Claudin 18.2 antibody, method for producing the same, and use thereof

Abstract

Antibodies and compositions against Claudin 18.2 and their use are provided herein.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority and benefit of U.S. Provisional Patent Application No. 63 / 347,647, filed on June 1, 2022, entitled "CLAUDIN 18.2 ANTIBODIES, METHODS OF MAKING THE SAME, AND USES THEREOF", which is hereby incorporated by reference in its entirety herein.

[0002] Cross - reference to Electronically Submitted Sequence Listing This application includes a sequence listing that was electronically submitted in XML file format and is hereby incorporated by reference in its entirety herein. The above - mentioned XML copy, created on June 1, 2023, is named "ITL - 020WO sequence listing.XML" and has a size of 32,768 bytes.

Background Art

[0003] Background Gastric tumors are often diagnosed and treated at an advanced tumor stage with a poor prognosis. Recent studies have identified isoform 2 of claudin - 18 ( "claudin 18.2"), a tight - junction protein, as a promising target in the treatment of gastric tumors. Claudin 18.2 is expressed in gastric tumors but not in normal adult tissues except for gastric mucosa. Thus, the relatively specific expression of claudin 18.2 in gastric tumors makes it an attractive target. Due to its high similarity to claudin 18.1, it is difficult to specifically target claudin 18.2. Furthermore, its structurally complex antigen makes it difficult to produce antibodies against this target. Therefore, there is a need in the art for antibodies against claudin 18.2 that can be used in various therapeutic modalities. The embodiments provided herein meet these needs in addition to other needs.

Summary of the Invention

Means for Solving the Problem

[0004] Summary In some embodiments, a recombinant antibody that binds to Claudin 18.2 protein, or an antigen-binding fragment thereof, is provided. In some embodiments, the recombinant antibody or an antigen-binding fragment thereof binds to the Claudin 18.2 protein in its native conformation. In some embodiments, the antibody or an antigen-binding fragment thereof specifically binds to Claudin 18.2. In some embodiments, the antibody or an antigen-binding fragment thereof does not specifically bind to Claudin 18.1.

[0005] In some embodiments, the antibody or an antigen-binding fragment thereof binds to the human Claudin 18.2 protein. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a humanized antibody. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a chicken antibody. In some embodiments, the antibody or an antigen fragment thereof is generated by inducing an immune response against Claudin 18.2 in chickens.

[0006] In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a monoclonal antibody. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a scFv antibody.

[0007] In some embodiments, the antibody or antigen-binding fragment comprises a variable light (VL) region comprising light chain complementarity determining region 1 (LCDR1), light chain complementarity determining region 2 (LCDR2), and light chain complementarity determining region 3 (LCDR3), wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VL region comprising LCDR1, LCDR2, and LCDR3, wherein the antibody, or antigen-binding fragment thereof, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19.

[0008] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a variable light (VL) region having an amino acid sequence with at least 85% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13. In some embodiments, the antibody that binds to Claudin 18.2, or an antigen-binding fragment thereof, comprises a VL region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13. In some embodiments, the antibody or antigen-binding fragment thereof that binds to Claudin 18.2 comprises a VL region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VL region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or any variant thereof having 1 to 10 substitutions, deletions, or insertions. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VL region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or any variant thereof having 1 to 10 conservative substitutions. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VL region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13.

[0009] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable (VH) region comprising heavy chain complementarity determining region 1 (HCDR1), heavy chain complementarity determining region 2 (HCDR2), and heavy chain complementarity determining region 3 (HCDR3), where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment comprises a VH region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0010] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a heavy chain variable (VH) region having at least 85% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VH region having an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VH region having an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VH region having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, or any variant thereof having 1 to 10 substitutions, deletions, or insertions. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VH region having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, or any variant thereof having 1 to 10 conservative substitutions. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a VH region having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12.

[0011] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a VH region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0012] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a VH region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0013] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a VH region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0014] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a VH region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0015] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a VH region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0016] In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region having the amino acid sequence of SEQ ID NO: 5, or a variant thereof; and (ii) a VH region having the amino acid sequence of SEQ ID NO: 4, or a variant thereof. In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region having the amino acid sequence of SEQ ID NO: 7, or a variant thereof; and (ii) a VH region having the amino acid sequence of SEQ ID NO: 6, or a variant thereof. In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region having the amino acid sequence of SEQ ID NO: 9, or a variant thereof; and (ii) a VH region having the amino acid sequence of SEQ ID NO: 8, or a variant thereof. In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region having the amino acid sequence of SEQ ID NO: 11, or a variant thereof; and (ii) a VH region having the amino acid sequence of SEQ ID NO: 10, or a variant thereof. In some embodiments, the antibody or antigen-binding fragment comprises: (i) a VL region having the amino acid sequence of SEQ ID NO: 13, or a variant thereof; and (ii) a VH region having the amino acid sequence of SEQ ID NO: 12, or a variant thereof.

[0017] In some embodiments, the antibody or antigen-binding fragment that binds to the Claudin 18.2 protein comprises a VL region and a VH region that are not linked by a linker. In some embodiments, the antibody or antigen-binding fragment that binds to the Claudin 18.2 protein comprises a VL region and a VH region that are linked by a peptide linker. In some embodiments, the antibody or antigen-binding fragment that binds to the Claudin 18.2 protein comprises a peptide linker comprising the sequence GQSSRSSGGGGSSGGGGS (SEQ ID NO: 14); (GGGGS)n (SEQ ID NO: 15); (GGGGA)n (SEQ ID NO: 16), or any combination thereof, wherein each n is independently 1 to 5. In some embodiments, the antibody or antigen-binding fragment that binds to the Claudin 18.2 protein comprises a peptide linker that does not comprise the sequence GQSSRSSGGGGSSGGGGS (SEQ ID NO: 14).

[0018] In some embodiments, an antibody that binds to Claudin 18.2, or an antigen-binding fragment thereof, further comprises at least one additional peptide that binds to a different target protein. In some embodiments, an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein further comprises at least one additional peptide that binds to a different target protein, wherein the different target protein is CD3 or CD28. In some embodiments, an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein further comprises at least one additional peptide that binds to a different target protein, wherein the at least one additional peptide is an antibody or an antigen-binding fragment thereof.

[0019] In some embodiments, the antibody or an antigen-binding fragment thereof binds to residues E56, N153, Y155, M158, and G159 of the Claudin 18.2 protein. In some embodiments, the antibody, or an antigen-binding fragment thereof, binds to residues V40, E56, N153, Y155, M158, G159, and G160 of the Claudin 18.2 protein.

[0020] In some embodiments, a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein is provided.

[0021] In some embodiments, a vector comprising a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein is provided.

[0022] In some embodiments, provided are cells comprising a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein. In some embodiments, provided are cells comprising a vector comprising a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein.

[0023] In some embodiments, provided are pharmaceutical compositions comprising an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein. In some embodiments, provided are pharmaceutical compositions comprising a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein. In some embodiments, provided are pharmaceutical compositions comprising a vector comprising a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein. In some embodiments, the pharmaceutical composition is an injectable pharmaceutical composition. In some embodiments, the pharmaceutical composition is sterile or pyrogen-free. In some embodiments, an antibody or an antigen-binding fragment thereof that does not bind to Claudin 18.2 is not included in the pharmaceutical composition.

[0024] In some embodiments, provided is a method of treating a subject having a tumor or a gastric tumor, the method comprising administering to the subject a therapeutically effective amount of a Claudin 18.2 antibody or an antigen-binding fragment thereof described herein. In some embodiments, provided is a method of treating a subject having a tumor or a gastric tumor, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a Claudin 18.2 antibody or an antigen-binding fragment thereof described herein. In some embodiments, the tumor or gastric tumor is gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, pancreatic adenocarcinoma, or non-small cell lung cancer. In some embodiments, the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken.

[0025] In some embodiments, provided is a method for detecting the presence or absence of Claudin 18.2 in a sample, the method comprising contacting the sample with an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 as described herein, and detecting binding of the antibody or its antigen-binding fragment to the Claudin 18.2 antigen, wherein detection of binding indicates the presence of Claudin 18.2; or failure to detect binding to Claudin 18.2 indicates the absence of Claudin 18.2.

[0026] In some embodiments, provided is a method for inducing an immune response against the Claudin 18.2 protein in a subject, the method comprising administering to the subject a virus-like particle comprising the Claudin 18.2 protein under conditions sufficient to induce an immune response. In some embodiments, the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken.

[0027] In some embodiments, provided is a method for generating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein. In some embodiments, the method for generating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises administering to a subject a virus-like particle comprising the Claudin 18.2 protein on its surface under conditions sufficient to induce an immune response against the Claudin 18.2 protein. In some embodiments, the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken.

[0028] In some embodiments, a method of generating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein further comprises isolating an antibody that binds to the Claudin 18.2 protein. In some embodiments, the generated antibody, or an antigen-binding fragment thereof, binds to the extracellular domain of the Claudin 18.2 protein. In some embodiments, a method of generating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein further comprises generating virus-like particles comprising the Claudin 18.2 protein. In some embodiments, a method of generating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein further comprises transfecting or transducing cells with the Claudin 18.2 protein and a retroviral gag protein under conditions sufficient to produce virus-like particles comprising the Claudin 18.2 protein. In some embodiments, the cells are HEK-293T cells. In some embodiments, the gag protein is the MLV gag protein. In some embodiments, the retroviral gag protein is a murine leukemia virus (MLV), gag, HIV gag, or RSV gag protein.

[0029] In some embodiments, methods of modulating Claudin 18.2 activity are provided. In some embodiments, a method of modulating Claudin 18.2 activity comprises contacting a cell that expresses Claudin 18.2 with a Claudin 18.2 antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 on the cell surface. In some embodiments, a method of modulating Claudin 18.2 activity comprises contacting a cell that expresses Claudin 18.2 with a pharmaceutical composition comprising a Claudin 18.2 antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 on the cell surface. In some embodiments, a method of modulating Claudin 18.2 activity comprises administering to a subject an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein as defined herein. In some embodiments, a method of modulating Claudin 18.2 activity comprises administering to a subject a pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein as defined herein.

[0030] In some embodiments, chimeric antigen receptors are provided that comprise an extracellular portion comprising an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 as defined herein. In some embodiments, the chimeric antigen receptor comprises an extracellular portion comprising an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 as defined herein, wherein the antibody or antigen-binding fragment thereof comprises a binding domain, and the binding domain is a scFv fragment.

[0031] In some embodiments, a multispecific molecule is provided that includes a first portion or domain that binds to the Claudin 18.2 protein and a second portion or domain that binds to a second molecule. In some embodiments, the multispecific molecule has a therapeutic effect on cells that express Claudin 18.2. In some embodiments, the first portion or domain that binds to Claudin 18.2 is an antibody or a binding fragment thereof as defined herein. In some embodiments, the first portion or domain that binds to Claudin 18.2 is an antibody or a binding fragment thereof that includes a binding domain as defined herein, where the binding domain is a scFv fragment.

Brief Description of the Drawings

[0032]

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[0033] Detailed Description Antibodies that bind to Claudin 18.2 protein, or antigen-binding fragments thereof, are provided herein. In some embodiments, an antibody that binds to Claudin 18.2, or an antigen-binding fragment thereof, is isolated. In some embodiments, an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 is recombinant. In some embodiments, the antibody or antigen-binding fragment thereof is a structural MAb (monoclonal antibody) that recognizes Claudin 18.2 in its native environment or native structure. Without being bound by a particular theory, Claudin 18.2 protein in its native environment or native structure refers to Claudin 18.2 protein in the plasma membrane (cell membrane) or bilayer structure. The native structure of the Claudin 18.2 protein in its native environment allows the Claudin 18.2 protein to fold so as to span the cell membrane or lipid bilayer multiple times. Thus, an antibody that binds to Claudin 18.2 protein in its native environment or native structure, or an antigen-binding fragment thereof, refers to an antibody that binds to Claudin 18.2 protein in the plasma membrane (cell membrane) or bilayer structure, or an antigen-binding fragment thereof. In some embodiments, an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 is specific for Claudin 18.2 and does not cross-react with, or does not significantly cross-react with, Claudin 18.1. Thus, the present disclosure provides surprising and unexpected results, which are, in part, antibodies that can bind to Claudin 18.2 in its native structure and / or its native environment without cross-reacting with Claudin 18.1. In some embodiments, an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 inhibits the activity of Claudin 18.2. In some embodiments, an antibody or an antigen-binding fragment thereof that binds to Claudin 18.2 recognizes a structural epitope on native Claudin 18.2 present on intact human cells.In some embodiments, an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein exhibits significant specificity within the Claudin family, reacts with the mouse ortholog, but does not react with most other members of the human membrane proteome. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein is MAb MAb1 (IM-44-09B03-1HB), MAb2 (IM-44-01E10-1HA), or MAb3 (IM-44-05H06-1HD).

[0034] As used herein, the term "antibody" refers to any form of antibody that exhibits the desired biological activity. Thus, it is used in the broadest sense and specifically includes, but is not limited to, monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), humanized, fully human antibodies, chimeric antibodies, and camelized single-domain antibodies. A "parent antibody" is an antibody obtained by exposing the immune system to an antigen prior to modification of the antibody for a desired use, e.g., for humanization of the antibody for use as a human therapeutic antibody. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a monoclonal antibody.

[0035] Unless otherwise indicated, as used herein, "antibody fragment" or "antigen-binding fragment" refers to an antigen-binding fragment of an antibody, i.e., an antibody fragment that retains the ability to specifically bind to an antigen bound by the full-length antibody, e.g., a fragment that retains one or more CDR regions. Examples of antibody-binding fragments include, but are not limited to, Fab, Fab’, F(ab’)2, and Fv fragments; bispecific antibodies (diabodies); linear antibodies; single-chain antibody molecules, e.g., sc-Fv; nanobodies; and multispecific antibodies formed from antibody fragments.

[0036] The "Fab fragment" consists of one light chain and the C H 1 and variable regions of one heavy chain. The heavy chain of the Fab molecule cannot form a disulfide bond with another heavy chain molecule.

[0037] The "Fc" region contains two heavy chain fragments that include the C H 1 and C H 2 domains. These two heavy chain fragments are linked by two or more disulfide bonds and by the hydrophobic interaction of the C H 3 domains.

[0038] The "Fab' fragment" consists of one light chain and part or a fragment of one heavy chain that contains the V H domain and the C H 1 domain and also contains the region between the C H 1 domain and the C H 2 domains. As a result, an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form an F(ab')2 molecule.

[0039] The "F(ab')2 fragment" contains two light chains and two heavy chains that contain part of the constant region between the C H 1 domain and the C H 2 domains. As a result, an interchain disulfide bond is formed between the two heavy chains. Thus, the F(ab')2 fragment is composed of two Fab' fragments linked by a disulfide bond between the two heavy chains.

[0040] The "Fv region" includes the variable regions from both the heavy and light chains but lacks the constant regions.

[0041] The term "single-chain Fv" or "scFv" antibody refers to the V H and V LRefers to an antibody fragment containing domains, where these domains are present in a single polypeptide chain. Generally, an Fv polypeptide enables the scFv to form a structure desirable for antigen binding, such as the V H and V L domains, and further includes a polypeptide linker between the domains. For a review of scFv, see Pluckthun (1994) THE PHARMACOLOGY OF MONOCLONAL ANTIBODIES, vol. 113, edited by Rosenberg and Moore, Springer-Verlag, New York, pp. 269-315. See also International Patent Application Publication No. WO88 / 01649 and U.S. Patent Nos. 4,946,778 and 5,260,203. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein is an scFv antibody.

[0042] A "domain antibody" is an immunologically functional immunoglobulin fragment containing only the variable region of the heavy chain or the variable region of the light chain. In some examples, two or more V H regions are covalently linked by a peptide linker to yield a bivalent domain antibody. The two V H regions of the bivalent domain antibody can target the same or different antigens.

[0043] A "bivalent antibody" contains two antigen-binding sites. In some examples, the two binding sites have the same antigen specificity. However, the bivalent antibody may be bispecific (see below).

[0044] In certain embodiments, the monoclonal antibodies described herein also include camelized single domain antibodies. See, for example, Muyldermans et al. (2001) Trends Biochem. Sci. 26:230; Reichmann et al. (1999) J. Immunol. Methods 231:25; WO 94 / 04678; WO94 / 25591; U.S. Patent No. 6,005,079. In one embodiment, the disclosure provides a single domain antibody comprising two VH domains modified to form a single domain antibody.

[0045] As used herein, the term "bispecific antibody" refers to small antibody fragments that have two antigen-binding sites, and these fragments have a heavy chain variable domain (V L ) connected to a light chain variable domain (V H ) in the same polypeptide chain (V H -V L or V L -V H ). By using a linker that is too short to allow pairing between the two domains on the same chain, these domains are forced to pair with complementary domains on another chain, resulting in two antigen-binding sites. Bispecific antibodies are described more fully, for example, in EP 404,097; WO93 / 11161; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. For a review of engineered antibody variants, see generally Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1136.

[0046] Typically, the variant antibodies provided herein, or antigen-binding fragments of such antibodies, when their activity is expressed on a molar basis, retain at least 10% of their Claudin 18.2 binding activity (when compared to the parental antibody being modified). In some embodiments, the variant antibody (or its antigen fragment), or the antigen-binding fragment of the antibody provided herein, retains at least 20%, 50%, 70%, 80%, 90%, 95% or 100% or more of the Claudin 18.2 binding affinity as the parental antibody. As described herein. It is also contemplated that the antibodies or antigen-binding fragments thereof of the present disclosure may contain conservative or non-conservative amino acid substitutions, which may be referred to as "conservative variants" or "functionally conserved variants" of the antibody, and substantially their biological activity remains unchanged.

[0047] "Isolated antibody" refers to the purified state of the binding compound, and in such context, it means that the molecule is substantially free of other biological molecules, such as nucleic acids, proteins, lipids, carbohydrates, or other substances such as cell debris and growth media. Generally, the term "isolated" is not intended to mean that such substances are completely absent, or that water, buffer, or salts are absent, provided that they are not present in an amount that substantially interferes with the experimental or therapeutic use of the binding compound described herein.

[0048] As used herein, the term "monoclonal antibody" refers to a substantially homogeneous population of antibodies, i.e., the antibody molecules that make up this population have the same amino acid sequence except for possible naturally occurring variations that may be present in small amounts. In contrast, conventional (polyclonal) antibody preparations typically contain a number of different antibodies having different amino acid sequences in their variable domains (especially their CDRs), which are often specific for different epitopes. The modifier "monoclonal" indicates the characteristic of the antibody being obtained from a substantially homogeneous population of antibodies and should not be construed to require that the production of the antibody be by any particular method. For example, a monoclonal antibody to be used in accordance with the present disclosure can be produced by the hybridoma method first described by Kohler et al. (1975) Nature 256:495 or by recombinant DNA methods (e.g., U.S. Patent No. 4,816,567). A "monoclonal antibody" can also be isolated from a phage antibody library using, for example, the techniques described in Clackson et al. (1991) Nature 352:624-628 and Marks et al. (1991) J. Mol. Biol. 222:581-597. See also Presta (2005) J. Allergy Clin. Immunol. 116:731.

[0049] As used herein, a "chimeric antibody" is an antibody having variable domains from a first antibody and constant domains from a second antibody, where the first and second antibodies are from different species (see U.S. Patent No. 4,816,567; and Morrison et al. (1984) Proc. Natl. Acad. Sci. USA 81: 6851-6855). Typically, the variable domains are obtained from an antibody from an experimental animal such as a rodent ("parent antibody"), and the constant domain sequences are obtained from a human antibody, such that the resulting chimeric antibody is less likely to elicit a harmful immune response in a human subject than the parent (e.g., rodent) antibody.

[0050] As used herein, the term "humanized antibody" refers to a form of antibody that contains sequences derived from both human and non-human (e.g., mouse, rat) antibodies. Generally, a humanized antibody contains substantially all of at least one, and typically two, variable domains, where all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework (FR) regions are the FR regions of human immunoglobulin sequences. A humanized antibody may optionally contain at least a portion of a human immunoglobulin constant region (Fc). In some embodiments, an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a humanized antibody.

[0051] The term "fully human antibody" refers to an antibody that contains only human immunoglobulin protein sequences. A fully human antibody may contain mouse hydrocarbon chains when produced in a mouse, in mouse cells, or in a hybridoma derived from mouse cells. Similarly, a "mouse antibody" refers to an antibody that contains only mouse immunoglobulin sequences. Alternatively, a fully human antibody may contain rat hydrocarbon chains when produced in a rat, in rat cells, or in a hybridoma derived from rat cells. Similarly, a "rat antibody" refers to an antibody that contains only rat immunoglobulin sequences. In some embodiments, an antibody or antigen-binding fragment thereof binds to the human Claudin 18.2 protein. In some embodiments, an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a chicken antibody. In some embodiments, an antibody or antigen fragment thereof is generated by inducing an immune response against Claudin 18.2 in a chicken.

[0052] Generally, the basic antibody structural unit consists of a tetramer. Each tetramer contains two identical pairs of polypeptide chains, and each pair has one "light" chain (about 25 kDa) and one "heavy" chain (about 50 - 70 kDa). The amino-terminal portion of each chain contains a variable region of about 100 - 110 or more amino acids that is mainly involved in antigen recognition. The carboxy-terminal portion of the heavy chain may define a constant region that is mainly involved in effector functions. Typically, human light chains are classified into kappa and lambda light chains. Furthermore, human heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon, and each defines the antibody isotype as IgM, IgD, IgG, IgA, and IgE, respectively. Within the light and heavy chains, the variable and constant regions are linked by a "J" region of about 12 or more amino acids, and the heavy chain also contains a "D" region of about 10 more amino acids. Generally, see Fundamental Immunology Ch.7 (Paul, W. ed., 2nd ed. Raven Press, N.Y. (1989)).

[0053] The variable regions of each light / heavy chain pair form the antibody binding site. Thus, generally, an intact antibody has two binding sites. Except for bifunctional or bispecific antibodies, the two binding sites are generally the same.

[0054] Typically, the variable domains of both the heavy and light chains contain three hypervariable regions, which are also called complementarity-determining regions (CDRs), and are located within relatively conserved framework regions (FRs). The CDRs are usually aligned with the framework regions and enable binding to specific epitopes. Generally, from the N-terminus to the C-terminus, the variable domains of both the light and heavy chains contain FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The amino acid assignments to each domain generally follow the definitions of Sequences of Proteins of Immunological Interest, Kabat et al.; National Institutes of Health, Bethesda, Md.; 5th edition; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chem. 32:1-75; Kabat et al. (1977) J. Biol. Chem. 252:6609-6616; Chothia et al. (1987) J Mol. Biol. 196:901-917 or Chothia et al. (1989) Nature 342:878-883.

[0055] As used herein, the term "hypervariable region" refers to the amino acid residues of an antibody or an antigen-binding fragment thereof that are involved in antigen binding. Hypervariable regions include "complementary determining regions" or "CDRs" (i.e., amino acid residues from residues 24-34 (CDRL1), 50-56 (CDRL2), and 89-97 (CDRL3) in the light chain variable domain and residues 31-35 (CDRH1), 50-65 (CDRH2), and 95-102 (CDRH3) in the heavy chain variable domain; Kabat et al. (1991) Sequences of Proteins of Immunological Interest, 5th ed. Public Health Service, National Institutes of Health, Bethesda, Md.) and / or residues from "hypervariable loops" (i.e., amino acid residues from residues 26-32 (CDRL1), 50-52 (CDRL2), and 91-96 (CDRL3) in the light chain variable domain and 26-32 (CDRH1), 53-55 (CDRH2), and 96-101 (CDRH3) in the heavy chain variable domain; Chothia and Lesk (1987) J. Mol. Biol. 196:901-917). As used herein, the term "framework" or "FR" residues refers to variable domain residues other than the hypervariable region residues defined herein as CDR residues. CDRs provide most of the contact residues for the binding of an antibody to its antigen or epitope. The CDRs of interest may be derived from donor antibody variable heavy and light chain sequences and include analogs of naturally occurring CDRs, which also share or retain the same antigen-binding specificity and / or neutralizing ability as the donor antibody from which they are derived.

[0056] The term "chicken antibody" refers to an antibody produced in a chicken. For example, a protein of interest can be introduced into a chicken with a VLP as provided herein, for example, to stimulate an immune response against the protein of interest and produce an antibody in the chicken. The antibody can then be humanized or otherwise modified as desired.

[0057] Furthermore, in some embodiments, the antibody or their antigen-binding fragments can be in the form of a full-length antibody, a single-domain antibody, a recombinant heavy-chain antibody (VHC), a single-chain antibody (scFv), a shark heavy-chain antibody (VNAR), a microprotein (cysteine knot protein, knottin), a DARPin; a tetranectin; an Affibody; a transbody; an anticalin; an AdNectin; an Affilin; a microbody; a peptide aptamer; an alterase; a plastic antibody; a phylomer; a stradobody; a maxibody; an evibody; a fynomer, an armadillo repeat protein, a Kunitz domain, an avimer, an atrimer, a probody, an immunobody, a triomab, a troybody; a pepbody; a vaccibody; a UniBody; an Affimer, a DuoBody, an Fv, a Fab, a Fab’, an F(ab’)2, a peptide mimetic molecule, or a synthetic molecule as described in U.S. Patent or Patent Publication Nos. US7,417,130, US2004 / 132094, US5,831,012, US2004 / 023334, US7,250,297, US6,818,418, US2004 / 209243, US7,838,629, US7,186,524, US6,004,746, US5,475,096, US2004 / 146938, US2004 / 157209, US6,994,982, US6,794,144, US2010 / 239633, US7,803,907, US2010 / 119446, and / or US7,166,697 (the contents of each of which are hereby incorporated by reference in their entireties). See also Storz MAbs. 2011 May-Jun;3(3): 310-317 (which is hereby incorporated by reference).

[0058] As used herein, the term "antigen" means any molecule having the ability to directly or indirectly generate an antibody. Nucleic acids encoding proteins are included within the definition of "antigen". An "antigen" may also be referred to as an antibody binding partner. In some embodiments, the antigen is the Claudin 18.2 protein expressed on the surface of a particle such as a cell or virus-like particle. In some embodiments, the cell is an intact cell. An intact cell is a cell that has not been lysed or disrupted using a surfactant or other reagent. A cell treated with a surfactant or other reagent that disrupts the cell or makes holes in the cell membrane is not an intact cell. By expressing a receptor on the surface of a cell or particle, such as a lipid particle, the receptor can exist as a structural epitope that might not otherwise exist if a purified protein were used. Examples are provided herein. In some embodiments, an adjuvant is not used, although an adjuvant may be used. In some embodiments, the particles are injected into a fowl (e.g., chicken) to stimulate an immune response and generate antibodies against the proteins present on the surface of the particles. Particles suitable for antibody production, and methods for their manufacture, are described, for example, in U.S. Pat. Nos. 8,377,691, 7,763,258, 8,158,130 and U.S. Patent Application Publication Nos. 20050123563 and 20120195882, which are hereby incorporated by reference in their entirety. These publications and patents describe the production of various particles, including lipid particles that can be used to express transmembrane proteins (e.g., multi-pass transmembrane proteins, ion channels, etc.). In some embodiments, Claudin 18.2 can be incorporated into lipid particles according to these methods or as shown herein.

[0059] For example, provided herein is a method for generating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein, the method comprising administering to a subject a virus-like particle comprising the Claudin 18.2 protein on its surface under conditions that induce an immune response against the Claudin 18.2 protein to generate an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein. In some embodiments, a nucleic acid molecule encoding the Claudin 18.2 protein is provided.

[0060] In some embodiments, the method further comprises isolating an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein. In some embodiments, the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken. In some embodiments, the generated antibody or an antigen-binding fragment thereof binds to the extracellular domain of the Claudin 18.2 protein. In some embodiments, the method comprises generating a virus-like particle comprising the Claudin 18.2 protein, the method comprising transfecting or transducing a cell with the Claudin 18.2 protein and a gag protein under conditions sufficient to produce a virus-like particle comprising the Claudin 18.2 protein. VLPs can be generated as described herein and in the above references. In some embodiments, the cell is a HEK-293T cell. In some embodiments, the gag protein is a retroviral gag protein. In some embodiments, the retroviral gag protein is a murine leukemia virus (MLV) gag protein. In some embodiments, Gag is HIV. In some embodiments, Gag is Rous sarcoma virus Gag.

[0061] As used herein, "specific binding" or "immunospecific binding" or "immunologically binds specifically" refers to an antibody or antibody fragment that binds to a given antigen (e.g., Claudin 18.2) or an epitope present on that antigen. In some embodiments, the antibody or its antigen-binding fragment binds with a dissociation constant (K -7 ) of 10 D M or less, and binds to the given antigen with a K D that is at most half of its K D for binding to non-specific antigens other than the given antigen (e.g., BSA, casein, or another non-specific polypeptide). The phrases "antibody that recognizes Claudin 18.2" and "antibody specific for Claudin 18.2" are used interchangeably herein with the term "antibody that immunospecifically binds to Claudin 18.2". Claudin 18.2 may be referenced in the present disclosure. In some embodiments, the antibody or its antigen-binding fragment binds specifically to Claudin 18.2 rather than to other proteins, including but not limited to, for example, Claudin 18.1. The degree of specificity required of an anti-Claudin 18.2 antibody or its antigen-binding fragment may depend on the intended use of the antibody and, in any event, is defined by its suitability for use for the intended purpose. In some embodiments, the antibody, or a binding compound derived from the antigen-binding site of the antibody of the contemplated method, binds to the antigen (Claudin 18.2) with an affinity that is at least 2-fold higher, at least 10-fold higher, at least 20-fold higher, or at least 100-fold higher than its affinity for any other antigen.

[0062] Methods for determining mAb specificity and affinity by competitive inhibition can be found in Harlow et al., Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1988), Colligan et al., Current Protocols in Immunology, Greene Publishing Assoc. and Wiley Interscience, N.Y., (1992, 1993), and Muller, Meth. Enzymol. 92:589 601 (1983), which are hereby incorporated by reference in their entirety.

[0063] The term "homolog" means a protein sequence having between 40% and 100% sequence homology or identity to a reference sequence. The percent identity between two peptide chains can be determined by pairwise alignment using the default settings of the AlignX module of Vector NTI v.9.0.0 (Invitrogen Corp., Carslbad, Calif.). In some embodiments, the antibody or antigen-binding fragment thereof has at least 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% homology or identity to the sequences described herein. In some embodiments, the antibody or antigen-binding fragment thereof has conservative substitutions as compared to the sequences described herein. Exemplary conservative substitutions are shown in Table 1 and are included within the scope of the disclosed subject matter. Conservative substitutions may be in the framework region or antigen-binding site as long as they do not have an adverse effect on the properties of the antibody. Substitutions may be made to improve the properties of the antibody, such as stability or affinity. Conservative substitutions result in molecules having functional and chemical characteristics similar to the molecule for which such modifications are made. Exemplary amino acid substitutions are shown in the following table.

[0064] [Table 1]

[0065] In some embodiments, variants of the proteins and peptides provided herein are provided. In some embodiments, the variants include substitutions, deletions, or insertions. In some embodiments, the variants include 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1 to 10) substitutions. As described herein, the substitutions can be conservative substitutions. In some embodiments, the substitutions are non-conservative. In some embodiments, the variants include 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1 to 10) deletions. In some embodiments, the variants include 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (e.g., 1 to 10) insertions. In some embodiments, the substitutions, deletions, or insertions are present in the CDRs provided herein. In some embodiments, the substitutions, deletions, or insertions are not present in the CDRs provided herein.

[0066] As used herein, the term "in combination with" means that the recited agent can be administered to an animal or subject together in a mixture, simultaneously as a single agent, or sequentially as a single agent in any order.

[0067] Techniques for generating antibodies against small peptide sequences that recognize and bind small peptide sequences, whether in free or conjugated form, or presented as a native sequence in the context of a larger protein, are well known in the art. Such antibodies include monoclonal antibodies, mouse-human, and human-human antibodies produced by hybridoma or recombinant techniques known in the art. Antibodies can also be produced in humans, mice, sheep, rats, rabbits, sharks, llamas, or chickens. In some embodiments, the antibody or antigen-binding fragment thereof is produced in chickens. Antibodies can also be produced in other small animals.

[0068] The term "epitope" means a portion of any molecule that has the ability to be recognized and bound by an antibody or an antigen-binding fragment thereof in one or more antigen-binding regions. Epitopes typically consist of a chemically active surface population of molecules such as amino acids or sugar side chains, and have specific three-dimensional structural features, as well as specific charge features. Examples of epitopes include, but are not limited to, the residues described herein that form the Claudin 18.2 epitope. In some embodiments, the epitope is present only in non-denatured proteins. In some embodiments, the epitope is present only in denatured proteins.

[0069] In some embodiments, sources of DNA encoding non-human antibodies or antigen-binding fragments thereof include cell lines that produce antibodies, such as hybrid cell lines commonly known as hybridomas.

[0070] Hybrid cells are formed by the fusion of cells that produce non-human antibodies, typically spleen cells of an animal immunized against a native or recombinant antigen, or a peptide fragment of an antigen protein sequence. Alternatively, the non-human antibody-producing cells may be B lymphocytes obtained from the blood, spleen, lymph nodes or other tissues of an animal immunized with an antigen.

[0071] The second fusion partner that provides the immortalizing function can be a lymphoblastoid cell or a plasmacytoma or myeloma cell, which is not itself an antibody-producing cell but is cancerous. Examples of fusion partner cells include, but are not limited to, hybridoma SP2 / 0-Ag14 (abbreviated as SP2 / 0 (ATCC CRL1581)) and myeloma P3X63Ag8 (ATCC TIB9), or derivatives thereof. See, for example, Ausubel (below), Harlow (below), and Colligan (below) (the contents of these references are hereby incorporated by reference in their entirety).

[0072] Antibodies can be generated according to the examples provided herein. If the sequence is known, antibodies can also be generated according to known methods. Antibodies can also be converted to different types, such as converting to human IgG. By converting the antibody to a human antibody, a human subject should not identify the antibody as foreign. The conversion of non-human IgG antibodies to human IgG antibodies is well known and can be routinely performed if the native sequence is known. As considered herein, antibodies can be modified according to known methods. Such methods are described, for example, in Riechmann L, Clark M, Waldmann H, Winter G (1988).Reshaping human antibodies for therapy」.Nature 332 (6162): 332-323; Tsurushita N, Park M, Pakabunto K, Ong K, Avdalovic A, Fu H, Jia A, Vasquez M, Kumar S.(2004); and 「Humanization of chicken anti-IL-12 monoclonal antibody」 Immunol Methods 295 (1-2): 9-19; Nishibori N, Horiuchi H, Furusawa S, Matsuda H.(2006) 「Humanization of chicken monoclonal antibody using phage display system」 Mol Immunol.43 (6): 634-42 (each of which is incorporated by reference in its entirety).

[0073] Antibody-producing cells that contribute to a nucleic acid sequence encoding an antigen-binding region of a chimeric antibody can also be produced by transformation of non-human cells, such as primate cells, or human cells. For example, B lymphocytes that produce antibodies can be infected and transformed with a virus such as Epstein-Barr virus to obtain immortal antibody-producing cells (Kozbor et al., Immunol. Today 4:72-79 (1983)). Alternatively, as is well known in the art, B lymphocytes can be transformed by supplying a transforming gene or a transforming gene product. See, for example, Ausubel (below), Harlow (below), and Colligan (below) (the contents of these references are hereby incorporated by reference in their entirety). Cell fusion is achieved by standard procedures well known to those skilled in the art of immunology. Methods for fusing and selecting fusion partner cell lines as well as hybridomas and screening for mAbs are well known in the art. See, for example, Ausubel (below), Harlow (below), and Colligan (below) (the contents of these references are hereby incorporated by reference in their entirety).

[0074] In some embodiments, the antibody or antigen-binding fragment thereof is a MAb that binds to Claudin 18.2. In some embodiments, the antibody or antigen-binding fragment thereof binds to the amino acids of an epitope of Claudin 18.2.

[0075] In some embodiments, the antibody or antigen-binding fragment thereof comprises a sequence provided herein.

[0076] The sequence of the antibody can be modified to obtain a human IgG antibody. The sequence conversions provided herein can be modified to obtain other types of antibodies. The CDRs can be linked to other antibodies, proteins, or molecules to generate antibody fragments that bind to Claudin 18.2. This may be in the form of an antibody-drug conjugate ("ADC"), a multispecific molecule, or a chimeric antigen receptor. The CDRs and antibody sequences provided herein are also humanized or fully humanized according to known methods. The sequences may be made into chimeric antibodies as described herein.

[0077] In some embodiments, the antibody or antigen-binding fragment thereof comprises an amino acid sequence comprising the sequences provided herein, or a fragment thereof. In some embodiments, the antibody or antigen-binding fragment thereof comprises one or more of the amino acid sequences provided herein, its antigen-binding fragment, or its human IgG variant. "Its human IgG variant" refers to an antibody modified to be human IgG when the starting antibody is not a human IgG antibody.

[0078] As described herein, the production of antibodies with known sequences is routine and can be performed by any method. Accordingly, in some embodiments, a nucleic acid encoding the antibody or antigen-binding fragment thereof is provided. In some embodiments, the nucleic acid encodes a sequence provided herein. The antibody can also be modified to be a chimeric or human antibody. The antibody can be used in an injectable pharmaceutical composition. Also as described herein, the antibody can be an isolated or engineered antibody.

[0079] In some embodiments, provided are "derivatives" of antibodies, antibody fragments, regions, or derivatives thereof, the term including proteins encoded by truncated or modified genes that give rise to molecular species functionally similar to immunoglobulin fragments. Modifications include, but are not limited to, the addition of gene sequences encoding cytotoxic proteins such as plant and bacterial toxins. Modifications may include reporter proteins such as fluorescent or chemiluminescent tags. Antibody fragments and derivatives may be produced by any method.

[0080] The identification of these antigen-binding regions and / or epitopes recognized by the Abs described herein provides the information necessary to generate additional monoclonal antibodies having similar binding characteristics and therapeutic or diagnostic utility equivalent to embodiments of the present application.

[0081] The nucleic acid sequence encoding the antibody or antigen-binding fragment thereof described herein can be genomic DNA or cDNA encoding at least one of the variable regions described herein, or RNA (e.g., mRNA). A convenient alternative to the use of chromosomal gene fragments as a source of DNA encoding V-region antigen-binding segments is, for example, the use of cDNA for the construction of chimeric immunoglobulin genes as reported by Liu et al. (Proc. Natl. Acad. Sci., USA 84:3439 (1987) and J. Immunology 139:3521 (1987), which references are incorporated herein by reference in their entirety). The use of cDNA requires that gene expression elements suitable for the host cell be combined with the gene to achieve synthesis of the desired protein. The use of cDNA sequences is advantageous over genomic sequences (containing introns) in that cDNA sequences can be expressed in bacteria or other hosts lacking appropriate RNA splicing systems.

[0082] For example, cDNA encoding a V region antigen-binding segment capable of detecting, binding to, or neutralizing the Claudin 18.2 antigen can be provided using known methods based on the use of the amino acid sequences provided herein. Since the genetic code is degenerate, more than one codon can be used to encode a particular amino acid (Watson et al., infra). Using the genetic code, one or more different oligonucleotides can be identified, each of which has the ability to encode an amino acid. The likelihood that a particular oligonucleotide actually constitutes the actual XXX-encoding sequence can be estimated by considering abnormal base pairing relationships in eukaryotic or prokaryotic cells expressing the antibody or antibody fragment and the frequency with which particular codons are actually used (to encode a particular amino acid). Such "codon usage rules" are disclosed by Lathe et al., J. Molec. Biol. 183:112 (1985). Using Lathe's "codon usage rules", a single oligonucleotide, or a set of oligonucleotides, containing the theoretical "most likely" nucleotide sequence capable of encoding the antibody variable or constant region sequence is identified.

[0083] The variable regions described herein can be combined with any type of constant region, including human or mouse constant regions. Human genes encoding the antibody, antibody fragment, and constant (C) region of the region can be derived from a human fetal liver library by known methods. The human C region gene can be derived from any human cell, including those that express and produce human immunoglobulins. The human C H region can be derived from known classes or isotypes of human H chains, including gamma, mu, alpha, delta, or epsilon, and their subtypes, such as any of G1, G2, G3, and G4. Since H chain isotypes are involved in the various effector functions of antibodies, the selection of the C H region is guided by the desired effector function, such as complement binding, or activity in antibody-dependent cell cytotoxicity (ADCC). Preferably, the CH The region is derived from gamma 1 (IgG1), gamma 3 (IgG3), gamma 4 (IgG4), or mu (IgM). Human C L The region can be derived from either the human light chain isotype, kappa or lambda. In some embodiments, the antibody or antigen-binding fragment thereof comprises an Fc domain. In some embodiments, the Fc domain comprises a mutation that extends the half-life of the antibody. In some embodiments, the Fc domain comprises a mutation as described in U.S. Patent No. 7,670,600, which is incorporated herein by reference in its entirety. In some embodiments, the constant region comprises a mutation at the position of amino acid residue 428 (numbered according to the Kabat EU numbering index) relative to the wild-type human IgG constant domain. Without being bound by any particular theory, an antibody comprising a mutation corresponding to residue 428 can have an increased half-life compared to the half-life of an IgG having a wild-type human IgG constant domain. In some embodiments, the mutation is a substitution with the natural residue threonine, leucine, phenylalanine, or serine. In some embodiments, the antibody or antigen-binding fragment thereof further comprises one or more amino acid substitutions relative to the corresponding wild-type human IgG constant domain at one or more of amino acid residues 251-256, 285-290, 308-314, 385-389, and 429-436 (numbered according to the Kabat EU numbering index). Specific mutations or substitutions at these positions are described in U.S. Patent No. 7,670,600, which is incorporated herein by reference in its entirety.

[0084] Genes encoding the human immunoglobulin C region can be obtained from human cells by standard cloning techniques (Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd ed., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989)) and Ausubel et al. eds. Current Protocols in Molecular Biology (1987 - 1993)). The human C region genes are readily available from known clones containing genes representing two classes of L chains, five classes of H chains, and their subclasses. Chimeric antibody fragments, such as F(ab’)2 and Fab, can be produced by designing appropriately cleaved chimeric H chain genes. For example, a chimeric gene encoding the H chain portion of an F(ab’)2 fragment would include the CH1 domain and hinge region of the H chain, followed by a DNA sequence encoding a translation stop codon to obtain a cleaved molecule.

[0085] In some embodiments, the antibodies, mouse antibodies, human antibodies, humanized antibodies, or chimeric antibodies, antibody fragments, and regions of antibodies described herein are produced by cloning DNA segments encoding the H chain and L chain antigen - binding regions of a Claudin 18.2 - specific antibody and ligating these DNA segments to DNA segments encoding the C H region and C L region, respectively, to produce a gene encoding a mouse, human, or chimeric immunoglobulin.

[0086] Thus, in some embodiments, a fused chimeric gene is generated that includes a first DNA segment encoding at least an antigen - binding region of non - human origin, such as a functionally rearranged V region having a joining (J) region, ligated to a second DNA segment encoding at least a portion of the human C region.

[0087] Accordingly, cDNA encoding the antibody V and C regions, and methods of manufacturing antibodies according to some of the embodiments described herein include several steps as exemplified below: 1. Isolating messenger RNA (mRNA) from a cell line producing anti-Claudin 18.2 antigen antibody and from any additional antibody supplying the heavy and light chain constant regions; and cloning from them to produce cDNA; 2. Producing a full-length cDNA library from purified mRNA such that appropriate V and / or C region gene segments of the L and H chain genes can be: (i) identified using appropriate probes, (ii) sequenced, and (iii) made compatible with C or V gene segments from another antibody for chimeric antibodies; 3. Constructing a complete H or L chain coding sequence by ligating the cloned specific V region gene segment to the cloned C region as described above; 4. Expressing and producing the L and H chains in a selected host including prokaryotic and eukaryotic cells to produce mouse-mouse, human-mouse, human-human or human-mouse antibodies.

[0088] Two coding DNA sequences are said to be "operably linked" if their ligation results in a sequence that can be translated continuously without alteration or interruption of the triplet reading frame. A DNA coding sequence is operably linked to a gene expression element if its ligation results in the proper functioning of that gene expression element and the expression of the coding sequence.

[0089] As used herein, the term "about" means that, unless otherwise indicated, its value can be changed by ±5%. Thus, about 100 means 95 to 105.

[0090] In some embodiments, the antibodies or their antigen-binding fragments described herein are used to detect the presence of an antigen. The antibodies or antigen-binding fragments of the present disclosure can be used in any device or method for detecting the presence of an antigen.

[0091] The term "purified" with respect to an antibody or antigen-binding fragment thereof refers to an antibody or antigen-binding fragment thereof that is substantially free of other substances that bind to that molecule in its natural environment. For example, a purified protein is substantially free of cellular material and other proteins from the cells or tissues from which it is derived. This term refers to preparations in which the isolated protein is pure enough for analysis, or at least 70% - 80% (mass / mass) pure, at least 80% - 90% (mass / mass) pure, 90 - 95% pure; and preparations that are at least 95%, 96%, 97%, 98%, 99%, or 100% (mass / mass) pure. In some embodiments, the antibody or antigen-binding fragment thereof is purified.

[0092] As an alternative to producing hybridomas that secrete monoclonal antibodies, a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) can be screened using the polypeptides described herein, thereby isolating immunoglobulin library members that bind to the polypeptide, to identify and isolate monoclonal antibodies against the polypeptide. Techniques and commercially available kits for generating and screening phage display libraries are well known to those of skill in the art. In addition, examples of methods and reagents particularly suitable for use in generating and screening antibody or antigen-binding protein display libraries can be found in the literature. Thus, the epitopes described herein can be used to screen for other antibodies that can be used therapeutically, diagnostically, or as research tools.

[0093] The antibodies provided herein may be conjugated to a chemical moiety. The chemical moiety can be, inter alia, a polymer, a radionuclide, or a cytotoxic agent. In some embodiments, this may be referred to as an antibody-drug conjugate. In some embodiments, the chemical moiety is a polymer that increases the half-life of the antibody molecule in the body of a subject. Suitable polymers include, but are not limited to, polyethylene glycol (PEG) (e.g., PEG having a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa, or 40 kDa), dextran, and monomethoxypolyethylene glycol (mPEG). Lee et al. (1999) (Bioconj. Chem. 10:973-981) disclose PEG-conjugated single-chain antibodies. Wen et al. (2001) (Bioconj. Chem. 12:545-553) disclose conjugating an antibody with PEG conjugated to a radioactive metal chelator (diethylenetriaminepentaacetic acid (DTPA)). Examples of chemical moieties include, but are not limited to, mitotic inhibitors such as calicheamicin (e.g., ozogamicin), monomethyl auristatin E, and mertansine. Other examples include, but are not limited to, biologically active microtubule inhibitors, alkylating agents, and DNA minor groove binders. Other examples are provided herein and below. The chemical moiety can be linked to the antibody via a linking group (maleimide), a cleavable linker, such as a cathepsin-cleavable linker (valine-citrulline), and in some embodiments, one or more spacers (e.g., para-aminobenzyl carbamate). Without being bound by any particular theory, when the antibody conjugate binds to Claudin 18.2, it can internalize, and the chemical moiety can kill the cell or inhibit its proliferation. In some embodiments, the cell is a gastric tumor cell.

[0094] The antibodies and antibody fragments of the present disclosure 99 Tc, 90 Y, 111 In, 32 P, 14 C, 125 I, 3 H, 131 I,11 C, 15 O, 13 N, 18 F, 35 S, 51 Cr, 57 To, 226 Ra, 60 Co, 59 Fe, 57 Se, 152 Eu, 67 CU, 217 Ci, 211 At, 212 Pb, 47 Sc, 109 Pd, 234 Th, and 40 K, 157 Gd, 55 Mn, 52 Tr and 56 may be combined with labels such as Fe.

[0095] Antibodies and antibody fragments may be conjugated to a fluorescent or chemiluminescent label, including fluorophores such as rare earth chelates, fluorescein and its derivatives, rhodamine and its derivatives, isothiocyanate, phycoerythrin, phycocyanin, allophycocyanin, o-phthalaldehyde, fluorescamine, 152 Eu, dansyl, umbelliferone, luciferin, luminal label, isoluminal label, aromatic acridinium ester label, imidazole label, acridimium salt label, oxalate ester label, aequorin label, 2,3-dihydrophthalazinedione, biotin / avidin, spin labels and stable free radicals.

[0096] The antibody or antibody fragment molecule may be conjugated to a cytotoxic agent, such as diphtheria toxin, the A chain of Pseudomonas aeruginosa exotoxin A, ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii protein and compounds (e.g., fatty acids), dianthin proteins, Phytolacca americana proteins PAPI, PAPII, and PAP-S, Momordica charantia inhibitor, curcin, crotin, Saponaria officinalis inhibitor, mitogellin, restrictocin, phenomycin, and enomycin.

[0097] Any method known in the art for conjugating the antibodies or antibody molecules of the present disclosure to various moieties can be used, including those described by Hunter et al. (1962) Nature 144:945; David et al. (1974) Biochemistry 13:1014; Pain et al. (1981) J. Immunol. Meth. 40:219; and Nygren, J. (1982) Histochem. and Cytochem. 30:407. Methods for conjugating antibodies are well known and conventional in the art.

[0098] The antibodies provided herein can also be incorporated into chimeric antigen receptors (“CARs”) that can be used, for example, in CAR-T cells. In some embodiments, the extracellular domain of the CAR may be an antibody or an antigen-binding fragment thereof provided herein. In some embodiments, the antibody or its antigen-binding fragment is in scFv format. CAR-T cells are a type of treatment that modifies a patient's T cells to attack cancer cells. The T cells are collected from the patient's blood. Then, the gene for a special receptor that binds to a specific protein on the patient's cancer cells is added in the laboratory. In some embodiments, this receptor binds to Claudin 18.2 using the binding region of an antibody provided herein. Then, CAR-T cells comprising the Claudin 18.2 antibody or its antigen-binding fragment can be used to treat tumors or gastric tumors as described herein.

[0099] As used herein, the term “recombinant antibody” refers to an antibody that does not occur naturally. In some embodiments, the term “recombinant antibody” refers to an antibody that is not isolated from a human subject.

[0100] In some embodiments, an antibody (e.g., an anti-Claudin 18.2 antibody), or an antigen-binding fragment thereof, is provided herein. In some embodiments, the antibody or an antigen-binding fragment thereof is a recombinant antibody that binds to the Claudin 18.2 protein. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a monoclonal antibody. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a humanized antibody. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a chicken antibody. In some embodiments, the antibody or an antigen fragment thereof is generated by inducing an immune response against Claudin 18.2 in a chicken. In some embodiments, the antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein is a scFv antibody.

[0101] In some embodiments, the antibody or an antigen-binding fragment thereof binds to the human Claudin 18.2 protein. In some embodiments, the antibody or an antigen-binding fragment thereof recognizes the Claudin 18.2 protein in its native (non-denatured) conformation. In some embodiments, the antibody or an antigen-binding fragment thereof does not specifically bind to the denatured Claudin 18.2 protein. In some embodiments, the antibody, or an antigen-binding fragment thereof, binds to a Claudin 18.2 protein comprising the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

[0102] [Table 2]

[0103] In some embodiments, the antibody or an antigen-binding fragment thereof does not specifically bind to Claudin 18.1.

[0104] In some embodiments, the antibody or antigen-binding fragment thereof comprises a peptide having an amino acid selected from the following table.

[0105]

Table 3

[0106] In some embodiments, the antibody or antigen-binding fragment comprises a light chain comprising light chain complementarity determining region 1 (LCDR1), light chain complementarity determining region 2 (LCDR2), and light chain complementarity determining region 3 (LCDR3). In some embodiments, the antibody or antigen-binding fragment comprises a light chain variable (V L ) region comprising LCDR1, LCDR2, and LCDR3. In some embodiments, the antibody or antigen-binding fragment comprises a light chain comprising a light chain variable (V L ) region comprising LCDR1, LCDR2, and LCDR3.

[0107] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising heavy chain complementarity determining region 1 (HCDR1), heavy chain complementarity determining region 2 (HCDR2), and heavy chain complementarity determining region 3 (HCDR3). In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable (V H ) region comprising HCDR1, HCDR2, and HCDR3. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain comprising a heavy chain variable (V H ) region comprising HCDR1, HCDR2, and HCDR3.

[0108] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain CDR or heavy chain CDR having the amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, or SEQ ID NO: 33.

[0109] Different CDR motifs can be combined in any combination, including those not shown in the table above. For example, the following embodiments are provided as non-limiting examples of such combinations.

[0110] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain CDR having the sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 23, or SEQ ID NO: 24. In some embodiments, the antibody or antigen-binding fragment comprises a light chain variable (V L ) region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0111] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain CDR having the sequence of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain variable (V H ) region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0112] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain having LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the sequence of SEQ ID NO: 17, LCDR2 has the sequence of SEQ ID NO: 18, and LCDR3 has the sequence of SEQ ID NO: 19.

[0113] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain having LCDR1, LCDR2, and LCDR3, where LCDR1 has the sequence of SEQ ID NO: 17, LCDR2 has the sequence of SEQ ID NO: 24, and LCDR3 has the sequence of SEQ ID NO: 19.

[0114] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain having LCDR1, LCDR2, and LCDR3, where LCDR1 has the sequence of SEQ ID NO: 23, LCDR2 has the sequence of SEQ ID NO: 18, and LCDR3 has the sequence of SEQ ID NO: 19.

[0115] In some embodiments, the antibody or antigen-binding fragment thereof comprises a light chain having LCDR1, LCDR2, and LCDR3, where LCDR1 has the sequence of SEQ ID NO: 23, LCDR2 has the sequence of SEQ ID NO: 24, and LCDR3 has the sequence of SEQ ID NO: 19.

[0116] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 22.

[0117] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 27.

[0118] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 30.

[0119] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 33.

[0120] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 22.

[0121] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 27.

[0122] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 30.

[0123] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 33.

[0124] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 22.

[0125] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 27.

[0126] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 30.

[0127] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 33.

[0128] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 22.

[0129] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 27.

[0130] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 30.

[0131] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 20, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 33.

[0132] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 22.

[0133] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 27.

[0134] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 30.

[0135] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 33.

[0136] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 22.

[0137] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 27.

[0138] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 30.

[0139] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 33.

[0140] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 22.

[0141] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 27.

[0142] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 30.

[0143] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 33.

[0144] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 22.

[0145] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 27.

[0146] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 30.

[0147] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 25, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 33.

[0148] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 22.

[0149] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 27.

[0150] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 30.

[0151] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 33.

[0152] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 22.

[0153] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 27.

[0154] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 30.

[0155] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 33.

[0156] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 22.

[0157] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 27.

[0158] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 30.

[0159] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 33.

[0160] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 22.

[0161] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 27.

[0162] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 30.

[0163] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 28, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 33.

[0164] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 22.

[0165] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 27.

[0166] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 30.

[0167] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 21, and HCDR3 has the sequence of SEQ ID NO: 33.

[0168] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 22.

[0169] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 27.

[0170] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 30.

[0171] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 26, and HCDR3 has the sequence of SEQ ID NO: 33.

[0172] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 22.

[0173] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 27.

[0174] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 30.

[0175] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 29, and HCDR3 has the sequence of SEQ ID NO: 33.

[0176] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 22.

[0177] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 27.

[0178] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 30.

[0179] In some embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain having HCDR1, HCDR2, and HCDR3, where HCDR1 has the sequence of SEQ ID NO: 31, HCDR2 has the sequence of SEQ ID NO: 32, and HCDR3 has the sequence of SEQ ID NO: 33.

[0180] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22].

[0181] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0182] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0183] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0184] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0185] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0186] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0187] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0188] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0189] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0190] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0191] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0192] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0193] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0194] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0195] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0196] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0197] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0198] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30].

[0199] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0200] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0201] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0202] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0203] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0204] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0205] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0206] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0207] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0208] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0209] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0210] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0211] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0212] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0213] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0214] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0215] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0216] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0217] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0218] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0219] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0220] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0221] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0222] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0223] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0224] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0225] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0226] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0227] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0228] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22].

[0229] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0230] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0231] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0232] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0233] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0234] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0235] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0236] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0237] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0238] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0239] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0240] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0241] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0242] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0243] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0244] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0245] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0246] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0247] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0248] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0249] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0250] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0251] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0252] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0253] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0254] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0255] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0256] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0257] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0258] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0259] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0260] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0261] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0262] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0263] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0264] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22].

[0265] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0266] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0267] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0268] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0269] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0270] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0271] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0272] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0273] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0274] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0275] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0276] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0277] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0278] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0279] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0280] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0281] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0282] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0283] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0284] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0285] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0286] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0287] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0288] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0289] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0290] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0291] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0292] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0293] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0294] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0295] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0296] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0297] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0298] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0299] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0300] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0301] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0302] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0303] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0304] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0305] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0306] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0307] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0308] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0309] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0310] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0311] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0312] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0313] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0314] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0315] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0316] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0317] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0318] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30].

[0319] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0320] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0321] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0322] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0323] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0324] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0325] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0326] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30].

[0327] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0328] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22].

[0329] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0330] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0331] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0332] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0333] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0334] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0335] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0336] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22].

[0337] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0338] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0339] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0340] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0341] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0342] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0343] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0344] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0345] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0346] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0347] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0348] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0349] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0350] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0351] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0352] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0353] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0354] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0355] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0356] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0357] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0358] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0359] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0360] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0361] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0362] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0363] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0364] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0365] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0366] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0367] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0368] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0369] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0370] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0371] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0372] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0373] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0374] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0375] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0376] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0377] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0378] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0379] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0380] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0381] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0382] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0383] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0384] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0385] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0386] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0387] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0388] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0389] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0390] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0391] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0392] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0393] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0394] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0395] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0396] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0397] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0398] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0399] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0400] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0401] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0402] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0403] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0404] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0405] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0406] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0407] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0408] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0409] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0410] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0411] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0412] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0413] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

[0414] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30].

[0415] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0416] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0417] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0418] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0419] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0420] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0421] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0422] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 30].

[0423] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 33].

[0424] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3 [wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 [wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 22].

[0425] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0426] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0427] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0428] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0429] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0430] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0431] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0432] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22.

[0433] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 27.

[0434] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 30.

[0435] In some embodiments, the antibody or antigen-binding fragment thereof comprises: (i) a light chain variable region comprising LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33.

[0436] In some embodiments, the antibody or antigen-binding fragment thereof comprises one or more peptides having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13, or variants thereof.

[0437] [Table 4]

[0438] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a light chain variable (V L) includes a domain, provided that V L The domain includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0439] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V domain having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 L includes a domain, provided that, V L The domain includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0440] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V domain having an amino acid sequence with at least 90% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 L includes a domain, provided that, V L The domain includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V domain having an amino acid sequence with at least 91% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 L includes a domain, provided that, V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes an amino acid sequence having at least 92% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes an amino acid sequence having at least 93% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes an amino acid sequence having at least 94% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 98% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, and has a V L region, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 99% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, and has a V L region, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0441] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, and has a V L region, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0442] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 90% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 91% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 92% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 92% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 92% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 92% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 93% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 V L region, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 94% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 V L region, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 V L region, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes an amino acid sequence having at least 96% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes an amino acid sequence having at least 97% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region that includes an amino acid sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence that has at least 99% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, and has a V L region, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0443] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or any variant thereof having 1 to 10 substitutions, deletions, or insertions, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0444] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or any variant thereof having 1 to 10 conservative substitutions, provided that the V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0445] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V L region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13.

[0446] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a V L region having the amino acid sequence of SEQ ID NO: 5, or a variant thereof, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0447] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a V L region having the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or a variant thereof, provided that the V L region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19.

[0448] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a heavy chain variable (V H) includes a domain, provided that V H The domain includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0449] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H includes a domain, provided that V H The domain includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0450] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 90% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H includes a domain, provided that V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 91% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 92% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 93% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 94% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence having at least 95% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein, has an amino acid sequence having at least 96% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence that has at least 97% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence that has at least 98% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has an amino acid sequence that has at least 99% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 V H region, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0451] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0452] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 90% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 91% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 92% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 93% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V H region that includes an amino acid sequence having at least 94% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V H region that includes an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V H region that includes an amino acid sequence having at least 96% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 97% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 98% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V region having an amino acid sequence with at least 99% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 H region, provided that the V HThe region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0453] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V H region having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, or any variant thereof having 1 to 10 substitutions, deletions, or insertions, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0454] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein, a V H region having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12, or any variant thereof having 1 to 10 conservative substitutions, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33.

[0455] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein has a V H region having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12.

[0456] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a V H region having the amino acid sequence of SEQ ID NO: 4, or a variant thereof, provided that the V H region comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22.

[0457] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a V H region having the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 8, or a variant thereof, provided that the V H region comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 27.

[0458] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a V H region having the amino acid sequence of SEQ ID NO: 10, or a variant thereof, provided that the V H region comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 30.

[0459] In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a V H region having the amino acid sequence of SEQ ID NO: 12, or a variant thereof, provided that the V H region comprises HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 33.

[0460] In some embodiments, the antibody or antigen-binding fragment thereof comprises SEQ ID NO: 4 and SEQ ID NO: 5, or the CDR regions thereof.

[0461] In some embodiments, the antibody or antigen-binding fragment thereof comprises SEQ ID NO: 6 and SEQ ID NO: 7, or the CDR regions thereof.

[0462] In some embodiments, the antibody or antigen-binding fragment thereof comprises SEQ ID NO: 8 and SEQ ID NO: 9, or the CDR regions thereof.

[0463] In some embodiments, the antibody or antigen-binding fragment thereof comprises SEQ ID NO: 10 and SEQ ID NO: 11, or the CDR regions thereof.

[0464] In some embodiments, the antibody or antigen-binding fragment thereof comprises SEQ ID NO: 12 and SEQ ID NO: 13, or the CDR regions thereof.

[0465] In some embodiments, the antibody or antigen-binding fragment is: (i) a V L region comprising LCDR1, LCDR2, and LCDR3 [where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V HA region, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33].

[0466] In some embodiments, the antibody or antigen-binding fragment is: (i) a V L region having the amino acid sequence of SEQ ID NO: 5, or a variant thereof, provided that the V L region comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V H region having the amino acid sequence of SEQ ID NO: 4, or a variant thereof, provided that the V H region comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 22].

[0467] In some embodiments, the antibody or antigen-binding fragment is: (i) a V L region having the amino acid sequence of SEQ ID NO: 7, or a variant thereof, provided that the V L region comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V H region having the amino acid sequence of SEQ ID NO: 6, or a variant thereof, provided that the V H region comprises HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 27].

[0468] In some embodiments, the antibody or antigen-binding fragment has: (i) a V L region, or a variant thereof, [wherein V L the region comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO:23; LCDR2 has the amino acid sequence of SEQ ID NO:24; and LCDR3 has the amino acid sequence of SEQ ID NO:19; and (ii) a V having the amino acid sequence of SEQ ID NO:8 H region, or a variant thereof, [wherein V H The region comprises HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO:25; HCDR2 has the amino acid sequence of SEQ ID NO:26; and HCDR3 has the amino acid sequence of SEQ ID NO:27.

[0469] In some embodiments, the antibody or antigen-binding fragment has: (i) a V L region, or a variant thereof, [wherein V L the region comprises LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO:23; LCDR2 has the amino acid sequence of SEQ ID NO:24; and LCDR3 has the amino acid sequence of SEQ ID NO:19; and (ii) a V having the amino acid sequence of SEQ ID NO:10 H region, or a variant thereof, [wherein V H The region comprises HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO:28; HCDR2 has the amino acid sequence of SEQ ID NO:29; and HCDR3 has the amino acid sequence of SEQ ID NO:30.

[0470] In some embodiments, the antibody or antigen-binding fragment has: (i) a V L region, or a variant thereof, [wherein V LThe region includes LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and the LCDR3 sequence has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V having the amino acid sequence of SEQ ID NO: 12 H region, or a variant thereof, provided that the V H region includes HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and the HCDR3 sequence has the amino acid sequence of SEQ ID NO: 33].

[0471] In some embodiments, LCDR1 is replaced with any of other LCDR1 sequences. In some embodiments, LCDR2 is replaced with any of other LCDR2 sequences. In some embodiments, LCDR3 is replaced with any of other LCDR3 sequences. In some embodiments, HCDR1 is replaced with any of other LCDR1 sequences. In some embodiments, HCDR2 is replaced with any of other LCDR2 sequences. In some embodiments, HCDR3 is replaced with any of other LCDR3 sequences.

[0472] In some embodiments, the antibody or an antigen-binding fragment thereof is a V H region and a V L region, where the V H region includes the sequence of SEQ ID NO: 4, and the V L region includes the sequence of SEQ ID NO: 5.

[0473] In some embodiments, the antibody or an antigen-binding fragment thereof is a V H region and a V L region, where the V H region includes the sequence of SEQ ID NO: 4, and the V L region includes the sequence of SEQ ID NO: 7.

[0474] In some embodiments, the antibody or an antigen-binding fragment thereof is a VH Region and V L contains the region, where V H the region contains the sequence of SEQ ID NO: 4, and V L the region contains the sequence of SEQ ID NO: 9.

[0475] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L contains the region, where V H the region contains the sequence of SEQ ID NO: 4, and V L the region contains the sequence of SEQ ID NO: 11.

[0476] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L contains the region, where V H the region contains the sequence of SEQ ID NO: 4, and V L the region contains the sequence of SEQ ID NO: 13.

[0477] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L contains the region, where V H the region contains the sequence of SEQ ID NO: 6, and V L the region contains the sequence of SEQ ID NO: 5.

[0478] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L contains the region, where V H the region contains the sequence of SEQ ID NO: 6, and V L the region contains the sequence of SEQ ID NO: 7.

[0479] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L contains the region, where V H the region contains the sequence of SEQ ID NO: 6, and V L the region contains the sequence of SEQ ID NO: 9.

[0480] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 6, and the V L region comprises the sequence of SEQ ID NO: 11.

[0481] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 6, and the V L region comprises the sequence of SEQ ID NO: 13.

[0482] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 8, and the V L region comprises the sequence of SEQ ID NO: 5.

[0483] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 8, and the V L region comprises the sequence of SEQ ID NO: 7.

[0484] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 8, and the V L region comprises the sequence of SEQ ID NO: 9.

[0485] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 8, and the V L region comprises the sequence of SEQ ID NO: 11.

[0486] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 8, and the V L region comprises the sequence of SEQ ID NO: 13.

[0487] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 10, and the V L region comprises the sequence of SEQ ID NO: 5.

[0488] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 10, and the V L region comprises the sequence of SEQ ID NO: 7.

[0489] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 10, and the V L region comprises the sequence of SEQ ID NO: 9.

[0490] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V H region comprises the sequence of SEQ ID NO: 10, and the V L region comprises the sequence of SEQ ID NO: 11.

[0491] In some embodiments, the antibody or antigen-binding fragment thereof comprises a V H region and a V L region, where the V HThe region includes the array of array number 10, and V L The region includes the array of array number 13.

[0492] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L region, where V H region includes the array of array number 12, and V L region includes the array of array number 5.

[0493] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L region, where V H region includes the array of array number 12, and V L region includes the array of array number 7.

[0494] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L region, where V H region includes the array of array number 12, and V L region includes the array of array number 9.

[0495] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L region, where V H region includes the array of array number 12, and V L region includes the array of array number 11.

[0496] In some embodiments, the antibody or antigen-binding fragment thereof is V H region and V L region, where V H region includes the array of array number 12, and V L region includes the array of array number 13.

[0497] In addition to these specific combinations, V H region and VL All of the regions can be combined with each other.

[0498] In some embodiments, the antibody or antigen-binding fragment thereof comprises a peptide having an amino acid sequence shown in any of SEQ ID NOs: 4-13 and SEQ ID NOs: 17-33.

[0499] In some embodiments, the antibody or antigen-binding fragment thereof comprises any of the foregoing sequences or any of the foregoing variants.

[0500] In some embodiments, the antibody or antigen-binding fragments thereof comprise variants of the amino acid sequences of SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13.

[0501] V L and V H The sequences can be in any format, including, but not limited to, the scFv format in which the V L and V H regions are linked by a peptide linker. As provided herein, the various variable regions (V H or V L ) may be linked by a peptide linker or rather adjacent sequences without being linked by a peptide linker. Examples of peptides that can be used to link the various peptides provided herein include, but are not limited to: GQSSRSSGGGGSSGGGGS (SEQ ID NO: 14); (GGGGS) n (SEQ ID NO: 15); (GGGGA) n (SEQ ID NO: 16), or any combination thereof, where each n is independently 1-5. In some embodiments, the variable regions are linked by a peptide linker. In some embodiments, the peptide linker is GQSSRSSGGGGSSGGGGS (SEQ ID NO: 14); (GGGGS) n (SEQ ID NO: 15); (GGGGA) n(SEQ ID NO: 16), or an array of any combination thereof, where each n is independently from 1 to 5. The linked peptide form is of formula V H -Z-V L or V L -Z-V H [wherein, Z is a peptide linker] can be represented. In some embodiments, Z is GQSSRSSGGGGSSGGGGS (SEQ ID NO: 14); (GGGGS) n (SEQ ID NO: 15); (GGGGA) n (SEQ ID NO: 16), or any combination thereof, where each n is independently from 1 to 5. In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a peptide linker that does not contain the sequence of GQSSRSSGGGGSSGGGGS (SEQ ID NO: 14). In some embodiments, the antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein comprises a peptide linker that does not contain the sequence of (GGGGS) n (SEQ ID NO: 15); (GGGGA) n (SEQ ID NO: 16) or any combination thereof, where each n is independently from 1 to 5. In some embodiments, the variable regions are not linked by a peptide linker.

[0502] In some embodiments, the antibody or antigen-binding fragment thereof comprises a variant of the amino acid sequence of SEQ ID NO: 14, 15, or 16.

[0503] Furthermore, the antibodies provided herein may be multispecific antibodies in that the antibody is capable of having multiple binding regions that target different proteins or target the same protein at different epitopes. In some embodiments, the antibody or antigen-binding fragment thereof is a bispecific anti-CD3 x anti-CLDN18.2 antibody or a trispecific anti-CD3 x anti-CD28 x anti-CLDN 18.2 antibody.

[0504] In some embodiments, the antibody or antigen-binding fragment thereof binds to residues E56, N153, Y155, M158, and G159 of the Claudin 18.2 protein. In some embodiments, the antibody or antigen-binding fragment thereof binds to residues V40, E56, N153, Y155, M158, G159, and G160 of the Claudin 18.2 protein.

[0505] In some embodiments, provided is a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein.

[0506] In some embodiments, provided is a vector comprising a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein.

[0507] In some embodiments, provided is a cell comprising a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein. In some embodiments, provided is a cell comprising a vector comprising a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein.

[0508] Pharmaceutical composition In some embodiments, provided is a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein.

[0509] In some embodiments, provided is a pharmaceutical composition comprising a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof that binds to the Claudin 18.2 protein provided herein.

[0510] In some embodiments, there is provided a pharmaceutical composition comprising a vector comprising a nucleic acid molecule encoding an antibody or an antigen-binding fragment thereof that binds to the Claudin 18.2 protein described herein.

[0511] In some embodiments, to produce the pharmaceutical composition or sterile pharmaceutical composition of the anti-Claudin 18.2 antibody or other protein provided herein, the antibody or antigen-binding fragment thereof, or other protein provided herein is mixed with a pharmaceutically acceptable carrier or excipient. See, for example, Remington’s Pharmaceutical Sciences and U.S.Pharmacopeia: National Formulary, Mack Publishing Company, Easton, PA (1984).

[0512] Formulations of therapeutic and diagnostic agents can be prepared by mixing them, for example, in the form of lyophilized powder, slurry, aqueous solution or suspension, with an acceptable carrier, excipient, or stabilizer (see, e.g., Hardman et al. (2001) Goodman and Gilman’s The Pharmacological Basis of Therapeutics, McGraw-Hill, New York, NY; Gennaro (2000) Remington: The Science and Practice of Pharmacy, Lippincott, Williams, and Wilkins, New York, NY; Avis et al. (eds.) (1993) Pharmaceutical Dosage Forms: Parenteral Medications, Marcel Dekker, NY; Lieberman et al. (eds.) (1990) Pharmaceutical Dosage Forms: Tablets, Marcel Dekker, NY; Lieberman et al. (eds.) (1990) Pharmaceutical Dosage Forms: Disperse Systems, Marcel Dekker, NY; Weiner and Kotkoskie (2000) Excipient Toxicity and Safety, Marcel Dekker, Inc., New York, NY). In some embodiments, the antibody is diluted to an appropriate concentration in sodium acetate solution pH 5-6, and NaCl or sucrose is added for osmotic pressure. Additional agents such as polysorbate 20 or polysorbate 80 may be added to enhance stability.

[0513] The toxicity and therapeutic efficacy of pharmaceutical compositions administered alone or in combination with another agent can be determined, for example, in cell cultures or experimental animals, by standard pharmaceutical procedures for determining, e.g., the ...

Claims

1. A recombinant antibody, or an antigen-binding fragment thereof, that binds to the Claudin 18.2 protein in its native conformation.

2. The antibody or antigen-binding fragment thereof according to claim 1, wherein the Claudin 18.2 protein is a human Claudin 18.2 protein.

3. The antibody or antigen-binding fragment thereof according to claim 1, which is a humanized antibody.

4. The antibody or antigen-binding fragment thereof according to claim 1, which is a chicken antibody.

5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, which is a monoclonal antibody.

6. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, which is a scFv antibody.

7. The antibody or antigen-binding fragment comprises a light chain variable (V Ｌ ) region that includes a light chain CDR1 (LCDR1), a light chain CDR2 (LCDR2), and a light chain CDR3 (LCDR3), where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19, the antibody or antigen-binding fragment thereof according to any one of claims 1 to 6.

8. The antibody or antigen-binding fragment thereof has a V region having an amino acid sequence having at least 85% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO:

13. Ｌ The antibody or antigen-binding fragment thereof according to claim 7, comprising a region.

9. The antibody or antigen-binding fragment thereof has a V region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% homology to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO:

13. Ｌ The antibody or antigen-binding fragment thereof according to claim 7, comprising the region.

10. The antibody or antigen-binding fragment thereof has a V region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO:

13. Ｌ The antibody or antigen-binding fragment thereof according to claim 7, comprising a region.

11. The antibody or its antigen-binding fragment is a V having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11 or SEQ ID NO: 13 Ｌ The antibody or its antigen-binding fragment according to claim 7, comprising a region or any variant thereof having 1 to 10 substitutions, deletions or insertions.

12. The antibody or its antigen-binding fragment comprises a V region having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13, or any variant thereof having 1 to 10 conservative substitutions, the antibody or its antigen-binding fragment according to claim 7. Ｌ region, or any variant thereof having 1 to 10 conservative substitutions, the antibody or its antigen-binding fragment according to claim 7.

13. The antibody or antigen-binding fragment thereof is a V having the amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, or SEQ ID NO: 13 Ｌ region-containing antibody or antigen-binding fragment thereof according to claim 7.

14. The antibody or antigen-binding fragment thereof comprises a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19, the antibody or antigen-binding fragment thereof according to any one of claims 7 to 13. Ｌ The antibody or antigen-binding fragment thereof according to any one of claims 7 to 13, which comprises a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO:

19.

15. The antibody or its antigen-binding fragment comprises a V region containing LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 comprises the amino acid sequence of SEQ ID NO: 19, the antibody or its antigen-binding fragment according to any one of claims 7 to 13. Ｌ The antibody or its antigen-binding fragment according to any one of claims 7 to 13, comprising a V region containing LCDR1, LCDR2, and LCDR3, wherein LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 comprises the amino acid sequence of SEQ ID NO:

19.

16. The antibody, or antigen-binding fragment, comprises a heavy-chain variable (V Ｈ ) region that includes heavy-chain CDR1 (HCDR1), heavy-chain CDR2 (HCDR2), and heavy-chain CDR3 (HCDR3), wherein HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33, the antibody, or antigen-binding fragment thereof, according to any one of claims 1 to 15.

17. The antibody, or antigen-binding fragment thereof, has a V region having an amino acid sequence with at least 85% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO:

12. Ｈ The antibody or antigen-binding fragment thereof according to claim 16, comprising a region.

18. The antibody, or antigen-binding fragment thereof, has a V region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homology to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 Ｈ The antibody or antigen-binding fragment thereof according to claim 16, comprising the region.

19. The antibody or antigen-binding fragment thereof has a V region having an amino acid sequence with at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO:

12. Ｈ The antibody or antigen-binding fragment thereof according to claim 16, comprising a V region.

20. The antibody or antigen-binding fragment thereof is a V having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 Ｈ region, or an antibody according to claim 16, or an antigen-binding fragment thereof, comprising any variant thereof having 1 to 10 substitutions, deletions, or insertions.

21. The antibody or antigen-binding fragment thereof is a V having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10 or SEQ ID NO: 12 Ｈ region, or the antibody according to claim 16, or an antigen-binding fragment thereof, comprising any variant thereof having 1 to 10 conservative substitutions.

22. The antibody, or antigen-binding fragment thereof, has a V amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12 Ｈ The antibody, or antigen-binding fragment thereof, according to claim 16, comprising a Ｈ region

23. The antibody or antigen-binding fragment thereof comprises a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, the antibody or antigen-binding fragment thereof according to any one of claims 16-22. Ｈ ​

24. The antibody or antigen-binding fragment thereof comprises a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27, the antibody or antigen-binding fragment thereof according to any one of claims 16 to 22. Ｈ The antibody or antigen-binding fragment thereof according to any one of claims 16 to 22, comprising a V region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO:

27.

25. The antibody or antigen-binding fragment thereof comprises a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30, the antibody or antigen-binding fragment thereof according to any one of claims 16-22. Ｈ The antibody or antigen-binding fragment thereof according to any one of claims 16-22, comprising a V region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO:

30.

26. The antibody or antigen-binding fragment thereof comprises a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33, the antibody or antigen-binding fragment thereof according to any one of claims 16 to 22. Ｈ The antibody or antigen-binding fragment thereof according to any one of claims 16 to 22, comprising a V region comprising HCDR1, HCDR2, and HCDR3, wherein HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO:

33.

27. The antibody or antigen-binding fragment comprises (i) a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33, the antibody or antigen-binding fragment thereof according to any one of claims 1 to 26. Ｌ region [where LCDR1 has the amino acid sequence of SEQ ID NO: 17 or SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, Ｈ region [where HCDR1 has the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 25, SEQ ID NO: 28, or SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 29, or SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, SEQ ID NO: 27, SEQ ID NO: 30, or SEQ ID NO: 33] comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 26.

28. The antibody or antigen-binding fragment comprises (i) a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22, the antibody or antigen-binding fragment thereof according to claim 27. Ｌ region [where LCDR1 has the amino acid sequence of SEQ ID NO: 17; LCDR2 has the amino acid sequence of SEQ ID NO: 18; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, Ｈ region [where HCDR1 has the amino acid sequence of SEQ ID NO: 20; HCDR2 has the amino acid sequence of SEQ ID NO: 21; and HCDR3 has the amino acid sequence of SEQ ID NO: 22], the antibody or antigen-binding fragment thereof according to claim 27.

29. The antibody or antigen-binding fragment thereof comprises (i) a V region having the amino acid sequence of SEQ ID NO: 5, or a variant thereof, and (ii) a V region having the amino acid sequence of SEQ ID NO: 4, or a variant thereof, as claimed in claim 28. Ｌ region, or a variant thereof, and (ii) a V region having the amino acid sequence of SEQ ID NO: 4, or a variant thereof, as claimed in claim 28. Ｈ region, or a variant thereof, as claimed in claim 28.

30. The antibody or antigen-binding fragment comprises (i) a V region comprising LCDR1, LCDR2 and LCDR3 [where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3 [where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27], the antibody according to claim 27, or an antigen-binding fragment thereof. Ｌ The antibody or antigen-binding fragment according to claim 27, comprising (i) a V region comprising LCDR1, LCDR2 and LCDR3 [where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3 [where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27]. Ｈ The antibody or antigen-binding fragment according to claim 27, comprising (i) a V region comprising LCDR1, LCDR2 and LCDR3 [where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3 [where HCDR1 has the amino acid sequence of SEQ ID NO: 25; HCDR2 has the amino acid sequence of SEQ ID NO: 26; and HCDR3 has the amino acid sequence of SEQ ID NO: 27].

31. The antibody or antigen-binding fragment has: (i) a V region having the amino acid sequence of SEQ ID NO: 7, or a variant thereof; and (ii) a V region having the amino acid sequence of SEQ ID NO: 6, or a variant thereof, the antibody or antigen-binding fragment according to claim 30. Ｌ region, or a variant thereof; and (ii) a V region having the amino acid sequence of SEQ ID NO: 6, or a variant thereof, the antibody or antigen-binding fragment according to claim 30. Ｈ region, or a variant thereof, the antibody or antigen-binding fragment according to claim 30.

32. The antibody or antigen-binding fragment has a V region having the amino acid sequence of SEQ ID NO: 9, or a variant thereof; and a V region having the amino acid sequence of SEQ ID NO: 8, or a variant thereof, as claimed in claim 30, or an antigen-binding fragment thereof. Ｌ region, or a variant thereof; and (ii) a V region having the amino acid sequence of SEQ ID NO: 8, or a variant thereof, Ｈ The antibody or antigen-binding fragment according to claim 30, or an antigen-binding fragment thereof, comprising a region, or a variant thereof.

33. The antibody or antigen-binding fragment comprises (i) a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO: 30, the antibody according to claim 27, or an antigen-binding fragment thereof. Ｌ The antibody or antigen-binding fragment according to claim 27, or an antigen-binding fragment thereof, comprising (i) a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO:

30. Ｈ The antibody or antigen-binding fragment according to claim 27, or an antigen-binding fragment thereof, comprising (i) a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 28; HCDR2 has the amino acid sequence of SEQ ID NO: 29; and HCDR3 has the amino acid sequence of SEQ ID NO:

30.

34. The antibody or antigen-binding fragment thereof comprises (i) a V region having the amino acid sequence of SEQ ID NO: 11, or a variant thereof; and (ii) a V region having the amino acid sequence of SEQ ID NO: 10, or a variant thereof, the antibody or antigen-binding fragment thereof according to claim 33. Ｌ region, or a variant thereof; and (ii) a V region having the amino acid sequence of SEQ ID NO: 10, or a variant thereof, the antibody or antigen-binding fragment thereof according to claim 33. Ｈ region, or a variant thereof, the antibody or antigen-binding fragment thereof according to claim 33.

35. The antibody or antigen-binding fragment comprises (i) a V region comprising LCDR1, LCDR2, and LCDR3, where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO: 33, the antibody or antigen-binding fragment thereof according to claim 27. Ｌ region [where LCDR1 has the amino acid sequence of SEQ ID NO: 23; LCDR2 has the amino acid sequence of SEQ ID NO: 24; and LCDR3 has the amino acid sequence of SEQ ID NO: 19]; and (ii) a V region comprising HCDR1, HCDR2, and HCDR3, where HCDR1 has the amino acid sequence of SEQ ID NO: 31; HCDR2 has the amino acid sequence of SEQ ID NO: 32; and HCDR3 has the amino acid sequence of SEQ ID NO:

33. Ｈ The antibody or antigen-binding fragment thereof according to claim 27.

36. The antibody or antigen-binding fragment thereof comprises (i) a V region having the amino acid sequence of SEQ ID NO: 13, or a variant thereof; and (ii) a V region having the amino acid sequence of SEQ ID NO: 12, or a variant thereof, as claimed in claim 35, or an antigen-binding fragment thereof. Ｌ region, or a variant thereof; and (ii) a V Ｈ region, or a variant thereof, as claimed in claim 35, or an antigen-binding fragment thereof.

37. The antibody, or antigen-binding fragment thereof, is a V region and a V region not linked by a linker Ｌ region and V Ｈ region, and the antibody or antigen-binding fragment thereof according to any one of claims 27 to 36.

38. The antibody, or antigen-binding fragment thereof, is a V region and a V region linked by a peptide linker, and is the antibody, or antigen-binding fragment thereof, according to any one of claims 7 to 24. Ｌ region and V Ｈ region.

39. The peptide linker comprises the sequence GQSSRSSGGGGSSGGGG S (SEQ ID NO: 14); (GGGG S) ｎ (SEQ ID NO: 15); (GGGG A) ｎ (SEQ ID NO: 16), or any combination thereof, wherein each n is independently from 1 to 5, the antibody or antigen-binding fragment thereof according to claim 38.

40. The antibody or antigen-binding fragment thereof according to claim 38, wherein the peptide linker does not contain the sequence of GQSSRSSGGGGSSGGGGSS (SEQ ID NO: 14).

41. The antibody, or antigen-binding fragment thereof, according to any one of claims 1 to 40, further comprising at least one additional peptide that binds to a different target protein.

42. The antibody, or antigen-binding fragment thereof, according to claim 41, wherein the different target protein is CD3 or CD28.

43. The antibody, or antigen-binding fragment thereof, according to claim 40 or claim 41, wherein the at least one additional peptide is an antibody or antigen-binding fragment thereof.

44. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 43, wherein the antibody, or antigen-binding fragment thereof, binds to residues E56, N153, Y155, M158, and G159 of the Claudin 18.2 protein.

45. The antibody, or antigen-binding fragment thereof, binds to residues V40, E56, N153, Y155, M158, G159, and G160 of the Claudin 18.2 protein, and is the antibody or antigen-binding fragment thereof according to any one of claims 1 to 44.

46. A nucleic acid molecule encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45.

47. A vector containing the nucleic acid molecule according to claim 46.

48. A cell containing the nucleic acid molecule according to claim 46 or the vector according to claim 47.

49. A pharmaceutical composition comprising the antibody according to any one of claims 1 to 45, or antigen-binding fragment thereof; the nucleic acid molecule according to claim 46; or the vector according to claim 47.

50. The pharmaceutical composition according to claim 49, which is an injectable pharmaceutical composition.

51. The pharmaceutical composition according to claim 49 or claim 50, which is sterile or pyrogen-free.

52. The pharmaceutical composition according to any one of claims 49 to 51, wherein an antibody or antigen-binding fragment thereof that does not bind to Claudin 18.2 is not included in the pharmaceutical composition.

53. A method for treating a tumor or gastric tumor in a subject, the method comprising administering the Claudin 18.2 antibody according to any one of claims 1 to 45, or antigen-binding fragment thereof, or the pharmaceutical composition according to any one of claims 49 to 52.

54. The method according to claim 53, wherein the tumor or gastric tumor is gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or pancreatic adenocarcinoma or non-small cell lung cancer.

55. The method according to claim 53 or claim 54, wherein the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken.

56. A method for detecting the presence or absence of Claudin 18.2 in a sample, the method comprising contacting the sample with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 45, and detecting the binding of the antibody or antigen-binding fragment thereof to the Claudin 18.2 antigen, wherein detection of binding indicates the presence of Claudin 18.2; or the absence of detection of binding to Claudin 18.2 indicates the absence of Claudin 18.

2.

57. A method for inducing an immune response against Claudin 18.2 protein in a subject, comprising administering to the subject virus-like particles containing Claudin 18.2 protein under conditions sufficient to induce an immune response.

58. The method according to claim 57, wherein the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken.

59. A method for generating an antibody that binds to Claudin 18.2 protein or an antigen-binding fragment thereof, comprising administering to a subject virus-like particles containing Claudin 18.2 protein on its surface under conditions sufficient to induce an immune response against Claudin 18.2 protein to generate an antibody that binds to Claudin 18.2 protein or an antigen-binding fragment thereof.

60. The method according to claim 59, wherein the subject is a human, mouse, sheep, rat, rabbit, shark, llama, or chicken.

61. The method according to claim 59 or claim 60, further comprising isolating an antibody that binds to Claudin 18.2 protein.

62. The method according to any one of claims 59 to 61, wherein the generated antibody or its antigen-binding fragment binds to the extracellular domain of Claudin 18.2 protein.

63. The method according to any one of claims 59 to 62, further comprising generating virus-like particles containing Claudin 18.2 protein, the method comprising transfecting or transducing cells with Claudin 18.2 protein and retroviral gag protein under conditions sufficient to produce virus-like particles containing Claudin 18.2 protein.

64. The method according to claim 63, wherein the cells are HEK-293T cells.

65. The method according to claim 63 or claim 64, wherein the gag protein is an MLV gag protein.

66. The method according to any one of claims 63 to 65, wherein the retroviral gag protein is a murine leukemia virus (MLV) gag, HIV gag, or RSV gag protein.

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