population of immune cells of the subject with a pharmaceutical composition comprising an effective amount of the antigen-binding protein according to item 1 under conditions such that the immune system is modulated. (Item 25) 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 occurs against a tumor antigen. (Item 26) The method according to item 24 or item 25, wherein the subject is a human subject. (Item 27) The method according to item 25, wherein the antigen-binding protein comprises a bispecific antibody or a complex-forming antigen-binding protein. (Item 28) The antigen-binding protein, the bispecific antibody, or the complex-forming antigen-binding protein is, in the subject: a) reducing CD39 ATPase activity in a target cell population; b) reducing the suppression of effector T cell activity by regulatory T cells; c) reducing the level 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 The method according to item 27, which is administered in an amount sufficient to achieve 1, 2, 3, 4, 5, 6, or 7 of the above. (Item 29) The method according to item 28, wherein the target cell population comprises T cells, B cells, monocytes, macrophages, dendritic cells, bone marrow-derived suppressor cells, and / or tumor cells. (Item 30) The following: a) performing chemotherapy; b) performing radiotherapy; and / or c) administering one or more additional therapeutic agents The method according to item 25, further comprising one or more of the above. (Item 31) The method according to item 30, wherein the one or more additional therapeutic agents comprise one or more immunostimulants. (Item 32) The method according to item 31, wherein the one or more immunostimulants comprise antagonists against inhibitory receptors of immune cells. (Item 33) The method according to item 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) The method according to item 31, wherein the one or more immunostimulants comprise agonists of co-stimulatory receptors of immune cells. (Item 35) The method according to item 34, wherein the co-stimulatory 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) The method according to item 35, wherein the co-stimulatory receptor or ligand LFA-1 further comprises LFA-1 β-chain CD18 and / or LFA-1 α-chain CD11a. (Item 37) The method according to item 31, wherein the one or more immunostimulants comprise cytokines. (Item 38) The method according to item 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) The method according to item 31, wherein the one or more immunostimulants comprise oncolytic viruses. (Item 40) The method according to item 39, wherein the oncolytic virus is herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, or Maraba virus. (Item 41) The method according to item 31, wherein the one or more immunostimulants comprise chimeric antigen-engineered T cells. (Item 42) The method according to item 31, wherein the one or more immunostimulants comprise bispecific or multispecific T cell-engaging antibodies. (Item 43) The method according to item 25, wherein the one or more additional therapeutic agents comprise at least one trap for an immunosuppressant. (Item 44) The method according to item 43, wherein said at least one trap for an immunosuppressive agent 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) The method according to any one of items 3 to 44, wherein administration of said pharmaceutical composition results in induction or enhancement of proliferation of T-effector cells, or modulation of Ι-kappaΒ and / or NF-κΒ in T cells, or modulation of CD39 activity in T cells, or T cell receptor-induced signal transduction in T-effector cells, or a combination thereof. (Item 46) A method of screening a test compound comprising an antigen-binding protein according to item 1 capable of inhibiting the activity of CD39, comprising the step of contacting a test sample containing CD39 with the test compound; comparing the activity of said test sample with that of a control sample and; wherein a decrease in the activity of CD39 in said test sample as compared to said control sample identifies said compound as an inhibitor of the activity of CD39. (Item 47) The method according to item 46, wherein said control sample comprises a sample not 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), wherein VH is: a) VHCDR1 having an amino acid sequence that is at least 90% identical to the sequences shown in SEQ ID NOs: 1 to 45, b) VHCDR2 having an amino acid sequence that is at least 90% identical to the sequences shown in SEQ ID NOs: 46 to 81, and c) VHCDR3 having an amino acid sequence that is at least 90% identical to the sequences shown in SEQ ID NOs: 82 to 109 comprising at least one of; VL is as follows: a) VLCDR1 having an amino acid sequence that is at least 90% identical to the sequences shown in SEQ ID NOs: 110 - 124, b) VLCDR2 having an amino acid sequence that is at least 90% identical to the sequences shown in SEQ ID NOs: 125 - 140, and c) VLCDR3 having an amino acid sequence that is at least 90% identical to the sequences shown in SEQ ID NOs: 141 - 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 as follows: a) VHCDR1 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 1 - 45, b) VHCDR2 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 46 - 81, and c) VHCDR3 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 82 - 109 comprising at least one of; VL is as follows: a) VLCDR1 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 110 - 124, b) VLCDR2 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 125 - 140, and c) an isolated antibody molecule comprising at least one of VLCDR3 having an amino acid sequence homologous to the sequences shown in SEQ ID NOs: 141 - 166. (Item 50) An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain and a light chain, wherein the heavy chain comprises one or more molecules having a sequence consisting 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, and the light chain comprises one or more molecules having a sequence consisting of one of 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 a sequence consisting of SEQ ID NO: 255, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 256; b) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 257, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 258; c) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 259, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 260; d) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 261, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 262; e) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 263, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 264; f) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 265, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 266; g) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 267, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 268; h) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 269, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 270; i) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 271, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 272; j) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 273, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 274; k) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 275, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 276; l) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 277, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 278 m) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 279, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 280; n) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 281, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 282; o) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 283, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 284; p) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 285, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 286; q) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 287, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 288; r) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 289, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 290; s) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 291, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 292; t) whether the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 293, and the light chain comprises one or more molecules, each molecule having a 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 a sequence consisting of SEQ ID NO: 295, and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 296. (Item 52) An isolated nucleic acid encoding the antigen-binding protein according to any one of Items 48 to 51. (Item 53) 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 VH and / or VL is as follows: a) (i) Consensus sequence S-Y-Δ 3 -M-Δ 5 (SEQ ID NOs: 25-29 and 44-45) (where Δ 3 is E, F, Q, or Y; Δ 5 is H or Y) and is defined by the Kabat CDRH1 sequence; (ii) Consensus sequence θ 1 -θ 2 -θ 3 -I-S (SEQ ID NOs: 30-37) (where θ 1 is A, H, K, L, S, or W; θ 2 is L, M, N, or T; θ 3 is A or P) and is defined by the Kabat CDR-H1 sequence; (iii) Consensus sequence η 1 -Y-η 3 -I-S (SEQ ID NOs: 38-41) (where η 1 is S, K, N, or R; η 3 is A or G) and is defined by the Kabat CDR-H1 sequence; (iv) Consensus sequence G-Y-T-F-Ω 5 -S-Y (SEQ ID NOs: 1-2 and 4-6) (where Ω 5 is T, K, Q, F, or V) and is defined by the Chothia CDR-H1 sequence; (v) Consensus sequence G-G-T-F-ν 5 -ν 6 -Y (SEQ ID NOs: 17-22 and 24) (where ν 5 is S, G, or E; ν 6 is S, K, R, or S) and is defined by the Chothia CDR-H1 sequence; or (vi) Consensus sequence G-G-T-F-κ 5 -κ 6 -κ 7 (SEQ ID NOs: 7-16) (where κ5 is S, Q, P, or A; κ 6 is S, K, H, L, A, or W; κ 7 is defined by Y, L, T, N, or M) the Chothia CDR-H1 consensus sequence VH CDR1 sequence containing, b)(i) consensus sequence ε 1 -I-N-P-ε 5- ε 6 -G-S-T-ε 10 -Y-A-Q-K-F-Q-G (SEQ ID NOs: 63-66 and 68) (where ε 1 is K, S, R, or V; ε 5 is L, R, or S; ε 6 is G or V; ε 10 is S or W) the Kabat CDR-H2 sequence defined by; (ii) consensus sequence G-I-α 3 -α 4 -α 5 -α 6 -G-T-A-N-Y-A-Q-K-F-Q-G (SEQ ID NOs: 69-72) (where α 3 is I or L, or absent; α 4 is P, or absent; α 5 is I, G, or R; α 6 is A, F, or G) the Kabat CDR-H2 sequence defined by; (iii) consensus sequence β 1 -I-I-P-β 5 -β 6 -G-β 8 -A-N-Y-A-Q-K-F-G-Q (SEQ ID NOs: 74 and 76-79) (where β 1 is S or G; β 5 is I, E, S, or T; β 6 is F, I, or S; β 8 is I or T) the Kabat CDR-H2 sequence defined by; (iv) consensus sequence N-P-ε 5- ε6 -G-S-T (SEQ ID NO: 46-48) (where ε 5 is L, R, or S, and ε 6 is G or V) - defined Chothia CDR-H2 sequence; (v) Consensus sequence α 3 -α 4 -α 5 -α 6 -G-T-A (SEQ ID NO: 51-54) (where α 3 is I or L, or absent; α 4 is P, or absent; α 5 is I, G, or R; α 6 is A, F, or G) - defined Chothia CDR-H2 sequence; or (vi) Consensus sequence I-P-β 5 -β 6 -G-β 8 -A (SEQ ID NO: 56-60) (where β 5 is I, E, S, or T; β 6 is F, I, or S; β 8 is I or T) - defined Chothia CDR-H2 sequence including VH CDR2 sequence, c) (i) Consensus sequence G-K-R-E-G-G-T-E-Y-L-R-У 12 (SEQ ID NO: 82-86) (where У 12 is H, K, S, N, or V) - defined CDR-H3 sequence; (ii) Consensus sequence E-S-G-Ф 4 -Y-R-D-H-R-L-Ф 11 -V (SEQ ID NO: 94-96) (where Ф 4 is G or T, and Ф 11 is D or G) - defined CDR-H3 sequence; or (iii) Consensus sequence G-G-A-K-Y-A-Э 7 -Э 8 -Э 9 -G-M-D-V (SEQ ID NO: 87-93) (where Э 7is S, V, G, or R; Э 8 is T, Q, K, G, or R; Э 9 a VH CDR3 sequence comprising a CDR-H3 sequence defined by (is Y, H, L, or W)) d)(i) consensus sequence φ 1 -A-S-φ 4 -φ 5 -V-φ 7 -φ 8 -φ 9 -Y-L-A (SEQ ID NOS: 1101-114) (where φ 1 is E, K, or R; φ 4 is Q or E; φ 5 is S or Y; φ 7 is S or A; φ 8 is S or Y; φ 9 is D or S) defining a CDR-L1 sequence; (ii) consensus sequence б 1 -A-S-Q-б 5 -б 6 -б 7 -б 8 -б 9 -L-б 11 (SEQ ID NOS: 118 and 120-123) (where б 1 is Q or R1; б 5 is D or S; б 6 is I or V; б 7 is G or S; б 8 is N, R, or S; б 9 is N, Y, or W; б 11 is A or N) defining a CDR-L1 sequence; or (iii) consensus sequence K-S-S-Г 4 -S-V-L-Г 8 -S-Г 10 -N-N-K-N-Y-L-A (SEQ ID NOS: 115-117) (where Г 4 is Q, R or K; Г 8 is F or Y; Г 10 is S or N) defining a CDR-L1 sequence The VLCDR1 array containing e) (i) The consensus sequence ψ 1 -A-S-ψ 4 -R-ψ 6 -ψ 7 (SEQ ID NOs: 125 to 136) (where ψ 1 is G or Y, and ψ 4 is S or N; ψ 6 is A or H; ψ 7 is T, Y, or N) - defined CDR-L2 array; (ii) The consensus sequence D-A-S-χ 4 -R-A-T (SEQ ID NOs: 138 and 139) (where £ 4 is N or K) - defined CDR-L2 array; or (iii) The consensus sequence W-A-S-T-R-σ 6 -S (SEQ ID NOs: 131 and 133 to 134) (where σ 6 is A, E, or Q) - defined CDR-L2 array The VLCDR2 array containing, and f) (i) The consensus sequence Q-Q-Y-π 4 -π 5 -π 6 -π 7 -T (SEQ ID NOs: 141 to 147) (where π 4 is G, H, or Y; π 5 is S, N, F, G, or R; π 6 is S, Y, A, G, or R; π 7 is P, I, or L) - defined CDR-L3 array; (ii) The consensus sequence Q-Q-λ 3 -λ 4 -λ 5 -λ 6 -P-T (SEQ ID NOs: 148 to 150) (where λ 3 is R, F, H, S, L, D, Y, or V; λ 4 is S, V, T, G, L, Y, or N; λ 5 is N, L, F, K, or V; λ 6a CDR-L3 sequence defined by (where ρ is W, F, Y, or L); (iii) consensus sequence Q-Q-Y-ρ 3 -ρ 4 -W-P-L-T (SEQ ID NOs: 151 and 152) (where ρ 3 is N or L and ρ 4 is N or L); or (iv) consensus sequence Q-Q-ω 3 -ω 4 -ω 5 -ω 6 -P-ω 8 -T (SEQ ID NOs: 153-156) (where ω 3 is Y or F; ω 4 is Y or W; ω 5 is S, L, T, or F; ω 6 is T, Y, or F; ω 8 is L or P); a VLCDR3 sequence comprising 1, 2, 3, 4, 5, or 6 of the foregoing, an isolated antibody molecule. BRIEF DESCRIPTION OF THE DRAWINGS

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BEST MODE FOR CARRYING OUT THE INVENTION

[0037] 1. Definitions Unless otherwise defined, all technical terms, notations, and other scientific terms used in this specification are intended to have the meanings commonly understood by those of ordinary skill in the technical field related to the present invention. In some cases, terms with commonly understood meanings are defined in this specification for the sake of clarity and / or for easy reference, and including such definitions in this specification should not necessarily be construed as indicating a difference from what is generally understood in the art. The techniques and procedures described or referenced in this specification are generally well understood, and for example, those commonly used by those of ordinary skill in the art using conventional methods such as the widely used molecular cloning methods described in Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Procedures involving the use of commercially available kits and reagents are generally carried out according to the protocols and / or parameters defined by the manufacturer, unless otherwise specified.

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

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

[0040] The term "these combinations" includes all possible combinations of the elements to which the term refers.

[0041] The terms "CD39", "CD39 antigen", and "surface antigen classification 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 is also referred to as ATPDase and SPG64. Each of the terms described may be used interchangeably. Unless otherwise specified, the term includes any variant, isoform, and species homolog of human CD39 that is naturally expressed by a cell or expressed by a cell transfected with the CD39 gene. In some embodiments, the CD39 protein includes mouse CD39. In some embodiments, the CD39 protein includes cynomolgus monkey CD39.

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

[0043] The term "antibody" refers to 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. An antibody contains at least one antigen-binding domain. One example of an antigen-binding domain is the V H -V L antigen-binding domain formed by a dimer. "CD39 antibody", "anti-CD39 antibody", "CD39 Ab", "CD39-specific antibody" or "anti-CD39 Ab" are antibodies described herein that specifically bind to the antigen CD39. In some embodiments, the antibody binds to the extracellular domain of CD39.

[0044] V H and V L regions can be further subdivided into hypervariable regions ( "hypervariable regions (HVR)"; also called "complementary determining regions" (CDR)) in which more conserved regions are interspersed. The more conserved regions are called framework regions (FR). V H and V L each generally contain three CDRs and four FRs, which are arranged in the following order (from N-terminus to C-terminus): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. 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 content of which is 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 the 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 as α, δ, ε, γ, and μ, respectively. The IgG and IgA classes are further divided into subclasses based on differences in sequence and function. 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 a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat numbering scheme”); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia numbering scheme”); MacCallum et al., 1996, J. Mol. Biol. 262:732-745 (“Contact numbering scheme”); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT numbering scheme”); and Honegge and Plueckthun, J. Mol. Biol., 2001, 309:657-70 (“AHo numbering scheme”), each of which is incorporated by reference in its entirety.

[0048] Table 1 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 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 specific CDRs in this specification is the Kabat / Chothia numbering scheme. If the residues encompassed by these two numbering schemes are different, the numbering scheme is specified as either Kabat or Chothia. [Table 1]

[0050] When referring to residues in the constant region of an antibody heavy chain (e.g., as reported by Kabat et al., supra), the "EU numbering scheme" is commonly used. Unless otherwise stated, the EU numbering scheme is used to refer to residues in the constant region of the antibody heavy chain described in this specification.

[0051] "Antibody fragment" includes a portion of an intact antibody, such as the antigen-binding or variable region of an intact antibody. Examples of antibody fragments include Fv fragments, Fab fragments, F(ab’) 2 fragments, Fab’ fragments, single-chain Fv (scFv) fragments, and scFv-Fc fragments.

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

[0053] A "Fab" fragment includes, in addition to the heavy and light chain variable domains, the constant domain of the light chain and the first constant domain (C H1 ) of the heavy chain. A Fab fragment may be produced, for example, by papain digestion of a full-length antibody.

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

[0055] A “single-chain Fv” or “sFv” or “scFv” antibody fragment contains V H domains and V L domains in a single polypeptide chain. The V H and V L are generally linked by a peptide linker. See Plueckthun A. (1994). Antibodies from Escherichia coli. In Rosenberg M. & Moore G.P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, the entire contents of which are incorporated herein by reference. An “scFv-Fc” fragment contains an scFv bound to an Fc domain. For example, the Fc domain may be bound to the C-terminus of the scFv. The Fc domain can follow the V H -V L or V L -V H orientation (i.e., V H or V L ) in the scFv. 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 antibodies that is substantially homogeneous. A population of antibodies that is substantially homogeneous is substantially similar and includes antibodies that bind to the same epitope, typically excluding variants that may arise during the production of monoclonal antibodies. Such variants generally occur in only trace amounts. Monoclonal antibodies are typically obtained by a process that involves selecting a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a particular clone from 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 a 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 chain and / or light chain is from a particular source or species, while the remainder of the heavy chain and / or light chain is from a different source or species.

[0058] The "humanized" form of a non-human antibody is a chimeric antibody containing a minimal sequence derived from a non-human antibody. A humanized antibody is generally a human immunoglobulin (recipient antibody) 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 having the desired specificity, affinity, or biological effect. Optionally, selected framework region residues of the recipient antibody are replaced with the corresponding framework region residues from the donor antibody. A humanized antibody may also contain residues 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 herein by reference in its entirety.

[0059] A "human antibody" has an amino acid sequence corresponding to that of an antibody that is produced by a human or human cell or that is derived from a non-human source using a human antibody repertoire or a sequence encoding a human antibody (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 the components of its natural environment. Components of the natural environment can include enzymes, hormones, and other proteinaceous or non-proteinaceous materials. In some embodiments, the isolated antibody is purified to such an extent that at least 15 residues of the N-terminal or internal amino acid sequence are obtained, for example, by using a spinning cup sequencer. In some embodiments, the isolated antibody is purified to homogeneity by gel electrophoresis (e.g., SDS-PAGE) under reducing or non-reducing conditions using detection by Coomassie blue or silver staining. An isolated antibody includes an in situ antibody in a recombinant cell because at least one component of the antibody's natural environment is absent. In some aspects, the isolated antibody is prepared by at least one purification step.

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

[0062] "Affinity" refers to the total strength 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 that 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 can generally be represented by the dissociation constant (K D ). Affinity can be measured by conventional methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) techniques such as a Biacore® instrument.

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

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

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

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

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

[0068] An "affinity matured" antibody has one or more alterations in one or more CDRs or FRs which result in an improvement in the affinity of the antibody for its antigen as compared to the parent antibody which does not have those alterations. In one embodiment, the affinity matured antibody has a 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 herein by reference) describe affinity maturation by V H and V L domain shuffling. Random mutagenesis of CDR and / or framework residues has been described, for example, by Barbas et al. (Proc. Nat. Acad. Sci. U.S.A., 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 herein by reference in its entirety.

[0069] As used herein in the context of two or more antibodies, the terms "competes with" or "cross-competes with" indicate that two or more antibodies compete with respect to binding to an antigen (e.g., CD39). In one exemplary assay, CD39 is coated onto a plate, a first antibody is bound, 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 "competes with" also includes combinations of antibodies 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 binding to each other 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" means 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 non-conformational epitopes are distinguished in that binding to the former is lost in the presence of a denaturing solvent, but not to the latter. An epitope may include amino acid residues directly involved in binding and 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 testing the binding of an antibody to CD39 variants having different point mutations, for example.

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

[0072] "Conservative substitution" or "conservative amino acid substitution" refers to substituting one or more amino acids with one or more amino acids that are chemically or functionally similar. Tables of conservative substitutions providing similar amino acids are well known in the art. A polypeptide sequence having such substitutions is known as a "conservatively modified variant". Such conservatively modified variants are in addition to polymorphic variants, interspecies homologs and alleles and do not exclude these. By way of 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, NY. Antibodies generated by making one or more conservative substitutions of amino acid residues in a parent antibody are designated "conservatively modified variants".

[0073] The term "amino acid" refers to 20 common naturally occurring amino acids. Naturally occurring amino acids include 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" or "treatment" of any disease or disorder, in certain embodiments, refers to ameliorating a disease or disorder present in a subject. In another embodiment, "treating" or "treatment" includes an improvement in at least one physical parameter, which may or may not be discernible by the subject. In yet another embodiment, "treating" or "treatment" includes modulating a 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 is effective for treating a disease or disorder when administered to a subject.

[0076] As used herein, the term "subject" means 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 a cancer, autoimmune disease or condition, and / or an infectious disease that can be treated with the antibodies provided herein. In some embodiments, the subject is a human suspected of having a cancer, autoimmune disease or condition, and / or an infectious disease.

[0077] 2. Antibodies Antibodies that selectively bind to human CD39 and nucleic acids encoding the antibodies are provided herein. In some aspects, the antibody selectively binds 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, the antibody has one or more CDRs having a specific length with respect to 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 embodiments, the light chain is a kappa light chain. In some embodiments, the light chain is a lambda light chain.

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

[0083] In some embodiments, the antibody is an antibody fragment. In some embodiments, the antibody fragment is an Fv fragment. In some embodiments, the antibody fragment is a Fab fragment. In some embodiments, the antibody fragment is an F(ab’) 2 fragment. In some embodiments, the antibody fragment is a Fab’ fragment. In some embodiments, the antibody fragment is a scFv (sFv) fragment. In some embodiments, the antibody fragment is a 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 the present disclosure.

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

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

[0089] In some embodiments, the antibody increases T effector cell function. In some embodiments, the antibody decreases the number of regulatory T cells in tissues or in 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 decreases or prevents the activation of phospho antigen-specific T cells selected from MAIT cells and gamma delta T cells.

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

[0091] Since CD39 degrades ATP and ADP to adenosine, CD39 can be regarded as an immunological switch that shifts ATP-driven pro-inflammatory immune cell activity towards an anti-inflammatory state mediated by adenosine. CD39 has a role in the regulation of the functions of several immune cell types, including lymphocytes, neutrophils, monocytes / macrophages, dendritic cells, and endothelial cells, and shifting the switch can have a significant impact on disease. For example, adenosine production via CD39 is recognized as a major mechanism of the immunosuppressive function of regulatory T cells (Tregs).

[0092] The antibodies provided herein may be useful for the treatment of various diseases and conditions, including cancer, autoimmune diseases, and infectious diseases. In some embodiments, the antibody inhibits CD39 function against 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 in the promotion of 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 the proliferation of CD4 and CD8 T cells, as well as 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, consists of, or consists essentially of a CDR-H3 sequence comprising a sequence selected from SEQ ID NOs: 82-109. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 82. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 83. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 84. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 85. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 86. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 87. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 88. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 89. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 90. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 91. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 92. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 93. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 94. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 95. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 96. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 97.In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 98. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 99. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 100. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 101. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 102. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 103. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 104. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 105. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 106. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 107. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising SEQ ID NO: 108. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-H3 sequence comprising 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 sequences provided in this disclosure. 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 in this disclosure. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-H3 sequences provided in this disclosure and has 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0096] 2.2. V sequences containing exemplary CDRs H sequence In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of one or more CDR-H sequences comprising, consisting of, or consisting essentially of one or more of the exemplary CDR-H sequences provided in this disclosure, H and variants thereof.

[0097] 2.2.1. V sequences containing exemplary Kabat CDRs H sequence In some embodiments, the antibody comprises a V sequence comprising, consisting of, or consisting essentially of one or more Kabat CDR-H sequences comprising, consisting of, or consisting essentially of one or more of the exemplary Kabat CDR-H sequences provided in this disclosure, H and variants thereof.

[0098] 2.2.1.1. Kabat CDR-H3 In some embodiments, the antibody comprises a V 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 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 82. HIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 83 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 84 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 85 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 86 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 87 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 88 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 89 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 90 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 91 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 92 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 93 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 94 and a V HIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 95 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 96 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 97 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 99 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 100 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 101 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 102 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 103 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 104 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 105 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 106 and a V HIt includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 107 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 108 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H3 sequence that includes SEQ ID NO: 109 and a V H It includes an array.

[0099] 2.2.1.2. Kabat CDR-H2 In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence selected from the sequences of SEQ ID NOs: 63 - 81 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence that includes SEQ ID NO: 63 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence that includes SEQ ID NO: 64 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence that includes SEQ ID NO: 65 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence that includes SEQ ID NO: 66 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence that includes SEQ ID NO: 67 and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence and a V H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H2 sequence that includes SEQ ID NO: 69 and a V HIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 70 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 71 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 72 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 73 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 74 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 75 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 76 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 77 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 78 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 79 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 80 and a V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H2 sequence including SEQ ID NO: 81 and a V H It includes an array.

[0100] 2.2.1.3. Kabat CDR-H1 In some embodiments, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence selected from the sequences of SEQ ID NOs: 25-45 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 25 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 26 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 27 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 28 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 29 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 31 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 32 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 33 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Kabat CDR-H1 sequence comprising SEQ ID NO: 34 and comprises a V HIt includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 35 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 36 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 37 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 38 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 39 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 40 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 41 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 42 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 43 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 44 and a V H It includes a sequence. In some embodiments, the antibody includes, consists of, or consists essentially of a Kabat CDR-H1 sequence that includes SEQ ID NO: 45 and a V H It includes a sequence.

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

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

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

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

[0105] In some embodiments, the antibody comprises a V 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 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 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 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 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: 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 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 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. HIt contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 29, a Kabat CDR-H2 sequence containing SEQ ID NO: 68, and a Kabat CDR-H3 sequence containing SEQ ID NO: 82 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 26, a Kabat CDR-H2 sequence containing SEQ ID NO: 64, and a Kabat CDR-H3 sequence containing SEQ ID NO: 82 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 30, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence containing SEQ ID NO: 87 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 31, a Kabat CDR-H2 sequence containing SEQ ID NO: 70, and a Kabat CDR-H3 sequence containing SEQ ID NO: 88 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 32, a Kabat CDR-H2 sequence containing SEQ ID NO: 71, and a Kabat CDR-H3 sequence containing SEQ ID NO: 89 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 33, a Kabat CDR-H2 sequence containing SEQ ID NO: 70, and a Kabat CDR-H3 sequence containing SEQ ID NO: 90 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 34, a Kabat CDR-H2 sequence containing SEQ ID NO: 72, and a Kabat CDR-H3 sequence containing SEQ ID NO: 91 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 30, a Kabat CDR-H2 sequence containing SEQ ID NO: 71, and a Kabat CDR-H3 sequence containing SEQ ID NO: 92 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 35, a Kabat CDR-H2 sequence containing SEQ ID NO: 70, and a Kabat CDR-H3 sequence containing SEQ ID NO: 93 in its V HIt contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 33, a Kabat CDR-H2 sequence containing SEQ ID NO: 70, and a Kabat CDR-H3 sequence containing SEQ ID NO: 92 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 36, a Kabat CDR-H2 sequence containing SEQ ID NO: 72, and a Kabat CDR-H3 sequence containing SEQ ID NO: 87 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 30, a Kabat CDR-H2 sequence containing SEQ ID NO: 73, and a Kabat CDR-H3 sequence containing SEQ ID NO: 87 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 37, a Kabat CDR-H2 sequence containing SEQ ID NO: 74, and a Kabat CDR-H3 sequence containing SEQ ID NO: 87 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 38, a Kabat CDR-H2 sequence containing SEQ ID NO: 75, and a Kabat CDR-H3 sequence containing SEQ ID NO: 94 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 39, a Kabat CDR-H2 sequence containing SEQ ID NO: 76, and a Kabat CDR-H3 sequence containing SEQ ID NO: 95 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 40, a Kabat CDR-H2 sequence containing SEQ ID NO: 76, and a Kabat CDR-H3 sequence containing SEQ ID NO: 96 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 39, a Kabat CDR-H2 sequence containing SEQ ID NO: 76, and a Kabat CDR-H3 sequence containing SEQ ID NO: 94 in its V H It contains a sequence. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 38, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence in its V HIt contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 41, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence containing SEQ ID NO: 98 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 41, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence containing SEQ ID NO: 99 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 41, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence containing SEQ ID NO: 100 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 38, a Kabat CDR-H2 sequence containing SEQ ID NO: 75, and a Kabat CDR-H3 sequence containing SEQ ID NO: 101 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 42, a Kabat CDR-H2 sequence containing SEQ ID NO: 78, and a Kabat CDR-H3 sequence containing SEQ ID NO: 102 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 38, a Kabat CDR-H2 sequence containing SEQ ID NO: 75, and a Kabat CDR-H3 sequence containing SEQ ID NO: 103 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 43, a Kabat CDR-H2 sequence containing SEQ ID NO: 79, and a Kabat CDR-H3 sequence containing SEQ ID NO: 104 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 38, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence containing SEQ ID NO: 103 in its V H It contains an array. In some embodiments, the antibody contains a Kabat CDR-H1 sequence containing SEQ ID NO: 38, a Kabat CDR-H2 sequence containing SEQ ID NO: 69, and a Kabat CDR-H3 sequence containing SEQ ID NO: 106 in its VH comprises an array. 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: 107 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array.

[0106] In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V Hcomprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V H comprises an array. In some embodiments, the antibody comprises 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 in the V HIt contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V H It contains a sequence. In some embodiments, the antibody contains 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 in the V HIt includes a sequence. In some embodiments, the antibody includes 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 in its V H It includes a sequence. In some embodiments, the antibody includes 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 in its V H It includes a sequence. In some embodiments, the antibody includes 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 in its V H It includes a sequence.

[0107] 2.2.1.8. V containing exemplary Kabat CDRs H Variants of the sequence In some embodiments, the V provided herein H The sequence includes 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 includes, consists of, or consists essentially of a variant of the exemplary Kabat CDR-H3 sequence provided in this disclosure. In some embodiments, the Kabat CDR-H3 sequence includes, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the exemplary Kabat CDR-H3 sequences provided in this disclosure. In some embodiments, the Kabat CDR-H3 sequence includes, consists of, or consists essentially of any of the exemplary Kabat CDR-H3 sequences provided in this disclosure and has 1, 2, or 3 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 one 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 one of the exemplary Kabat CDR-H2 sequences provided herein and has 1, 2, or 3 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 one 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 one of the exemplary Kabat CDR-H1 sequences provided herein and has 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0111] 2.2.2. V comprising exemplary Chothia CDRs H Sequence In some embodiments, the antibody comprises a V comprising one or more Chothia CDR-H sequences that comprise, consist of, or consist essentially of one or more of the exemplary Chothia CDR-H sequences provided herein H and variants thereof.

[0112] 2.2.2.1.Chothia CDR-H3 In some embodiments, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence selected from the sequences of SEQ ID NOs: 82-109 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 82 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 83 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 84 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 85 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 86 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 87 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 88 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 89 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 90 and comprises a V H sequence. In some aspects, the antibody comprises, consists of, or consists essentially of a Chothia CDR-H3 sequence comprising SEQ ID NO: 91 and comprises a V HIt includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 92 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 93 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 94 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 95 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 96 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 97 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 98 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 99 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 100 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 101 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 102 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V array comprising a Chothia CDR-H3 sequence comprising SEQ ID NO: 103 HIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H3 sequence including SEQ ID NO: 104 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H3 sequence including SEQ ID NO: 105 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H3 sequence including SEQ ID NO: 106 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H3 sequence including SEQ ID NO: 107 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H3 sequence including SEQ ID NO: 108 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H3 sequence including SEQ ID NO: 109 H It includes an array.

[0113] 2.2.2.2. Chothia CDR-H2 In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H2 sequence selected from SEQ ID NOs: 46 - 62 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H2 sequence including SEQ ID NO: 46 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H2 sequence including SEQ ID NO: 47 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H2 sequence including SEQ ID NO: 48 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence that includes a Chothia CDR-H2 sequence including SEQ ID NO: 49H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 50 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 51 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 52 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 53 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 54 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 55 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 56 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 58 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 59 H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a V sequence including a Chothia CDR-H2 sequence of SEQ ID NO: 60 HIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H2 sequence including SEQ ID NO: 61 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H2 sequence including SEQ ID NO: 62 in its V H It includes an array.

[0114] 2.2.2.3. Chothia CDR-H1 In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence selected from the sequences of SEQ ID NOs: 1-24 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 1 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 2 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 3 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 4 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 5 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 6 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 7 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence including SEQ ID NO: 8 in its V HIt includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 9 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 10 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 11 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 12 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 13 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 15 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 16 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 17 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 18 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 19 H It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a V sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 20 HIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence that includes SEQ ID NO: 21 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence that includes SEQ ID NO: 22 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence that includes SEQ ID NO: 23 in its V H It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a Chothia CDR-H1 sequence that includes SEQ ID NO: 24 in its V H It includes an array.

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

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

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

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

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

[0120] In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 2, a Chothia CDR-H2 sequence containing SEQ ID NO: 46, and a Chothia CDR-H3 sequence containing SEQ ID NO: 83 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 2, a Chothia CDR-H2 sequence containing SEQ ID NO: 46, and a Chothia CDR-H3 sequence containing SEQ ID NO: 84 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 2, a Chothia CDR-H2 sequence containing SEQ ID NO: 46, and a Chothia CDR-H3 sequence containing SEQ ID NO: 85 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 2, a Chothia CDR-H2 sequence containing SEQ ID NO: 46, and a Chothia CDR-H3 sequence containing SEQ ID NO: 86 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 2, a Chothia CDR-H2 sequence containing SEQ ID NO: 47, and a Chothia CDR-H3 sequence containing SEQ ID NO: 84 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 2, a Chothia CDR-H2 sequence containing SEQ ID NO: 47, and a Chothia CDR-H3 sequence containing SEQ ID NO: 86 HIt includes an array. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 1, a Chothia CDR-H2 sequence containing SEQ ID NO: 46, and a Chothia CDR-H3 sequence containing SEQ ID NO: 83 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 1, a Chothia CDR-H2 sequence containing SEQ ID NO: 46, and a Chothia CDR-H3 sequence containing SEQ ID NO: 86 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 53, and a Chothia CDR-H3 sequence containing SEQ ID NO: 93 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 55, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 54, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 52, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 8, a Chothia CDR-H2 sequence containing SEQ ID NO: 52, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 and includes a V H sequence. In some embodiments, the antibody includes a Chothia CDR-H1 sequence containing SEQ ID NO: 8, a Chothia CDR-H2 sequence containing SEQ ID NO: 53, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 and includes a V HIt contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 9, a Chothia CDR-H2 sequence containing SEQ ID NO: 53, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 H It contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 53, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 H It contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 54, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 H It contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 52, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 H It contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 53, and a Chothia CDR-H3 sequence containing SEQ ID NO: 93 H It contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 10, a Chothia CDR-H2 sequence containing SEQ ID NO: 52, and a Chothia CDR-H3 sequence containing SEQ ID NO: 93 H It contains an array. In some embodiments, the antibody contains a Chothia CDR-H1 sequence containing SEQ ID NO: 11, a Chothia CDR-H2 sequence containing SEQ ID NO: 54, and a V that includes a Chothia CDR-H3 sequence containing SEQ ID NO: 87 H It contains an array. In some embodiments, the antibody contains a V that includes a Chothia CDR-H1 sequence containing SEQ ID NO: 12, a Chothia CDR-H2 sequence containing SEQ ID NO: 53, and a Chothia CDR-H3 sequence containing SEQ ID NO: 87 HIt includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence including SEQ ID NO: 13, a Chothia CDR-H2 sequence including SEQ ID NO: 52, and a Chothia CDR-H3 sequence including SEQ ID NO: 87 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence including SEQ ID NO: 13, a Chothia CDR-H2 sequence including SEQ ID NO: 52, and a Chothia CDR-H3 sequence including SEQ ID NO: 90 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence including SEQ ID NO: 15, a Chothia CDR-H2 sequence including SEQ ID NO: 52, and a Chothia CDR-H3 sequence including SEQ ID NO: 87 H It includes an array. In some embodiments, the antibody includes a V that includes a Chothia CDR-H1 sequence including SEQ ID NO: 18, a Chothia CDR-H2 sequence including SEQ ID NO: 57, and a Chothia CDR-H3 sequence including SEQ ID NO: 94 H It includes an array.

[0121] 2.2.2.8. V including exemplary Chothia CDRs H Variants of the sequence In some embodiments, the V provided herein H The sequence includes 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 sequences provided in this disclosure. 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 in this disclosure. In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of any of the exemplary Chothia CDR-H3 sequences provided in this disclosure and has 1, 2, or 3 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 in this disclosure. 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 in this disclosure. In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of any of the exemplary Chothia CDR-H2 sequences provided in this disclosure and has 1, 2, or 3 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 in this disclosure. 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 with any of the exemplary Chothia CDR-H1 sequences provided in this disclosure. In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of any of the exemplary Chothia CDR-H1 sequences provided in this disclosure and has 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

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

[0126] 2.3.1.V H Variant of the sequence In some embodiments, the V sequence provided herein H comprises, consists of, or consists essentially of a variant of the exemplary V sequence provided by this disclosure H In some embodiments, the V sequence comprises, consists of, or consists essentially of a variant of the exemplary V sequence provided by this disclosure.

[0127] In some embodiments, the V H sequence comprises, consists of, or consists essentially of a variant of the exemplary V sequence provided by this disclosure H In some embodiments, the V sequence comprises, consists of, or consists essentially of a variant of the exemplary V sequence provided by this disclosure. In some embodiments, the V H sequence comprises, consists of, or consists essentially of a variant of the exemplary V sequence provided by this disclosure H and comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity with any of the sequences provided by this disclosure

[0128] In some embodiments, the V H sequence has 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 compared to the exemplary V sequence provided by this disclosure HComprising, consisting of, or consisting essentially of any of the arrays. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

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

[0130] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an exemplary CDR-L3 sequence provided in this disclosure. 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 to any one of the exemplary CDR-L3 sequences provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any one of the exemplary CDR-L3 sequences provided in this disclosure and has 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0131] 2.5. V Containing Exemplary CDRs L Sequence In some embodiments, the antibody comprises, consists of, or consists essentially of one or more CDR-L sequences comprising one or more of the exemplary CDR-L sequences provided herein, and variants thereof. L sequences, including variants thereof.

[0132] 2.5.1.CDR-L3 In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising a sequence selected from SEQ ID NOs: 141-166, and variants thereof. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 141. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 142. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 143. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 144. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 145. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 146. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 147. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 148. L sequences. In some aspects, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 149. LIt includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 150 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 151 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 152 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 153 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 154 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 155 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 156 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 157 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 158 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 159 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 160 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 161 and a V L It includes an array. In some embodiments, the antibody comprises, consists of, or consists essentially of a CDR-L3 sequence comprising SEQ ID NO: 162 and a V LIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L3 sequence that includes SEQ ID NO: 163 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L3 sequence that includes SEQ ID NO: 164 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L3 sequence that includes SEQ ID NO: 165 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L3 sequence that includes SEQ ID NO: 166 and a V L It includes an array.

[0133] 2.5.2.CDR-L2 In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence selected from the sequences of SEQ ID NOs: 125-140 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 125 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 126 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 127 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 128 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 129 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 130 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence that includes SEQ ID NO: 131 and a V LIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 132 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 133 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 134 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 135 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 136 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 137 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 138 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 139 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L2 sequence including SEQ ID NO: 140 and a V L It includes an array.

[0134] 2.5.3.CDR-L1 In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence selected from the sequences of SEQ ID NOs: 110 to 124 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence including SEQ ID NO: 110 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence including SEQ ID NO: 111 and a V LIt includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 112 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 113 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 114 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 115 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 116 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 117 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 118 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 119 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 120 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 121 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 122 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 123 and a V L It includes an array. In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence comprising SEQ ID NO: 124 and a V L It includes an array.

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

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

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

[0138] 2.5.7. CDR-L1 + CDR-L2 + CDR-L3 In some embodiments, the antibody includes, consists of, or consists essentially of a CDR-L1 sequence selected from the sequences of SEQ ID NOs: 110 to 124, a CDR-L2 sequence selected from the sequences of SEQ ID NOs: 125 to 140, and a CDR-L3 sequence selected from the sequences of SEQ ID NOs: 141 to 166, and includes a V L array. In some embodiments, all of the CDR-L1 array, the CDR-L2 array, and the CDR-L3 array are from a single exemplary V L array provided in this disclosure. For example, in some embodiments, all of CDR-L1, CDR-L2, and CDR-L3 are from a single exemplary V L array selected from SEQ ID NOs: 219 to 248.

[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, and a VL sequence comprising SEQ ID NO: 141. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. 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: 143 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence. In some embodiments, the antibody comprises 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 and a VL sequence.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, and a VL sequence comprising SEQ ID NO: 144. 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 VL sequence comprising a CDR-L3 sequence comprising SEQ ID NO: 144. In some embodiments, the antibody comprises a CDR-L1 sequence comprising SEQ ID NO: 110, a CDR-L2 sequence comprising SEQ ID NO: 126, and a VL sequence comprising a CDR-L3 sequence selected from the sequences of SEQ ID NO: 144. In some embodiments, the antibody comprises a CDR-L1 sequence comprising SEQ ID NO: 116, a CDR-L2 sequence comprising SEQ ID NO: 131, and a VL sequence comprising a CDR-L3 sequence comprising SEQ ID NO: 150. In some embodiments, the antibody comprises a CDR-L1 sequence comprising SEQ ID NO: 117, a CDR-L2 sequence comprising SEQ ID NO: 134, and a VL sequence comprising a CDR-L3 sequence comprising SEQ ID NO: 150.

[0141] 2.5.8. V comprising exemplary CDR-Ls L Variants of the sequences In some embodiments, the V provided herein L sequences comprise 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 in this disclosure. 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 to any of the exemplary CDR-L3 sequences provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L3 sequences provided in this disclosure and has 1, 2, or 3 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 in this disclosure. 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 in this disclosure. In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L2 sequences provided in this disclosure and has 1, 2, or 3 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 in this disclosure. 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 in this disclosure. In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of any of the exemplary CDR-L1 sequences provided in this disclosure and has 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

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

[0146] 2.6.1.V L Variant of the array In some embodiments, the V provided herein L The array comprises, consists of, or consists essentially of a variant of the exemplary V provided in this disclosure L The array.

[0147] In some embodiments, V L the array comprises, consists of, or consists essentially of a variant of the exemplary V array provided by this disclosure. In some embodiments, V L the array comprises, consists of, or consists essentially of a variant of the exemplary V array provided by this disclosure. In some embodiments, V L the array comprises, consists of, or consists essentially of a variant of the exemplary V array provided by this disclosure. In some embodiments, V L the array comprises, consists of, or consists essentially of an array having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.05% identity to any of the exemplary V arrays provided by this disclosure.

[0148] In some embodiments, V L the array comprises, consists of, or consists essentially of an exemplary V array provided by this disclosure having 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 embodiments, the amino acid substitutions are conservative amino acid substitutions.

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

[0150] In some embodiments, the CDR-H3 sequence is a CDR-H3 sequence that comprises, consists of, or consists essentially of SEQ ID NOs: 82-109, and the CDR-L3 sequence is a CDR-L3 sequence that 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 to 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 embodiments, the CDR-L3 sequence is SEQ ID NO: 152. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 153. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 154. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 155. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 156. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 157. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 158. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 159. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 160. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 161. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 162. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 163. In some embodiments, 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 include variants of the exemplary CDR-H3 and / or CDR-L1 sequences provided in the present disclosure.

[0180] In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of the exemplary CDR-H3 sequences provided in this disclosure. 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 one of the exemplary CDR-H3 sequences provided in this disclosure. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of any one of the exemplary CDR-H3 sequences provided in this disclosure and has 1, 2, or 3 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 sequences provided in this disclosure. 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 to any one of the exemplary CDR-L3 sequences provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any one of the exemplary CDR-L3 sequences provided in this disclosure and has 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions.

[0182] 2.7.2.V H -V L vs In some embodiments, the antibody comprises a V H sequence and a V L sequence.

[0183] In some embodiments, the V H sequence is a V H sequence comprising, consisting of, or consisting essentially of SEQ ID NOs: 179 to 218, and the V L sequence is a VL It is an array.

[0184] In some embodiments, V H The array is Array No. 179, and V L The array is selected from Array Nos. 219 to 248. In some embodiments, V L The array is Array No. 219. In some embodiments, V L The array is Array No. 220. In some embodiments, V L The array is Array No. 221. In some embodiments, V L The array is Array No. 222. In some embodiments, V L The array is Array No. 223. In some embodiments, V L The array is Array No. 224. In some embodiments, V L The array is Array No. 225. In some embodiments, V L The array is Array No. 226. In some embodiments, V L The array is Array No. 227. In some embodiments, V L The array is Array No. 228. In some embodiments, V L The array is Array No. 229. In some embodiments, V L The array is Array No. 230. In some embodiments, V L The array is Array No. 231. In some embodiments, V L The array is Array No. 232. In some embodiments, V L The array is Array No. 233. In some embodiments, V L The array is Array No. 234. In some embodiments, V L The array is Array No. 235. In some embodiments, V L The array is Array No. 236. In some embodiments, V L The array is Array No. 237. In some embodiments, V L The array is Array No. 238. In some embodiments, V L The array is Array No. 239. In some embodiments, V L The array is Array No. 240. In some embodiments, V L The array is Array No. 241. In some embodiments, V LThe array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0185] In some embodiments, V H The array is array number 180, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V LThe array has an array number of 236. In some embodiments, V L The array has an array number of 237. In some embodiments, V L The array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V L The array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0186] In some embodiments, V H The array has an array number of 181, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V LThe array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0187] In some embodiments, V H The array is array number 182, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V LThe array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0188] In some embodiments, V H The array is array number 183, and V LThe array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, VL The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0189] In some embodiments, V H The array is array number 184, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, VL The array has the array number 239. In some embodiments, V L The array has the array number 240. In some embodiments, V L The array has the array number 241. In some embodiments, V L The array has the array number 242. In some embodiments, V L The array has the array number 243. In some embodiments, V L The array has the array number 244. In some embodiments, V L The array has the array number 245. In some embodiments, V L The array has the array number 246. In some embodiments, V L The array has the array number 247. In some embodiments, V L The array has the array number 248.

[0190] In some embodiments, V H The array has the array number 185, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has the array number 219. In some embodiments, V L The array has the array number 220. In some embodiments, V L The array has the array number 221. In some embodiments, V L The array has the array number 222. In some embodiments, V L The array has the array number 223. In some embodiments, V L The array has the array number 224. In some embodiments, V L The array has the array number 225. In some embodiments, V L The array has the array number 226. In some embodiments, V L The array has the array number 227. In some embodiments, V L The array has the array number 228. In some embodiments, V L The array has the array number 229. In some embodiments, V L The array has the array number 230. In some embodiments, V L The array has the array number 231. In some embodiments, V L The array has the array number 232. In some embodiments, VL The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0191] In some embodiments, V H The array is array number 186, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, VL The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0192] In some embodiments, V H The array is array number 187, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, VL The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, VL The array is array number 248.

[0193] In some embodiments, V H The array is array number 188, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, VL The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0194] In some embodiments, V H The array has an array number of 189, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V L The array has an array number of 232. In some embodiments, V L The array has an array number of 233. In some embodiments, V L The array has an array number of 234. In some embodiments, V L The array has an array number of 235. In some embodiments, VL The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0195] In some embodiments, V H The array is array number 190, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, VL The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0196] In some embodiments, V H The array is array number 191, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, VL The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0197] In some embodiments, V H The array is array number 192, and VL The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V LThe array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0198] In some embodiments, V H The array has an array number of 193, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V L The array has an array number of 232. In some embodiments, V L The array has an array number of 233. In some embodiments, V L The array has an array number of 234. In some embodiments, V L The array has an array number of 235. In some embodiments, V L The array has an array number of 236. In some embodiments, V L The array has an array number of 237. In some embodiments, V LThe array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V L The array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0199] In some embodiments, V H The array has an array number of 194 and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V LThe array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0200] In some embodiments, V H The array is array number 195, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V LThe array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0201] In some embodiments, V H The array is array number 196, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V LThe array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V LThe array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0202] In some embodiments, V H The array has an array number of 197, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V L The array has an array number of 232. In some embodiments, V L The array has an array number of 233. In some embodiments, V L The array has an array number of 234. In some embodiments, V L The array has an array number of 235. In some embodiments, V L The array has an array number of 236. In some embodiments, V L The array has an array number of 237. In some embodiments, V L The array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V LThe array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0203] In some embodiments, V H The array has an array number of 198, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V L The array has an array number of 232. In some embodiments, V L The array has an array number of 233. In some embodiments, V L The array has an array number of 234. In some embodiments, V LThe array has an array number of 235. In some embodiments, V L The array has an array number of 236. In some embodiments, V L The array has an array number of 237. In some embodiments, V L The array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V L The array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0204] In some embodiments, V H The array has an array number of 199, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V LThe array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0205] In some embodiments, V H The array is array number 200, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V LThe array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0206] In some embodiments, V HThe array has an array number of 201, V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V L The array has an array number of 232. In some embodiments, V L The array has an array number of 233. In some embodiments, V L The array has an array number of 234. In some embodiments, V L The array has an array number of 235. In some embodiments, V L The array has an array number of 236. In some embodiments, V L The array has an array number of 237. In some embodiments, V L The array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V L The array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V LThe array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0207] In some embodiments, V H The array is array number 202, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V LThe array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V L The array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0208] In some embodiments, V H The array has an array number of 203, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V L The array has an array number of 223. In some embodiments, V L The array has an array number of 224. In some embodiments, V L The array has an array number of 225. In some embodiments, V L The array has an array number of 226. In some embodiments, V L The array has an array number of 227. In some embodiments, V L The array has an array number of 228. In some embodiments, V L The array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V LThe array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0209] In some embodiments, V H The array is array number 204, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V LThe array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0210] In some embodiments, V H The array is array number 205, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V LThe array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V LThe array is array number 247. In some embodiments, V L The array is array number 248.

[0211] In some embodiments, V H The array is array number 206, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V LThe array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0212] In some embodiments, V H The array is array number 207, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V LThe array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241. In some embodiments, V L The array is array number 242. In some embodiments, V L The array is array number 243. In some embodiments, V L The array is array number 244. In some embodiments, V L The array is array number 245. In some embodiments, V L The array is array number 246. In some embodiments, V L The array is array number 247. In some embodiments, V L The array is array number 248.

[0213] In some embodiments, V H The array is array number 208, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array is array number 219. In some embodiments, V L The array is array number 220. In some embodiments, V L The array is array number 221. In some embodiments, V L The array is array number 222. In some embodiments, V L The array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V LThe array has an array number of 229. In some embodiments, V L The array has an array number of 230. In some embodiments, V L The array has an array number of 231. In some embodiments, V L The array has an array number of 232. In some embodiments, V L The array has an array number of 233. In some embodiments, V L The array has an array number of 234. In some embodiments, V L The array has an array number of 235. In some embodiments, V L The array has an array number of 236. In some embodiments, V L The array has an array number of 237. In some embodiments, V L The array has an array number of 238. In some embodiments, V L The array has an array number of 239. In some embodiments, V L The array has an array number of 240. In some embodiments, V L The array has an array number of 241. In some embodiments, V L The array has an array number of 242. In some embodiments, V L The array has an array number of 243. In some embodiments, V L The array has an array number of 244. In some embodiments, V L The array has an array number of 245. In some embodiments, V L The array has an array number of 246. In some embodiments, V L The array has an array number of 247. In some embodiments, V L The array has an array number of 248.

[0214] In some embodiments, V H The array has an array number of 209, and V L The array is selected from array numbers 219 to 248. In some embodiments, V L The array has an array number of 219. In some embodiments, V L The array has an array number of 220. In some embodiments, V L The array has an array number of 221. In some embodiments, V L The array has an array number of 222. In some embodiments, V LThe array is array number 223. In some embodiments, V L The array is array number 224. In some embodiments, V L The array is array number 225. In some embodiments, V L The array is array number 226. In some embodiments, V L The array is array number 227. In some embodiments, V L The array is array number 228. In some embodiments, V L The array is array number 229. In some embodiments, V L The array is array number 230. In some embodiments, V L The array is array number 231. In some embodiments, V L The array is array number 232. In some embodiments, V L The array is array number 233. In some embodiments, V L The array is array number 234. In some embodiments, V L The array is array number 235. In some embodiments, V L The array is array number 236. In some embodiments, V L The array is array number 237. In some embodiments, V L The array is array number 238. In some embodiments, V L The array is array number 239. In some embodiments, V L The array is array number 240. In some embodiments, V L The array is array number 241...

Claims

1. A pharmaceutical composition comprising an isolated antibody molecule capable of binding to human CD39 (hCD39), the isolated antibody molecule comprising a heavy chain variable region (VH) and a light chain variable region (VL); The VH is: a) a VHCDR1 having the sequence shown in SEQ ID NO:2 or SEQ ID NO:26; b) a VHCDR2 having the sequence set forth in SEQ ID NO: 47 or SEQ ID NO: 64, and c) a VHCDR3 having the sequence shown in SEQ ID NO: 83 Including; The VL is a) a VLCDR1 having the sequence shown in SEQ ID NO: 111; b) a VLCDR2 having the sequence set forth in SEQ ID NO: 126, and c) a VLCDR3 having the sequence shown in SEQ ID NO: 142 23. A pharmaceutical composition comprising:

2. The pharmaceutical composition described in claim 1, wherein the VH comprises a VH having an array set forth in SEQ ID NO: 180, and the VL comprises a VL having an array set forth in SEQ ID NO:

220.

3. The pharmaceutical composition described in claim 1, wherein the heavy chain of the isolated antibody molecule comprises a molecule having a sequence consisting of SEQ ID NO:255 and the light chain of the isolated antibody molecule comprises a molecule having a sequence consisting of SEQ ID NO:

256.

4. The antibody which specifically binds to human CD39 (hCD39) and has: a) inhibiting the binding of CD39 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 in the 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 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) increasing the proliferation of stimulated CD4 + and CD8 + T cells; and / or r) increasing the secretion of INF-γ, TNF-α, IL-2 and / or IL-1β by stimulated PBMCs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 of the above may be present.

5. A polypeptide that binds to hCD39 and has the following properties: a) blocking or reducing hydrolysis of ATP to ADP and / or ADP to AMP as determined by at least one of: (i) a decrease in release of phosphate (Pi); (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 decreasing 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) increasing the proliferation of stimulated CD4 + and CD8 + T cells; and / or r) increasing the secretion of INF-γ, TNF-α, IL-2, and / or IL-1β by stimulated PBMCs.

2. The pharmaceutical composition of claim 1, further comprising an effective amount of an antibody having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 of the following:

6. 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 h) small molecule inhibitors; The pharmaceutical composition of claim 1, further comprising at least one of:

7. a) an antibody against an inhibitory receptor or ligand, and / or b) an antibody against a costimulatory receptor or ligand; 7. The pharmaceutical composition of claim 5 or 6, further comprising one or both of: (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 a killer cell immunoglobulin-like receptor (KIR); and / or (ii) the pharmaceutical composition of claim 7, 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.

9. The pharmaceutical composition of claim 8, wherein the costimulatory receptor or ligand LFA-1 further comprises the LFA-1 β chain CD18 and / or the LFA-1 α chain CD11a.

10. The pharmaceutical composition of claim 1, further comprising a pharmaceutical excipient.

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