Anti-mucin 17 antibody, conjugate thereof and use thereof

Abstract

An antibody specifically binding to mucin 17(MUC17), an antibody-drug conjugate and a method for using same, and a composition containing a molecule and a detection system. The anti-MUC17 antibody, the conjugate thereof, or the composition thereof can be used as an independent therapy for the treatment of cancer / tumor, etc., or in combination with other therapies / or other anti-cancer agents.

Description

Anti-Mucin 17 antibodies, conjugates thereof and uses thereof Technical Field

[0001] The present invention relates to an antibody that specifically binds to a target mucin 17 (MUC17), an antibody-drug conjugate thereof and a use thereof, as well as a composition and a detection system containing the antibody-like molecule. Background Art

[0002] Mucins (MUCs) are high-molecular-weight glycoproteins produced and secreted by epithelial cells, with mucus as the primary component. To date, over twenty mucin proteins have been discovered, and they are divided into two categories based on their function: membrane-bound and secreted mucins. Secreted mucins form a physical barrier, acting as a mucus gel to protect respiratory and gastrointestinal epithelial cells. Transmembrane mucins form rod-like structures through O-glycosylated tandem repeats in their extracellular domains, building a protective mucus gel layer.

[0003] MUC17 (Mucin-17) is a transmembrane mucin encoded by the MUC17 gene located at locus q22 on chromosome 7. Discovered and characterized in 2002, MUC17 consists of three segments: a transmembrane segment, an intracellular segment, and an extracellular segment. From the amino terminus, the sequence is a mucin-like structure (tandem repeats), an EGF (epidermal growth factor)-like region, an N-glycosylated region, a second EGF-like region, a hydrophobic transmembrane segment, and a shuttle terminus within the cytoplasm. MUC17 binds to the cell membrane via the transmembrane region near the carboxyl terminus and participates in intracellular signaling. The extracellular segment determines the MUC-specific spatial structure and immunogenicity. MUC17 expression can strengthen the intestinal mucus barrier and promote inflammatory healing. In epithelial cells, MUC17 participates in signal transduction, maintains luminal structure, provides cellular protection, and imparts anti-adhesion properties to cancer cells that have lost polarity, thereby causing tumor cells to lose polarity.

[0004] MUC17 is primarily expressed in the intestine. Studies have shown that MUC17 expression increases significantly throughout the progression of normal gastric mucosa, intestinal metaplasia, and advanced gastric cancer, with low MUC17 expression being associated with a poor prognosis in gastric cancer. Further research has shown that MUC17 expression is negatively correlated with the degree of tumor differentiation, suggesting that MUC17 may serve as a diagnostic and therapeutic target for gastric cancer.

[0005] MUC17 is a membrane-bound mucin with important biological functions. Its expression level is associated with various inflammatory conditions and tumor cell proliferation. Numerous studies have suggested that mucins are overexpressed in different malignant tumors. The close relationship between mucins and tumors and the immune response they induce provide important clues for the design of mucin-based anti-tumor drugs. However, there are still unmet medical needs for diseases or conditions that express MUC17. Summary of the Invention

[0006] The present invention provides novel anti-MUC17 antibodies or antigen-binding fragments thereof, which have advantages such as high affinity and high specificity for human MUC17. The anti-MUC17 antibodies provided by the present invention can be used as a stand-alone therapy or in combination with other therapies and / or other anti-cancer agents for the treatment of, for example, cancer / tumors. The MUC17 antibodies can be used in diagnostic methods on tissue samples collected from individuals, particularly those that may be suffering from MUC17-mediated tumors and / or cancers, or tumors and / or cancers associated with abnormal MUC17 expression, and / or tumors and / or cancers that can be identified by abnormal MUC17 expression. The present invention also provides nucleic acid molecules encoding the antibody molecules, expression vectors, host cells, and methods for producing the antibody molecules.

[0007] In a first aspect, the present invention provides an antibody or antigen-binding fragment thereof that can specifically bind to MUC17, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain complementary determining region (HCDRs) and / or a light chain complementary determining region (LCDRs) selected from the group consisting of:

[0008] (1) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 7 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 8 or variants thereof; or,

[0009] (2) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 17 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 18 or variants thereof; or

[0010] (3) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 24 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 25 or a variant thereof; or

[0011] (4) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 24 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 31 or a variant thereof; or

[0012] (5) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 34 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 35 or a variant thereof; or

[0013] (6) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 40 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 41 or variants thereof; or

[0014] (7) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 47 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 48 or a variant thereof; or

[0015] (8) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 47 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 53 or a variant thereof; or

[0016] (9) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 59 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 60 or a variant thereof; or

[0017] (10) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 69 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 70 or a variant thereof; or

[0018] (11) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 77 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 78 or a variant thereof; or

[0019] (12) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 87 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 88 or a variant thereof; or

[0020] (13) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 97 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 98 or a variant thereof; or

[0021] (14) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 104 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 105 or a variant thereof; or

[0022] (15) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 114 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 115 or a variant thereof; or

[0023] (16) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 114 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 119 or a variant thereof; or

[0024] (17) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 125 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 126 or a variant thereof; or

[0025] (18) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 135 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 136 or a variant thereof; or

[0026] (19) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 97 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 140 or a variant thereof; or

[0027] (20) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 149 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 150 or a variant thereof; or

[0028] (21) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 158 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 159 or a variant thereof; or

[0029] (22) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 167 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 168 or a variant thereof; or

[0030] (23) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 172 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 173 or a variant thereof; or

[0031] (24) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 179 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 180 or a variant thereof; or

[0032] (25) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 189 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 190 or a variant thereof; or

[0033] (26) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 198 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 199 or a variant thereof; or

[0034] (27) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 204 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 205 or a variant thereof; or

[0035] (28) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 214 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 215 or a variant thereof;

[0036] (29) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 259 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 263 or a variant thereof;

[0037] (30) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 259 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 260 or a variant thereof;

[0038] (31) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 261 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 260 or variants thereof;

[0039] (32) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 259 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 262 or a variant thereof;

[0040] (33) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 261 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 262 or a variant thereof;

[0041] wherein the variant in any one of (1)-(33) has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which it is derived, or the variant has one or more amino acid substitutions, deletions or additions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived; in some embodiments, the substitutions are conservative substitutions.

[0042] In some embodiments, the HCDR1, HCDR2 and HCDR3 contained in the heavy chain variable region (VH), and / or the LCDR1, LCDR2 and LCDR3 contained in the light chain variable region (VL) are defined by the Kabat, AbM, Chothia or IMGT numbering systems.

[0043] In some embodiments, the antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining regions (HCDRs) and / or light chain complementarity determining regions (LCDRs) selected from the group consisting of:

[0044] (1) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 7; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 8; or

[0045] (2) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 17; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 18; or

[0046] (3) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 24; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 25; or

[0047] (4) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 24; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 31; or

[0048] (5) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 34; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 35; or

[0049] (6) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 40; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 41; or

[0050] (7) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 47; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 48; or

[0051] (8) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 47; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 53; or

[0052] (9) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 59; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 60; or

[0053] (10) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 69; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 70; or

[0054] (11) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 77; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 78; or

[0055] (12) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 87; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 88; or

[0056] (13) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 97; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 98; or

[0057] (14) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 104; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 105; or

[0058] (15) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 114; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 115; or

[0059] (16) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 114; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 119; or

[0060] (17) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 125; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 126; or

[0061] (18) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 135; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 136; or

[0062] (19) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 97; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 140; or

[0063] (20) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 149; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 150; or

[0064] (21) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 158; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 159; or

[0065] (22) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 167; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 168; or

[0066] (23) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 172; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 173; or

[0067] (24) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 179; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 180; or

[0068] (25) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 189; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 190; or

[0069] (26) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 198; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 199; or

[0070] (27) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 204; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 205; or

[0071] (28) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 214; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 215;

[0072] (29) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 259; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 263;

[0073] (30) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 259; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 260;

[0074] (31) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 261; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 260;

[0075] (32) the three CDRs (HCDR1, HCDR2, HCDR3) contained in the VH as shown in SEQ ID NO: 259; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in the VL as shown in SEQ ID NO: 262;

[0076] (33) The three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 261; and / or, the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 262.

[0077] In some embodiments, the HCDR1, HCDR2 and HCDR3 contained in the heavy chain variable region (VH), and / or the LCDR1, LCDR2 and LCDR3 contained in the light chain variable region (VL) are defined by the Kabat, AbM, Chothia or IMGT numbering systems.

[0078] As a specific embodiment, the present invention provides an antibody or antigen-binding fragment thereof that specifically binds to MUC17, which comprises a complementarity determining region (CDR) selected from the following group:

[0079] The following three CDRs (HCDR1, HCDR2, HCDR3) of the heavy chain variable region (VH), and / or the following three CDRs (LCDR1, LCDR2, LCDR3) of the light chain variable region (VL), wherein the HCDR1, HCDR2 and HCDR3 contained in the heavy chain variable region (VH), and / or the LCDR1, LCDR2 and LCDR3 contained in the light chain variable region (VL) are defined by the Kabat numbering system:

[0080] (1) HCDR1 having the sequence shown in SEQ ID NO: 1, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 1;

[0081] HCDR2 having the sequence shown in SEQ ID NO: 2, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 2;

[0082] HCDR3 having the sequence shown in SEQ ID NO: 3, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 3;

[0083] LCDR1 having the sequence shown in SEQ ID NO: 4, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 4;

[0084] LCDR2 having the sequence shown in SEQ ID NO: 5, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 5;

[0085] LCDR3 having the sequence shown in SEQ ID NO: 6, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 6;

[0086] or,

[0087] (2) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0088] HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12;

[0089] A HCDR3 having the sequence shown in SEQ ID NO: 13, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 13;

[0090] LCDR1 having the sequence shown in SEQ ID NO: 14, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 14;

[0091] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0092] LCDR3 having the sequence shown in SEQ ID NO: 16, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 16;

[0093] or,

[0094] (3) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0095] HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12;

[0096] A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21;

[0097] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0098] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0099] LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23;

[0100] or,

[0101] (4) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0102] HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12;

[0103] A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21;

[0104] LCDR1 having the sequence shown in SEQ ID NO: 28, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 28;

[0105] LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29;

[0106] LCDR3 having the sequence shown in SEQ ID NO: 30, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 30;

[0107] or,

[0108] (5) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0109] HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12;

[0110] A HCDR3 having the sequence shown in SEQ ID NO: 33, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 33;

[0111] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0112] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0113] LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23;

[0114] or,

[0115] (6) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0116] HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12;

[0117] A HCDR3 having the sequence shown in SEQ ID NO: 38, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 38;

[0118] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0119] LCDR2 having the sequence shown in SEQ ID NO: 39, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 39;

[0120] LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23;

[0121] or,

[0122] (7) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0123] HCDR2 having the sequence shown in SEQ ID NO: 44, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 44;

[0124] A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45;

[0125] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0126] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0127] LCDR3 having the sequence shown in SEQ ID NO: 46, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 46;

[0128] or,

[0129] (8) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0130] HCDR2 having the sequence shown in SEQ ID NO: 44, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 44;

[0131] A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45;

[0132] LCDR1 having the sequence shown in SEQ ID NO: 51, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 51;

[0133] LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29;

[0134] LCDR3 having the sequence shown in SEQ ID NO: 52, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 52;

[0135] or,

[0136] (9) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11;

[0137] HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12;

[0138] A HCDR3 having the sequence shown in SEQ ID NO: 55, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 55;

[0139] LCDR1 having the sequence shown in SEQ ID NO: 56, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 56;

[0140] LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57;

[0141] LCDR3 having the sequence shown in SEQ ID NO: 58, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 58;

[0142] or,

[0143] (10) HCDR1 having the sequence shown in SEQ ID NO: 63, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 63;

[0144] HCDR2 having the sequence shown in SEQ ID NO: 64, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 64;

[0145] A HCDR3 having the sequence shown in SEQ ID NO: 65, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 65;

[0146] LCDR1 having the sequence shown in SEQ ID NO: 66, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 66;

[0147] LCDR2 having the sequence shown in SEQ ID NO: 67, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 67;

[0148] LCDR3 having the sequence shown in SEQ ID NO: 68, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 68;

[0149] or,

[0150] (11) HCDR1 having the sequence shown in SEQ ID NO: 1, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 1;

[0151] HCDR2 having the sequence shown in SEQ ID NO: 73, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 73;

[0152] A HCDR3 having the sequence shown in SEQ ID NO: 74, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 74;

[0153] LCDR1 having the sequence shown in SEQ ID NO: 75, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 75;

[0154] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0155] LCDR3 having the sequence shown in SEQ ID NO: 76, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 76;

[0156] or,

[0157] (12) HCDR1 having the sequence shown in SEQ ID NO: 81, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 81;

[0158] HCDR2 having the sequence shown in SEQ ID NO: 82, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 82;

[0159] A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83;

[0160] LCDR1 having the sequence shown in SEQ ID NO: 84, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 84;

[0161] LCDR2 having the sequence shown in SEQ ID NO: 85, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 85;

[0162] LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86;

[0163] or,

[0164] (13) HCDR1 having the sequence shown in SEQ ID NO: 91, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 91;

[0165] HCDR2 having the sequence shown in SEQ ID NO: 92, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 92;

[0166] A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93;

[0167] LCDR1 having the sequence shown in SEQ ID NO: 94, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 94;

[0168] LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95;

[0169] LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96;

[0170] or,

[0171] (14) HCDR1 having the sequence shown in SEQ ID NO: 81, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 81;

[0172] HCDR2 having the sequence shown in SEQ ID NO: 101, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 101;

[0173] A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83;

[0174] LCDR1 having the sequence shown in SEQ ID NO: 102, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 102;

[0175] LCDR2 having the sequence shown in SEQ ID NO: 103, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 103;

[0176] LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86;

[0177] or,

[0178] (15) HCDR1 having the sequence shown in SEQ ID NO: 108, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 108;

[0179] HCDR2 having the sequence shown in SEQ ID NO: 109, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 109;

[0180] A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110;

[0181] LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111;

[0182] LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112;

[0183] LCDR3 having the sequence shown in SEQ ID NO: 113, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 113;

[0184] or,

[0185] (16) HCDR1 having the sequence shown in SEQ ID NO: 108, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 108;

[0186] HCDR2 having the sequence shown in SEQ ID NO: 109, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 109;

[0187] A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110;

[0188] LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111;

[0189] LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112;

[0190] LCDR3 having the sequence shown in SEQ ID NO: 118, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 118;

[0191] or,

[0192] (17) HCDR1 having the sequence shown in SEQ ID NO: 121, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 121;

[0193] HCDR2 having the sequence shown in SEQ ID NO: 122, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 122;

[0194] A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93;

[0195] LCDR1 having the sequence shown in SEQ ID NO: 123, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 123;

[0196] LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95;

[0197] LCDR3 having the sequence shown in SEQ ID NO: 124, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 124;

[0198] or,

[0199] (18) HCDR1 having the sequence shown in SEQ ID NO: 129, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 129;

[0200] HCDR2 having the sequence shown in SEQ ID NO: 130, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 130;

[0201] A HCDR3 having the sequence shown in SEQ ID NO: 131, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 131;

[0202] LCDR1 having the sequence shown in SEQ ID NO: 132, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 132;

[0203] LCDR2 having the sequence shown in SEQ ID NO: 133, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 133;

[0204] LCDR3 having the sequence shown in SEQ ID NO: 134, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 134;

[0205] or,

[0206] (19) HCDR1 having the sequence shown in SEQ ID NO: 91, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 91;

[0207] HCDR2 having the sequence shown in SEQ ID NO: 92, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 92;

[0208] A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93;

[0209] LCDR1 having the sequence shown in SEQ ID NO: 139, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 139;

[0210] LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112;

[0211] LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96;

[0212] or,

[0213] (20) HCDR1 having the sequence shown in SEQ ID NO: 143, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 143;

[0214] HCDR2 having the sequence shown in SEQ ID NO: 144, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 144;

[0215] A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145;

[0216] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0217] LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147;

[0218] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0219] or,

[0220] (21) HCDR1 having the sequence shown in SEQ ID NO: 81, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 81;

[0221] HCDR2 having the sequence shown in SEQ ID NO: 153, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 153;

[0222] A HCDR3 having the sequence shown in SEQ ID NO: 154, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 154;

[0223] LCDR1 having the sequence shown in SEQ ID NO: 155, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 155;

[0224] LCDR2 having the sequence shown in SEQ ID NO: 156, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 156;

[0225] LCDR3 having the sequence shown in SEQ ID NO: 157, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 157;

[0226] or,

[0227] (22) HCDR1 having the sequence shown in SEQ ID NO: 162, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 162;

[0228] HCDR2 having the sequence shown in SEQ ID NO: 163, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 163;

[0229] A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164;

[0230] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0231] LCDR2 having the sequence shown in SEQ ID NO: 165, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 165;

[0232] LCDR3 having the sequence shown in SEQ ID NO: 166, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 166;

[0233] or,

[0234] (23) HCDR1 having the sequence shown in SEQ ID NO: 143, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 143;

[0235] HCDR2 having the sequence shown in SEQ ID NO: 144, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 144;

[0236] A HCDR3 having the sequence shown in SEQ ID NO: 171, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 171;

[0237] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0238] LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147;

[0239] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0240] or,

[0241] (24) HCDR1 having the sequence shown in SEQ ID NO: 176, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 176;

[0242] HCDR2 having the sequence shown in SEQ ID NO: 177, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 177;

[0243] A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164;

[0244] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0245] LCDR2 having the sequence shown in SEQ ID NO: 178, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 178;

[0246] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0247] or,

[0248] (25) HCDR1 having the sequence shown in SEQ ID NO: 183, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 183;

[0249] HCDR2 having the sequence shown in SEQ ID NO: 184, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 184;

[0250] A HCDR3 having the sequence shown in SEQ ID NO: 185, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 185;

[0251] LCDR1 having the sequence shown in SEQ ID NO: 186, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 186;

[0252] LCDR2 having the sequence shown in SEQ ID NO: 187, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 187;

[0253] LCDR3 having the sequence shown in SEQ ID NO: 188, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 188;

[0254] or,

[0255] (26) HCDR1 having the sequence shown in SEQ ID NO: 193, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 193;

[0256] HCDR2 having the sequence shown in SEQ ID NO: 194, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 194;

[0257] A HCDR3 having the sequence shown in SEQ ID NO: 195, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 195;

[0258] LCDR1 having the sequence shown in SEQ ID NO: 196, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 196;

[0259] LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57;

[0260] LCDR3 having the sequence shown in SEQ ID NO: 197, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 197;

[0261] or,

[0262] (27) HCDR1 having the sequence shown in SEQ ID NO: 202, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 202;

[0263] HCDR2 having the sequence shown in SEQ ID NO: 144, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 144;

[0264] A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145;

[0265] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0266] LCDR2 having the sequence shown in SEQ ID NO: 203, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 203;

[0267] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0268] or,

[0269] (28) HCDR1 having the sequence shown in SEQ ID NO: 208, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 208;

[0270] HCDR2 having the sequence shown in SEQ ID NO: 209, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 209;

[0271] A HCDR3 having the sequence shown in SEQ ID NO: 210, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 210.

[0272] LCDR1 having the sequence shown in SEQ ID NO: 211, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 211;

[0273] LCDR2 having the sequence shown in SEQ ID NO: 212, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 212;

[0274] LCDR3 having the sequence shown in SEQ ID NO: 213, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 213.

[0275] In some embodiments, the substitution described in any one of (1) to (28) is a conservative substitution.

[0276] As a specific embodiment, the present invention provides an antibody or antigen-binding fragment thereof that specifically binds to MUC17, which comprises the following three HCDRs (HCDR1, HCDR2, HCDR3) of the heavy chain variable region (VH), and / or, the following three LCDRs (LCDR1, LCDR2, LCDR3) of the light chain variable region (VL), wherein the HCDR1, HCDR2 and HCDR3 contained in the heavy chain variable region (VH), and / or the LCDR1, LCDR2 and LCDR3 contained in the light chain variable region (VL) are defined by the AbM numbering system:

[0277] (1) HCDR1 having the sequence shown in SEQ ID NO: 225, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 225;

[0278] HCDR2 having the sequence shown in SEQ ID NO: 226, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 226;

[0279] HCDR3 having the sequence shown in SEQ ID NO: 3, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 3;

[0280] LCDR1 having the sequence shown in SEQ ID NO: 4, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 4;

[0281] LCDR2 having the sequence shown in SEQ ID NO: 5, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 5;

[0282] LCDR3 having the sequence shown in SEQ ID NO: 6, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 6;

[0283] or,

[0284] (2) HCDR1 having the sequence as shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0285] HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228;

[0286] A HCDR3 having the sequence shown in SEQ ID NO: 13, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 13;

[0287] LCDR1 having the sequence shown in SEQ ID NO: 14, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 14;

[0288] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0289] LCDR3 having the sequence shown in SEQ ID NO: 16, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 16;

[0290] or,

[0291] (3) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0292] HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228;

[0293] A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21;

[0294] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0295] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0296] LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23;

[0297] or,

[0298] (4) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0299] HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228;

[0300] A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21;

[0301] LCDR1 having the sequence shown in SEQ ID NO: 28, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 28;

[0302] LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29;

[0303] LCDR3 having the sequence shown in SEQ ID NO: 30, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 30;

[0304] or,

[0305] (5) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0306] HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228;

[0307] A HCDR3 having the sequence shown in SEQ ID NO: 33, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 33;

[0308] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0309] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0310] LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23;

[0311] or,

[0312] (6) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0313] HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228;

[0314] A HCDR3 having the sequence shown in SEQ ID NO: 38, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 38;

[0315] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0316] LCDR2 having the sequence shown in SEQ ID NO: 39, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 39;

[0317] LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23;

[0318] or,

[0319] (7) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0320] HCDR2 having the sequence shown in SEQ ID NO: 229, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 229;

[0321] A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45;

[0322] LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22;

[0323] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0324] LCDR3 having the sequence shown in SEQ ID NO: 46, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 46;

[0325] or,

[0326] (8) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0327] HCDR2 having the sequence shown in SEQ ID NO: 229, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 229;

[0328] A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45;

[0329] LCDR1 having the sequence shown in SEQ ID NO: 51, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 51;

[0330] LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29;

[0331] LCDR3 having the sequence shown in SEQ ID NO: 52, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 52;

[0332] or,

[0333] (9) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227;

[0334] HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228;

[0335] A HCDR3 having the sequence shown in SEQ ID NO: 55, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 55;

[0336] LCDR1 having the sequence shown in SEQ ID NO: 56, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 56;

[0337] LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57;

[0338] LCDR3 having the sequence shown in SEQ ID NO: 58, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 58;

[0339] or,

[0340] (10) HCDR1 having the sequence shown in SEQ ID NO: 230, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 230;

[0341] HCDR2 having the sequence shown in SEQ ID NO: 231, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 231;

[0342] A HCDR3 having the sequence shown in SEQ ID NO: 65, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 65;

[0343] LCDR1 having the sequence shown in SEQ ID NO: 66, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 66;

[0344] LCDR2 having the sequence shown in SEQ ID NO: 67, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 67;

[0345] LCDR3 having the sequence shown in SEQ ID NO: 68, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 68;

[0346] or,

[0347] (11) HCDR1 having the sequence shown in SEQ ID NO: 232, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 232;

[0348] HCDR2 having the sequence shown in SEQ ID NO: 233, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 233;

[0349] A HCDR3 having the sequence shown in SEQ ID NO: 74, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 74;

[0350] LCDR1 having the sequence shown in SEQ ID NO: 75, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 75;

[0351] LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15;

[0352] LCDR3 having the sequence shown in SEQ ID NO: 76, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 76;

[0353] or,

[0354] (12) HCDR1 having the sequence shown in SEQ ID NO: 234, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 234;

[0355] HCDR2 having the sequence shown in SEQ ID NO: 235, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 235;

[0356] A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83;

[0357] LCDR1 having the sequence shown in SEQ ID NO: 84, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 84;

[0358] LCDR2 having the sequence shown in SEQ ID NO: 85, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 85;

[0359] LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86;

[0360] or,

[0361] (13) HCDR1 having the sequence shown in SEQ ID NO: 236, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 236;

[0362] HCDR2 having the sequence shown in SEQ ID NO: 237, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 237;

[0363] A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93;

[0364] LCDR1 having the sequence shown in SEQ ID NO: 94, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 94;

[0365] LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95;

[0366] LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96;

[0367] or,

[0368] (14) HCDR1 having the sequence shown in SEQ ID NO: 234, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 234;

[0369] HCDR2 having the sequence shown in SEQ ID NO: 238, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 238;

[0370] A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83;

[0371] LCDR1 having the sequence shown in SEQ ID NO: 102, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 102;

[0372] LCDR2 having the sequence shown in SEQ ID NO: 103, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 103;

[0373] LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86;

[0374] or,

[0375] (15) HCDR1 having the sequence shown in SEQ ID NO: 239, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 239;

[0376] HCDR2 having the sequence shown in SEQ ID NO: 240, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 240;

[0377] A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110;

[0378] LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111;

[0379] LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112;

[0380] LCDR3 having the sequence shown in SEQ ID NO: 113, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 113;

[0381] or,

[0382] (16) HCDR1 having the sequence shown in SEQ ID NO: 239, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 239;

[0383] HCDR2 having the sequence shown in SEQ ID NO: 240, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 240;

[0384] A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110;

[0385] LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111;

[0386] LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112;

[0387] LCDR3 having the sequence shown in SEQ ID NO: 118, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 118;

[0388] or,

[0389] (17) HCDR1 having the sequence shown in SEQ ID NO: 241, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 241;

[0390] HCDR2 having the sequence shown in SEQ ID NO: 242, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 242;

[0391] A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93;

[0392] LCDR1 having the sequence shown in SEQ ID NO: 123, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 123;

[0393] LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95;

[0394] LCDR3 having the sequence shown in SEQ ID NO: 124, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 124;

[0395] or,

[0396] (18) HCDR1 having the sequence shown in SEQ ID NO: 243, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 243;

[0397] HCDR2 having the sequence shown in SEQ ID NO: 244, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 244;

[0398] A HCDR3 having the sequence shown in SEQ ID NO: 131, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 131;

[0399] LCDR1 having the sequence shown in SEQ ID NO: 132, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 132;

[0400] LCDR2 having the sequence shown in SEQ ID NO: 133, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 133;

[0401] LCDR3 having the sequence shown in SEQ ID NO: 134, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 134;

[0402] or,

[0403] (19) HCDR1 having the sequence shown in SEQ ID NO: 236, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 236;

[0404] HCDR2 having the sequence shown in SEQ ID NO: 237, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 237;

[0405] A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93;

[0406] LCDR1 having the sequence shown in SEQ ID NO: 139, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 139;

[0407] LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112;

[0408] LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96;

[0409] or,

[0410] (20) HCDR1 having the sequence shown in SEQ ID NO: 245, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 245;

[0411] HCDR2 having the sequence shown in SEQ ID NO: 246, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 246;

[0412] A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145;

[0413] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0414] LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147;

[0415] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0416] or,

[0417] (21) HCDR1 having the sequence shown in SEQ ID NO: 234, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 234;

[0418] HCDR2 having the sequence shown in SEQ ID NO: 247, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 247;

[0419] A HCDR3 having the sequence shown in SEQ ID NO: 154, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 154;

[0420] LCDR1 having the sequence shown in SEQ ID NO: 155, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 155;

[0421] LCDR2 having the sequence shown in SEQ ID NO: 156, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 156;

[0422] LCDR3 having the sequence shown in SEQ ID NO: 157, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 157;

[0423] or,

[0424] (22) HCDR1 having the sequence shown in SEQ ID NO: 248, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 248;

[0425] HCDR2 having the sequence shown in SEQ ID NO: 249, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 249;

[0426] A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164;

[0427] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0428] LCDR2 having the sequence shown in SEQ ID NO: 165, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 165;

[0429] LCDR3 having the sequence shown in SEQ ID NO: 166, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 166;

[0430] or,

[0431] (23) HCDR1 having the sequence shown in SEQ ID NO: 245, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 245;

[0432] HCDR2 having the sequence shown in SEQ ID NO: 246, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 246;

[0433] A HCDR3 having the sequence shown in SEQ ID NO: 171, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 171;

[0434] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0435] LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147;

[0436] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0437] or,

[0438] (24) HCDR1 having the sequence shown in SEQ ID NO: 250, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 250;

[0439] HCDR2 having the sequence shown in SEQ ID NO: 251, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 251;

[0440] A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164;

[0441] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0442] LCDR2 having the sequence shown in SEQ ID NO: 178, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 178;

[0443] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0444] or,

[0445] (25) HCDR1 having the sequence shown in SEQ ID NO: 252, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 252;

[0446] HCDR2 having the sequence shown in SEQ ID NO: 253, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 253;

[0447] A HCDR3 having the sequence shown in SEQ ID NO: 185, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 185;

[0448] LCDR1 having the sequence shown in SEQ ID NO: 186, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 186;

[0449] LCDR2 having the sequence shown in SEQ ID NO: 187, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 187;

[0450] LCDR3 having the sequence shown in SEQ ID NO: 188, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 188;

[0451] or,

[0452] (26) HCDR1 having the sequence shown in SEQ ID NO: 254, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 254;

[0453] HCDR2 having the sequence shown in SEQ ID NO: 255, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 255;

[0454] A HCDR3 having the sequence shown in SEQ ID NO: 195, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 195;

[0455] LCDR1 having the sequence shown in SEQ ID NO: 196, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 196;

[0456] LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57;

[0457] LCDR3 having the sequence shown in SEQ ID NO: 197, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 197;

[0458] or,

[0459] (27) HCDR1 having the sequence shown in SEQ ID NO: 256, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 256;

[0460] HCDR2 having the sequence shown in SEQ ID NO: 246, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 246;

[0461] A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145;

[0462] LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146;

[0463] LCDR2 having the sequence shown in SEQ ID NO: 203, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 203;

[0464] LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148;

[0465] or,

[0466] (28) HCDR1 having the sequence shown in SEQ ID NO: 257, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 257;

[0467] HCDR2 having the sequence shown in SEQ ID NO: 258, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 258;

[0468] A HCDR3 having the sequence shown in SEQ ID NO: 210, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 210.

[0469] LCDR1 having the sequence shown in SEQ ID NO: 211, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 211;

[0470] LCDR2 having the sequence shown in SEQ ID NO: 212, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 212;

[0471] LCDR3 having the sequence shown in SEQ ID NO: 213, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 213.

[0472] In some embodiments, the substitution described in any one of (1) to (28) is a conservative substitution.

[0473] In some embodiments, the present invention provides anti-MUC17 antibodies and antigen-binding fragments thereof that specifically bind to MUC17, comprising a heavy chain variable region (VH), wherein:

[0474] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 7, or consists of SEQ ID NO: 7;

[0475] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 17, or consists of SEQ ID NO: 17;

[0476] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 24, or consists of SEQ ID NO: 24;

[0477] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 34, or consists of SEQ ID NO: 34;

[0478] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:40, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:40, or consists of SEQ ID NO:40;

[0479] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 47, or consists of SEQ ID NO: 47;

[0480] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 59, or consists of SEQ ID NO: 59;

[0481] (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:69, or consists of SEQ ID NO:69;

[0482] (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 77, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 77, or consists of SEQ ID NO: 77;

[0483] (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 87, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 87, or consists of SEQ ID NO: 87;

[0484] (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 97, or consists of SEQ ID NO: 97;

[0485] (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 104, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 104, or consists of SEQ ID NO: 104;

[0486] (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 114, or consists of SEQ ID NO: 114;

[0487] (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 125, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 125, or consists of SEQ ID NO: 125;

[0488] (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 135, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 135, or consists of SEQ ID NO: 135;

[0489] (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 149, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 149, or consists of SEQ ID NO: 149;

[0490] (17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 158, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 158, or consists of SEQ ID NO: 158;

[0491] (18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 167, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 167, or consists of SEQ ID NO: 167;

[0492] (19) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 172, or consists of SEQ ID NO: 172;

[0493] (20) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 179, or consists of SEQ ID NO: 179;

[0494] (21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 189, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 189, or consists of SEQ ID NO: 189;

[0495] (22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 198, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 198, or consists of SEQ ID NO: 198;

[0496] (23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 204, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 204, or consists of SEQ ID NO: 204;

[0497] (24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 214, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 214, or consists of SEQ ID NO: 214;

[0498] (25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259;

[0499] (26) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; or

[0500] (27) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264.

[0501] In some embodiments, the present invention provides anti-MUC17 antibodies and antigen-binding fragments thereof that specifically bind to MUC17, comprising a light chain variable region (VL), wherein:

[0502] (1) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 8, or consists of SEQ ID NO: 8;

[0503] (2) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 18, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 18, or consists of SEQ ID NO: 18;

[0504] (3) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 25, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 25, or consists of SEQ ID NO: 25;

[0505] (4) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 31, or consists of SEQ ID NO: 31;

[0506] (5) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 35, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 35, or consists of SEQ ID NO: 35;

[0507] (6) the light chain variable region comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:41, or consists of SEQ ID NO:41;

[0508] (7) the light chain variable region comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:48, or consists of SEQ ID NO:48;

[0509] (8) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 53, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 53, or consists of SEQ ID NO: 53;

[0510] (9) the light chain variable region comprises the amino acid sequence of SEQ ID NO:60, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:60, or consists of SEQ ID NO:60;

[0511] (10) the light chain variable region comprises the amino acid sequence of SEQ ID NO:70, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:70, or consists of SEQ ID NO:70;

[0512] (11) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 78, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 78, or consists of SEQ ID NO: 78;

[0513] (12) the light chain variable region comprises the amino acid sequence of SEQ ID NO:88, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:88, or consists of SEQ ID NO:88;

[0514] (13) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 98, or consists of SEQ ID NO: 98;

[0515] (14) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 105, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 105, or consists of SEQ ID NO: 105;

[0516] (15) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 115, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 115, or consists of SEQ ID NO: 115;

[0517] (16) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 119, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 119, or consists of SEQ ID NO: 119;

[0518] (17) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 126, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 126, or consists of SEQ ID NO: 126;

[0519] (18) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 136, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 136, or consists of SEQ ID NO: 136;

[0520] (19) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 140, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 140, or consists of SEQ ID NO: 140;

[0521] (20) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 150, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 150, or consists of SEQ ID NO: 150;

[0522] (21) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 159, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 159, or consists of SEQ ID NO: 159;

[0523] (22) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 168, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 168, or consists of SEQ ID NO: 168;

[0524] (23) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 173, or consists of SEQ ID NO: 173;

[0525] (24) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 180, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 180, or consists of SEQ ID NO: 180;

[0526] (25) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 190, or consists of SEQ ID NO: 190;

[0527] (26) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 199, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 199, or consists of SEQ ID NO: 199;

[0528] (27) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 205, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 205, or consists of SEQ ID NO: 205;

[0529] (28) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 215, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 215, or consists of SEQ ID NO: 215;

[0530] (29) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263;

[0531] (30) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260;

[0532] (31) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262;

[0533] (32) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265;

[0534] (33) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266; or

[0535] (34) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267.

[0536] In another embodiment, the present invention provides an anti-MUC17 antibody and antigen-binding fragment thereof that specifically binds to MUC17, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0537] (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 7, or consists of SEQ ID NO: 7; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 8, or consists of SEQ ID NO: 8;

[0538] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 17, or consists of SEQ ID NO: 17; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 18, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 18, or consists of SEQ ID NO: 18;

[0539] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 24, or consists of SEQ ID NO: 24; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 25, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 25, or consists of SEQ ID NO: 25;

[0540] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:24, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:24, or consists of SEQ ID NO:24; the light chain variable region comprises the amino acid sequence of SEQ ID NO:31, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:31, or consists of SEQ ID NO:31;

[0541] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:34, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:34, or consists of SEQ ID NO:34; the light chain variable region comprises the amino acid sequence of SEQ ID NO:35, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:35, or consists of SEQ ID NO:35;

[0542] (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:40, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:40, or consists of SEQ ID NO:40; the light chain variable region comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:41, or consists of SEQ ID NO:41;

[0543] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:47, or consists of SEQ ID NO:47; the light chain variable region comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:48, or consists of SEQ ID NO:48;

[0544] (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:47, or consists of SEQ ID NO:47; the light chain variable region comprises the amino acid sequence of SEQ ID NO:53, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:53, or consists of SEQ ID NO:53;

[0545] (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:59, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:59, or consists of SEQ ID NO:59; the light chain variable region comprises the amino acid sequence of SEQ ID NO:60, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:60, or consists of SEQ ID NO:60;

[0546] (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:69, or consists of SEQ ID NO:69; the light chain variable region comprises the amino acid sequence of SEQ ID NO:70, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:70, or consists of SEQ ID NO:70;

[0547] (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 77, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 77, or consists of SEQ ID NO: 77; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 78, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 78, or consists of SEQ ID NO: 78;

[0548] (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:87, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:87, or consists of SEQ ID NO:87; the light chain variable region comprises the amino acid sequence of SEQ ID NO:88, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:88, or consists of SEQ ID NO:88;

[0549] (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 97, or consists of SEQ ID NO: 97; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 98, or consists of SEQ ID NO: 98;

[0550] (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 104, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 104, or consists of SEQ ID NO: 104; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 105, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 105, or consists of SEQ ID NO: 105;

[0551] (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 114, or consists of SEQ ID NO: 114; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 115, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 115, or consists of SEQ ID NO: 115;

[0552] (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 114, or consists of SEQ ID NO: 114; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 119, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 119, or consists of SEQ ID NO: 119;

[0553] (17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 125, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 125, or consists of SEQ ID NO: 125; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 126, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 126, or consists of SEQ ID NO: 126;

[0554] (18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 135, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 135, or consists of SEQ ID NO: 135; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 136, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 136, or consists of SEQ ID NO: 136;

[0555] (19) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 97, or consists of SEQ ID NO: 97; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 140, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 140, or consists of SEQ ID NO: 140;

[0556] (20) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 149, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 149, or consists of SEQ ID NO: 149; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 150, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 150, or consists of SEQ ID NO: 150;

[0557] (21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 158, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 158, or consists of SEQ ID NO: 158; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 159, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 159, or consists of SEQ ID NO: 159;

[0558] (22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 167, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 167, or consists of SEQ ID NO: 167; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 168, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 168, or consists of SEQ ID NO: 168;

[0559] (23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 172, or consists of SEQ ID NO: 172; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 173, or consists of SEQ ID NO: 173;

[0560] (24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 179, or consists of SEQ ID NO: 179; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 180, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 180, or consists of SEQ ID NO: 180;

[0561] (25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 189, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 189, or consists of SEQ ID NO: 189; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 190, or consists of SEQ ID NO: 190;

[0562] (26) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 198, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 198, or consists of SEQ ID NO: 198; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 199, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 199, or consists of SEQ ID NO: 199;

[0563] (27) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 204, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 204, or consists of SEQ ID NO: 204; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 205, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 205, or consists of SEQ ID NO: 205;

[0564] (28) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 214, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 214, or consists of SEQ ID NO: 214; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 215, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 215, or consists of SEQ ID NO: 215;

[0565] (29) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263;

[0566] (30) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260;

[0567] (31) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260;

[0568] (32) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262;

[0569] (33) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262;

[0570] (34) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263;

[0571] (35) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263;

[0572] (36) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265;

[0573] (37) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265;

[0574] (38) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265;

[0575] (39) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260;

[0576] (40) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266;

[0577] (41) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266;

[0578] (42) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266;

[0579] (43) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267;

[0580] (44) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267;

[0581] (45) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267;

[0582] (46) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262.

[0583] In a specific embodiment, the present invention provides an anti-MUC17 antibody and an antigen-binding fragment thereof that specifically binds to MUC17, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:

[0584] (1) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 7 or consists of SEQ ID NO: 7; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 8 or consists of SEQ ID NO: 8;

[0585] (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17 or consists of SEQ ID NO: 17; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 18 or consists of SEQ ID NO: 18;

[0586] (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24 or consists of SEQ ID NO: 24; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 25 or consists of SEQ ID NO: 25;

[0587] (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24 or consists of SEQ ID NO: 24; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 31 or consists of SEQ ID NO: 31;

[0588] (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34 or consists of SEQ ID NO: 34; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 35 or consists of SEQ ID NO: 35;

[0589] (6) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 40 or consists of SEQ ID NO: 40; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 41 or consists of SEQ ID NO: 41;

[0590] (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47 or consists of SEQ ID NO: 47; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 48 or consists of SEQ ID NO: 48;

[0591] (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 47 or consists of SEQ ID NO: 47; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 53 or consists of SEQ ID NO: 53;

[0592] (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 59 or consists of SEQ ID NO: 59; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 60 or consists of SEQ ID NO: 60;

[0593] (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 69 or consists of SEQ ID NO: 69; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 70 or consists of SEQ ID NO: 70;

[0594] (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 77 or consists of SEQ ID NO: 77; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 78 or consists of SEQ ID NO: 78;

[0595] (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 87 or consists of SEQ ID NO: 87; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 88 or consists of SEQ ID NO: 88;

[0596] (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97 or consists of SEQ ID NO: 97; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 98 or consists of SEQ ID NO: 98;

[0597] (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 104 or consists of SEQ ID NO: 104; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 105 or consists of SEQ ID NO: 105;

[0598] (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114 or consists of SEQ ID NO: 114; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 115 or consists of SEQ ID NO: 115;

[0599] (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114 or consists of SEQ ID NO: 114; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 119 or consists of SEQ ID NO: 119;

[0600] (17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 125 or consists of SEQ ID NO: 125; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 126 or consists of SEQ ID NO: 126;

[0601] (18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 135 or consists of SEQ ID NO: 135; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 136 or consists of SEQ ID NO: 136;

[0602] (19) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 97 or consists of SEQ ID NO: 97; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 140 or consists of SEQ ID NO: 140;

[0603] (20) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 149 or consists of SEQ ID NO: 149; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 150 or consists of SEQ ID NO: 150;

[0604] (21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 158 or consists of SEQ ID NO: 158; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 159 or consists of SEQ ID NO: 159;

[0605] (22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 167 or consists of SEQ ID NO: 167; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 168 or consists of SEQ ID NO: 168;

[0606] (23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 172 or consists of SEQ ID NO: 172; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 173 or consists of SEQ ID NO: 173;

[0607] (24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 179 or consists of SEQ ID NO: 179; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 180 or consists of SEQ ID NO: 180;

[0608] (25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 189 or consists of SEQ ID NO: 189; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 190 or consists of SEQ ID NO: 190;

[0609] (26) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 198 or consists of SEQ ID NO: 198; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 199 or consists of SEQ ID NO: 199;

[0610] (27) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 204 or consists of SEQ ID NO: 204; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 205 or consists of SEQ ID NO: 205;

[0611] (28) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 214 or consists of SEQ ID NO: 214; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 215 or consists of SEQ ID NO: 215;

[0612] (29) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 259 or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 263 or consists of SEQ ID NO: 263;

[0613] (30) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259 or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260 or consists of SEQ ID NO: 260;

[0614] (31) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 261 or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 260 or consists of SEQ ID NO: 260;

[0615] (32) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259 or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262 or consists of SEQ ID NO: 262;

[0616] (33) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 261 or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 262 or consists of SEQ ID NO: 262;

[0617] (34) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264 or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263 or consists of SEQ ID NO: 263;

[0618] (35) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261 or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263 or consists of SEQ ID NO: 263;

[0619] (36) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264 or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265 or consists of SEQ ID NO: 265;

[0620] (37) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259 or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265 or consists of SEQ ID NO: 265;

[0621] (38) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 261 or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 265 or consists of SEQ ID NO: 265;

[0622] (39) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 264 or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 260 or consists of SEQ ID NO: 260;

[0623] (40) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264 or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266 or consists of SEQ ID NO: 266;

[0624] (41) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259 or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266 or consists of SEQ ID NO: 266;

[0625] (42) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 261 or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 266 or consists of SEQ ID NO: 266;

[0626] (43) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264 or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267 or consists of SEQ ID NO: 267;

[0627] (44) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259 or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267 or consists of SEQ ID NO: 267;

[0628] (45) the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 261 or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 267 or consists of SEQ ID NO: 267;

[0629] (46) The heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 264 or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 262 or consists of SEQ ID NO: 262.

[0630] In some embodiments, the above-mentioned antibodies or antigen-binding fragments thereof further comprise a heavy constant region or a variant thereof derived from a human antibody germline consensus sequence, and a light chain constant region or a variant thereof, wherein the variant has one or more amino acid substitutions, deletions, or additions compared to the wild-type sequence from which it is derived (e.g., up to 20, up to 15, up to 10, or up to 5 amino acid substitutions, deletions, or additions; for example, 1, 2, 3, 4, or 5 amino acid substitutions, deletions, or additions). In some embodiments, the heavy chain constant region is an IgG heavy chain constant region, such as an IgG1, IgG2, IgG3, or IgG4 heavy chain constant region; and the light chain constant region is selected from a kappa or lambda light chain constant region. In another embodiment, the heavy chain constant region comprises or consists of the sequence set forth in SEQ ID NO: 223. In one embodiment, the light chain constant region comprises or consists of the sequence set forth in SEQ ID NO: 224.

[0631] It will be appreciated that sequence variants of these constant region domains may also be used, for example comprising one or more amino acid modifications, wherein amino acid positions are identified according to the EU index system of Kabat et al. (1991).

[0632] As a specific embodiment, the heavy chain variable region (VH) and / or the light chain variable region (VL) are defined by the Kabat numbering system.

[0633] As a specific embodiment, the heavy chain variable region (VH) and / or the light chain variable region (VL) are defined by the AbM numbering system.

[0634] In one embodiment, the present invention provides an anti-MUC17 antibody and antigen-binding fragment thereof that specifically binds to MUC17, comprising a heavy chain and a light chain, wherein:

[0635] (1) the heavy chain comprises the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 9, or consists of SEQ ID NO: 9; the light chain comprises the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 10, or consists of SEQ ID NO: 10;

[0636] (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 19, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 19, or consists of SEQ ID NO: 19; the light chain comprises the amino acid sequence of SEQ ID NO: 20, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 20, or consists of SEQ ID NO: 20;

[0637] (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 26, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 26, or consists of SEQ ID NO: 26; the light chain comprises the amino acid sequence of SEQ ID NO: 27, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 27, or consists of SEQ ID NO: 27;

[0638] (4) the heavy chain comprises the amino acid sequence of SEQ ID NO:26, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:26, or consists of SEQ ID NO:26; the light chain comprises the amino acid sequence of SEQ ID NO:32, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:32, or consists of SEQ ID NO:32;

[0639] (5) the heavy chain comprises the amino acid sequence of SEQ ID NO: 36, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 36, or consists of SEQ ID NO: 36; the light chain comprises the amino acid sequence of SEQ ID NO: 37, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 37, or consists of SEQ ID NO: 37;

[0640] (6) the heavy chain comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:42, or consists of SEQ ID NO:42; the light chain comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:43, or consists of SEQ ID NO:43;

[0641] (7) the heavy chain comprises the amino acid sequence of SEQ ID NO:49, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:49, or consists of SEQ ID NO:49; the light chain comprises the amino acid sequence of SEQ ID NO:50, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:50, or consists of SEQ ID NO:50;

[0642] (8) the heavy chain comprises the amino acid sequence of SEQ ID NO:49, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:49, or consists of SEQ ID NO:49; the light chain comprises the amino acid sequence of SEQ ID NO:54, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:54, or consists of SEQ ID NO:54;

[0643] (9) the heavy chain comprises the amino acid sequence of SEQ ID NO:61, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:61, or consists of SEQ ID NO:61; the light chain comprises the amino acid sequence of SEQ ID NO:62, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:62, or consists of SEQ ID NO:62;

[0644] (10) the heavy chain comprises the amino acid sequence of SEQ ID NO:71, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:71, or consists of SEQ ID NO:71; the light chain comprises the amino acid sequence of SEQ ID NO:72, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:72, or consists of SEQ ID NO:72;

[0645] (11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 79, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 79, or consists of SEQ ID NO: 79; the light chain comprises the amino acid sequence of SEQ ID NO: 80, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 80, or consists of SEQ ID NO: 80;

[0646] (12) the heavy chain comprises the amino acid sequence of SEQ ID NO:89, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:89, or consists of SEQ ID NO:89; the light chain comprises the amino acid sequence of SEQ ID NO:90, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:90, or consists of SEQ ID NO:90;

[0647] (13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 99, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 99, or consists of SEQ ID NO: 99; the light chain comprises the amino acid sequence of SEQ ID NO: 100, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 100, or consists of SEQ ID NO: 100;

[0648] (14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 106, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 106, or consists of SEQ ID NO: 106; the light chain comprises the amino acid sequence of SEQ ID NO: 107, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 107, or consists of SEQ ID NO: 107;

[0649] (15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 116, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 116, or consists of SEQ ID NO: 116; the light chain comprises the amino acid sequence of SEQ ID NO: 117, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 117, or consists of SEQ ID NO: 117;

[0650] (16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 116, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 116, or consists of SEQ ID NO: 116; the light chain comprises the amino acid sequence of SEQ ID NO: 120, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 120, or consists of SEQ ID NO: 120;

[0651] (17) the heavy chain comprises the amino acid sequence of SEQ ID NO: 127, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 127, or consists of SEQ ID NO: 127; the light chain comprises the amino acid sequence of SEQ ID NO: 128, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 128, or consists of SEQ ID NO: 128;

[0652] (18) the heavy chain comprises the amino acid sequence of SEQ ID NO: 137, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 137, or consists of SEQ ID NO: 137; the light chain comprises the amino acid sequence of SEQ ID NO: 138, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 138, or consists of SEQ ID NO: 138;

[0653] (19) the heavy chain comprises the amino acid sequence of SEQ ID NO: 141, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 141, or consists of SEQ ID NO: 141; the light chain comprises the amino acid sequence of SEQ ID NO: 142, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 142, or consists of SEQ ID NO: 142;

[0654] (20) the heavy chain comprises the amino acid sequence of SEQ ID NO: 151, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 151, or consists of SEQ ID NO: 151; the light chain comprises the amino acid sequence of SEQ ID NO: 152, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 152, or consists of SEQ ID NO: 152;

[0655] (21) the heavy chain comprises the amino acid sequence of SEQ ID NO: 160, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 160, or consists of SEQ ID NO: 160; the light chain comprises the amino acid sequence of SEQ ID NO: 161, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 161, or consists of SEQ ID NO: 161;

[0656] (22) the heavy chain comprises the amino acid sequence of SEQ ID NO: 169, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 169, or consists of SEQ ID NO: 169; the light chain comprises the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 170, or consists of SEQ ID NO: 170;

[0657] (23) the heavy chain comprises the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 174, or consists of SEQ ID NO: 174; the light chain comprises the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 175, or consists of SEQ ID NO: 175;

[0658] (24) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 181, or consists of SEQ ID NO: 181; the light chain comprises the amino acid sequence of SEQ ID NO: 182, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 182, or consists of SEQ ID NO: 182;

[0659] (25) the heavy chain comprises the amino acid sequence of SEQ ID NO: 191, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 191, or consists of SEQ ID NO: 191; the light chain comprises the amino acid sequence of SEQ ID NO: 192, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 192, or consists of SEQ ID NO: 192;

[0660] (26) the heavy chain comprises the amino acid sequence of SEQ ID NO: 200, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 200, or consists of SEQ ID NO: 200; the light chain comprises the amino acid sequence of SEQ ID NO: 201, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 201, or consists of SEQ ID NO: 201;

[0661] (27) the heavy chain comprises the amino acid sequence of SEQ ID NO: 206, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 206, or consists of SEQ ID NO: 206; the light chain comprises the amino acid sequence of SEQ ID NO: 207, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 207, or consists of SEQ ID NO: 207;

[0662] (28) The heavy chain comprises the amino acid sequence of SEQ ID NO: 216, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 216, or consists of SEQ ID NO: 216; the light chain comprises the amino acid sequence of SEQ ID NO: 217, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 217, or consists of SEQ ID NO: 217.

[0663] In the antibody embodiments of any of the preceding items, the antibody is a monoclonal antibody.

[0664] In an antibody embodiment of any of the preceding items, the antibody is a full length antibody.

[0665] In some embodiments, the antibody or antigen-binding fragment of the present invention is a murine antibody, a chimeric antibody, a humanized antibody, or a fully human antibody.

[0666] In some embodiments, the anti-MUC17 antibodies of the invention are whole antibodies, eg, IgG1, IgG2, IgG3, IgG4 antibodies.

[0667] In another embodiment, the anti-MUC17 antibodies of the present invention encompass only the antigen-binding portion thereof, such as Fab, Fab'-SH, Fv, scFv, or (Fab')2 fragments.

[0668] In another aspect, the present invention provides an isolated polynucleotide molecule encoding any one of the MUC17 antibodies or antigen-binding fragments thereof described herein.

[0669] In another aspect, the present invention provides an expression vector comprising the nucleotide molecule of the present invention. In one embodiment, the vector is a eukaryotic expression vector.

[0670] In another aspect, the present invention provides a host cell comprising the expression vector or nucleotide molecule of the present invention. In some embodiments, the host cell is prokaryotic, such as Escherichia coli. In other embodiments, the host cell is eukaryotic, such as 293 cells, CHO cells, yeast cells, or plant cells.

[0671] Furthermore, the present invention provides a pharmaceutical composition comprising the anti-MUC17 antibody or antigen-binding fragment thereof described in the present invention, or the polynucleotide molecule described in the present invention, or the expression vector described in the present invention, or the host cell described in the present invention, and a pharmaceutically acceptable carrier or excipient.

[0672] The present invention provides a method for preparing the anti-MUC17 antibody or antigen-binding fragment thereof described herein, comprising expressing the antibody or antigen-binding fragment thereof in a host cell described herein under conditions suitable for expression of the antibody or antigen-binding fragment thereof, and recovering the expressed antibody or antigen-binding fragment thereof from the host cell or a culture medium containing the host cell.

[0673] The anti-MUC17 antibodies or antigen-binding fragments thereof or pharmaceutical compositions of the present invention can also be administered in combination with one or more other therapies, such as treatment modalities and / or other therapeutic agents, for the purposes described herein, such as for preventing and / or treating the diseases or conditions mentioned herein.

[0674] The present invention also provides pharmaceutical combinations comprising an antibody or antigen-binding fragment thereof or a pharmaceutical composition as described herein, and one or more additional therapeutic agents.

[0675] The present invention provides a method for preventing or treating a MUC17-mediated disease in a subject in need thereof, comprising administering to the subject a prophylactically or therapeutically effective amount of an antibody or antigen-binding fragment thereof, a polynucleotide molecule described herein, an expression vector described herein, a host cell described herein, a pharmaceutical composition described herein, or a pharmaceutical combination described herein, wherein the disease or condition is a MU17-related tumor and / or cancer, and the tumor and / or cancer is gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, large intestine cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer, and rectal cancer.

[0676] The present invention provides for the use of an antibody or antigen-binding fragment thereof, a polynucleotide molecule, an expression vector, a host cell, a pharmaceutical composition, or a pharmaceutical combination as described herein in the preparation of a medicament for treating and / or preventing a disease or condition mediated by MUC17. In one embodiment, the disease or condition is a MUC17-associated tumor and / or cancer. In one embodiment, the MUC17-associated tumor and / or cancer is selected from gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, colorectal cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer, and rectal cancer.

[0677] In one embodiment, the present invention provides an antibody or antigen-binding fragment thereof described herein, a polynucleotide molecule described herein, an expression vector described herein, a host cell described herein, a pharmaceutical composition described herein, or a pharmaceutical combination described herein for use as a medicament.

[0678] In one embodiment, the present invention provides an antibody or antigen-binding fragment thereof described herein, a polynucleotide molecule described herein, an expression vector described herein, a host cell described herein, a pharmaceutical composition described herein, or a pharmaceutical combination described herein for use in therapy.

[0679] In one embodiment, the present invention provides an antibody or antigen-binding fragment thereof as described herein, a polynucleotide molecule as described herein, an expression vector as described herein, a host cell as described herein, a pharmaceutical composition as described herein, or a pharmaceutical combination as described herein for use in treating a MUC17-associated tumor and / or cancer. In one embodiment, the MUC17-associated tumor and / or cancer is selected from gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, large intestine cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer, and rectal cancer.

[0680] The present invention also provides a kit comprising an anti-MUC17 antibody or antigen-binding fragment thereof of the present invention, a polynucleotide molecule of the present invention, an expression vector of the present invention, a host cell of the present invention, a pharmaceutical composition of the present invention, or a pharmaceutical combination of the present invention, and instructions for use. The kit may also comprise a suitable container. In certain embodiments, the kit further comprises a device for administration. The kit generally includes a label indicating the intended use and / or instructions for use of the kit contents. The term "label" includes any written or recorded material on, provided with, or otherwise provided with the kit.

[0681] The present invention provides a method for detecting the presence of MUC17 in a sample using the antibody or antigen-binding fragment thereof of the present invention or a detection composition containing the antibody or antigen-binding fragment thereof.

[0682] The present invention provides a method for detecting MUC17, wherein a sample to be detected is contacted with the antibody or antigen-binding fragment of the present invention under conditions where a complex can be formed between the antibody or antigen-binding fragment of the present invention and MUC17.

[0683] In some embodiments, the antibodies or antigen-binding fragments thereof described herein are linked to a detectable label.

[0684] In some embodiments, the detectable label is selected from an enzyme (e.g., horseradish peroxidase or alkaline phosphatase), a chemiluminescent reagent (e.g., acridinium ester compounds, luminol and its derivatives, or ruthenium derivatives), a fluorescent dye (e.g., fluorescein or fluorescent protein), a radionuclide, or biotin.

[0685] In some embodiments, the method for detecting MUC17 further comprises: after contacting the sample to be tested with the antibody or antigen-binding fragment of the present invention, using another reagent (e.g., a secondary antibody) to specifically recognize the antibody or antigen-binding fragment of the present invention. In some embodiments, the other reagent (e.g., a secondary antibody) further comprises a detectable label, such as an enzyme (e.g., horseradish peroxidase or alkaline phosphatase), a chemiluminescent reagent (e.g., an acridinium ester compound, luminol and its derivatives, or a ruthenium derivative), a fluorescent dye (e.g., fluorescein or fluorescent protein), a radionuclide, or biotin.

[0686] The present invention provides a kit comprising the antibody or antigen-binding fragment thereof, expression vector, host cell, polynucleotide fragment or pharmaceutical composition according to the present invention.

[0687] The present invention provides a detection system comprising the antibody or antigen-binding fragment thereof according to the present invention. The present invention also provides use of the detection system in a diagnostic method.

[0688] In some embodiments, in the detection system, the antibody or antigen-binding fragment thereof described herein is free or binds to an antigen (e.g., an antigen present in a sample to be tested) to form a complex. Therefore, in some embodiments, the detection system further comprises a complex of the antibody or antigen-binding fragment thereof described herein bound to an antigen.

[0689] In some embodiments, the antibodies or antigen-binding fragments thereof described herein are linked to a detectable label.

[0690] In some embodiments, the detectable label is selected from an enzyme (e.g., horseradish peroxidase or alkaline phosphatase), a chemiluminescent reagent (e.g., acridinium ester compounds, luminol and its derivatives, or ruthenium derivatives), a fluorescent dye (e.g., fluorescein or fluorescent protein), a radionuclide, or biotin.

[0691] In some embodiments, the detection system further comprises other reagents (e.g., a second antibody) that specifically recognize the antibody or antigen-binding fragment thereof described herein. In some embodiments, the other reagents (e.g., a second antibody) further comprise a detectable label, such as an enzyme (e.g., horseradish peroxidase or alkaline phosphatase), a chemiluminescent reagent (e.g., an acridinium ester compound, luminol and its derivatives, or a ruthenium derivative), a fluorescent dye (e.g., fluorescein or fluorescent protein), a radionuclide, or biotin.

[0692] The present invention provides a method for detecting tumor growth, comprising using the antibody or antigen-binding fragment thereof of the present invention to determine the expression level of MUC17 in a sample from a patient suspected of having cancer and optionally a negative control sample and further optionally a positive control sample.

[0693] The method of detecting tumor growth of the present invention comprises: determining the expression level of MUC17 in a sample from a patient suspected of having cancer and in a negative control sample, further comprising comparing the expression level of MUC17 between these samples, optionally wherein the expression level in the negative control and / or the positive control can be derived from stored data of at least one negative control sample and / or at least one positive control sample obtained in the method of detecting tumor growth, the method comprising determining the expression level of MUC17, further optionally wherein the expression level in the negative control sample and / or the positive control sample can be derived from stored data comprising the average expression level of more than one negative control sample and / or more than one positive control sample obtained in the method of detecting tumor growth, the method comprising determining the expression level of MUC17.

[0694] The samples and controls in the detection method of the present invention can be positive expressing cells, solid tissue samples or liquid tissue samples.

[0695] The present invention provides a method for detecting and / or quantifying MUC17 in a sample, comprising (a) using an antibody according to any one of the preceding embodiments or produced according to any one of the preceding embodiments, or using a detection system as described above, to determine the amount of MUC17 expression in the sample; and (b) comparing the amount of MUC17 expression determined in step (a) with: (i) a predefined value for MUC17 expression, (ii) the amount of MUC17 expression determined in a control sample, or (iii) the amount of MUC17 expression determined in a sample obtained from the same source or subject at a previous time point.

[0696] The antibody or antigen-binding fragment thereof targeting human MUC17 provided by the present invention has the following advantages:

[0697] (1) Binds to target cells expressing human MUC17 with high affinity, ranging from 10-100 nM, more preferably from 0-10 nM; and has cross-binding activity with monkey antigens;

[0698] (2) Ability to enter cells through endocytosis and kill target cells; in some embodiments, the antibodies of the present invention have high endocytosis efficiency;

[0699] (3) treating, preventing, or improving a subject's MUC17-related disorder (e.g., cancer), or treating, preventing, or improving one or more symptoms of the disease;

[0700] (4) reducing or inhibiting tumor growth or progression in a subject;

[0701] (5) inducing MUC17-related tumor regression (e.g., long-term regression);

[0702] (6) Exerts cytotoxic activity in MUC17-related cells.

[0703] In another aspect of the present invention, the present invention provides an anti-MUC17 antibody drug conjugate, an isomer thereof, a pharmaceutically acceptable salt thereof, or a mixture thereof as described in formula (I):

[0704] Ab-(LD)m[Formula (I)]

[0705] in,

[0706] L is the joint unit;

[0707] D is a small molecule drug with cytotoxicity;

[0708] m is the average number of LD units coupled to Ab, and m is selected from 1 to 10, preferably 2 to 8;

[0709] Ab is an anti-MUC17 antibody or an antigen-binding fragment thereof, preferably the anti-MUC17 antibody or an antigen-binding fragment thereof described above.

[0710] In some embodiments, the small molecule drug D of the present invention is a monomethyl auristatin compound, a camptothecin compound, or a maytansine alkaloid.

[0711] In some embodiments, the monomethyl auristatin compound may be monomethyl auristatin E (MMAE).

[0712] or monomethyl auristatin F (MMAF)

[0713] In some embodiments, the maytansine alkaloid may be DM1, DM3 or DM4.

[0714] In some embodiments, the camptothecin derivative compound may be

[0715] In some embodiments, the antibody drug conjugate comprises multiple D components, and the multiple D components can be a combination of different therapeutically active substances or pharmaceutically active ingredients, or a combination of the same therapeutically active substance or pharmaceutically active ingredient.

[0716] In some embodiments, the antibody drug conjugate has a drug to antibody ratio (DAR) of 1-15, such as a DAR of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

[0717] In some embodiments, the DAR is an average DAR.

[0718] In some embodiments, the average DAR is 1-15, such as 1-10.

[0719] As a specific embodiment, the average DAR of the antibody-drug conjugate of the present invention is preferably 2-10, such as 2-8.

[0720] As a specific embodiment, when D is a camptothecin compound, the average DAR of the antibody-drug conjugate of the present invention is preferably 4-8.

[0721] In some embodiments, the cytotoxin is covalently linked to the anti-MUC17 antibody or antigen-binding fragment thereof in a non-site-specific manner or in a site-specific manner via a linker.

[0722] As used herein, "linker," "linker unit," and "linker" are used interchangeably.

[0723] The "drug-containing linker" used in the present invention refers to a compound obtained by directly or indirectly covalently bonding a drug, such as a small molecule drug with cytotoxicity as described in D, to a linker.

[0724] In some embodiments, the L is a combination of one or more L'.

[0725] In some embodiments, the L' is selected from carbonyl, amino, amide, aminoacyl, -(PEG) n -、-(CH2) n -, containing heteroatoms -(CH2) n -, -(C≡C)-, -(CH=CH)-, -O-, -S-, maleimido (mc), maleimidopropionyl (MP), methylsulfonylpyrimidinyl, valine-citrulline (val-cit), valine-alanine (val-ala), N-succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), alanine-phenylalanine (ala-phe), phenylalanine-lysine (phe-lys), p-aminobenzyloxycarbonyl (PAB), dimethylethylenediamine (DMED), N-succinimidyl-4-(2 -pyridylthio) pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (SMCC), N-succinimidyl (4-iodo-acetyl) aminobenzoate (SIAB), N-succinimidyl-4-(2-pyridyldithio) butyrate (SPDB), N-succinimidyl 3-(pyridin-2-yldithio)-propionate (SPDP), glycine-glycine-phenylalanine-glycine (GGFG), acetyl-lysine-valine-citrulline-p-aminobenzyloxycarbonyl (AcLys-vc-PABC).

[0726] In some embodiments, n is independently selected from integers ranging from 1 to 20.

[0727] As a specific embodiment, when L' is selected as (PEG) n When n is independently preferably 2, 4, 6 or 8.

[0728] As a specific embodiment, when L' is selected as (CH2) n When n is independently an integer of 1 to 16,

[0729] As a specific embodiment, when L' is selected as (CH2) containing heteroatoms nWhen n is independently an integer of 1 to 16, the heteroatom is selected from N, O or S, and the number of heteroatoms is independently an integer of 1 to 8.

[0730] In some embodiments, the L may be J-L1-L2-X-L3.

[0731] In some embodiments, the J is selected from

[0732] In some embodiments, L1 is selected from a single bond, -(PEG) n -or-(CH2) n -, the -(CH2) n - may optionally contain 1 to 6 heteroatoms selected from N, O, and S; wherein n is independently selected from an integer from 1 to 20. Preferably, L1 is selected from -(PEG) n -, wherein n is independently 2, 4, 6 or 8.

[0733] In some embodiments, L2 is selected from a single bond, -O-, -S-, -CH2-, -NH-, -C(O)-, or a combination of one or more thereof; wherein the -CH2- and -NH- may be optionally replaced by C 1～6 Alkyl or halogen substituted 1 to 3 times.

[0734] In some embodiments, X is selected from a single bond or a combination of 1 to 4 X', wherein X' is independently selected from amino acids, such as glycine, alanine, phenylalanine, valine, lysine, and citrulline. In some embodiments, X is selected from a single bond or valine-citrulline (val-cit), valine-alanine (val-ala), alanine-phenylalanine (ala-phe), phenylalanine-lysine (phe-lys), glycine-glycine-phenylalanine-glycine (GGFG).

[0735] In some embodiments, L3 is selected from a single bond, -O-, -S-, -CH2-, -NH-, -C(O)-, -phenyl-, -cyclopropyl-, -cyclobutyl-, -cyclohexyl-, or a combination of one or more thereof; wherein the -CH2-, -NH-, -phenyl-, -cyclopropyl-, -cyclobutyl-, -cyclohexyl- may be optionally replaced by C 1～6 Alkyl, halogen, cyano or hydroxyl groups are substituted 1 to 3 times.

[0736] Furthermore, the present invention provides three linker units of formula (LD) - cytotoxic small molecule drugs, as shown in formula Cpd3, formula Cpd5 and formula Cpd6:

[0737] In some embodiments, the linker units and cytotoxic small molecule drugs (linker-toxins) provided herein, such as those represented by Formulas Cpd3, Cpd5, and Cpd6, are suitable for conjugating antibodies, such as anti-MUC17 antibodies or antigen-binding fragments thereof, or HER2 antibodies or antigen-binding fragments thereof, with high conjugation efficiency and mild reaction conditions. For example, as demonstrated in the following examples, Cpd3, as a hydrophilic linker-toxin, can be used to prepare ADCs with high DAR values ​​(DAR of approximately 8) while maintaining excellent purity.

[0738] In some embodiments, the present invention provides an anti-MUC17 antibody drug conjugate, an isomer thereof, a pharmaceutically acceptable salt thereof, or a mixture thereof, wherein the anti-MUC17 antibody drug conjugate has a structure as shown in Formula (I-C3), Formula (I-C5), and Formula (I-C6):

[0739] in,

[0740] m is the average number of connections, and m is independently selected from 1 to 10, such as 2 to 8, especially 4 to 8;

[0741] Ab is the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0742] In some embodiments, the Ab of the present invention comprises three complementarity determining regions (HCDRs) from the heavy chain variable region, HCDR1, HCDR2, and HCDR3, which are the complementarity determining regions (HCDRs) of the heavy chain variable region of the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0743] In some embodiments, the Ab of the present invention comprises three complementarity determining regions (LCDRs) from the light chain variable region, LCDR1, LCDR2, and LCDR3, which are the complementarity determining regions (LCDRs) of the light chain variable region of the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0744] In some embodiments, the Ab of the present invention comprises three complementarity determining regions (HCDRs) from the heavy chain variable region and three complementarity determining regions (LCDRs) from the light chain variable region, which are the complementarity determining regions (HCDRs) of the heavy chain variable region and the complementarity determining regions (LCDRs) of the light chain variable region of the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0745] In some embodiments, Ab comprises a heavy chain variable region (VH), which is the heavy chain variable region (VH) of the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0746] In some embodiments, the heavy chain variable region comprises three complementarity determining regions (HCDRs) from a heavy chain variable region.

[0747] In some embodiments, the Ab comprises a light chain variable region (VL), which is the light chain variable region (VL) of the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0748] In some embodiments, the light chain variable region comprises three complementarity determining regions (LCDRs) from a heavy chain variable region.

[0749] In some embodiments, the heavy chain variable region (VH) and light chain variable region (VL) of Ab are the heavy chain variable region (VH) and light chain variable region (VL) of the aforementioned anti-MUC17 antibody or antigen-binding fragment thereof of the present invention.

[0750] The present invention provides an antibody-drug conjugate targeting human MUC17, its isomer, its pharmaceutically acceptable salt or a mixture thereof, wherein the antibody-drug conjugate has the following advantages:

[0751] (1) Binds to target cells expressing human MUC17 with high affinity, ranging from 10-100 nM, more preferably from 0-10 nM; and has cross-binding activity with monkey antigens;

[0752] (2) Ability to enter cells through endocytosis and kill target cells; in some embodiments, the ADC of the present invention has high endocytosis efficiency;

[0753] (3) treating, preventing, or improving a subject's MUC17-related disorder (e.g., cancer), or treating, preventing, or improving one or more symptoms of the disease;

[0754] (4) reducing or inhibiting the growth or progression of tumors (tumors associated with MUC17) in subjects;

[0755] (5) inducing MUC17-related tumor regression (e.g., long-term regression);

[0756] (6) exert cytotoxic activity in MUC17-related cells;

[0757] (7) It has bystander killing activity.

[0758] In another aspect, the present invention provides a use of the antibody-drug conjugate, wherein the antibody-drug conjugate is used for (1) preparing a diagnostic reagent; and / or, (2) preparing a drug for preventing and / or treating MUC17-related diseases or conditions.

[0759] In another aspect, the present invention provides a use of an active ingredient, wherein the active ingredient is selected from: the heavy chain variable region (VH) of the anti-MUC17 antibody or its antigen-binding fragment described in the present invention; and / or, the light chain variable region (VL) of the anti-MUC17 antibody or its antigen-binding fragment described in the present invention; and / or, the heavy chain of the anti-MUC17 antibody or its antigen-binding fragment described in the present invention; and / or, the light chain of the anti-MUC17 antibody or its antigen-binding fragment described in the present invention; and / or, the antibody-drug conjugate targeting human MUC17, its isomers, pharmaceutically acceptable salts thereof, or mixtures thereof described in the present invention; the active ingredient is used for: (a) preparing a medicament for preventing and / or treating MUC17-related diseases or conditions; (b) a method for preventing or treating MUC17-mediated diseases; or (c) preparing a detection reagent, detection plate, or kit.

[0760] The present invention also provides a pharmaceutical composition comprising the anti-MUC17 antibody-drug conjugate, its isomers, its pharmaceutically acceptable salts or mixtures thereof, and a pharmaceutically acceptable carrier or excipient.

[0761] The present invention provides a pharmaceutical combination comprising the anti-MUC17 antibody-drug conjugate, its isomers, pharmaceutically acceptable salts thereof, or mixtures thereof, or the pharmaceutical composition, and one or more other therapeutic agents.

[0762] The present invention provides a kit comprising the anti-MUC17 antibody-drug conjugate, its isomers, its pharmaceutically acceptable salts or mixtures thereof, or the pharmaceutical composition.

[0763] The present invention provides use of the anti-MUC17 antibody-drug conjugate, its isomers, pharmaceutically acceptable salts thereof, or mixtures thereof, or the pharmaceutical composition, or the pharmaceutical combination, or the kit in preparing a medicament for treating and / or preventing MUC17-mediated diseases or conditions.

[0764] The present invention provides the anti-MUC17 antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof, or the pharmaceutical composition, or the pharmaceutical combination, or the kit described herein for use as a medicament.

[0765] The present invention provides the anti-MUC17 antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof, or the pharmaceutical composition, or the pharmaceutical combination, or the kit described herein for use in treatment.

[0766] The present invention provides the anti-MUC17 antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof, or the pharmaceutical composition, or the pharmaceutical combination, or the kit described herein for treating MUC17-related tumors and / or cancers.

[0767] In one embodiment, the MUC17-associated tumor and / or cancer is selected from gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, large intestine cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer, and rectal cancer.

[0768] The present invention provides a method for treating and / or preventing a disease or condition mediated by MUC17, comprising administering the antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof, or the pharmaceutical composition to a subject in need thereof.

[0769] In some embodiments, the MUC17-associated and / or MUC17-mediated disease or condition is a MUC17-associated cancer and / or tumor.

[0770] In some embodiments, the MUC17-associated cancer and / or tumor is selected from gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, large intestine cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer, and rectal cancer.

[0771] Furthermore, the present invention provides a method for preparing the aforementioned MUC17-targeting antibody-drug conjugate, its isomers, pharmaceutically acceptable salts thereof, or mixtures thereof, comprising: combining an antibody with a linker-toxin compound under conditions sufficient to form an antibody-drug conjugate.

[0772] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one.

[0773] Definition of terms

[0774] The practice of the present invention will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are within the skill of the art.

[0775] In order to make it easier to understand the present invention, certain scientific and technological terms are specifically defined as follows. Unless otherwise clearly defined in other parts of this article, the scientific and technological terms used herein have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs. Regarding the definitions and terms in this area, professionals can specifically refer to Current Protocols in Molecular Biology (Ausubel). The abbreviations of amino acid residues are standard 3-letter and / or 1-letter codes used in the art to refer to one of the 20 commonly used L-amino acids. The singular form used herein (including the claims) includes its corresponding plural form, unless otherwise clearly provided in the text.

[0776] The term "about" when used in conjunction with a numerical value is meant to encompass the numerical value within a range having a lower limit that is 5% less than the specified numerical value and an upper limit that is 5% greater than the specified numerical value.

[0777] The term "and / or" should be understood to mean any one of the alternatives or a combination of any two or more of the alternatives.

[0778] The term "MUC17" refers to any recombinant or naturally occurring form of mucin 17 (MUC17), variant or homolog thereof that maintains, for example, at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of the activity of MUC17. The variant or homolog has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the naturally occurring FGFR2 protein over the entire sequence or a partial sequence (e.g., a 50, 100, 150 or 200 contiguous amino acid portion).

[0779] The term "antibody" is used in the broadest sense herein and encompasses a variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen-binding activity. A complete antibody will generally comprise at least two full-length heavy chains and two full-length light chains, but may comprise fewer chains in certain circumstances, e.g., antibodies naturally occurring in camels may comprise only heavy chains.

[0780] The term "antigen binding molecule" is used in the broadest sense to refer to a molecule that specifically binds to an antigen. Exemplarily, antigen binding molecules include, but are not limited to, antibodies or antibody mimetics. "Antibody mimetics" refers to organic compounds or binding domains that are capable of specifically binding to an antigen but are unrelated to the structure of an antibody. Exemplarily, antibody mimetics include, but are not limited to, affibodies, affitins, affilins, designed ankyrin repeat proteins (DARPins), nucleic acid aptamers, or Kunitz-type domain peptides.

[0781] The term "anti-MUC17 antibody" refers to an antibody molecule that specifically binds to MUC17 and is capable of inhibiting MUC17 activity. The anti-MUC17 antibody can inhibit MUC17 activity relative to the absence of the MUC17 antibody, for example, by at least partially or completely blocking MUC17 stimulation, reducing, preventing, or delaying MUC17 activation, or inactivating, desensitizing, or downregulating MUC17 signaling, activity, or amount. In some embodiments, the antibody can inhibit MUC17 activity by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more, relative to a control.

[0782] The terms "MUC17-related cancers and / or tumors," "MUC17-mediated cancers and / or tumors," or "cancers and / or tumors associated with abnormal MUC1 expression" are used interchangeably to refer to various types of tumors that are commonly found in the gastrointestinal tract, pancreas, liver, gallbladder, and other parts of the body due to abnormal expression, mutation, or dysfunction of the MUC17 gene or protein, which leads to abnormal cell proliferation, invasion, metastasis, and other malignant behaviors.

[0783] The term "antibody fragment" refers to a molecule other than an intact antibody that comprises a portion of an intact antibody and is capable of binding to the antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibodies (e.g., scFv); single-domain antibodies; bivalent or bispecific antibodies or fragments thereof; camelid antibodies (heavy chain antibodies); and multispecific antibodies (e.g., bispecific antibodies) formed from antibody fragments.

[0784] The term "valent" refers to the presence of a specified number of binding sites in an antibody / antigen-binding molecule. Thus, the terms "monovalent," "divalent," "tetravalent," and "hexavalent" refer to the presence of one, two, four, and six binding sites, respectively, in an antibody / antigen-binding molecule.

[0785] The terms "antigen-binding fragment" and "antibody fragment" are used interchangeably herein and do not have the entire structure of an intact antibody, but only comprise a portion or partial variant of an intact antibody that has the ability to bind to an antigen. "Antigen-binding fragment" or "antibody fragment" herein includes, but is not limited to, Fab, Fab', Fab'-SH, F(ab')2, Fd, Fv, scFv, diabodies, and single-domain antibodies.

[0786] The term "chimeric antibody" refers to an antibody in which a portion of its light chain and / or heavy chain is derived from one antibody (which may be derived from a particular species or belong to a particular antibody class or subclass), and another portion of its light chain and / or heavy chain is derived from another antibody (which may be derived from the same or different species or belong to the same or different antibody class or subclass), but in any case, it still retains binding activity to the target antigen. For example, the term "chimeric antibody" may include antibodies (e.g., human-mouse chimeric antibodies) in which the heavy and light chain variable regions of the antibody are derived from a first antibody (e.g., a murine antibody), and the heavy and light chain constant regions of the antibody are derived from a second antibody (e.g., a human antibody).

[0787] The term "humanized antibody" refers to a non-human antibody that has been genetically engineered and whose amino acid sequence has been modified to increase homology with the sequence of a human antibody. Generally speaking, all or part of the CDR region of a humanized antibody comes from a non-human antibody (donor antibody), and all or part of the non-CDR region (e.g., variable region FR and / or constant region) comes from a human immunoglobulin (recipient antibody). Humanized antibodies generally retain or partially retain the expected properties of the donor antibody, including but not limited to antigen specificity, affinity, reactivity, ability to increase immune cell activity, ability to enhance immune response, etc.

[0788] The term "fully human antibody" refers to an antibody having a variable region in which both FR and CDR are derived from human germline immunoglobulin sequences. In addition, if the antibody comprises a constant region, the constant region is also derived from human germline immunoglobulin sequences. Fully human antibodies herein may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutations in vivo). However, "fully human antibodies" herein do not include antibodies in which the CDR sequences derived from the germline of another mammalian species (e.g., mouse) have been transplanted to human framework sequences.

[0789] The term "variable region" or "variable domain" refers to the domain of an antibody heavy chain or light chain that is involved in binding an antibody to an antigen. The variable domains of the heavy and light chains of natural antibodies generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three complementarity determining regions (CDRs) (see, e.g., Kindt et al., Kuby Immunology, 6th ed., WH Freeman and Co., p. 91 (2007)). A single VH or VL domain is sufficient to confer antigen binding specificity.

[0790] The term "complementarity determining region" or "CDR region" or "CDR" is a region in an antibody variable domain that is highly variable in sequence and forms structurally defined loops ("hypervariable loops") and / or contains antigen contact residues ("antigen contact points"). CDRs are primarily responsible for binding to antigenic epitopes. The CDRs in the variable domain are typically referred to as CDR1, CDR2, and CDR3 and are numbered sequentially starting from the N-terminus. In a given variable region amino acid sequence, the precise amino acid sequence boundaries of each CDR can be determined using any one or a combination of a number of well-known antibody CDR assignment systems, including, for example, Chothia based on the three-dimensional structure of antibodies and the topology of the CDR loops (Chothia et al. (1989) Nature 342:877-883, Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), Kabat based on antibody sequence variability (Kabat et al., Sequences of Proteins of Immunological Interest, 4th Edition, US Department of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), International ImMunoGeneTics The IMGT database (http: / / imgt.cines.fr / ) and the North CDR definition were based on affinity propagation clustering using a large number of crystal structures.

[0791] It should be noted that the boundaries of the CDRs of the variable regions of the same antibody obtained based on different assignment systems may be different. That is, the CDR sequences of the variable regions of the same antibody defined under different assignment systems may be different. Therefore, when referring to antibodies defined by specific CDR sequences defined in the present invention, the scope of the antibodies also covers antibodies whose variable region sequences contain the specific CDR sequences, but whose claimed CDR boundaries are different from the specific CDR boundaries defined in the present invention due to the application of different schemes (e.g., different assignment systems or combinations).

[0792] Unless otherwise indicated, in the present invention, the term "CDR" or "CDR sequence" encompasses CDR sequences determined in any of the above-mentioned ways.

[0793] CDRs can also be identified based on having the same Kabat or AbM numbering position as a reference CDR sequence (e.g., any of the CDRs exemplified herein). In some embodiments, the CDRs of the antibodies of the invention are positioned according to the Kabat or AbM numbering scheme.

[0794] Unless otherwise indicated, throughout the present invention, references to residue positions in antibody variable regions and CDRs (including heavy chain variable region residues) refer to positions numbered according to the Kabat or AbM numbering systems.

[0795] As used herein, the terms "comprising" or "including" are intended to include the recited elements, integers, or steps, but do not exclude any other elements, integers, or steps. In this document, when the terms "comprising" or "including" are used, unless otherwise indicated, the context of consisting of the recited elements, integers, or steps is also encompassed. For example, when reference is made to an antibody variable region "comprising" a specific sequence, it is intended to encompass an antibody variable region consisting of that specific sequence.

[0796] The term "Fc region" is used to define the C-terminal region of an immunoglobulin heavy chain that includes at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In some embodiments, the human IgG heavy chain Fc region extends from Cys226 or Pro230 to the carboxyl terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present (the numbering in this paragraph is according to the EU numbering system, also known as the EU index, as in Rabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991).

[0797] The term "conservative amino acid" generally refers to amino acids that belong to the same class or have similar characteristics (eg, charge, side chain size, hydrophobicity, hydrophilicity, main-chain conformation, and rigidity).

[0798] The term "affinity" or "binding affinity" refers to the intrinsic binding affinity that reflects the interaction between members of a binding pair. The affinity of a molecule X for its partner Y can generally be represented by the equilibrium dissociation constant (KD), which is the ratio of the dissociation rate constant and the association rate constant (kdis and kon, respectively). Affinity can be measured by common methods known in the art. One specific method for measuring affinity is the ForteBio kinetic binding assay herein.

[0799] The term "not binding" to a protein or cell means that the protein or cell does not bind to the protein or cell, or does not bind to the protein or cell with high affinity, i.e., the KD of the binding protein or cell is 1.0×10 -6 M or higher, more preferably 1.0×10 -5 M or higher, more preferably 1.0×10 -4 M or higher, 1.0×10 -3 M or higher, more preferably 1.0×10 -2 M or higher.

[0800] The term "high affinity" for IgG antibodies refers to a KD of 1.0 × 10 -6 M or less, preferably 5.0×10 -8 M or less, more preferably 1.0×10 -8 M or lower, 5.0×10 -9 M or less, more preferably 1.0×10 -9 M or lower. For other antibody subtypes, “high affinity” binding may vary. For example, “high affinity” binding for the IgM subtype is defined as a KD of 10 -6 M or less, preferably 10 -7 M or less, more preferably 10 -8 M or lower.

[0801] As used herein, the term "binding" or "specific binding" means that the binding effect is selective for the antigen and can be distinguished from unwanted or non-specific interactions. The ability of an antigen binding site to bind to a specific antigen can be determined by enzyme-linked immunosorbent assay (ELISA) or conventional binding assays known in the art, such as by radioimmunoassay (RIA) or thin-layer interferometry or MSD assays or surface plasmon resonance (SPR).

[0802] The term "median effective concentration (EC50) 50 )" refers to the concentration of drug, antibody or toxic agent that induces a response that is 50% between baseline and maximum after a specified exposure time.

[0803] The term "therapeutic agent" encompasses any substance effective in preventing or treating tumors, such as cancer, including chemotherapeutic agents, cytokines, angiogenesis inhibitors, cytotoxic agents, other antibodies, small molecule drugs, or immunomodulators (e.g., immunosuppressants).

[0804] The term "expression vector" refers to a nucleic acid molecule capable of amplifying another nucleic acid to which it is linked. The term includes vectors that are self-replicating nucleic acid structures as well as vectors that integrate into the genome of a host cell into which the vector has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as "expression vectors."

[0805] The term "host cell" refers to a cell into which an exogenous nucleic acid has been introduced, including the progeny of such a cell. Host cells include "transformants" and "transformed cells," which include the primary transformed cell and progeny derived therefrom, without regard to the number of passages. Progeny may not be completely identical to the parent cell in nucleic acid content, but may contain mutations. Mutant progeny having the same function or biological activity as that screened or selected for in the initially transformed cell are included herein.

[0806] The term "antibody drug conjugate" or "ADC" refers to an antibody or antibody fragment covalently coupled to a therapeutically active substance or active pharmaceutical ingredient, such that the therapeutically active substance or active pharmaceutical ingredient is targeted to the binding target of the antibody to exhibit its pharmacological function. The therapeutically active substance or active pharmaceutical ingredient may be a cytotoxin that can kill cells (preferably cancer cells) targeted by the ADC. The covalent attachment of the therapeutically active substance, active pharmaceutical ingredient, or cytotoxin may be performed in a non-site-specific manner using a linker, or in a site-specific manner.

[0807] The term "site-specific conjugation" refers to a method of specifically linking a therapeutically active substance or active pharmaceutical ingredient to a specific site of an antibody. In some embodiments, the conjugation is accomplished with the aid of a linker.

[0808] The term "cytotoxic agent" is used interchangeably with "cytotoxin" and, as used herein, refers to a substance that inhibits or disrupts cellular function and / or causes cell death or destruction.

[0809] The terms "linker," "linker unit," and "linker" are used interchangeably herein to refer to a chemical moiety that covalently links an antibody to a therapeutically active substance or active pharmaceutical ingredient in an ADC. In some embodiments, the linker may comprise amino acid residues that connect the antigen to the payload. The amino acid residues may form dipeptide, tripeptide, tetrapeptide, pentapeptide, hexapeptide, heptapeptide, octapeptide, nonapeptide, decapeptide, undecapeptide, or dodecapeptide units. The amino acid residues include naturally occurring ones as well as non-naturally occurring amino acid analogs, such as citrulline or β-amino acids, such as β-alanine, or ω-amino acids such as 4-amino-butyric acid.

[0810] According to the property classification, the linkers suitable for the present invention can be tissue protease-degradable linkers, such as valine-citrulline (val-cit) linkers, cBu-Cit linkers and CX linkers; non-cleavable linkers such as SMCC linkers or MD linkers; acid-sensitive linkers, silicone-structured linkers, disulfide-carbamate linkers, MC-GGFG linkers, TRX linkers, galactoside-containing linkers, pyrophosphate linkers, near-infrared-sensitive linkers, ultraviolet-sensitive linkers such as PC4AP.

[0811] The linker of the present invention can also be a combination of one or more linkers. For example, a cathepsin-degradable linker can be combined with other types of linkers to form a new linker. Therefore, the "linker" described in the present invention encompasses a single type of linker or a combination of different types of linkers, as long as it is capable of conjugating the antibody of the present invention to the drug.

[0812] The term "load" or "drug load" or "payable load" refers to the average effective load per antibody within the ADC molecule ("payable load" is used interchangeably herein with "therapeutically active substance or active pharmaceutical ingredient"). Drug load can range from 1-20 therapeutically active substances or active pharmaceutical ingredients per antibody. The term "drug / antibody ratio" or "DAR" refers to the ratio of the therapeutically active substance or active pharmaceutical ingredient (D) conjugated to the antibody to the antibody. The ADCs described herein typically have a DAR of 1-20, and in certain embodiments have a DAR of 1-8, 2-8, 2-6, 2-5, 2-18, 4-16, 5-12, 6-10, 3-8, 4-6, 6-10, and 2-4. Representative DAR values ​​are 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15, typically expressed as a combination of the letter D and a number, wherein the number represents the numerical value of the DAR, for example, D2 represents a drug / antibody ratio with a DAR value of 2. In some embodiments, the DAR is the average DAR, i.e., the total ratio of the small molecule drug moiety (D) coupled to the Ab moiety described herein to the Ab moiety in the product as measured by a detection method (e.g., by conventional methods such as UV / visible spectroscopy, mass spectrometry, ELISA assay, and HPLC). The DAR may be limited by the number of attachment sites on the antibody. For example, in the case where the attachment site is a cysteine ​​thiol, the antibody may have only one or a few cysteine ​​thiol groups or may have only one or a few sufficiently reactive thiol groups through which the drug can be attached.

[0813] The term "treat" refers to slowing, interrupting, arresting, alleviating, stopping, reducing, or reversing the progression or severity of an existing symptom, disorder, condition, or disease. Desired therapeutic effects include, but are not limited to, preventing the onset or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, ameliorating or alleviating the disease state, and alleviating or improving prognosis. In some embodiments, the antibodies of the present invention are used to delay disease development or to slow the progression of a disease.

[0814] The term "prevent" includes the inhibition of the development or progression of a disease or condition or symptoms of a particular disease or condition. In some embodiments, subjects with a family history of cancer are candidates for a preventative regimen. Generally, in the context of cancer, the term "prevent" refers to the administration of a drug before the development of signs or symptoms of cancer, particularly in a subject at risk for cancer.

[0815] The term "effective amount" refers to the amount or dosage of an antibody, conjugate, or composition of the invention that produces the desired effect in a patient in need of treatment or prevention after administration to the patient in a single or multiple doses. The effective amount can be readily determined by the attending physician, who is skilled in the art, by considering a variety of factors such as the species of mammal; weight, age, and general health; the specific disease involved; the extent or severity of the disease; the response of the individual patient; the specific antibody administered; the mode of administration; the bioavailability characteristics of the administered formulation; the selected dosing regimen; and the use of any concomitant therapy.

[0816] The term "therapeutically effective amount" refers to an amount effective to achieve the desired therapeutic outcome at the desired dosage and for the desired period of time. The therapeutically effective amount of an antibody or antibody fragment or conjugate or composition thereof can vary depending on a variety of factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody or antibody portion to elicit the desired response in the individual. A therapeutically effective amount is also an amount in which any toxic or deleterious effects of the antibody or antibody fragment or conjugate or composition are outweighed by the therapeutically beneficial effects. A "therapeutically effective amount" preferably inhibits a measurable parameter (e.g., tumor growth rate, tumor volume, etc.) by at least about 20%, more preferably at least about 40%, even more preferably at least about 50%, 60%, or 70%, and still more preferably at least about 80% or 90% relative to an untreated subject. The ability of a compound to inhibit a measurable parameter (e.g., cancer) can be evaluated in an animal model system that is predictive of efficacy in human tumors.

[0817] The term "prophylactically effective amount" refers to an amount effective to achieve the desired preventive result at the required dosage and for the required period of time. Typically, since a prophylactic dose is used in a subject before or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.

[0818] The term "pharmaceutical composition" refers to a composition that is in form permitting the biological activity of the active ingredient contained therein to be effective, and that contains no additional ingredients that are unacceptably toxic to a subject to which the composition would be administered.

[0819] The term "in combination with" refers to the administration of one or more additional therapeutic agents and includes simultaneous (concurrent) and consecutive administration in either order.

[0820] The term "pharmaceutically acceptable salt" refers to a salt of the drug conjugate of the present application. Such salts may be safe and / or effective when used in mammals and may have the desired biological activity. The antibody drug conjugate of the present application may form a salt with an acid.

[0821] The term "pharmaceutically acceptable carrier" refers to ingredients in a pharmaceutical preparation or composition other than the active ingredient that are non-toxic to the subject.

[0822] The term "subject" includes any human or non-human animal. The term "non-human animal" includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0823] Figure 1: Elisa detection of the binding of the recombinant antibodies M1 to M19 described in Example 6.1 to the huMucin17-His protein.

[0824] Figure 2: Elisa detection of the binding of the recombinant antibodies M20 to M27 described in Example 6.1 to the huMucin17-His protein.

[0825] Figure 3: Cross-species (monkey) binding assay of candidate antibodies described in Example 7.

[0826] Figure 4: Effects of the candidate antibody drug conjugates described in Example 12 on tumor volume in an animal model.

[0827] Figure 5: Results of the antibody endocytosis experiment described in Example 9.

[0828] FIG6 : FACS binding activity results of the humanized antibody described in Example 13.

[0829] Figure 7: Killing results of antibody drug conjugate M21-17-Cpd3 in tumor cells.

[0830] Figure 8: Experimental results of the bystander effect of the antibody drug conjugate M21-17-Cpd3.

[0831] FIG9 : The results of the inhibition of GSU tumor volume by the antibody drug conjugate M21-17-Cpd3.

[0832] FIG10 : The results of the inhibition of NUGC4 tumor volume by the antibody drug conjugate M21-17-Cpd3.

[0833] FIG11 : The results of the inhibition of SW480 tumor volume by the antibody drug conjugate M21-17-Cpd3.

[0834] Figure 12: SEC profile of antibody drug conjugate Trastuzumab-Cpd3.

[0835] Figure 13: HIC profile of the antibody-drug conjugate Trastuzumab-Cpd3.

[0836] Figure 14: RP profile of antibody drug conjugate Trastuzumab-Cpd3. DETAILED DESCRIPTION

[0837] The following examples further illustrate the present invention. However, it should be understood that the examples are described by way of illustration and not limitation, and that various modifications can be made by those skilled in the art. Where specific conditions are not specified in the examples, the experiments were carried out according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be obtained commercially.

[0838] In some embodiments, the present invention provides a method for producing an anti-MUC17 antibody, wherein the method comprises culturing a host cell comprising a nucleic acid encoding an anti-MUC17 antibody or an expression vector comprising the nucleic acid under conditions suitable for expression of the nucleic acid encoding the anti-MUC17 antibody, and optionally isolating the anti-MUC17 antibody. In certain embodiments, the method further comprises recovering the anti-MUC17 antibody from the host cell (or host cell culture medium).

[0839] To recombinantly produce an anti-MUC17 antibody of the invention, nucleic acid encoding the anti-MUC17 antibody of the invention is first isolated and inserted into a vector for further cloning and / or expression in a host cell. Such nucleic acid is readily isolated and sequenced using conventional procedures, for example, by using oligonucleotide probes that are capable of specifically binding to the nucleic acid encoding the anti-MUC17 antibody of the invention.

[0840] The anti-MUC17 antibodies of the present invention, prepared as described herein, can be purified by known techniques such as high performance liquid chromatography, ion exchange chromatography, gel electrophoresis, affinity chromatography, size exclusion chromatography, and the like. The actual conditions used to purify a particular protein will also depend on factors such as net charge, hydrophobicity, hydrophilicity, and the like, and will be apparent to those skilled in the art. The purity of the anti-MUC17 antibodies of the present invention can be determined by any of a variety of well-known analytical methods, including size exclusion chromatography, gel electrophoresis, high performance liquid chromatography, and the like.

[0841] The prior art describes various methods for conjugating cytotoxic agents or other therapeutic agents to antibodies. For example, conjugation can occur via the amino group of a lysine side chain and the amino group at the N-terminus of the antibody, the carboxyl group at the C-terminus of aspartic acid, glutamic acid, or an activated cysteine ​​sulfhydryl group in the antibody.

[0842] The sequence of the DNA molecule of the antibody of the present invention or its fragment can be obtained by conventional techniques, such as utilizing PCR amplification or genomic library screening. In addition, the coding sequences of the light chain and the heavy chain can be fused together to form a single-chain antibody.

[0843] Once the relevant sequence is obtained, it can be obtained in large quantities by recombinant methods. This is usually done by cloning it into a vector, then transferring it into cells, and then isolating the relevant sequence from the propagated host cells by conventional methods.

[0844] In addition, artificial synthesis methods can also be used to synthesize relevant sequences, especially when the sequence fragment length is short. Usually, a long sequence fragment can be obtained by synthesizing multiple small fragments first and then connecting them.

[0845] The practice of the present invention will employ, unless explicitly indicated to the contrary, conventional methods of chemistry, biochemistry, organic chemistry, molecular biology, microbiology, recombinant DNA techniques, genetics, immunology and cell biology, which are within the skill of the art.

[0846] The structures of the compounds disclosed herein can be confirmed by conventional methods well known to those skilled in the art. If the disclosure involves the absolute configuration of the compounds, the absolute configuration can be confirmed by conventional technical means in the art.

[0847] Compounds are named according to the conventional nomenclature in the art or using For software naming, commercially available compounds use the supplier's catalog name. When the compound name is inconsistent with the compound structure, the compound structure shall prevail.

[0848] Example 1: Preparation and identification of raw materials

[0849] 1.1 Preparation and identification of Mucin17 control antibodies

[0850] Preparation of Mucin17 control antibody: This application prepared the anti-Mucin17 antibody Tab1 as a positive control antibody with reference to the sequence disclosed in patent WO / 2021 / 188851. Gene synthesis was performed by GenScript Biotechnology to construct an expression plasmid. The specific heavy and light chain sequences of Tab-1 are shown in SEQ ID NO: 218 and SEQ ID NO: 219, respectively. Expi293F (Gibco) cells were transiently transfected, cultured for 6 days, and the supernatant was collected and purified using a Protein A affinity column (Cytiva).

[0851] Identification of Mucin17 control antibody: The activity of the prepared positive control antibody Tab-1 was detected using purchased Mucin17-His antigen protein (Acro Biosysterm, MU7-H52H3). The specific method is as follows: Mucin17-His (0.5 μg / mL, 100 μL / well) was coated on a 96-well ELISA plate and coated overnight at 4°C for 16 hours; after washing the plate once, it was blocked with 1% BSA prepared in PBS for 1 hour; after washing the plate three times, the control antibody Tab-1 was added in a gradient dilution with PBS and incubated at room temperature for 1 hour; after washing the plate, the secondary antibody: Anti-Human IgG (H&L) (GOAT) Antibody Peroxidase diluted in PBS was added. Conjugated (Rockland, 609-103-123) was incubated at 37°C for 1 hour, and the plate was washed three times. TMB was added and incubated at room temperature (25°C) for 5-20 minutes. After color development was stopped, the OD450 data was read using a microplate reader (Thermo Fisher Scientific (Shanghai) Instrument Co., Ltd., MultiskanFC). The results showed that the expressed control antibody Tab-1 bound to Mucin17-His protein in a concentration-dependent manner. EC 50 The concentration of the control antibody was 3.545 ng / ml, indicating that the control antibody had normal anti-Mucin17 activity.

[0852] Table 1: OD450 readings of control antibody Elisa binding assay

[0853] The sequences of the Tab1 heavy chain and light chain are shown in SEQ ID NO: 218 and SEQ ID NO: 219.

[0854] 1.2 Preparation of Mucin17 immune antigen

[0855] The extracellular domain of Mucin 17 (NP_001035194.1) was linked to a murine Fc fragment (SEQ ID NO: 220). Plasmid construction was commissioned by HOEKBIO and transiently transfected into Expi293F cells. After 6 days of culture, the supernatant was collected and purified using a Protein A affinity column. The eluate was collected and dialyzed at 2-8°C for 16 hours to replace the eluate. The antibody was then stored in a dialysis bag.

[0856] Antigen identification: Mucin17-Mouse FC (0.5 μg / mL, 100 μL / well) protein was coated on a 96-well ELISA plate and detected using Tab 1 antibody. The specific implementation method is shown in Example 1.1. The results showed that the expressed Mucin17-Mouse FC could be bound by Tab-1 in a concentration-dependent manner. EC 50 is 5.299ng / ml,

[0857] Example 2: Construction and identification of cell lines overexpressing human and monkey Mucin17

[0858] Construction of CHO-K1 (ECACC) cell lines overexpressing human and monkey Mucin17 (hereinafter referred to as huMucin17-CHO K1; cynoMucin17-CHO K1): The coding nucleic acid sequences of the extracellular region fragments of human Mucin17 protein (NP_001035194.1) and monkey Mucin17 protein (XM_045389603.1) SEQ ID NO: 221, 222 were constructed into a proprietary lentiviral vector (GenScript Pengbo Bio). Then, the lentiviral plasmid was transfected into HEK293T cells (Clontech, 632180) for viral packaging. After culturing for 4 days, the cell culture supernatant was collected. The harvested lentiviral supernatant was used to transfect CHO-K1 cells, and Puromycin was used as a screening pressure. After 3 days of screening, the antigen expression of the cell pool was screened by flow cytometry. After obtaining the positive cell pool, single cell clones were selected from the positive cell pool by limiting dilution or flow sorting. After single clone selection, continue culturing for 1 week for the identification of cell line antigen expression.

[0859] Flow cytometric identification of cell line antigen expression: Cells from the aforementioned cell lines in logarithmic growth phase were digested and plated into 96-well plates. After washing with FACS buffer (99% DPBS + 1% FBS), the primary antibody Tab 1 (10 ng / ml) was added and incubated at 4°C for 60 minutes. After washing, the prepared fluorescent secondary antibody, PE Goat anti-mouse IgG antibody (BioLegend, Cat. NO: 410708), was added and incubated at 4°C for 20 minutes. Finally, flow cytometry (BD FACS Celesta) was used to detect the expression of antigens in the huMucin17-CHO K1 and cynoMucin17-CHO K1 cell lines, which highly express human and monkey Mucin17 on their surfaces.

[0860] Example 3: Animal immunization and hybridoma cell screening

[0861] 3.1 Immunization regimen

[0862] Use the Mucin17-His or Mucin17-Mouse Fc protein antigen obtained in Example 2; Mucin17 expression plasmid-DNA antigen; Mucin17 overexpression CHO-K1 cells and multiple immunogens, alone or in combination, to immunize mice of different species (Balb / c, SJL, A / J). Depending on the type of antigen selected, immunize mice subcutaneously / intraperitoneally or by gene gun injection, once every two weeks, for a total of 3-5 immunizations. One week after the last immunization, collect mouse blood for immune titer testing, and finally, boost immunization with the above antigens once more.

[0863] 3.2 Detection of serum antibody titers in mice after immunization

[0864] Dilute the antigen to 0.5 μg / mL using coating solution, mix well, and add to the designed strips at 100 μL / well. Place in a 4°C refrigerator overnight for 16 hours. Discard the coating solution, wash the plate once, and pat dry the ELISA plate. Add 150 μL of blocking solution (1% BSA in PBS solution) to each well and place in a 37°C incubator (Shanghai Yiheng Scientific Co., Ltd.) for 1 hour. Remove the ELISA plate and discard the blocking solution. Serially dilute mouse serum and add 100 μL / well to the plate. Incubate in a 37°C incubator for 1 hour. Remove the ELISA plate, discard the internal solution, and wash the plate three times. Add 100 μL of diluted enzyme-labeled secondary antibody to each well and incubate in a 37°C incubator for 0.5 hours. Remove the ELISA plate, discard the internal solution, wash the plate three times, pat dry, add 100 μL of color development solution, and react at 25°C for 15 minutes. The reaction was terminated by adding 50 μL of 1 M HCl, and the OD at 450 nm was read using a microplate reader (Thermo Fisher Scientific (Shanghai) Instrument Co., Ltd., Multiskan FC). Mice with an immune titer greater than 512,000 were selected for hybridoma fusion.

[0865] 3.3 Hybridoma Cell Fusion

[0866] Prepare a myeloma cell (SP2 / 0, cell bank of the Chinese Academy of Sciences) suspension and calculate the total amount of SP2 / 0 cells using a hemocytometer. Prepare a spleen cell suspension and count the total number of cells using a hemocytometer. Take myeloma cells and spleen cells and mix them in a ratio of 1:2 for cell electrofusion. After cell fusion, mix the fused cells with HAT (Sigma) culture medium to make a cell suspension, and then use a multichannel pipette to spread the cells into a 96-well cell plate. Place the fused 96-well cell culture plate in a 5.5% carbon dioxide incubator and culture at a constant temperature of 37°C. After hybridoma cell culture, take the supernatant for mother clone screening, and screen the cell culture supernatant for antigen binding ability at the protein and cell levels. For specific screening methods, see Examples 1 and 2.

[0867] 3.4 Hybridoma subclone screening

[0868] After the first round of mother clone screening, retain the screened mother clone cell line. Use a pipette to gently blow the cells in the wells to be subcloned and mix them. Take out 20μl of cell suspension and add it to 20μl of trypan blue solution and mix it. Take out 20μl and count it with a hemocytometer. Using the limiting dilution method, replace the feeder cell culture medium with 1×HT and plate the cells in a 96-well cell culture plate. Mark the 96-well plate and culture it in a CO2 incubator. The 96-well plate after subcloning is placed in a 37°C, 5.5% carbon dioxide incubator for culture. After 7 days of culture, take the supernatant for single clone screening. For specific screening methods, see Examples 1 and 2.

[0869] After subclone screening, 28 antibodies were selected for sequencing, and the antibody sequences are shown in Table 2. The CDR sequences were determined using the Kabat and AbM definitions of CDR.

[0870] Table 2. Amino acid sequences of the CDR regions of 28 antibodies

[0871] Example 4: Antibody construction, expression and purification

[0872] 4.1 Plasmid construction

[0873] The VH coding sequence from the Fab sequences of 28 monoclonal clones was ligated with the coding sequence of the heavy chain constant region of human IgG1 (SEQ ID NO: 223) to obtain the heavy chain coding sequence of the human-mouse chimeric antibody. The VL coding sequence from the Fab sequence was ligated with the coding sequence of the kappa type human light chain constant region (CL) (SEQ ID NO: 224) to obtain the light chain coding sequence of the human-mouse chimeric antibody. The coding sequences of the antibody heavy and light chains were respectively inserted into a proprietary eukaryotic expression vector plasmid (pcDNA 3.4), transformed into Escherichia coli DH5α, and cultured overnight at 37°C. Plasmids were extracted using an endotoxin-free plasmid extraction kit (GenScript Biotech) to obtain endotoxin-free antibody plasmids for eukaryotic expression.

[0874] 4.2 Antibody Expression and Purification

[0875] Antibody expression: The full-length antibody sequence obtained above was expressed using the Expi293F transient expression system (Thermo Fisher, A14635) or the ExpiCHO-S transient expression system (Thermo Fisher, A29133). For specific methods, please refer to the corresponding kit operation guide of the supplier.

[0876] Antibody purification: The supernatant was collected and affinity purified using Protein A Magnetic Beads (GenScript Biotech). Protein A Magnetic Beads were added to the supernatant and incubated at room temperature for 2 hours. After incubation, the Protein A Magnetic Beads were equilibrated with Binding Buffer (PBS) for 10 column volumes. Elution buffer (0.1 M Glycine, pH 2.5) was added to the Protein A Magnetic Beads. The eluate was collected and adjusted to neutral pH by adding 1 / 10 volume of the eluate with Neutralizing Buffer (0.1 M Tris pH 9.0). After elution, the Protein A Magnetic Beads were equilibrated with Binding Buffer for 10 column volumes. The eluted and neutralized antibody was placed in a dialysis bag and dialyzed against Dialysis Buffer (PBS) at room temperature for 2 hours. The buffer was then replaced with Dialysis Buffer and dialyzed at 2-8°C for 16 hours. The antibody was transferred from the dialysis bag to a centrifuge tube and the volume was recorded.

[0877] Example 5: Detection of physicochemical properties of antibodies

[0878] In this example, the relative molecular weight and purity of the candidate antibodies were detected by SDS-PAGE and SEC-HPLC.

[0879] Antibody SDS-PAGE identification

[0880] Preparation of non-reducing solution: 3 μg of each obtained antibody was added to 2× SDS loading buffer, heated in a 99°C dry bath for 5 min, cooled to room temperature, and centrifuged at 12,000 rpm for 5 min to obtain the supernatant.

[0881] Reducing solution preparation: 3 μg of each antibody was added to 2× SDS loading buffer and 5 mM DTT, heated in a 99°C dry bath for 5 min, cooled to room temperature, and centrifuged briefly. The supernatant was loaded onto a Bis-tris 4-15% gradient gel (GenScript) for gel electrophoresis and visualized using Coomassie Brilliant Blue staining.

[0882] The protein gel with chromogenic protein bands was photographed using the Odyssey 9140 dual-color infrared laser imaging system (decolorization with destaining buffer was performed until the gel background was transparent), and the purity of the reduced and non-reduced bands was calculated using the built-in software.

[0883] The test results showed that the bands of each antibody in the non-reducing gel were around 150 kD, and the bands in the reducing gel were around 55 kD and 25 kD, which were consistent with the expected sizes, as recorded in Table 3.

[0884] Table 3. Expression levels and physicochemical properties of candidate antibodies

[0885] Example 6: Antigen Binding Activity Detection of Antibodies

[0886] In this example, the binding of the expressed antibody to the human Mucin17 antigen protein huMucin17-His was detected based on the ELISA method, and the binding of the expressed antibody to the human Mucin17 overexpressing cell huMucin17-CHO K1 was also detected based on the FACS method.

[0887] 6.1 ELISA-based detection of antibody binding ability to antigen protein huMucin17-His

[0888] A 96-well ELISA plate (30 μL / well) was coated with 0.5 μg / mL human Mucin17 antigen protein at 4°C overnight. The next day, the plate was washed three times with PBST and blocked with 5% skim milk for 2 hours. After washing the plate three times with PBST, a series of dilutions (1 μg / ml, 3-fold series dilution, 9 concentration points) of each antibody and the positive control antibody Tab1 were added and incubated for 1 hour. After washing three times with PBST, the secondary antibody Goat-anti-human Fc-HRP (Abcam, Ab97225) was added and incubated for 30 minutes. After incubation, the plate was washed six times with PBST and TMB was added for color development. The color was developed at 25°C for 15 minutes, and the reaction was terminated by adding 1 M HCl. The absorbance was read at OD450 using a microplate reader.

[0889] The results are shown in Figures 1-2. Both the antibodies obtained in this application and the antigen protein huMucin17 have good binding ability.

[0890] 6.2 FACS-based detection of antibody binding to huMucin17-CHO K1 cells

[0891] In this example, human Mucin17-overexpressing cells huMucin17-CHO K1 were used to evaluate the binding activity of the antibody.

[0892] The specific method is as follows: huMucin17-CHO K1 cells in the logarithmic growth phase were prepared into a single cell suspension and the density was adjusted to 2×10 610 cells / mL, add 50 μL per well to a 96-well round-bottom plate, centrifuge at 300 g at 4°C, and remove the supernatant. Add the detection antibody and positive control antibody Tab 1 to the corresponding wells, mix well, and incubate at 4°C for 40 minutes. After washing the incubated cell mixture three times, add 100 μL of diluted secondary antibody Goat F(ab')2 Anti-Human IgG-Fc and incubate at 4°C in the dark for 30 minutes. After washing three times, analyze the cells by flow cytometry and read the mean fluorescence intensity (MFI).

[0893] The results are shown in Table 4. On huMucin17-CHO K1 cells, all the tested antibodies had good binding ability to the antigen-overexpressing cells.

[0894] Table 4. FACS detection of recombinant antibodies binding to huMucin17-CHO K1 cells

[0895] Example 7: Antibody cross-species activity detection

[0896] In this example, the cross-reactivity of each antibody obtained in this application on human and monkey antigens was tested. Binding capacity was determined using the antibodies prepared in Example 4 and a CHO K1 cell line expressing monkey Mucin17. For specific procedures, refer to Example 6.

[0897] The results are shown in Figure 3. All antibodies obtained in this application can bind to cell lines expressing monkey proteins and show good human monkey fork activity.

[0898] Example 8: Antibody affinity detection

[0899] In this embodiment, the affinity of the antibody obtained in this application and the positive control antibody Tab-1 to the antigen protein huMucin17-His was detected based on the Biacore device. The anti-Mucin17 antibody sample was diluted to 10ug / mL using running buffer HBS-EP+ (10mM HEPES, 150mM NaCl, 3mM EDTA and 0.05% P20, pH 7.4) (BR100826, GE), and the human Mucin17 antigen protein was diluted to between 0.03125nM and 2nM with HBS-EP+ buffer in a 2-fold gradient. The anti-Mucin17 antibody was affinity captured using a Protein A biosensor chip (BR100354, GE), and the capture time was set to 60s and the flow rate was 30μL / min. The human Mucin17 samples diluted to different concentrations were then injected sequentially from zero to the highest concentration, and the binding time was set to 120s, the dissociation time was set to 360s, and the flow rate was 30uL / min. The reaction signal was detected in real time using a Biacore X100 instrument to obtain binding and dissociation curves. After each experimental cycle of dissociation was completed, the Protein A biosensor chip was cleaned and regenerated with 10mM Glycine-HCl (pH1.5) (29127558, GE), and the regeneration time was set to 30s and the flow rate was 30uL / min. Parameter fitting: The experiment was run in single cycle mode, with the analysis time as the horizontal coordinate and the response value as the vertical coordinate. After the obtained data were double-referenced and deducted, they were fitted by BIAcore X100 (GE) analysis software. The fitting model adopted was a 1:1 Langmuir binding model to determine affinity indicators such as its binding dissociation constant. The results are shown in Table 5. The antibodies obtained in this application have higher affinity than the positive control antibody Tab1.

[0900] Table 5. KD values ​​of antibodies

[0901] Example 9: Antibody endocytosis detection

[0902] The ability of recombinant antibodies to be internalized by target cells (huMucin17-CHO K1) was assessed using the Incucyte (Sartorius, Incucyte S3) assay. Target cells were digested, harvested, and resuspended in assay buffer. The cell suspension was transferred to a 96-well assay plate at a density of 5,000 cells per well. The plates were incubated overnight in a cell culture incubator (37°C / 5% CO2). Test / control working solutions and labeling reagent working solution (4×) were prepared in assay buffer. The test / control working solutions and labeling reagent working solution were mixed at a 1:3 molar ratio and a 1:1 volume ratio, respectively. The mixture was incubated in a cell culture incubator (37°C / 5% CO2) for 15 minutes to allow for complete conjugation. The conjugation mixture was transferred to the corresponding wells of the 96-well assay plate. The plates were incubated in a cell culture incubator (37°C / 5% CO2) for the desired time, and images were taken at designated time points using an Incucyte instrument compatible with the detection band.

[0903] The original data and results of the experiment were Live-Cell Analysis System analysis and export. The analysis results are expressed as: Total Red Object Integrated Intensity (GCU×μm 2 / Image). The raw data were further analyzed and plotted using Microsoft Office Excel 2016 and GraphPad Prism 6 software. The experimental results are shown in Figure 5, which demonstrate that all tested molecules exhibited a strong endocytic effect, with antibody endocytosis increasing over time.

[0904] Example 10: Preparation of Linker-Toxin

[0905] The preparation of the linkers and toxins used in the present invention, such as deruxtecan, GGFG-Dxd, Dxd, GGFG-Exd, and Val-Ala-PAB, refers to WO2014057687, WO1997046260, and CN101795711, the entire text of which is incorporated herein by reference.

[0906] The linker-toxin Cpd3 used in the present invention and its preparation method are as follows:

[0907] Step 1: (9H-fluoren-9-yl)methyl((S)-3-methyl-1-(((S)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxopropan-2-yl)amino)-1-oxobutan-2-yl)carbamate (3-1, 2.5 g, 3.6 mmol), (1S,9S)-1-amino-9-ethyl-5-fluoro-9-hydroxy-4-methyl -1,2,3,9,12,15-Hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione (3-2, 1.6 g, 3.6 mmol) and N,N-diisopropylethylamine (965 mg, 7.5 mmol) were dissolved in anhydrous N,N-dimethylformamide (20 mL), and the reaction solution was stirred at room temperature for 16 hours. The reaction was monitored by LCMS to yield 4-((S)-2-(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-methylbutyrylamino)propionylamino)benzyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (3-3). LCMS (ESI) m / z: 977.3 [M+H] + .

[0908] Step 2: Hexahydropyridine (464 mg, 5.4 mmol) was added directly to the reaction mixture in Step 1, and the reaction mixture was stirred at room temperature for 2 hours. LCMS monitored the reaction completion of the raw material, and the reaction mixture was directly purified by C18 column chromatography to obtain 4-((S)-2-((S)-2-amino-3-methylbutyrylamino)propionylamino)benzyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (3-4) (1.8 g). LCMS (ESI) m / z: 755.2 [M+H] + .

[0909] Step 3: 1-(9H-fluoren-9-yl)-3-oxo-2,7,10,13,16,19,22,25,28-nonaoxa-4-aza-triacont-31-oic acid (3-5, 1.8 g, 2.38 mmol), 4-((S)-2-((S)-2-amino-3-methylbutyrylamino)propionylamino)benzyl ((1S,9S)-9-ethyl 1-H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (3-4, 1.8 g, 2.38 mmol), N,N-diisopropylethylamine (614 mg, 4.7 The mixture was stirred at room temperature for 3 h. The reaction was monitored by LCMS to obtain 4-((33S,36S)-1-(9H-fluoren-9-yl)-33-isopropyl-36-methyl-3,31,34-trioxo-2,7,10,13,16,19,25,25,28-nonaoxa-4,32- ,35-triaza-heptahistrazino-37-amido)-benzyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (3-6). LCMS(ESI)m / z:1400.5[M+H] + .

[0910] Step 4: Piperidine (409 mg, 4.76 mmol) was directly added to the reaction solution of step 3, and the reaction solution was stirred at room temperature for 2 hours. The reaction of the raw materials was completed by LCMS monitoring, and the reaction solution was directly purified by C18 column chromatography to obtain 4-((29S,32S)-1-amino-29-isopropyl-32-methyl-27,30-dioxo-3,6,9,12,15,18,21,24-octaoxa-28,31-diaza-triacontria-33-amido)benzyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (3-7) (1.2 g). LCMS (ESI) m / z: 1178.4 [M+H] + .

[0911] Step 5: 4-((29S,32S)-1-amino-29-isopropyl-32-methyl-27,30-dioxo-3,6,9,12,15,18,21,24-octaoxa-28,31-diaza-triacontria-33-amido)benzyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4 ':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (3-7, 20 mg, 0.017 mmol), 2-(methylsulfonyl)pyrimidine-5-carboxylic acid (3-8, 13.7 mg, 0.068 mmol), and 4-(4,6-dimethoxytriazin-2-yl)-4-methylmorpholine tetrafluoroborate (22.3 mg, 0.068 mmol) were dissolved in anhydrous N,N-dimethylacetamide (3 mL), and the reaction solution was stirred at room temperature for 16 hours. After separation and purification by C18 column chromatography, 4-((31S,34S)-31-isopropyl-34-methyl-1-(2-(methylsulfonyl)pyrimidin-5-yl)-1,29,32-trioxo-5,8,11,14,17,20,23,26-octaoxa-2,30,33-triaza-triazolyl-35-amido-benzyl(1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (2.3 mg, yield: 10%), namely Cpd3, was obtained. 1 H NMR (400MHz, DMSO-d6) δ9.95(s,1H),9.37(s,1H),9.14(s,1H),8.46(s,1H),8.21(d,J=6.8Hz,1H),8.06(d,J=7.8H z,1H),7.89(d,J=8.3Hz,1H),7.78(d,J=10.9Hz,1H),7.60(d,J=8.4Hz,2H),7.36(d,J=8.1Hz,2H),7.31(s,1H),6. 53(s,1H),5.45(s,2H),5.28(s,3H),5.08(s,2H),4.42–4.34(m,1H),4.22–4.17(m,1H),3.62–3.53(m,10H),3.52– 3.46(m,28H),2.38(s,3H),2.33(s,1H),2.20(s,3H),2.01–1.81(m,4H),1.30(d,J=7.0Hz,3H),0.90–0.80(m,9H).

[0912] The linker-toxin Cpd5 used in the present invention and its preparation method are as follows:

[0913] Step 1: 1-(9H-fluoren-9-yl)-3,6-dioxo-2,9-dioxa-4,7-diazaundecane-11-oic acid (5-1,440 mg, 1.15 mmol), (1S,9S)-1-amino-9-ethyl-5-fluoro-9-hydroxy-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2 -b]Quinoline-10,13-dione (500 mg, 1.15 mmol) was dissolved in anhydrous N,N-dimethylformamide (20 mL), and N,N'-dicyclohexylcarbodiimide (308 mg, 1.5 mmol), N-hydroxysuccinimide (132 mg, 1.15 mmol) and N,N-diisopropylethylamine (148 mg, 1.15 mmol) were added under ice bath, and then the reaction solution was stirred at room temperature for 16 hours. The reaction was monitored by LCMS. The organic phase was extracted with ethyl acetate and water, concentrated, and purified on a silica gel column using a methanol and dichloromethane system (1:20) to give (9H-fluoren-9-yl)methyl (2-(((2-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-2-oxoethoxy)methyl)amino)-2-oxoethyl)carbamate (5-3,650 mg). LCMS (ESI) m / z: 802.3 [M+H] + .

[0914] Step 2: (9H-Fluoren-9-yl)methyl (2-(((2-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-2-oxoethoxy)methyl)amino)-2-oxoethyl)carbamate (5-3, 650 mg, 0.81 mmol) was dissolved in N,N-dimethylformamide (10 mL), and then hexahydropyridine (69 mg, 5.4 mmol) was added and the reaction was stirred at room temperature for 2 hours. The reaction of the raw material was completed by LCMS monitoring, and the reaction solution was directly purified by C18 column chromatography to obtain 2-amino-N-((2-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-2-oxoethoxy)methyl)acetamide (5-4,420 mg). LCMS (ESI) m / z: 580.2 [M+H] + .

[0915] Step 3: 2-amino-N-((2-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-2-oxoethoxy)methyl)acetamide (5-4, 420 mg, 0.73 mmol), (((9H-fluorene-9 -yl) methoxy) carbonyl) glycylglycyl-L-phenylalanine (5-5, 370 mg, 0.73 mmol) was dissolved in anhydrous N,N-dimethylformamide (10 mL), and N,N'-dicyclohexylcarbodiimide (195 mg, 0.95 mmol), N-hydroxysuccinimide (84 mg, 0.73 mmol) and N,N-diisopropylethylamine (94 mg, 0.73 mmol) were added under ice bath, and the reaction solution was stirred at room temperature for 16 hours. The reaction was monitored by LCMS. The organic phase was extracted with ethyl acetate and water, concentrated, and purified on a silica gel column using a methanol:dichloromethane system (1:15) to give (9H-fluoren-9-yl)methyl((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa-5,8,11,14-tetraazahexadec-16-yl)carbamate (5-6,550 mg). LCMS (ESI) m / z: 1063.5 [M+H] + .

[0916] Step 4: (9H-Fluoren-9-yl)methyl((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa-5,8,11,14-tetraazahexadec-16-yl)carbamate (5-6,550 mg, 0.52 mmol) was dissolved in N,N-dimethylformamide (5 mL), and then hexahydropyridine (44 mg, 0.52 mmol) was added and the reaction solution was stirred at room temperature for 2 hours. The reaction of the raw material was completed as monitored by LCMS, and the reaction solution was directly purified by C18 column chromatography to obtain ((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa-5,8,11,14-tetraazahexadec-16-yl)amine (5-7, 400 mg). LCMS (ESI) m / z: 841.4 [M+H] + .

[0917] Step 5: 1-(9H-fluoren-9-yl)-3-oxo-2,7,10,13,16,19,22,25,28-nonaoxa-4-aza-triacont-31-oic acid (347 mg, 0.52 mmol), HATU (274 mg, 0.72 mmol) and N,N-diisopropylethylamine (124 mg, 0.96 mmol) were dissolved in anhydrous N,N-dimethylformamide (5 mL). Then, the mixture was stirred at room temperature for 1 h, and then ((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa- The mixture was stirred at room temperature for 16 h. The reaction was monitored by LCMS. The reaction solution was directly purified by C18 column chromatography to obtain (9H-fluoren-9-yl)methyl ((S)-10-benzyl-1-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,1 0,13,15-Hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15,18-hexaoxo-3,21,24,27,30,33,36,39,42-nonaoxa-5,8,11,14,17-pentaazatetradecane-44-yl)carbamate (5-9, 350 mg). LCMS (ESI) m / z: 1486.6 [M+H] + .

[0918] Step 6: (9H-fluoren-9-yl)methyl((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,1 5,18-Hexaoxo-3,21,24,27,30,33,36,39,42-nonaoxa-5,8,11,14,17-pentaazatetradec-44-yl)carbamate (5-9, 350 mg, 0.24 mmol) was dissolved in N,N-dimethylformamide (5 mL), and then hexahydropyridine (20 mg, 0.24 mmol) was added, and the reaction solution was stirred at room temperature for 2 hours. The reaction of the raw material was completed after LCMS monitoring, and the reaction solution was directly purified and separated by C18 column chromatography to give 1-amino-N-((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa-5,8,11,14-tetraazahexadec-16-yl)-3,6,9,12,15,18,21,24-octaoxaheptacosane-27-amide (5-10, 200 mg). LCMS (ESI) m / z: 1264.6 [M+H] + .

[0919] Step 7: 1-amino-N-((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15-pentaoxo-3-oxa-5,8,11,14-tetraazahexadec-16-yl)-3, 6,9,12,15,18,21,24-Octoxaheptacosane-27-carboxamide (5-10, 100 mg, 0.079 mmol), 2-(methylsulfonyl)pyrimidine-5-carboxylic acid (64 mg, 0.3 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (53 mg, 0.3 mmol), and N-methylmorpholine (182 mg, 1.8 mmol) were dissolved in anhydrous N,N-dimethylacetamide (5 mL), and the reaction solution was stirred at room temperature for 16 hours. The product was separated and purified by C18 column chromatography to give N-((S)-10-benzyl-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1,6,9,12,15,18-hexaoxo-3,21,24,27,30,33,36,39,42-nonaoxa-5,8,11,14,17-pentaazatetradecane-44-yl)-2-(methylsulfonyl)pyrimidine-5-carboxamide (5 mg), namely Cpd5. LCMS (ESI) m / z: 1448.6 [M+H] + .

[0920] 1H NMR (400MHz, DMSO-d6) δ9.37(d,J=2.1Hz,2H),9.12(s,1H),8.63(s,1H),8.51(d,J=8.6Hz,1H),8.29(s,1H),8.21–8.07(m,2H ),7.99(s,1H),7.78(d,J=10.9Hz,1H),7.31(s,1H),7.21(t,J=15.2Hz,5H),6.52(s,1H),5.60(s,1H),5.42(s,2H),5.20(s,2H ),4.64(d,J=6.3Hz,2H),4.47(s,1H),4.02(s,2H),3.76–3.66(m,4H),3.59–3.53(m,8H),3.51–3.45(m,29H),2.39(s,5H),2.1 8(s,2H),2.00(d,J=7.9Hz,1H),1.84(dd,J=15.4,7.8Hz,2H),1.33–1.20(m,5H),1.12(d,J=6.6Hz,1H),0.87(t,J=6.3Hz,3H).

[0921] The linker-toxin Cpd6 used in the present invention and its preparation method are as follows:

[0922] Step 1: (((9H-fluoren-9-yl)methoxy)carbonyl)-L-valyl-L-alanine (6-1, 943 mg, 2.3 mmol), (1S,9S)-1-amino-9-ethyl-5-fluoro-9-hydroxy-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b] Quinoline-10,13-dione (1 g, 2.3 mmol) was dissolved in anhydrous N,N-dimethylformamide (20 mL). N,N'-dicyclohexylcarbodiimide (616 mg, 3 mmol), N-hydroxysuccinimide (264 mg, 2.3 mmol) and N,N-diisopropylethylamine (297 mg, 2.3 mmol) were added under ice-cooling, and the reaction solution was stirred at room temperature for 16 hours. The reaction was completed by LCMS monitoring. The organic phase was extracted with ethyl acetate and water, concentrated, and purified on a silica gel column using a methanol:dichloromethane system (1:20) to give (9H-fluoren-9-yl)methyl ((S)-1-(((S)-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate (6-3,730 mg). LCMS (ESI) m / z: 828.3 [M+H] + .

[0923] Step 2: (9H-Fluoren-9-yl)methyl ((S)-1-(((S)-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate (6-3, 730 mg, 0.88 mmol) was dissolved in N,N-dimethylformamide (10 mL), and then hexahydropyridine (75 mg, 0.88 mmol) was added and the reaction was stirred at room temperature for 2 hours. The reaction of the raw material was completed by LCMS monitoring, and the reaction solution was directly purified by C18 column chromatography to obtain (S)-2-amino-N-((S)-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1-oxopropan-2-yl)-3-methylbutanamide (6-4,450 mg). LCMS (ESI) m / z: 606.2 [M+H] + .

[0924] Step 3: 1-(9H-fluoren-9-yl)-3-oxo-2,7,10,13,16,19,22,25,28-nonaoxa-4-azatriacont-31-oic acid (592 mg, 0.89 mmol), HATU (422 mg, 1.11 mmol) and N,N-diisopropylethylamine (143 mg, 1.11 mmol) were dissolved in anhydrous N,N-dimethylformamide. (5 mL), and then stirred at room temperature for 1 h, and then (S)-2-amino-N-((S)-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)- The mixture was stirred at room temperature for 4 h. The reaction was monitored by LCMS. The reaction solution was directly purified by C18 column chromatography to give (9H-fluoren-9-yl)methyl ((29S,32S)-33-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,1 0,13,15-Hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-29-isopropyl-32-methyl-27,30,33-trioxo-3,6,9,12,15,18,21,24-octaoxa-28,31-diaza-triacontanoyl)carbamate (6-5,400 mg). LCMS (ESI) m / z: 1251.6 [M+H] + .

[0925] Step 4: (9H-fluoren-9-yl)methyl((29S,32S)-33-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-29-isopropyl 400 mg, 0.32 mmol) was dissolved in N,N-dimethylformamide (5 mL) and then piperidine (27 mg, 0.32 mmol) was added. The reaction solution was stirred at room temperature for 2 hours. The reaction of the raw material was completed by LCMS monitoring, and the reaction solution was directly purified and separated by C18 column chromatography to obtain 1-amino-N-((S)-1-(((S)-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)-3,6,9,12,15,18,21,24-octaoxa-heptacosane-27-amide (6-6, 210 mg). LCMS (ESI) m / z: 1029.6 [M+H] + .

[0926] Step 5: 1-amino-N-((S)-1-(((S)-1-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-1-oxopropan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)-3,6,9,12 ,15,18,21,24-Octaoxa-heptacosa-27-amide (6-6, 100 mg, 0.097 mmol), 2-(methylsulfonyl)pyrimidine-5-carboxylic acid (78 mg, 0.39 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (68 mg, 0.39 mmol) and N-methylmorpholine (59 mg, 0.582 mmol) were dissolved in anhydrous N,N-dimethylacetamide (5 mL), and the reaction solution was stirred at room temperature for 16 hours. The product was purified and separated by C18 column chromatography to obtain N-((29S,32S)-33-(((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl)amino)-29-isopropyl-32-methyl-27,30,33-trioxo-3,6,9,12,15,18,21,24-octaoxa-28,31-diaza-tricarboxyl)-2-(methylsulfonyl)pyrimidine-5-carboxamide (11.5 mg), namely Cpd6. LCMS (ESI) m / z: 1213.6 [M+H] +

[0927] 1H NMR (400MHz, DMSO-d6) δ9.36(s,2H),9.13(s,1H),8.41(d,J=8.9Hz,1H),8.10(d,J=6.9Hz,1H),7.86(d,J=8.4Hz,1H),7. 79(d,J=11.0Hz,1H),7.30(s,1H),6.53(s,1H),5.54(s,1H),5.42(s,2H),5.24(d,J=18.9Hz,1H),5.11(d,J=19.0Hz,1H) ,4.32–4.21(m,1H),4.17–4.06(m,1H),3.58–3.52(m,8H),3.48(s,25H),3.44(s,6H),2.40(s,3H),2.29(dd,J=13.7,7.1 Hz,1H),2.13(s,2H),1.91(ddd,J=23.2,22.6,7.6Hz,4H),1.27(d,J=7.0Hz,3H),0.87(t,J=7.4Hz,3H),0.83–0.72(m,6H)

[0928] Example 11: Preparation and Validation of MUC17-ADC

[0929] The antibody stock solution was removed from the refrigerator (-80°C), thawed, and added to a centrifuge tube. PB buffer (20 mM, pH 7.2, 751 uL), DTPA-3Na (10 mM, 375 uL), and TCEP (10 mM, 94 uL) were then added and reacted at 25°C for 2 hours. The linker-toxin described in Example 10, such as Cpd3, was then added and the reaction continued at 25°C for another 2 hours. After the reaction, the solution was transferred to an ultrafiltration centrifuge tube (30 kDa) and dialyzed against His / His-HCl (10 mM, pH 5.5) to obtain an ADC stock solution (DAR: 7.5-8.5, SEC purity ≥95%).

[0930] The linker-toxin used in the above experiments was Cpd3, described in Example 10, as an example. The antibody stock solution can be any clone from M1 to M27; the linker-toxin can be a combination of a linker and a camptothecin compound commonly used in the art, including but not limited to deruxtecan, Cpd3, Cpd5, and Cpd6.

[0931] The above experiments were performed using clone M26 and other linker-toxins. Each ADC sample was validated, and the test results are shown in Table 6 below.

[0932] Table 6. ADC sample test results

[0933] Example 12: ADC drug activity detection

[0934] Balb / c nude mice weighing 18-20g (source: Shanghai Lingchang) were used for animal efficacy evaluation experiments. Upon arrival, the animals were housed in separate cages, 5 per cage, in a barrier environment (independent ventilation system). All cages, bedding, and drinking water were sterilized before use. After 7 days of adaptive feeding, 10*10 6 100ul of GSU tumor cell suspension (Riken, RCB2278) was mixed with Matrigel at a ratio of 1:1 and then inoculated subcutaneously on the right upper back of mice.

[0935] Body weight was measured using a scale, and the long and short diameters of the tumor were measured using an electronic digital caliper (manual caliper, OMC Fontana). The tumor volume (mm 3 ). Tumor volume (mm 3 )=1 / 2×long diameter (mm)×[short diameter (mm)] 2 , measured twice a week. 7 days after inoculation, when the average tumor volume reached 279mm 3 At the same time, 36 experimental animals were randomly divided into 6 groups, and the test ADC drugs or control PBS were administered through the tail vein according to the following doses on the same day.

[0936] Experimental group 1: PBS control group (Vehicle Single), which was given a single dose of the same ADC dose.

[0937] Experimental group 2: M21-Deruxtecan, 3 mg / kg, single administration.

[0938] Experimental group 3: M26-Deruxtecan, 3 mg / kg, single administration.

[0939] Experimental group 4: M26-Cpd 3, 3 mg / kg, single administration.

[0940] Experimental group five: M26-Cpd 5, 3 mg / kg, single administration.

[0941] Experimental group six: M26-Cpd 6, 3 mg / kg, single administration.

[0942] All data are presented as mean values. All data were analyzed using Microsoft Excel 2016. The tumor inhibition rates in mice are shown in Table 7 below.

[0943] TGI (Tumor Growth Inhibition) refers to the tumor growth inhibition rate. TGI is often used to evaluate the effect of a treatment or intervention on tumor growth. Specifically, TGI can be calculated using the following formula:

[0944] TGI=(1-tumor weight of treatment group / tumor weight of control group)×100%.

[0945] In this application, the TGI of other groups was calculated based on experimental group one.

[0946] Table 7. Tumor inhibition rate of ADC in mice

[0947] The experimental results, shown in Figure 4 and Table 7, demonstrate that M21 and M26 antibodies significantly inhibited tumor growth when conjugated to deruxtecan or Cpd3 or Cpd5. The M26-Cpd3 ADC demonstrated superior tumor growth inhibition compared to the M26-deruxtecan ADC, while the M26-Cpd5 ADC demonstrated similar tumor growth inhibition to the M26-deruxtecan ADC. No weight loss was observed in any of the experimental animals during the experimental period.

[0948] Example 13: Humanization of Chimeric Antibodies and Characterization of Humanized Antibodies

[0949] A. Humanization of Chimeric Antibodies

[0950] Humanization method: The parent antibody structure is modeled by computer-assisted homology modeling. A natural human germline sequence with high homology to the parent sequence is selected. Humanized antibodies are designed using CDR grafting technology. Simply put, the CDRs of the parent antibody are grafted into the natural human germline sequence to obtain a humanized chimeric antibody of the parent antibody. The different amino acid residues of the chimeric antibody and the parent antibody are compared, and the key points that will affect the subsequent affinity are determined based on the classic residues, interaction loop regions, core regions, mutation hotspots, etc., and the appropriate sites are selected for back mutation to obtain humanized antibodies. The heavy and light chains of the humanized antibodies are randomly paired for antibody production and identification.

[0951] Humanized Molecular Screening: Humanized sequences were designed for the chimeric antibody M21 according to the aforementioned humanization design principles and the method disclosed in Example 4. The VH coding sequence of the humanized antibody was ligated with the coding sequence of the heavy chain constant region of human IgG1 to obtain the heavy chain coding sequence, and the VL coding sequence of the humanized antibody was ligated with the coding sequence of the kappa subtype of the light chain constant region to obtain the light chain coding sequence. The heavy and light chain coding sequences were then inserted into the eukaryotic expression vector PCDNA 3.4 for combined expression, purification, and detection. Finally, the humanized antibodies obtained were: M21-01, M21-02, M21-03, M21-04, M21-05, M21-06, M21-07, M21-08, M21-09, M21-10, M21-11, M21-12, M21-13, M21-14, M21-15, M21-16, M21-17, and M21-18.

[0952] B: Characterization of humanized antibodies

[0953] B.1 ELISA: Coat a 96-well ELISA plate (100 μL / well) with 1 μg / mL human Mucin17 antigen protein at 4°C overnight. The next day, wash the plate three times with PBST and block with 1% bovine serum albumin in PBST for 1 hour. After washing the plate three times with PBST, add a series of dilutions of each humanized antibody (10 nM, 5-fold dilutions, 7 concentration points) and incubate at 37°C for 1 hour. After washing the plate three times with PBST, add the secondary antibody anti-human IgG-HRP (Sigma, Cat#A 0170) and incubate for 45 minutes. After incubation, wash the plate three times with PBST and develop the color with TMB. Develop the color at 25°C for 15 minutes. The reaction is terminated by adding 1 M HCl and the absorbance is read at OD450 using a microplate reader. The ELISA results are shown in Table 8 below.

[0954] Table 8. Humanized antibody ELISA results

[0955] B.2 FACS binding activity: HEK293 cells highly expressing huMucin17 protein were constructed using conventional methods. huMucin17-HEK293 cells in the logarithmic growth phase were prepared into a single-cell suspension and the density was adjusted to 2×10 6Cells / mL were added to a 96-well round-bottom plate at 100 μL per well, centrifuged at 4°C and 300g, and the supernatant was removed. The antibodies to be detected were added to the corresponding wells, mixed, and incubated at 4°C for 1 hour. The incubated cell mixture was washed 3 times and then 100 μL of diluted secondary antibody Goat F(ab')2Anti-Human IgG-Fc (source: Jackson, item number: 109-136-098) was added. The cells were incubated in the dark for 30 minutes at 4°C, washed 3 times, and detected by flow cytometry to read the mean fluorescence intensity (MFI). The FACS test results are shown in Figures 6A-6B, where the prefix "Hu" in the antibody name indicates a humanized antibody, "Hu112" refers to a humanized antibody of the chimeric antibody M21, and the suffix numbers indicate the sequence numbers of the humanized antibodies derived from the chimeric antibody M21, and the numbers correspond to the corresponding clones obtained in Part A of this Example.

[0956] B.3 Endocytosis activity assay: GSU cells (Riken, RC2278) were incubated with the primary antibody (100 nM) at 4°C for 30 min and washed twice. After incubation at 4°C and / or 37°C for 0, 2, 4, and 6 hours, the cells were fixed with 2% PFA on ice for 10 min and washed twice. A fluorescent secondary antibody (Alexa 488 Goat Anti-Human IgG, Fcγfragment specific, Jackson, Cat#109-545-098) was added and incubated on ice in the dark for 1 hour. FACS analysis was performed, and the results are shown in Table 9 below, showing that all humanized antibodies exhibited significant internalization.

[0957] Table 9 Endocytosis activity results of humanized antibodies

[0958] B.4 BiaCore affinity detection: Affinity analysis was performed using BIAcore 8K according to the method disclosed in Example 8, with the flow cell and sample chamber temperature set at 25°C. The results are shown in Table 10 below.

[0959] Table 10. Humanized antibody affinity test results

[0960] Example 14: Binding of humanized antibodies or antibody-drug conjugates to tumor cells

[0961] A. Construction of Humanized Antibody Drug Conjugates

[0962] Antibody drug conjugates of humanized antibodies were prepared using clone M21-17 and linker-toxin according to the method of Example 11.

[0963] The linker-toxin used in the above experiments is Cpd3 described in Example 10 as an example. The linker-toxin can be a combination of a linker and a camptothecin compound commonly used in the art, including but not limited to deruxtecan, Cpd3, Cpd5, Cpd6, etc.

[0964] B. Validation and Characterization of Antibody Drug Conjugates

[0965] Each ADC sample was verified, and the test results are shown in the table below.

[0966] C. Binding of humanized antibodies and their conjugates to tumor cells

[0967] Experimental method: GSU cells (Riken, RC2278) or NUGC4 cells (Nanjing Kebai Biotechnology Co., Ltd.) in the logarithmic growth phase were prepared into single-cell suspensions with a density of 2×10 6 100 μL of the culture medium was added to each well of a 96-well round-bottom plate. The cells were centrifuged at 300 g at 4°C and the supernatant removed. The antibody to be tested, ADC, or the positive control AMG199 antibody (commercially available) was added to the corresponding wells, mixed thoroughly, and incubated at 4°C for 30 minutes. After washing the incubated cell mixture three times, 100 μL of diluted secondary antibody, Goat Anti-Human IgG (Jackson 109-136-098), was added and incubated at 4°C in the dark for 30 minutes. After washing three times, the cells were analyzed by flow cytometry and the mean fluorescence intensity (MFI) was measured.

[0968] The experimental results show that the maximum MFI value of the candidate molecule binding to the cells is higher than that of the positive control molecule on the tumor cell lines tested. Table 11 shows the binding data of the humanized antibody and its ADC to tumor cells (GSU and NUGC4).

[0969] Table 11. Binding activity of target antibodies to tumor cells

[0970] Example 15: In vitro study of tumor cell killing by antibody-drug conjugates

[0971] Experimental method: CHO-K1 cells and tumor cells (NUGC4, GSU ​​and SW480 cells) with high expression of MUC17 in the logarithmic growth phase were taken, and the cell suspensions were adjusted to 1.5×10 4Prepare cell working solution at a cell density of 100 μL / well in a 96-well cell culture plate. Place the cell culture plate in a 37°C, 5% CO2 cell culture incubator and incubate overnight. Add the ADC sample M21-17-Cpd3 to the corresponding wells and incubate in a cell culture incubator for 5 days. Place the cell culture plate at room temperature for 10 minutes and equilibrate to room temperature. Add 75 μL of the luminescent cell viability assay kit solution (Promega) to each well. Mix at room temperature for 2 minutes using an orbital shaker and incubate at room temperature for 10 minutes. Use a microplate reader to read the plate, read the fluorescence signal value, and calculate the cell viability.

[0972] Experimental results: The in vitro cell-killing ability of the candidate ADC molecules was positively correlated with the expression level of the MUC17 molecule on the cell surface. Higher expression levels resulted in a greater cytotoxic effect of the ADC. The cell-killing results of the antibody-drug conjugate M21-17-Cpd3 in three tumor cell lines are shown in Figure 7.

[0973] Example 16: Bystander effect of antibody-drug conjugates on tumor cells

[0974] This example investigates whether ADCs have a bystander killing effect. Bystander killing refers to the killing effect of ADC drugs on cells surrounding or adjacent to target antigen-positive cells.

[0975] Antigen-high-expressing cells (positive cells: NUGC4 or GSU) and negative cells (MDA-MB-468 (source: Chinese Academy of Sciences Cell Bank) or HCC827 cells (source: Nanjing Kebai Biotechnology)) were respectively cultured at 1×10 5 The cells were mixed at a density of 100 μg / ml to prepare a mixed cell working solution. The working solution was added to 12-well cell culture plates at a volume of 1 ml / well and incubated overnight at 37°C, 5% CO2. The ADC sample to be tested, M21-17-Cpd3, was added to the corresponding wells and incubated in a cell culture incubator for 5 days. After digestion and centrifugation, the cells were resuspended and counted. The cells were transferred to a 96-well plate for flow cytometry analysis. The ratio of the two cell types was calculated, and the number of viable cells for each cell type was calculated. Histograms were plotted using GraphPad software.

[0976] The bystander killing effect of M21-17-Cpd3 was detected by co-culturing target-negative cells with target-positive cells and measuring the number of surviving negative cells. The results are shown in Figures 8A-8C, which show that the antibody-drug conjugate of the present invention has a bystander killing effect, wherein the molecule M21-Dxd refers to the antibody conjugate formed by coupling the M21 antibody to the toxin linker (Dxd) of DS8201.

[0977] Example 17: Verification of the anti-tumor effect of humanized ADC in human gastric cancer GSU transplant tumor model

[0978] The experimental method described in Example 12 was used to detect the anti-tumor activity of the antibody-drug conjugate M21-17-Cpd3 of the present application.

[0979] The experimental design is as follows:

[0980] Experimental group 1: PBS control group, a single administration of the same dose of ADC.

[0981] Experimental group 2: M21-17-Cpd3, 0.3 mg / kg, single administration.

[0982] Experimental group three: M21-17-Cpd3, 1 mg / kg, single administration.

[0983] Experimental group 4: M21-17-Cpd3, 10 mg / kg, single administration.

[0984] Experimental group five: M21-17-Cpd3, 30 mg / kg, single administration.

[0985] Experimental group 6: M21-17-Cpd3, 10 mg / kg, QW*3.

[0986] All data are expressed as mean values. The efficacy indicators in mice are shown in Table 12 below.

[0987] Table 12. Efficacy of humanized ADC in mice (GSU cells)

[0988] Note: Complete response (CR) means tumor volume (TV) = 0 mm 3 ; Partial response (PR) refers to a reduction of tumor volume by at least 30% relative to baseline; Complete response rate (CRR) refers to the proportion of subjects with complete elimination of tumor, that is, CR / number of animals used in the experiment; Partial response rate (PRR) refers to the proportion of subjects with partial reduction of tumor after treatment, that is, PR / CR / number of animals used in the experiment; TGI refers to tumor growth inhibition rate; T / C refers to relative tumor proliferation rate, T / C (%) = T / C × 100 (T: average tumor volume of treatment group; C: average tumor volume of solvent control group); IR refers to tumor weight inhibition rate, IR (%) = [1-(average tumor weight of treatment group / average tumor weight of solvent control group)] × 100.

[0989] The experimental results showed that a single administration of 0.3-30 mg / kg M21-17-Cpd3 inhibited the growth of GSU xenografts in a dose-dependent manner. The tumor volume data for each experimental group are shown in Figure 9. No weight loss was observed in any of the experimental animals during the experimental period.

[0990] Example 18: Verification of the anti-tumor effect of humanized ADC in a human gastric cancer NUGC-4 xenograft model

[0991] The experimental method described in Example 12 was used to detect the anti-tumor activity of the antibody-drug conjugate M21-17-Cpd3 of the present application.

[0992] The experimental design is as follows:

[0993] Experimental group 1: PBS control group, a single administration of the same dose of ADC.

[0994] Experimental group 2: M21-17-Cpd3, 1 mg / kg, single administration.

[0995] Experimental group three: M21-17-Cpd3, 3 mg / kg, single administration.

[0996] Experimental group 4: M21-17-Cpd3, 10 mg / kg, single administration.

[0997] Experimental group five: M21-17-Cpd3, 30 mg / kg, single administration.

[0998] Experimental group 6: M21-17-Cpd3, 10 mg / kg, QW*3.

[0999] All data are expressed as mean values. The efficacy indicators in mice are shown in Table 13 below.

[1000] Table 13. Efficacy of humanized ADC in mice (NUGC4 cells)

[1001] Note: Complete response (CR) means tumor volume (TV) = 0 mm 3; Partial response (PR) refers to a reduction of tumor volume by at least 30% relative to baseline; Complete response rate (CRR) refers to the proportion of subjects with complete elimination of tumor, that is, CR / number of animals used in the experiment; Partial response rate (PRR) refers to the proportion of subjects with partial reduction of tumor after treatment, that is, PR / CR / number of animals used in the experiment; TGI refers to tumor growth inhibition rate; T / C refers to relative tumor proliferation rate, T / C (%) = T / C × 100 (T: average tumor volume of treatment group; C: average tumor volume of solvent control group); IR refers to tumor weight inhibition rate, IR (%) = [1-(average tumor weight of treatment group / average tumor weight of solvent control group)] × 100.

[1002] The experimental results showed that a single administration of 1-30 mg / kg M21-17-Cpd3 could inhibit the growth of NUGC-4 transplanted tumors in a dose-dependent manner; the tumor volume detection data of each experimental group are shown in Figure 10.

[1003] Example 19: Verification of the anti-tumor effect of humanized ADC in human colon cancer SW480 xenograft model

[1004] The anti-tumor activity of the antibody-drug conjugate M21-17-Cpd3 of the present application was detected using the experimental method described in Example 12. SW480 cells were purchased from ATCC, CCL-228.

[1005] The experimental design is as follows:

[1006] Experimental group 1: PBS control group, a single administration of the same dose of ADC.

[1007] Experimental group 2: M21-17-Cpd3, 3 mg / kg, single administration.

[1008] Experimental group three: M21-17-Cpd3, 10 mg / kg, single administration.

[1009] Experimental group 4: M21-17-Cpd3, 30 mg / kg, single administration.

[1010] Experimental group five: M21-17-Cpd3, 3 mg / kg, QW*3.

[1011] Experimental group 6: M21-17-Cpd3, 10 mg / kg, QW*3.

[1012] All data are expressed as mean values. The efficacy indicators in mice are shown in Table 14 below.

[1013] Table 14. Efficacy of humanized ADC in mice (SW480 cells)

[1014] Note: Complete response (CR) means tumor volume (TV) = 0 mm 3 ; Partial response (PR) refers to a reduction of tumor volume by at least 30% relative to baseline; Complete response rate (CRR) refers to the proportion of subjects with complete elimination of tumor, that is, CR / number of animals used in the experiment; Partial response rate (PRR) refers to the proportion of subjects with partial reduction of tumor after treatment, that is, PR / CR / number of animals used in the experiment; TGI refers to tumor growth inhibition rate; T / C refers to relative tumor proliferation rate, T / C (%) = T / C × 100 (T: average tumor volume of treatment group; C: average tumor volume of solvent control group); IR refers to tumor weight inhibition rate, IR (%) = [1-(average tumor weight of treatment group / average tumor weight of solvent control group)] × 100.

[1015] The experimental results showed that a single administration of 3-30 mg / kg M21-17-Cpd3 could dose-dependently inhibit the growth of SW480 transplanted tumors; the tumor volume detection data of each experimental group are shown in FIG11 .

[1016] Example 20: Verification of Plasma Stability of Linker-Toxin Cpd3

[1017] The test ADC molecule, M21-17-Cpd3 (at a concentration of 0.2 mg / mL), was incubated at 37°C in plasma from different species (human, monkey, rat, and mouse) for 21 days. The plasma concentrations of free drug (e.g., Cpd3 or Dxd) were measured at various time points using LC-MS / MS. The control sample in this example was DS-8201 (commercially available). Table 15 below summarizes the experimental parameters for M21-17-Cpd3 (analyte Cpd3) and the reference DS-8201 (analyte Dxd).

[1018] The release rate (%) refers to the free drug content in plasma measured after incubation of ADC and plasma for a certain period of time, and the free drug shedding rate in plasma is calculated based on the ratio of the free drug content in plasma to the total amount of drug in ADC.

[1019] Table 14. ADC Plasma Stability

[1020] Experimental results demonstrate that the humanized antibody M21-17 conjugated to Cpd3 (DAR8) exhibits excellent plasma stability across diverse species. Cpd3 exhibits exceptional stability in both humans and monkeys, and outperforms the linker-toxin Dxd of the control DS-8201.

[1021] Example 21: Verification of the coupling properties of linker-toxin Cpd3 ...

Claims

1. An anti-MUC17 antibody or an antigen-binding fragment thereof, wherein: The antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining regions (HCDRs) and / or light chain complementarity determining regions (LCDRs) selected from the group consisting of: (1) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 7 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 8 or variants thereof; or, (2) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 17 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 18 or variants thereof; or (3) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 24 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 25 or a variant thereof; or (4) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 24 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 31 or a variant thereof; or (5) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 34 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 35 or a variant thereof; or (6) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 40 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 41 or variants thereof; or (7) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 47 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 48 or a variant thereof; or (8) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 47 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 53 or a variant thereof; or (9) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 59 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 60 or a variant thereof; or (10) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 69 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 70 or a variant thereof; or (11) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 77 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 78 or a variant thereof; or (12) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 87 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 88 or a variant thereof; or (13) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 97 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 98 or a variant thereof; or (14) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 104 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 105 or a variant thereof; or (15) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 114 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 115 or a variant thereof; or (16) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 114 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 119 or a variant thereof; or (17) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 125 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 126 or a variant thereof; or (18) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 135 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 136 or a variant thereof; or (19) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 97 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 140 or a variant thereof; or (20) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 149 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 150 or a variant thereof; or (21) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 158 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 159 or a variant thereof; or (22) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 167 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 168 or a variant thereof; or (23) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 172 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 173 or a variant thereof; or (24) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 179 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 180 or a variant thereof; or (25) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 189 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 190 or a variant thereof; or (26) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 198 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 199 or a variant thereof; or (27) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 204 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 205 or a variant thereof; or (28) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 214 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 215 or a variant thereof; (29) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 259 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 263 or a variant thereof; (30) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 259 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 260 or a variant thereof; (31) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 261 or variants thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 260 or variants thereof; (32) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 259 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 262 or a variant thereof; (33) the three CDRs (HCDR1, HCDR2, HCDR3) contained in VH as shown in SEQ ID NO: 261 or a variant thereof; and / or the three CDRs (LCDR1, LCDR2, LCDR3) contained in VL as shown in SEQ ID NO: 262 or a variant thereof; wherein the variant in any one of (1) to (33) has one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence from which it is derived; preferably, the substitutions are conservative substitutions; Preferably, the CDRs are defined by the Kabat, AbM, Chothia or IMGT numbering systems.

2. The anti-MUC17 antibody or antigen-binding fragment thereof of claim 1, comprising a complementarity determining region (CDR) selected from the group consisting of: (I) the following three HCDRs (HCDR1, HCDR2, HCDR3) of the heavy chain variable region (VH), and / or the following three LCDRs (LCDR1, LCDR2, LCDR3) of the light chain variable region (VL), wherein: The HCDR1, HCDR2, HCDR3, and / or LCDR1, LCDR2, LCDR3 are defined by the Kabat numbering system: (1) HCDR1 having the sequence shown in SEQ ID NO: 1, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 1; HCDR2 having the sequence shown in SEQ ID NO: 2, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 2; HCDR3 having the sequence shown in SEQ ID NO: 3, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 3; LCDR1 having the sequence shown in SEQ ID NO: 4, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 4; LCDR2 having the sequence shown in SEQ ID NO: 5, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 5; LCDR3 having the sequence shown in SEQ ID NO: 6, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 6; or, (2) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12; A HCDR3 having the sequence shown in SEQ ID NO: 13, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 13; LCDR1 having the sequence shown in SEQ ID NO: 14, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 14; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 16, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 16; or, (3) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12; A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23; or, (4) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12; A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21; LCDR1 having the sequence shown in SEQ ID NO: 28, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 28; LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29; LCDR3 having the sequence shown in SEQ ID NO: 30, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 30; or, (5) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12; A HCDR3 having the sequence shown in SEQ ID NO: 33, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 33; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23; or, (6) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12; A HCDR3 having the sequence shown in SEQ ID NO: 38, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 38; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 39, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 39; LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23; or, (7) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 44, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 44; A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 46, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 46; or, (8) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 44, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 44; A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45; LCDR1 having the sequence shown in SEQ ID NO: 51, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 51; LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29; LCDR3 having the sequence shown in SEQ ID NO: 52, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 52; or, (9) HCDR1 having the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 11; HCDR2 having the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 12; A HCDR3 having the sequence shown in SEQ ID NO: 55, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 55; LCDR1 having the sequence shown in SEQ ID NO: 56, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 56; LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57; LCDR3 having the sequence shown in SEQ ID NO: 58, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 58; or, (10) HCDR1 having the sequence shown in SEQ ID NO: 63, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 63; HCDR2 having the sequence shown in SEQ ID NO: 64, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 64; A HCDR3 having the sequence shown in SEQ ID NO: 65, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 65; LCDR1 having the sequence shown in SEQ ID NO: 66, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 66; LCDR2 having the sequence shown in SEQ ID NO: 67, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 67; LCDR3 having the sequence shown in SEQ ID NO: 68, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 68; or, (11) HCDR1 having the sequence shown in SEQ ID NO: 1, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 1; HCDR2 having the sequence shown in SEQ ID NO: 73, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 73; A HCDR3 having the sequence shown in SEQ ID NO: 74, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 74; LCDR1 having the sequence shown in SEQ ID NO: 75, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 75; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 76, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 76; or, (12) HCDR1 having the sequence shown in SEQ ID NO: 81, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 81; HCDR2 having the sequence shown in SEQ ID NO: 82, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 82; A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83; LCDR1 having the sequence shown in SEQ ID NO: 84, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 84; LCDR2 having the sequence shown in SEQ ID NO: 85, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 85; LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86; or, (13) HCDR1 having the sequence shown in SEQ ID NO: 91, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 91; HCDR2 having the sequence shown in SEQ ID NO: 92, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 92; A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93; LCDR1 having the sequence shown in SEQ ID NO: 94, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 94; LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95; LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96; or, (14) HCDR1 having the sequence shown in SEQ ID NO: 81, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 81; HCDR2 having the sequence shown in SEQ ID NO: 101, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 101; A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83; LCDR1 having the sequence shown in SEQ ID NO: 102, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 102; LCDR2 having the sequence shown in SEQ ID NO: 103, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 103; LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86; or, (15) HCDR1 having the sequence shown in SEQ ID NO: 108, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 108; HCDR2 having the sequence shown in SEQ ID NO: 109, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 109; A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110; LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111; LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112; LCDR3 having the sequence shown in SEQ ID NO: 113, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 113; or, (16) HCDR1 having the sequence shown in SEQ ID NO: 108, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 108; HCDR2 having the sequence shown in SEQ ID NO: 109, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 109; A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110; LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111; LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112; LCDR3 having the sequence shown in SEQ ID NO: 118, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 118; or, (17) HCDR1 having the sequence shown in SEQ ID NO: 121, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 121; HCDR2 having the sequence shown in SEQ ID NO: 122, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 122; A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93; LCDR1 having the sequence shown in SEQ ID NO: 123, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 123; LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95; LCDR3 having the sequence shown in SEQ ID NO: 124, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 124; or, (18) HCDR1 having the sequence shown in SEQ ID NO: 129, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 129; HCDR2 having the sequence shown in SEQ ID NO: 130, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 130; A HCDR3 having the sequence shown in SEQ ID NO: 131, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 131; LCDR1 having the sequence shown in SEQ ID NO: 132, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 132; LCDR2 having the sequence shown in SEQ ID NO: 133, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 133; LCDR3 having the sequence shown in SEQ ID NO: 134, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 134; or, (19) HCDR1 having the sequence shown in SEQ ID NO: 91, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 91; HCDR2 having the sequence shown in SEQ ID NO: 92, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 92; A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93; LCDR1 having the sequence shown in SEQ ID NO: 139, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 139; LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112; LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96; or, (20) HCDR1 having the sequence shown in SEQ ID NO: 143, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 143; HCDR2 having the sequence shown in SEQ ID NO: 144, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 144; A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (21) HCDR1 having the sequence shown in SEQ ID NO: 81, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 81; HCDR2 having the sequence shown in SEQ ID NO: 153, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 153; A HCDR3 having the sequence shown in SEQ ID NO: 154, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 154; LCDR1 having the sequence shown in SEQ ID NO: 155, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 155; LCDR2 having the sequence shown in SEQ ID NO: 156, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 156; LCDR3 having the sequence shown in SEQ ID NO: 157, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 157; or, (22) HCDR1 having the sequence shown in SEQ ID NO: 162, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 162; HCDR2 having the sequence shown in SEQ ID NO: 163, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 163; A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 165, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 165; LCDR3 having the sequence shown in SEQ ID NO: 166, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 166; or, (23) HCDR1 having the sequence shown in SEQ ID NO: 143, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 143; HCDR2 having the sequence shown in SEQ ID NO: 144, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 144; A HCDR3 having the sequence shown in SEQ ID NO: 171, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 171; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (24) HCDR1 having the sequence shown in SEQ ID NO: 176, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 176; HCDR2 having the sequence shown in SEQ ID NO: 177, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 177; A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 178, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 178; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (25) HCDR1 having the sequence shown in SEQ ID NO: 183, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 183; HCDR2 having the sequence shown in SEQ ID NO: 184, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 184; A HCDR3 having the sequence shown in SEQ ID NO: 185, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 185; LCDR1 having the sequence shown in SEQ ID NO: 186, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 186; LCDR2 having the sequence shown in SEQ ID NO: 187, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 187; LCDR3 having the sequence shown in SEQ ID NO: 188, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 188; or, (26) HCDR1 having the sequence shown in SEQ ID NO: 193, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 193; HCDR2 having the sequence shown in SEQ ID NO: 194, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 194; A HCDR3 having the sequence shown in SEQ ID NO: 195, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 195; LCDR1 having the sequence shown in SEQ ID NO: 196, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 196; LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57; LCDR3 having the sequence shown in SEQ ID NO: 197, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 197; or, (27) HCDR1 having the sequence shown in SEQ ID NO: 202, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 202; HCDR2 having the sequence shown in SEQ ID NO: 144, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 144; A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 203, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 203; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (28) HCDR1 having the sequence shown in SEQ ID NO: 208, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 208; HCDR2 having the sequence shown in SEQ ID NO: 209, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 209; A HCDR3 having the sequence shown in SEQ ID NO: 210, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO:

210. LCDR1 having the sequence shown in SEQ ID NO: 211, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 211; LCDR2 having the sequence shown in SEQ ID NO: 212, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 212; LCDR3 having the sequence shown in SEQ ID NO: 213, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 213; wherein the substitution described in any one of (1) to (28) is a conservative substitution; or, (II) the following three CDRs (HCDR1, HCDR2, HCDR3) of a heavy chain variable region (VH), and / or the following three CDRs (LCDR1, LCDR2, LCDR3) of a light chain variable region (VL), wherein the HCDR1, HCDR2, HCDR3, and / or LCDR1, LCDR2, LCDR3 are defined by the AbM numbering system: (1) HCDR1 having the sequence shown in SEQ ID NO: 225, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 225; HCDR2 having the sequence shown in SEQ ID NO: 226, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 226; HCDR3 having the sequence shown in SEQ ID NO: 3, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 3; LCDR1 having the sequence shown in SEQ ID NO: 4, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 4; LCDR2 having the sequence shown in SEQ ID NO: 5, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 5; LCDR3 having the sequence shown in SEQ ID NO: 6, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 6; or, (2) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228; A HCDR3 having the sequence shown in SEQ ID NO: 13, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 13; LCDR1 having the sequence shown in SEQ ID NO: 14, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 14; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 16, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 16; or, (3) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228; A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23; or, (4) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228; A HCDR3 having the sequence shown in SEQ ID NO: 21, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 21; LCDR1 having the sequence shown in SEQ ID NO: 28, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 28; LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29; LCDR3 having the sequence shown in SEQ ID NO: 30, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 30; or, (5) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228; A HCDR3 having the sequence shown in SEQ ID NO: 33, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 33; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23; or, (6) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228; A HCDR3 having the sequence shown in SEQ ID NO: 38, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 38; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 39, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 39; LCDR3 having the sequence shown in SEQ ID NO: 23, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 23; or, (7) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 229, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 229; A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45; LCDR1 having the sequence shown in SEQ ID NO: 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 22; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 46, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 46; or, (8) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 229, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 229; A HCDR3 having the sequence shown in SEQ ID NO: 45, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 45; LCDR1 having the sequence shown in SEQ ID NO: 51, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 51; LCDR2 having the sequence shown in SEQ ID NO: 29, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 29; LCDR3 having the sequence shown in SEQ ID NO: 52, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 52; or, (9) HCDR1 having the sequence shown in SEQ ID NO: 227, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 227; HCDR2 having the sequence shown in SEQ ID NO: 228, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 228; A HCDR3 having the sequence shown in SEQ ID NO: 55, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 55; LCDR1 having the sequence shown in SEQ ID NO: 56, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 56; LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57; LCDR3 having the sequence shown in SEQ ID NO: 58, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 58; or, (10) HCDR1 having the sequence shown in SEQ ID NO: 230, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 230; HCDR2 having the sequence shown in SEQ ID NO: 231, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 231; A HCDR3 having the sequence shown in SEQ ID NO: 65, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 65; LCDR1 having the sequence shown in SEQ ID NO: 66, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 66; LCDR2 having the sequence shown in SEQ ID NO: 67, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 67; LCDR3 having the sequence shown in SEQ ID NO: 68, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 68; or, (11) HCDR1 having the sequence shown in SEQ ID NO: 232, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 232; HCDR2 having the sequence shown in SEQ ID NO: 233, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 233; A HCDR3 having the sequence shown in SEQ ID NO: 74, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 74; LCDR1 having the sequence shown in SEQ ID NO: 75, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 75; LCDR2 having the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 15; LCDR3 having the sequence shown in SEQ ID NO: 76, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 76; or, (12) HCDR1 having the sequence shown in SEQ ID NO: 234, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 234; HCDR2 having the sequence shown in SEQ ID NO: 235, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 235; A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83; LCDR1 having the sequence shown in SEQ ID NO: 84, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 84; LCDR2 having the sequence shown in SEQ ID NO: 85, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 85; LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86; or, (13) HCDR1 having the sequence shown in SEQ ID NO: 236, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 236; HCDR2 having the sequence shown in SEQ ID NO: 237, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 237; A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93; LCDR1 having the sequence shown in SEQ ID NO: 94, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 94; LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95; LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96; or, (14) HCDR1 having the sequence shown in SEQ ID NO: 234, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 234; HCDR2 having the sequence shown in SEQ ID NO: 238, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 238; A HCDR3 having the sequence shown in SEQ ID NO: 83, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 83; LCDR1 having the sequence shown in SEQ ID NO: 102, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 102; LCDR2 having the sequence shown in SEQ ID NO: 103, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 103; LCDR3 having the sequence shown in SEQ ID NO: 86, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 86; or, (15) HCDR1 having the sequence shown in SEQ ID NO: 239, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 239; HCDR2 having the sequence shown in SEQ ID NO: 240, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 240; A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110; LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111; LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112; LCDR3 having the sequence shown in SEQ ID NO: 113, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 113; or, (16) HCDR1 having the sequence shown in SEQ ID NO: 239, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 239; HCDR2 having the sequence shown in SEQ ID NO: 240, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 240; A HCDR3 having the sequence shown in SEQ ID NO: 110, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 110; LCDR1 having the sequence shown in SEQ ID NO: 111, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 111; LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112; LCDR3 having the sequence shown in SEQ ID NO: 118, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 118; or, (17) HCDR1 having the sequence shown in SEQ ID NO: 241, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 241; HCDR2 having the sequence shown in SEQ ID NO: 242, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 242; A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93; LCDR1 having the sequence shown in SEQ ID NO: 123, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 123; LCDR2 having the sequence shown in SEQ ID NO: 95, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 95; LCDR3 having the sequence shown in SEQ ID NO: 124, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 124; or, (18) HCDR1 having the sequence shown in SEQ ID NO: 243, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 243; HCDR2 having the sequence shown in SEQ ID NO: 244, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 244; A HCDR3 having the sequence shown in SEQ ID NO: 131, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 131; LCDR1 having the sequence shown in SEQ ID NO: 132, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 132; LCDR2 having the sequence shown in SEQ ID NO: 133, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 133; LCDR3 having the sequence shown in SEQ ID NO: 134, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 134; or, (19) HCDR1 having the sequence shown in SEQ ID NO: 236, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 236; HCDR2 having the sequence shown in SEQ ID NO: 237, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 237; A HCDR3 having the sequence shown in SEQ ID NO: 93, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 93; LCDR1 having the sequence shown in SEQ ID NO: 139, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 139; LCDR2 having the sequence shown in SEQ ID NO: 112, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 112; LCDR3 having the sequence shown in SEQ ID NO: 96, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 96; or, (20) HCDR1 having the sequence shown in SEQ ID NO: 245, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 245; HCDR2 having the sequence shown in SEQ ID NO: 246, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 246; A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (21) HCDR1 having the sequence shown in SEQ ID NO: 234, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 234; HCDR2 having the sequence shown in SEQ ID NO: 247, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 247; A HCDR3 having the sequence shown in SEQ ID NO: 154, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 154; LCDR1 having the sequence shown in SEQ ID NO: 155, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 155; LCDR2 having the sequence shown in SEQ ID NO: 156, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 156; LCDR3 having the sequence shown in SEQ ID NO: 157, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 157; or, (22) HCDR1 having the sequence shown in SEQ ID NO: 248, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 248; HCDR2 having the sequence shown in SEQ ID NO: 249, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 249; A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 165, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 165; LCDR3 having the sequence shown in SEQ ID NO: 166, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 166; or, (23) HCDR1 having the sequence shown in SEQ ID NO: 245, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 245; HCDR2 having the sequence shown in SEQ ID NO: 246, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 246; A HCDR3 having the sequence shown in SEQ ID NO: 171, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 171; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 147, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 147; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (24) HCDR1 having the sequence shown in SEQ ID NO: 250, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 250; HCDR2 having the sequence shown in SEQ ID NO: 251, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 251; A HCDR3 having the sequence shown in SEQ ID NO: 164, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 164; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 178, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 178; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (25) HCDR1 having the sequence shown in SEQ ID NO: 252, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 252; HCDR2 having the sequence shown in SEQ ID NO: 253, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 253; A HCDR3 having the sequence shown in SEQ ID NO: 185, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 185; LCDR1 having the sequence shown in SEQ ID NO: 186, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 186; LCDR2 having the sequence shown in SEQ ID NO: 187, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 187; LCDR3 having the sequence shown in SEQ ID NO: 188, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 188; or, (26) HCDR1 having the sequence shown in SEQ ID NO: 254, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 254; HCDR2 having the sequence shown in SEQ ID NO: 255, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 255; A HCDR3 having the sequence shown in SEQ ID NO: 195, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 195; LCDR1 having the sequence shown in SEQ ID NO: 196, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 196; LCDR2 having the sequence shown in SEQ ID NO: 57, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 57; LCDR3 having the sequence shown in SEQ ID NO: 197, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 197; or, (27) HCDR1 having the sequence shown in SEQ ID NO: 256, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 256; HCDR2 having the sequence shown in SEQ ID NO: 246, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 246; A HCDR3 having the sequence shown in SEQ ID NO: 145, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 145; LCDR1 having the sequence shown in SEQ ID NO: 146, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 146; LCDR2 having the sequence shown in SEQ ID NO: 203, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 203; LCDR3 having the sequence shown in SEQ ID NO: 148, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 148; or, (28) HCDR1 having the sequence shown in SEQ ID NO: 257, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., substitutions, deletions or additions of 1, 2 or 3 amino acids) compared to the sequence of SEQ ID NO: 257; HCDR2 having the sequence shown in SEQ ID NO: 258, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 258; A HCDR3 having the sequence shown in SEQ ID NO: 210, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO:

210. LCDR1 having the sequence shown in SEQ ID NO: 211, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 211; LCDR2 having the sequence shown in SEQ ID NO: 212, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 212; LCDR3 having the sequence shown in SEQ ID NO: 213, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence of SEQ ID NO: 213; However, the substitution described in any one of (1) to (28) is a conservative substitution.

3. The anti-MUC17 antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein The antibody or antigen-binding fragment thereof comprises: (I) a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of: (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 7, or consists of SEQ ID NO: 7; (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 17, or consists of SEQ ID NO: 17; (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 24, or consists of SEQ ID NO: 24; (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 34, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 34, or consists of SEQ ID NO: 34; (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:40, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:40, or consists of SEQ ID NO:40; (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:47, or consists of SEQ ID NO:47; (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 59, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 59, or consists of SEQ ID NO: 59; (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:69, or consists of SEQ ID NO:69; (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 77, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 77, or consists of SEQ ID NO: 77; (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:87, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:87, or consists of SEQ ID NO:87; (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 97, or consists of SEQ ID NO: 97; (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 104, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 104, or consists of SEQ ID NO: 104; (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 114, or consists of SEQ ID NO: 114; (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 125, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 125, or consists of SEQ ID NO: 125; (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 135, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 135, or consists of SEQ ID NO: 135; (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 149, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 149, or consists of SEQ ID NO: 149; (17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 158, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 158, or consists of SEQ ID NO: 158; (18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 167, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 167, or consists of SEQ ID NO: 167; (19) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 172, or consists of SEQ ID NO: 172; (20) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 179, or consists of SEQ ID NO: 179; (21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 189, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 189, or consists of SEQ ID NO: 189; (22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 198, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 198, or consists of SEQ ID NO: 198; (23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 204, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 204, or consists of SEQ ID NO: 204; (24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 214, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 214, or consists of SEQ ID NO: 214; (25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; (26) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; or (27) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; and / or, (II) Light chain variable region (VL): (1) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 8, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 8, or consists of SEQ ID NO: 8; (2) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 18, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 18, or consists of SEQ ID NO: 18; (3) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 25, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 25, or consists of SEQ ID NO: 25; (4) the light chain variable region comprises the amino acid sequence of SEQ ID NO:31, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:31, or consists of SEQ ID NO:31; (5) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 35, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 35, or consists of SEQ ID NO: 35; (6) the light chain variable region comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:41, or consists of SEQ ID NO:41; (7) the light chain variable region comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:48, or consists of SEQ ID NO:48; (8) the light chain variable region comprises the amino acid sequence of SEQ ID NO:53, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:53, or consists of SEQ ID NO:53; (9) the light chain variable region comprises the amino acid sequence of SEQ ID NO:60, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:60, or consists of SEQ ID NO:60; (10) the light chain variable region comprises the amino acid sequence of SEQ ID NO:70, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:70, or consists of SEQ ID NO:70; (11) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 78, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 78, or consists of SEQ ID NO: 78; (12) the light chain variable region comprises the amino acid sequence of SEQ ID NO:88, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:88, or consists of SEQ ID NO:88; (13) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 98, or consists of SEQ ID NO: 98; (14) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 105, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 105, or consists of SEQ ID NO: 105; (15) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 115, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 115, or consists of SEQ ID NO: 115; (16) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 119, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 119, or consists of SEQ ID NO: 119; (17) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 126, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 126, or consists of SEQ ID NO: 126; (18) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 136, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 136, or consists of SEQ ID NO: 136; (19) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 140, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 140, or consists of SEQ ID NO: 140; (20) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 150, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 150, or consists of SEQ ID NO: 150; (21) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 159, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 159, or consists of SEQ ID NO: 159; (22) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 168, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 168, or consists of SEQ ID NO: 168; (23) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 173, or consists of SEQ ID NO: 173; (24) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 180, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 180, or consists of SEQ ID NO: 180; (25) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 190, or consists of SEQ ID NO: 190; (26) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 199, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 199, or consists of SEQ ID NO: 199; (27) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 205, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 205, or consists of SEQ ID NO: 205; (28) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 215, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 215, or consists of SEQ ID NO: 215; (29) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263; (30) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260; (31) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262; (32) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265; (33) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266; or (34) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO:

267.

4. The anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein: (1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:7, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:7, or consists of SEQ ID NO:7; the light chain variable region comprises the amino acid sequence of SEQ ID NO:8, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:8, or consists of SEQ ID NO:8; (2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 17, or consists of SEQ ID NO: 17; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 18, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 18, or consists of SEQ ID NO: 18; (3) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 24, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 24, or consists of SEQ ID NO: 24; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 25, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 25, or consists of SEQ ID NO: 25; (4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:24, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:24, or consists of SEQ ID NO:24; the light chain variable region comprises the amino acid sequence of SEQ ID NO:31, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:31, or consists of SEQ ID NO:31; (5) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:34, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:34, or consists of SEQ ID NO:34; the light chain variable region comprises the amino acid sequence of SEQ ID NO:35, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:35, or consists of SEQ ID NO:35; (6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:40, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:40, or consists of SEQ ID NO:40; the light chain variable region comprises the amino acid sequence of SEQ ID NO:41, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:41, or consists of SEQ ID NO:41; (7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:47, or consists of SEQ ID NO:47; the light chain variable region comprises the amino acid sequence of SEQ ID NO:48, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:48, or consists of SEQ ID NO:48; (8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:47, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:47, or consists of SEQ ID NO:47; the light chain variable region comprises the amino acid sequence of SEQ ID NO:53, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:53, or consists of SEQ ID NO:53; (9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:59, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:59, or consists of SEQ ID NO:59; the light chain variable region comprises the amino acid sequence of SEQ ID NO:60, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:60, or consists of SEQ ID NO:60; (10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:69, or consists of SEQ ID NO:69; the light chain variable region comprises the amino acid sequence of SEQ ID NO:70, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:70, or consists of SEQ ID NO:70; (11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 77, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 77, or consists of SEQ ID NO: 77; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 78, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 78, or consists of SEQ ID NO: 78; (12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:87, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:87, or consists of SEQ ID NO:87; the light chain variable region comprises the amino acid sequence of SEQ ID NO:88, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:88, or consists of SEQ ID NO:88; (13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 97, or consists of SEQ ID NO: 97; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 98, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 98, or consists of SEQ ID NO: 98; (14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 104, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 104, or consists of SEQ ID NO: 104; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 105, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 105, or consists of SEQ ID NO: 105; (15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 114, or consists of SEQ ID NO: 114; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 115, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 115, or consists of SEQ ID NO: 115; (16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 114, or consists of SEQ ID NO: 114; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 119, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 119, or consists of SEQ ID NO: 119; (17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 125, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 125, or consists of SEQ ID NO: 125; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 126, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 126, or consists of SEQ ID NO: 126; (18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 135, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 135, or consists of SEQ ID NO: 135; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 136, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 136, or consists of SEQ ID NO: 136; (19) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 97, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 97, or consists of SEQ ID NO: 97; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 140, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 140, or consists of SEQ ID NO: 140; (20) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 149, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 149, or consists of SEQ ID NO: 149; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 150, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 150, or consists of SEQ ID NO: 150; (21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 158, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 158, or consists of SEQ ID NO: 158; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 159, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 159, or consists of SEQ ID NO: 159; (22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 167, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 167, or consists of SEQ ID NO: 167; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 168, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 168, or consists of SEQ ID NO: 168; (23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 172, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 172, or consists of SEQ ID NO: 172; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 173, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 173, or consists of SEQ ID NO: 173; (24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 179, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 179, or consists of SEQ ID NO: 179; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 180, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 180, or consists of SEQ ID NO: 180; (25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 189, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 189, or consists of SEQ ID NO: 189; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 190, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 190, or consists of SEQ ID NO: 190; (26) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 198, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 198, or consists of SEQ ID NO: 198; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 199, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 199, or consists of SEQ ID NO: 199; (27) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 204, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 204, or consists of SEQ ID NO: 204; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 205, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 205, or consists of SEQ ID NO: 205; (28) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 214, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 214, or consists of SEQ ID NO: 214; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 215, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 215, or consists of SEQ ID NO: 215; (29) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263; (30) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260; (31) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260; (32) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262; (33) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO: 262; (34) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263; (35) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 263, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 263, or consists of SEQ ID NO: 263; (36) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265; (37) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265; (38) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 265, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 265, or consists of SEQ ID NO: 265; (39) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 260, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 260, or consists of SEQ ID NO: 260; (40) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266; (41) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266; (42) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 266, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 266, or consists of SEQ ID NO: 266; (43) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267; (44) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 259, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 259, or consists of SEQ ID NO: 259; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267; (45) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 261, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 261, or consists of SEQ ID NO: 261; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 267, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 267, or consists of SEQ ID NO: 267; (46) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 264, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 264, or consists of SEQ ID NO: 264; the light chain variable region comprises the amino acid sequence of SEQ ID NO: 262, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 262, or consists of SEQ ID NO:

262.

5. The anti-MUC17 antibody or antigen-binding fragment thereof of any one of claims 1 to 4, further comprising: a heavy chain constant region or a variant thereof, and a light chain constant region or a variant thereof of a human immunoglobulin, wherein the variant has one or more amino acid substitutions, deletions or additions (e.g., up to 20, up to 15, up to 10 or up to 5 amino acid substitutions, deletions or additions; for example, 1, 2, 3, 4 or 5 amino acid substitutions, deletions or additions) compared to the wild-type sequence from which it is derived; the heavy chain constant region is an IgG heavy chain constant region, such as an IgG1, IgG2, IgG3 or IgG4 heavy chain constant region; the light chain constant region is selected from a kappa or lambda light chain constant region; for example, the heavy chain constant region comprises or consists of the sequence set forth in SEQ ID NO: 223; for example, the light chain constant region comprises or consists of the sequence set forth in SEQ ID NO:

224. 6 . The anti-MUC17 antibody or antigen-binding fragment thereof according to claim 1 , which is a murine antibody, a chimeric antibody or a humanized antibody.

7. The anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 6, comprising a heavy chain and a light chain, wherein: (1) the heavy chain comprises the amino acid sequence of SEQ ID NO:9, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:9, or consists of SEQ ID NO:9; the light chain comprises the amino acid sequence of SEQ ID NO:10, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:10, or consists of SEQ ID NO:10; (2) the heavy chain comprises the amino acid sequence of SEQ ID NO: 19, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 19, or consists of SEQ ID NO: 19; the light chain comprises the amino acid sequence of SEQ ID NO: 20, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 20, or consists of SEQ ID NO: 20; (3) the heavy chain comprises the amino acid sequence of SEQ ID NO: 26, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 26, or consists of SEQ ID NO: 26; the light chain comprises the amino acid sequence of SEQ ID NO: 27, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 27, or consists of SEQ ID NO: 27; (4) the heavy chain comprises the amino acid sequence of SEQ ID NO:26, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:26, or consists of SEQ ID NO:26; the light chain comprises the amino acid sequence of SEQ ID NO:32, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:32, or consists of SEQ ID NO:32; (5) the heavy chain comprises the amino acid sequence of SEQ ID NO:36, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:36, or consists of SEQ ID NO:36; the light chain comprises the amino acid sequence of SEQ ID NO:37, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:37, or consists of SEQ ID NO:37; (6) the heavy chain comprises the amino acid sequence of SEQ ID NO:42, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:42, or consists of SEQ ID NO:42; the light chain comprises the amino acid sequence of SEQ ID NO:43, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:43, or consists of SEQ ID NO:43; (7) the heavy chain comprises the amino acid sequence of SEQ ID NO:49, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:49, or consists of SEQ ID NO:49; the light chain comprises the amino acid sequence of SEQ ID NO:50, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:50, or consists of SEQ ID NO:50; (8) the heavy chain comprises the amino acid sequence of SEQ ID NO:49, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:49, or consists of SEQ ID NO:49; the light chain comprises the amino acid sequence of SEQ ID NO:54, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:54, or consists of SEQ ID NO:54; (9) the heavy chain comprises the amino acid sequence of SEQ ID NO:61, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:61, or consists of SEQ ID NO:61; the light chain comprises the amino acid sequence of SEQ ID NO:62, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:62, or consists of SEQ ID NO:62; (10) the heavy chain comprises the amino acid sequence of SEQ ID NO:71, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:71, or consists of SEQ ID NO:71; the light chain comprises the amino acid sequence of SEQ ID NO:72, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:72, or consists of SEQ ID NO:72; (11) the heavy chain comprises the amino acid sequence of SEQ ID NO: 79, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 79, or consists of SEQ ID NO: 79; the light chain comprises the amino acid sequence of SEQ ID NO: 80, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 80, or consists of SEQ ID NO: 80; (12) the heavy chain comprises the amino acid sequence of SEQ ID NO:89, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:89, or consists of SEQ ID NO:89; the light chain comprises the amino acid sequence of SEQ ID NO:90, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO:90, or consists of SEQ ID NO:90; (13) the heavy chain comprises the amino acid sequence of SEQ ID NO: 99, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 99, or consists of SEQ ID NO: 99; the light chain comprises the amino acid sequence of SEQ ID NO: 100, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 100, or consists of SEQ ID NO: 100; (14) the heavy chain comprises the amino acid sequence of SEQ ID NO: 106, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 106, or consists of SEQ ID NO: 106; the light chain comprises the amino acid sequence of SEQ ID NO: 107, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 107, or consists of SEQ ID NO: 107; (15) the heavy chain comprises the amino acid sequence of SEQ ID NO: 116, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 116, or consists of SEQ ID NO: 116; the light chain comprises the amino acid sequence of SEQ ID NO: 117, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 117, or consists of SEQ ID NO: 117; (16) the heavy chain comprises the amino acid sequence of SEQ ID NO: 116, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 116, or consists of SEQ ID NO: 116; the light chain comprises the amino acid sequence of SEQ ID NO: 120, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 120, or consists of SEQ ID NO: 120; (17) the heavy chain comprises the amino acid sequence of SEQ ID NO: 127, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 127, or consists of SEQ ID NO: 127; the light chain comprises the amino acid sequence of SEQ ID NO: 128, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 128, or consists of SEQ ID NO: 128; (18) the heavy chain comprises the amino acid sequence of SEQ ID NO: 137, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 137, or consists of SEQ ID NO: 137; the light chain comprises the amino acid sequence of SEQ ID NO: 138, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 138, or consists of SEQ ID NO: 138; (19) The heavy chain comprises the amino acid sequence of SEQ ID NO: 141, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 141, or consists of SEQ ID NO: 141; the light chain comprises the amino acid sequence of SEQ ID NO: 142, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 142, or consists of SEQ ID NO: 142; (20) the heavy chain comprises the amino acid sequence of SEQ ID NO: 151, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 151, or consists of SEQ ID NO: 151; the light chain comprises the amino acid sequence of SEQ ID NO: 152, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 152, or consists of SEQ ID NO: 152; (21) the heavy chain comprises the amino acid sequence of SEQ ID NO: 160, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 160, or consists of SEQ ID NO: 160; the light chain comprises the amino acid sequence of SEQ ID NO: 161, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 161, or consists of SEQ ID NO: 161; (22) the heavy chain comprises the amino acid sequence of SEQ ID NO: 169, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 169, or consists of SEQ ID NO: 169; the light chain comprises the amino acid sequence of SEQ ID NO: 170, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 170, or consists of SEQ ID NO: 170; (23) the heavy chain comprises the amino acid sequence of SEQ ID NO: 174, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 174, or consists of SEQ ID NO: 174; the light chain comprises the amino acid sequence of SEQ ID NO: 175, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 175, or consists of SEQ ID NO: 175; (24) the heavy chain comprises the amino acid sequence of SEQ ID NO: 181, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 181, or consists of SEQ ID NO: 181; the light chain comprises the amino acid sequence of SEQ ID NO: 182, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 182, or consists of SEQ ID NO: 182; (25) the heavy chain comprises the amino acid sequence of SEQ ID NO: 191, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 191, or consists of SEQ ID NO: 191; the light chain comprises the amino acid sequence of SEQ ID NO: 192, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 192, or consists of SEQ ID NO: 192; (26) the heavy chain comprises the amino acid sequence of SEQ ID NO: 200, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 200, or consists of SEQ ID NO: 200; the light chain comprises the amino acid sequence of SEQ ID NO: 201, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 201, or consists of SEQ ID NO: 201; (27) the heavy chain comprises the amino acid sequence of SEQ ID NO: 206, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 206, or consists of SEQ ID NO: 206; the light chain comprises the amino acid sequence of SEQ ID NO: 207, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 207, or consists of SEQ ID NO: 207; (28) The heavy chain comprises the amino acid sequence of SEQ ID NO: 216, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 216, or consists of SEQ ID NO: 216; the light chain comprises the amino acid sequence of SEQ ID NO: 217, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the amino acid sequence of SEQ ID NO: 217, or consists of SEQ ID NO:

217.

8. The anti-MUC17 antibody or antigen-binding fragment thereof of any one of claims 1 to 7, wherein the antigen-binding fragment is selected from Fab, Fab'-SH, Fv, scFv, or (Fab')2 fragment.

9. The anti-MUC17 antibody or antigen-binding fragment thereof of any one of claims 1 to 8, wherein the antibody or antigen-binding fragment thereof is present at a concentration of about 1×10 -7 M or lower affinity binds to MUC17.

10. An isolated nucleotide molecule encoding the anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, or the heavy chain variable region and / or light chain variable region thereof, or the heavy chain and / or light chain thereof. An expression vector comprising the nucleotide molecule according to claim 10 .

12. A host cell comprising the nucleotide molecule of claim 10 or the expression vector of claim 11.

13. An anti-MUC17 antibody drug conjugate according to formula (I), its isomers, its pharmaceutically acceptable salts or mixtures thereof: Ab-(LD)m[Formula (I)] in, L is the joint unit; D is a small molecule drug with cytotoxicity; m is the average number of LD units coupled to Ab, and m is selected from 1 to 10, preferably 2 to 8; Ab is the anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9.

14. The anti-MUC17 antibody drug conjugate, its isomer, its pharmaceutically acceptable salt or a mixture thereof according to claim 13, wherein: D is a monomethyl auristatin compound, a camptothecin compound or a maytansine alkaloid; the monomethyl auristatin compound may be monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF); the camptothecin compound may be exitecan, Dxd(1), Dxd(2), or SN-38; the maytansine alkaloid may be DM1, DM3 or DM4; the antibody-drug conjugate comprises a plurality of D components, and the plurality of D components may be a combination of different therapeutically active substances or pharmaceutically active ingredients, or a combination of the same therapeutically active substance or pharmaceutically active ingredient; And / or, said L is a combination of one or more L', wherein said L' is selected from carbonyl, amino, amide, aminoacyl, -(PEG) n -、-(CH2) n -, containing heteroatoms -(CH2) n -, -(C≡C)-, -(CH=CH)-, -O-, -S-, maleimido (mc), maleimidopropionyl (MP), methylsulfonylpyrimidinyl, valine-citrulline (val-cit), valine-alanine (val-ala), N-succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), alanine-phenylalanine (ala-phe), phenylalanine-lysine (phe-lys), p-aminobenzyloxycarbonyl (PAB), dimethylethylenediamine (DMED), N-succinimidyl-4-(2-pyridylthio)pentanoic acid Ester (SPP), N-succinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (SMCC), N-succinimidyl (4-iodo-acetyl) aminobenzoate (SIAB), N-succinimidyl-4-(2-pyridyldithio) butyrate (SPDB), N-succinimidyl 3-(pyridin-2-yldithio)-propionate (SPDP), glycine-glycine-phenylalanine-glycine (GGFG), acetyl-lysine-valine-citrulline-p-aminobenzyloxycarbonyl (AcLys-vc-PABC); wherein n is independently selected from integers of 1 to 20; And / or, the L may be J-L1-L2-X-L3; the J is selected from L1 is selected from a single bond, -(PEG) n -or-(CH2) n -, the (CH2) n - may optionally contain 1 to 6 heteroatoms selected from N, O, and S; wherein n is independently selected from an integer from 1 to 20; L2 is selected from a combination of one or more of a single bond, -O-, -S-, -CH2-, -NH-, and -C(O)-; wherein the -CH2- and -NH- may be optionally replaced by C 1～6 The present invention relates to a cyclohexyl group comprising a cycloalkyl group or a halogen group, wherein the cyclohexyl group is substituted 1 to 3 times; X is selected from a single bond or a combination of 1 to 4 X', wherein the X' is independently selected from an amino acid; L3 is selected from a single bond, -O-, -S-, -CH2-, -NH-, -C(O)-, -phenyl-, -cyclopropyl-, -cyclobutyl-, -cyclohexyl- or a combination of one or more thereof; wherein the -CH2-, -NH-, -phenyl-, -cyclopropyl-, -cyclobutyl-, -cyclohexyl- may be optionally replaced by C 1～6 Alkyl, halogen, cyano or hydroxyl groups are substituted 1 to 3 times.

15. The anti-MUC17 antibody drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof according to claim 13, wherein the (LD) moiety is derived from the structures represented by Formula Cpd3, Formula Cpd5 and Formula Cpd6:

16. The anti-MUC17 antibody drug conjugate, its isomer, its pharmaceutically acceptable salt or a mixture thereof according to claim 13 or 15, wherein: The (LD) portion is connected to the thiol group on the Ab by forming a thiopyrimidine structure, and the antibody drug conjugate has the structure shown in Formula (I-C3), Formula (I-C5) and Formula (I-C6): wherein m is the average number of connections, and m is independently selected from 1 to 10; and Ab is the antibody or antigen-binding fragment thereof according to any one of claims 1 to 9.

17. Linker unit - cytotoxic small molecule drug selected from: its isomers, its pharmaceutically acceptable salts or mixtures thereof.

18. A composition comprising the anti-MUC17 antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or a mixture thereof according to any one of claims 13 to 16, wherein the molar ratio of D to Ab in the composition (DAR value) is a decimal or integer between 1 and 10.

19. A pharmaceutical composition comprising the anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, or the isolated nucleotide molecule according to claim 10, or the expression vector according to claim 11, or the host cell according to claim 12, or the anti-MUC17 antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof according to any one of claims 13 to 16, or the linker unit-cytotoxic small molecule drug according to claim 17, or the composition according to claim 18, and a pharmaceutically acceptable excipient.

20. Use of the anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, or the isolated nucleotide molecule according to claim 10, or the expression vector according to claim 11, or the host cell according to claim 12, or the anti-MUC17 antibody-drug conjugate, its isomer, its pharmaceutically acceptable salt or mixture thereof according to any one of claims 13 to 16, or the linker unit-cytotoxic small molecule drug according to claim 17, or the composition according to claim 18, or the pharmaceutical composition according to claim 19 in the preparation of a medicament for treating and / or preventing a disease or condition associated with MUC17.

21. A method for treating and / or preventing a MUC17-related disease or condition, comprising administering to a subject in need thereof an effective amount of the anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9, or the isolated nucleotide molecule according to claim 10, or the expression vector according to claim 11, or the host cell according to claim 12, or the anti-MUC17 antibody-drug conjugate, isomer thereof, pharmaceutically acceptable salt thereof, or a mixture thereof according to any one of claims 13 to 16, or the linker unit-cytotoxic small molecule drug according to claim 17, or the composition according to claim 18, or the pharmaceutical composition according to claim 19.

22. The use of claim 20 or the method of claim 21, wherein the MUC17-associated disease or condition is a cancer and / or tumor selected from the group consisting of gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, colorectal cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer, and rectal cancer.

23. A detection system comprising the anti-MUC17 antibody or antigen-binding fragment thereof according to any one of claims 1 to 9.

24. A method for detecting the presence or determining the level of MUC17 in a sample, comprising: (a) contacting the sample with the anti-MUC17 antibody or antigen-binding fragment thereof of any one of claims 1-9, and (b) detecting the formation of an immune complex between the anti-MUC17 antibody or antigen-binding fragment thereof and MUC17 in the sample or determining the content of the immune complex to detect the presence of MUC17 in the sample or determine the level of MUC17 in the sample; wherein the sample is a solid tissue sample or a liquid tissue sample.

25. Use of the anti-MUC17 antibody and antigen-binding fragment thereof according to any one of claims 1 to 9 in the detection system according to claim 23 or the detection method according to claim 24.

26. Use of the anti-MUC17 antibody and antigen-binding fragment thereof according to any one of claims 1 to 9, and the detection system according to claim 23 in a method for diagnosing whether a subject suffers from a MUC17-related disease or disorder. Preferably, the MUC17-associated disease or disorder is a cancer and / or a tumor, and the cancer and / or tumor is selected from the group consisting of: gastric cancer, esophageal cancer, pancreatic cancer, gastroesophageal adenocarcinoma, gastroesophageal junction cancer, gastric cardia cancer, gastric body cancer, gastric antrum cancer, liver cancer, bile duct cancer, gallbladder cancer, melanoma, endometrial cancer, kidney cancer, prostate cancer, breast cancer, triple-negative breast cancer, colon cancer, large intestine cancer, lung cancer, bone cancer, skin cancer, head and neck cancer, uterine cancer, cervical cancer, ovarian cancer and rectal cancer.

27. A method for detecting and / or quantifying MUC17 expression in a sample, comprising: (a) using the antibody or antigen-binding fragment thereof of any one of claims 1-9, or the detection system of claim 23, to determine the expression level of MUC17 in a sample; and (b) comparing the expression level of MUC17 determined in step (a) with: (i) a predefined value of MUC17 expression; (ii) the expression level of MUC17 determined in a control; or (iii) the expression level of MUC17 determined in a sample obtained from the same source or subject at a previous time point.

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