PTK7 binding proteins and uses thereof

Abstract

The invention relates to the field of disease treatment, in particular to an anti-PTK7 antibody or an antigen-binding fragment thereof, nucleic acid molecules encoding the antibody or the antigen-binding fragment, and a method for preparing the antibody or the antigen-binding fragment. The anti-PTK7 antibody or the antigen binding fragment thereof provided by the invention has high affinity binding and endocytosis activity to PTK7, and also has good hydrophilicity. Thus, the invention further relates to the use of said antibodies or antigen-binding fragments thereof in the treatment and diagnosis of disease.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese patent application No. 202210998273.4 filed on August 19, 2022 and Chinese patent application No. 202211260998.X filed on October 14, 2022, the disclosures of which are incorporated herein by reference in their entirety.

[0003] Sequence Listing

[0004] This application contains a computer readable sequence list, which has been submitted with this application in an XML file format, the entire contents of which are incorporated herein by reference. The sequence list XML file submitted with this application is titled "14463-063-228_SEQ_LISTING.xml", created on August 15, 2023, and is 152,208 bytes in size. Background of the Invention (1) Technical field

[0006] The present invention belongs to the field of therapeutic monoclonal antibodies, and more specifically, the present invention relates to an antibody against PTK7; and also relates to the use of the antibody in treating and diagnosing diseases.

[0007] (2) Description of related prior art

[0008] PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family and lacks kinase activity due to mutations in the kinase domain. PTK7 was originally identified in colon cancer cells and is therefore also known as CCK4 (colon carcinoma kinase-4). PTK7 consists of seven extracellular immunoglobulin domains, a transmembrane region, and an intracellular tyrosine kinase domain, and its ligand is unknown. The extracellular segment of PTK7 can be cleaved at the second position by ADAM proteases and MT1-MMP. Protease hydrolysis produces two soluble fragments of PTK7. PTK7 is an evolutionarily conserved transmembrane receptor whose functions involve multiple processes from embryonic morphogenesis to epidermal wound repair. It is also a multifunctional co-receptor that acts as a molecular switch in the Wnt, sema-plexin (semaphorin, axon guidance factor, plexin) and VEGF signaling pathways.

[0009] PTK7 is expressed in normal tissues such as the endometrium, ovary, and placenta, but is highly expressed in a variety of solid tumors: NSCLC 47.4%, H-score average 117.4; ovarian cancer 45.10%, H-score average 151; TNBC 28.6%, H-score average 159.2; It is reported that in esophageal cancer cases, more than 80% express PTK7, and 60% are 2 + or 3 + IHC staining is positive, while normal esophageal tissue is PTK7-negative, and high expression of PTK7 is associated with poor prognosis. Cofetuzumab Pelidotin, an ADC drug targeting PTK7 developed by Pfizer, has shown good safety and preliminary efficacy in Phase I clinical trials. Based on the high expression of PTK7 in a variety of tumors and the clinical demonstration of the safety and effectiveness of targeted drugs, PTK7 is an ideal therapeutic target.

[0010] There are currently no PTK7-targeted antibody drugs on the market. Therefore, it is urgent and necessary to develop antibodies targeting PTK7 with higher specificity, lower toxic side effects, better clinical efficacy, and more convenient administration, which will provide patients with more medication options. SUMMARY OF THE INVENTION

[0012] In the present application, the inventors have developed an anti-human PTK7 humanized antibody with good hydrophilicity and stability, which can specifically recognize / bind to human PTK7 with high affinity and can be efficiently internalized into PTK7-expressing cells, and can be used in corresponding treatment and diagnosis fields. Thus, the following invention is completed.

[0013] Antibodies of the present invention

[0014] In one aspect, the present invention provides an antibody or an antigen-binding fragment thereof that specifically binds to PTK7, wherein the antibody or the antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs):

[0015] (a) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 19; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 20;

[0016] (b) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 1; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 2;

[0017] (c) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 3; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 4;

[0018] (d) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:5; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:6;

[0019] (e) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:7; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:8;

[0020] (f) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:9; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:10;

[0021] (g) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 11; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 12;

[0022] (h) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 13; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 14;

[0023] (i) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 15; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 16;

[0024] (j) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 17; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 18;

[0025] (k) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:21; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:22;

[0026] (l) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:23; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:24; or

[0027] (m) CDR-H1, CDR-H2 and CDR-H3 contained in the following heavy chain variable region (VH), and / or CDR-L1, CDR-L2 and CDR-L3 contained in the following light chain variable region (VL), wherein, compared with the heavy chain variable region (VH) and / or light chain variable region (VL) described in any one of (a) to (l), at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) contains a mutation, and the mutation is a substitution, deletion or addition of one or several amino acids (for example, a substitution, deletion or addition of 1, 2 or 3 amino acids).

[0028] In certain embodiments, the substitutions are conservative substitutions.

[0029] In certain embodiments, the CDRs are defined according to the IMGT, Kabat, Chothia, or AbM numbering systems.

[0030] In certain embodiments, the PTK7 comprises human PTK7 and / or monkey PTK7. In certain embodiments, the monkey is a rhesus monkey (Macaca mulatta).

[0031] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined according to the Chothia numbering system:

[0032] (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 27 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 28 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0033] (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 41 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 42 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0034] (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 55 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 56 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof;

[0035] (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 68 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 69 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0036] (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 74 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 69 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 84 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 85 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 86 or a variant thereof;

[0037] (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 92 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 93 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 95 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 96 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 97 or a variant thereof;

[0038] (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 27 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 28 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 106 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 107 or a variant thereof;

[0039] (1h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 41 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 42 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0040] (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 41 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 42 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0041] (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 27 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 28 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0042] (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 55 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 56 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; or,

[0043] (11) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 74 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 69 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0044] Wherein, the variant described in any one of (1a)-(11) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0045] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined according to the Kabat numbering system:

[0046] (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 33 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 34 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0047] (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 33 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 35 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0048] (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 47 or a variant thereof; CDR-H2 of SEQ ID NO: 49 or a variant thereof; CDR-H3 of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44 or a variant thereof; CDR-L2 of SEQ ID NO: 45 or a variant thereof; CDR-L3 of SEQ ID NO: 46 or a variant thereof; or

[0049] (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 61 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 62 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof;

[0050] (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 75 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 76 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0051] (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 87 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 88 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 84 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 85 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 86 or a variant thereof;

[0052] (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 98 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 99 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 95 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 96 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 97 or a variant thereof;

[0053] (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 108 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 35 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 106 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 1007 or a variant thereof;

[0054] (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 47 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 48 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0055] (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 47 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 48 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0056] (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 61 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 62 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; or,

[0057] (21) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 75 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 76 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0058] Wherein, the variant described in any one of (2a)-(2l) has one or several amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived; in certain embodiments, the substitutions are conservative substitutions.

[0059] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined according to the IMGT numbering system:

[0060] (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 36 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 37 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 38 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 39 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 40 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0061] (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 50 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 51 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 52 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 53 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 54 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0062] (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 63 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 64 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 65 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 66 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 67 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof;

[0063] (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 77 or a variant thereof; CDR-H2 of SEQ ID NO: 78 or a variant thereof; CDR-H3 of SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 81 or a variant thereof; CDR-L2 of SEQ ID NO: 82 or a variant thereof; CDR-L3 of SEQ ID NO: 73 or a variant thereof;

[0064] (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 80 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 78 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 89 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 90 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 91 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 86 or a variant thereof;

[0065] (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 100 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 101 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 102 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 103 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 104 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 97 or a variant thereof;

[0066] (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 36 or a variant thereof; CDR-H2 of SEQ ID NO: 37 or a variant thereof; CDR-H3 of SEQ ID NO: 109 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 110 or a variant thereof; CDR-L2 of SEQ ID NO: 40 or a variant thereof; CDR-L3 of SEQ ID NO: 107 or a variant thereof;

[0067] (3h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 50 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 51 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 52 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 53 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 54 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0068] (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 50 or a variant thereof; CDR-H2 of SEQ ID NO: 51 or a variant thereof; CDR-H3 of SEQ ID NO: 52 or a variant thereof; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 53 or a variant thereof; CDR-L2 of SEQ ID NO: 54 or a variant thereof; CDR-L3 of SEQ ID NO: 46 or a variant thereof;

[0069] (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 36 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 37 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 38 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 39 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 40 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0070] (3k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 63 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 64 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 65 or a variant thereof; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 66 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 67 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; or,

[0071] (31) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 80 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 78 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 81 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 82 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0072] Wherein, the variant described in any one of (3a)-(3l) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0073] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined according to the AbM numbering system:

[0074] (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 113 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 114 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0075] (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 115 or a variant thereof; CDR-H2 of SEQ ID NO: 116 or a variant thereof; CDR-H3 of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44 or a variant thereof; CDR-L2 of SEQ ID NO: 45 or a variant thereof; CDR-L3 of SEQ ID NO: 46 or a variant thereof;

[0076] (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 117 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 118 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof;

[0077] (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 119 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 120 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0078] (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 122 or a variant thereof; CDR-H2 of SEQ ID NO: 123 or a variant thereof; CDR-H3 of SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 84 or a variant thereof; CDR-L2 of SEQ ID NO: 85 or a variant thereof; CDR-L3 of SEQ ID NO: 86 or a variant thereof;

[0079] (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 124 or a variant thereof; CDR-H2 of SEQ ID NO: 125 or a variant thereof; CDR-H3 of SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 95 or a variant thereof; CDR-L2 of SEQ ID NO: 96 or a variant thereof; CDR-L3 of SEQ ID NO: 97 or a variant thereof;

[0080] (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 126 or a variant thereof; CDR-H2 of SEQ ID NO: 114 or a variant thereof; CDR-H3 of SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 106 or a variant thereof; CDR-L2 of SEQ ID NO: 31 or a variant thereof; CDR-L3 of SEQ ID NO: 107 or a variant thereof;

[0081] (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 115 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 116 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof;

[0082] (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 115 or a variant thereof; CDR-H2 of SEQ ID NO: 116 or a variant thereof; CDR-H3 of SEQ ID NO: 43 or a variant thereof; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44 or a variant thereof; CDR-L2 of SEQ ID NO: 45 or a variant thereof; CDR-L3 of SEQ ID NO: 46 or a variant thereof;

[0083] (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 113 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 114 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof;

[0084] (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 117 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 118 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; or,

[0085] (41) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 121 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 120 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof;

[0086] Wherein, the variant described in any one of (4a)-(4l) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0087] In certain embodiments, the antibody or antigen-binding fragment thereof comprises framework regions (FRs) from human immunoglobulins.

[0088] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises:

[0089] (a) a VH comprising the sequence shown in SEQ ID NO: 19 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 20 or a variant thereof;

[0090] (b) a VH comprising the sequence shown in SEQ ID NO: 1 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 2 or a variant thereof;

[0091] (c) a VH comprising the sequence shown in SEQ ID NO: 3 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 4 or a variant thereof;

[0092] (d) a VH comprising the sequence shown in SEQ ID NO: 5 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 6 or a variant thereof;

[0093] (e) a VH comprising the sequence shown in SEQ ID NO: 7 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 8 or a variant thereof;

[0094] (f) a VH comprising the sequence shown in SEQ ID NO: 9 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 10 or a variant thereof;

[0095] (g) a VH comprising the sequence shown in SEQ ID NO: 11 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 12 or a variant thereof;

[0096] (h) a VH comprising the sequence shown in SEQ ID NO: 13 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 14 or a variant thereof;

[0097] (i) a VH comprising the sequence shown in SEQ ID NO: 15 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 16 or a variant thereof;

[0098] (j) a VH comprising the sequence shown in SEQ ID NO: 17 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 18 or a variant thereof;

[0099] (k) a VH comprising the sequence shown in SEQ ID NO: 21 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 22 or a variant thereof; or

[0100] (l) a VH comprising the sequence shown in SEQ ID NO: 23 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 24 or a variant thereof;

[0101] Wherein, the variant 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 compared to the sequence from which it is derived, or has one or more amino acid substitutions, deletions or additions (e.g., 1, 2, 3, 4 or 5 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0102] In certain embodiments, the antibody or antigen-binding fragment thereof described in any of the above embodiments further has a feature selected from the following:

[0103] (1) with an EC of less than about 50 ng / mL, such as less than about 40 ng / mL, 30 ng / mL, 25 ng / mL, 24 ng / mL, 23 ng / mL, 22 ng / mL, 21 ng / mL, 20 ng / mL, 19 ng / mL, 18 ng / mL, 17 ng / mL, 16 ng / mL, 15 ng / mL, 14 ng / mL, 13 ng / mL, 12 ng / mL, 11 ng / mL, 10 ng / mL, 9 ng / mL, 8 ng / mL, 7 ng / mL, 6 ng / mL or less. 50 Binds to PTK7 (eg, human or monkey PTK7); preferably, the EC 50 Measured by ELISA;

[0104] (2) binds to PTK7 (e.g., human or monkey PTK7) with a KD of less than about 100 nM, such as less than about 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 15 nM, 10 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM or less; preferably, the KD is determined by biofilm interferometry (BLI) (e.g., ForteBio ) measured;

[0105] (3) having ADCC and CDC activities, for example, inducing killing of cells expressing PTK7 (for example, tumor cells) through ADCC and CDC; in certain embodiments, the antibody or its antigen-binding fragment comprises a wild-type Fc region. In certain embodiments, the antibody or its antigen-binding fragment comprises a heavy chain constant region (CH) as shown in SEQ ID NO: 25.

[0106] Alternatively, it has no ADCC or CDC activity; in certain embodiments, the antibody or its antigen-binding fragment comprises a mutated or chemically modified Fc region. In certain embodiments, the antibody or its antigen-binding fragment comprises a heavy chain constant region (CH) as shown in SEQ ID NO: 131.

[0107] (4) inducing PTK7 internalization, e.g., as measured by flow cytometry;

[0108] (5) inhibiting cell proliferation; and / or

[0109] (6) Inhibit tumor growth.

[0110] In certain embodiments, the antibody or antigen-binding fragment thereof described in any of the above embodiments may comprise a constant region from or derived from a human immunoglobulin.

[0111] In certain embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain constant region from or derived from a human immunoglobulin (e.g., IgG1, IgG2, IgG3, or IgG4). In certain embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a wild-type Fc region, or comprises a mutated or chemically modified Fc region, which has a changed effector function (e.g., enhanced ADCC activity) compared to the wild-type Fc region. In certain embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a sequence as shown in SEQ ID NO: 25 or a variant thereof, and the variant has a substitution of up to 20 amino acids compared to SEQ ID NO: 25 (e.g., up to 15, up to 10, or up to 5 amino acids; e.g., 1, 2, 3, 4, or 5 amino acids). In certain embodiments, the substitution is a conservative substitution.

[0112] In certain embodiments, the variant has 3 amino acid substitutions compared to SEQ ID NO: 25. In certain embodiments, the variant has amino acid substitutions at positions 117, 118, and 120 corresponding to SEQ ID NO: 25. In certain embodiments, the variant has alanine substitutions at positions 117, 118, and 120 corresponding to SEQ ID NO: 25. In certain embodiments, the variant has a heavy chain constant region (CH) as shown in SEQ ID NO: 131.

[0113] In certain embodiments, the light chain of the antibody or its antigen-binding fragment comprises a light chain constant region from or derived from a human immunoglobulin (e.g., κ or λ). In certain embodiments, the light chain of the antibody or its antigen-binding fragment comprises a sequence as shown in SEQ ID NO: 26 or a variant thereof, wherein the variant has a substitution of up to 20 amino acids compared to SEQ ID NO: 26 (e.g., a substitution of up to 15, up to 10, or up to 5 amino acids; e.g., a substitution of 1, 2, 3, 4, or 5 amino acids). In certain embodiments, the substitution is a conservative substitution.

[0114] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) as shown in SEQ ID NO:25 and a light chain constant region (CL) as shown in SEQ ID NO:26.

[0115] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) as shown in SEQ ID NO:131 and a light chain constant region (CL) as shown in SEQ ID NO:26.

[0116] In certain embodiments, the antibody or antigen-binding fragment thereof having the above-mentioned heavy chain constant region does not bind to Fc receptors (e.g., CD16a protein, CD32a protein, CD32b protein, CD64 protein). Therefore, in such embodiments, the antibody or antigen-binding fragment thereof can reduce nonspecific killing mediated by Fc receptors and improve the safety of the antibody or antigen-binding fragment thereof in the subject. In certain embodiments, the antibody or antigen-binding fragment thereof having the above-mentioned heavy chain constant region can bind to FcRn. Therefore, in such embodiments, the antibody or antigen-binding fragment thereof has a longer half-life in the subject. In certain embodiments, the antibody or antigen-binding fragment thereof having the above-mentioned heavy chain constant region can induce PTK7-mediated endocytosis. Therefore, in such embodiments, the antibody or antigen-binding fragment thereof has the potential to be used as a carrier for targeted delivery of therapeutic drugs, toxins, enzymes or DNA.

[0117] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises:

[0118] (a) a heavy chain comprising the VH shown in SEQ ID NO: 19 and the heavy chain constant region (CH) shown in SEQ ID NO: 131, and a light chain comprising the VL sequence shown in SEQ ID NO: 20 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0119] (b) a heavy chain comprising the VH shown in SEQ ID NO: 19 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 20 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0120] (c) a heavy chain comprising the VH shown in SEQ ID NO: 1 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL sequence shown in SEQ ID NO: 2 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0121] (d) a heavy chain comprising the VH shown in SEQ ID NO: 1 and the heavy chain constant region (CH) shown in SEQ ID NO: 131, and a light chain comprising the VL sequence shown in SEQ ID NO: 2 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0122] (e) a heavy chain comprising the VH shown in SEQ ID NO:3 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:4 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0123] (f) a heavy chain comprising the VH shown in SEQ ID NO: 5 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 6 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0124] (g) a heavy chain comprising the VH shown in SEQ ID NO:7 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:8 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0125] (h) a heavy chain comprising the VH shown in SEQ ID NO:9 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:10 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0126] (i) a heavy chain comprising the VH shown in SEQ ID NO: 11 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL sequence shown in SEQ ID NO: 12 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0127] (j) a heavy chain comprising the VH shown in SEQ ID NO: 13 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL sequence shown in SEQ ID NO: 14 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0128] (k) a heavy chain comprising the VH shown in SEQ ID NO: 15 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 16 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0129] (l) a heavy chain comprising the VH shown in SEQ ID NO: 17 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL sequence shown in SEQ ID NO: 18 and the light chain constant region (CL) shown in SEQ ID NO: 26.

[0130] (m) a heavy chain comprising the VH shown in SEQ ID NO:21 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL of the sequence shown in SEQ ID NO:22 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0131] (n) a heavy chain comprising the VH shown in SEQ ID NO:23 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:24 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0132] (o) a heavy chain comprising the VH shown in SEQ ID NO:3 and the heavy chain constant region (CH) shown in SEQ ID NO:131, and a light chain comprising the VL of the sequence shown in SEQ ID NO:4 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0133] (p) a heavy chain comprising the VH shown in SEQ ID NO:5 and the heavy chain constant region (CH) shown in SEQ ID NO:131, and a light chain comprising the VL of the sequence shown in SEQ ID NO:6 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0134] (q) a heavy chain comprising the VH shown in SEQ ID NO:7 and the heavy chain constant region (CH) shown in SEQ ID NO:131, and a light chain comprising the VL of the sequence shown in SEQ ID NO:8 and the light chain constant region (CL) shown in SEQ ID NO:26;

[0135] (r) a heavy chain comprising the VH set forth in SEQ ID NO:9 and the heavy chain constant region (CH) set forth in SEQ ID NO:131, and a light chain comprising the VL set forth in SEQ ID NO:10 and the light chain constant region (CL) set forth in SEQ ID NO:26;

[0136] (s) a heavy chain comprising the VH shown in SEQ ID NO: 11 and the heavy chain constant region (CH) shown in SEQ ID NO: 131, and a light chain comprising the VL sequence shown in SEQ ID NO: 12 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0137] (t) a heavy chain comprising the VH shown in SEQ ID NO: 13 and the heavy chain constant region (CH) shown in SEQ ID NO: 131, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 14 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0138] (u) a heavy chain comprising the VH shown in SEQ ID NO: 15 and the heavy chain constant region (CH) shown in SEQ ID NO: 131, and a light chain comprising the VL of the sequence shown in SEQ ID NO: 16 and the light chain constant region (CL) shown in SEQ ID NO: 26;

[0139] (v) a heavy chain comprising the VH set forth in SEQ ID NO: 17 and the heavy chain constant region (CH) set forth in SEQ ID NO: 131, and a light chain comprising the VL set forth in SEQ ID NO: 18 and the light chain constant region (CL) set forth in SEQ ID NO: 26;

[0140] (w) a heavy chain comprising the VH shown in SEQ ID NO:21 and the heavy chain constant region (CH) shown in SEQ ID NO:131, and a light chain comprising the VL of the sequence shown in SEQ ID NO:22 and the light chain constant region (CL) shown in SEQ ID NO:26; or

[0141] (x) a heavy chain comprising the VH shown in SEQ ID NO:23 and the heavy chain constant region (CH) shown in SEQ ID NO:131, and a light chain comprising the VL of the sequence shown in SEQ ID NO:24 and the light chain constant region (CL) shown in SEQ ID NO:26.

[0142] In certain embodiments, the antibodies or antigen-binding fragments thereof of the invention are murine antibodies, chimeric antibodies, humanized antibodies, or fully human antibodies.

[0143] In certain embodiments, the antibody or antigen-binding fragment thereof described in any of the above embodiments is selected from ScFv, Fab, Fab', (Fab')2, Fab'-SH, Fv fragment, disulfide-linked Fv (dsFv), diabody, bispecific antibody and multispecific antibody.

[0144] Derivatized Antibodies

[0145] The antibodies or antigen-binding fragments thereof of the present invention may be derivatized, for example, linked to another molecule (e.g., another polypeptide or protein). Generally, the derivatization (e.g., labeling) of an antibody or antigen-binding fragment thereof will not adversely affect its binding to PTK7 (particularly human PTK7). Therefore, the antibodies or antigen-binding fragments thereof of the present invention are also intended to include such derivatized forms. For example, the antibodies or antigen-binding fragments thereof of the present invention may be functionally linked (by chemical coupling, genetic fusion, non-covalent linkage or other means) to one or more other molecular groups, such as another antibody (e.g., to form a bispecific antibody), a detection agent, a pharmaceutical agent, and / or a protein or polypeptide (e.g., avidin or a polyhistidine tag) that is capable of mediating the binding of the antibody or antigen-binding fragment to another molecule.

[0146] As one of the derivatives of the antibody, the present invention provides a conjugate, which comprises the antibody or antigen-binding fragment thereof of the present invention and a conjugated part.

[0147] In certain embodiments, the coupling moiety is selected from a detectable label. The detectable label of the present invention can be any substance that can be detected by fluorescence, spectroscopy, photochemistry, biochemistry, immunology, electricity, optics or chemical means. Such labels are well known in the art, and examples thereof include, but are not limited to, enzymes (e.g., horseradish peroxidase, alkaline phosphatase, β-galactosidase, urease, glucose oxidase, etc.), radionuclides (e.g., 3H, 125I, 35S, 14C or 32P), fluorescent dyes (e.g., fluorescein isothiocyanate (FITC), fluorescein, tetramethylrhodamine isothiocyanate (TRITC), phycoerythrin (PE), Texas Red, rhodamine, quantum dots or cyanine dye derivatives (e.g., Cy7, Alexa 750)), acridinium ester compounds, magnetic beads (e.g., ), calorimetric markers such as colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, latex, etc.) beads, and biotin for binding to avidin (e.g., streptavidin) modified with the above markers. In certain embodiments, such labels can be suitable for immunological detection (e.g., enzyme-linked immunosorbent assay, radioimmunoassay, fluorescent immunoassay, chemiluminescent immunoassay, etc.). In certain embodiments, the detectable label is selected from a radioisotope, a fluorescent substance, a luminescent substance, a colored substance or an enzyme. In certain embodiments, the detectable label as described above can be connected to the antibody or antigen-binding fragment thereof of the present invention by linkers of different lengths to reduce potential steric hindrance.

[0148] In certain embodiments, the conjugated moiety is selected from a therapeutic agent. In certain embodiments, the therapeutic agent is preferably an anti-tumor agent, such as a cytotoxic agent, a cytokine, a toxin or a radionuclide.

[0149] In certain embodiments, the conjugated moiety is selected from substances that can improve the biological properties of the antibody (eg, increase serum half-life), for example, a chemical group such as polyethylene glycol (PEG), methyl or ethyl, or a sugar group.

[0150] As one of the derivatives of the antibody, the present invention provides a multispecific antibody comprising the antibody of the present invention or an antigen-binding fragment thereof.

[0151] In certain embodiments, the multispecific antibody comprises an antibody of the present invention or an antigen-binding fragment thereof as a first antigen-binding domain, and further comprises at least one second antigen-binding domain directed against another target.

[0152] In certain embodiments, each antigen binding domain of the multispecific antibody retains its respective original binding specificity.

[0153] In certain embodiments, the multispecific antibody is a bispecific antibody or a trispecific antibody or a tetraspecific antibody.

[0154] Antibody preparation

[0155] The antibodies of the present invention can be prepared by various methods known in the art, such as by genetic engineering recombinant technology. For example, DNA molecules encoding the heavy chain and light chain genes of the antibodies of the present invention are obtained by chemical synthesis or PCR amplification. The resulting DNA molecules are inserted into expression vectors and then transfected into host cells. Then, the transfected host cells are cultured under specific conditions and express the antibodies of the present invention.

[0156] The antigen-binding fragments of the present invention can be obtained by hydrolyzing intact antibody molecules (see Morimoto et al., J. Biochem. Biophys. Methods 24: 107-117 (1992) and Brennan et al., Science 229: 81 (1985)). In addition, these antigen-binding fragments can also be directly produced by recombinant host cells (reviewed in Hudson, Curr. Opin. Immunol. 11: 548-557 (1999); Little et al., Immunol. Today, 21: 364-370 (2000)). For example, Fab' fragments can be directly obtained from host cells; Fab' fragments can be chemically coupled to form F(ab')2 fragments (Carter et al., Bio / Technology, 10: 163-167 (1992)). In addition, Fv, Fab or F(ab')2 fragments can also be directly isolated from the culture medium of recombinant host cells. Other techniques for preparing such antigen-binding fragments are well known to those of ordinary skill in the art.

[0157] Therefore, in another aspect, the present invention provides a kind of isolated nucleic acid molecule, it comprises the nucleotide sequence encoding the antibody of the present invention or its antigen-binding fragment, or its heavy chain variable region and / or light chain variable region.According to the codon degeneracy of this area, in certain embodiments, the nucleotide sequence can be replaced according to the codon degeneracy.In certain embodiments, the nucleotide sequence is codon optimized.

[0158] In certain embodiments, the isolated nucleic acid molecule comprises a nucleic acid molecule encoding an antibody heavy chain variable region, and / or a nucleic acid molecule encoding an antibody light chain variable region, wherein:

[0159] The nucleic acid molecule encoding the antibody heavy chain variable region comprises: (i) the nucleotide sequence shown in SEQ ID NO: 127, (ii) a sequence substantially identical to SEQ ID NO: 127 (e.g., a sequence having at least about 85%, 90%, 95%, 99% or higher sequence identity, or a sequence having one or more nucleotide substitutions compared to SEQ ID NO: 127), or (iii) a degenerate sequence of (i) or (ii); and / or,

[0160] The nucleic acid molecule encoding the antibody light chain variable region comprises: (iv) the nucleotide sequence shown in SEQ ID NO: 128, (v) a sequence substantially identical to SEQ ID NO: 128 (e.g., a sequence having at least about 85%, 90%, 95%, 99% or higher sequence identity, or a sequence having one or more nucleotide substitutions compared to SEQ ID NO: 128), or (vi) a degenerate sequence of (iv) or (v).

[0161] In another aspect of the present invention, the present invention provides a vector (e.g., a cloning vector or an expression vector) comprising an isolated nucleic acid molecule of the present invention. In certain embodiments, the vector of the present invention is, for example, a plasmid, a cosmid, a phage, a lentivirus, etc. In certain embodiments, the vector is capable of expressing an antibody or an antigen-binding fragment thereof of the present invention in a subject (e.g., a mammal, such as a human).

[0162] In certain embodiments, the vector comprises a first nucleotide sequence encoding a heavy chain or a heavy chain variable region of an antibody or an antigen-binding fragment thereof of the present invention and a second nucleotide sequence encoding a light chain or a light chain variable region thereof, wherein the first nucleotide sequence and the second nucleotide sequence are present on the same or different vectors. When the first nucleotide sequence and the second nucleotide sequence are present on different vectors, the vector of the present invention comprises a first vector containing the first nucleotide sequence and a second vector containing the second nucleotide sequence.

[0163] In certain embodiments, the antibodies or antigen binding fragments thereof of the present invention can be used to construct a chimeric antigen receptor (CAR), the chimeric antigen receptor comprising an extracellular antigen binding domain (e.g., scFv) that specifically binds to PTK7, a transmembrane domain, and one or more intracellular T cell signaling domains. In such embodiments, the isolated nucleic acid molecules of the present invention may include a nucleotide sequence encoding a chimeric antigen receptor, and the nucleotide sequence encoding the chimeric antigen receptor further includes a nucleotide sequence encoding an antibody or antigen binding fragment thereof (e.g., scFv) of the present invention. In certain embodiments, the isolated nucleic acid molecules of the present invention encode a chimeric antigen receptor comprising an antigen binding fragment (e.g., scFv) of an antibody of the present invention.

[0164] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention can be used to construct chimeric antigen receptor-modified immune cells, which comprise a chimeric antigen receptor (CAR) and an immune cell (eg, T lymphocyte, NK cell).

[0165] In another aspect of the present invention, the present invention provides a host cell comprising the isolated nucleic acid molecule of the present invention or the vector of the present invention. The host cell can be a eukaryotic cell (e.g., mammalian cell, insect cell, yeast cell) or a prokaryotic cell (e.g., Escherichia coli). Suitable eukaryotic cells include, but are not limited to, NSO cells, Vero cells, Hela cells, COS cells, CHO cells, ExpiCHO cells, HEK293 cells, Expi293 cells, BHK cells, and MDCKII cells. Suitable insect cells include, but are not limited to, Sf9 cells. In certain embodiments, the host cell of the present invention is a mammalian cell, such as CHO (e.g., CHO-K1, CHO-S, CHO DXB11, ExpiCHO, CHO DG44).

[0166] In certain embodiments, the host cell of the present invention may be a chimeric antigen receptor T cell (CAR-T). In such embodiments, the isolated nucleic acid molecule contained in the host cell may include a nucleotide sequence encoding a chimeric antigen receptor, and the nucleotide sequence encoding the chimeric antigen receptor further includes a nucleotide sequence encoding an antibody of the present invention or its antigen-binding fragment (eg, scFv). In certain embodiments, the isolated nucleic acid molecule contained in the host cell encodes a chimeric antigen receptor comprising an antigen-binding fragment (eg, scFv) of an antibody of the present invention.

[0167] In another aspect, the present invention provides a method for preparing the antibody or antigen-binding fragment thereof of the present invention, which comprises culturing the host cell of the present invention under conditions allowing expression of the antibody or antigen-binding fragment thereof, and recovering the antibody or antigen-binding fragment thereof from the cultured host cell culture.

[0168] Therapeutic applications

[0169] In another aspect, the present invention provides a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, or multispecific antibody of the present invention, and a pharmaceutically acceptable carrier and / or excipient.

[0170] In certain embodiments, the pharmaceutical composition of the present invention comprises the antibody or antigen-binding fragment thereof of the present invention, and a pharmaceutically acceptable carrier and / or excipient.

[0171] In certain embodiments, the pharmaceutical composition may also include another pharmaceutically active agent. In certain embodiments, the other pharmaceutically active agent is a drug with anti-tumor activity. In certain embodiments, the other pharmaceutically active agent is selected from: EGFR inhibitors, BCR-ABL, FLT3, KIT or RET inhibitors, HER2 inhibitors, HER3 inhibitors, HER4 inhibitors, IGFR-1 inhibitors, mTOR inhibitors, PI3 kinase inhibitors, c-met or VEGF inhibitors, PARP inhibitors, chemotherapeutic drugs or any combination thereof. In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention and the other pharmaceutically active agent are provided as independent components or as mixed components. Therefore, the antibody or antigen-binding fragment thereof of the present invention and the other pharmaceutically active agent can be administered simultaneously, separately or sequentially.

[0172] In certain embodiments, the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, or multispecific antibody in the pharmaceutical composition of the invention is sufficient (e.g., in a subject):

[0173] (a) inhibit cell proliferation;

[0174] (b) inhibiting tumor growth;

[0175] (c) inducing and / or increasing antibody-dependent cellular cytotoxicity activity;

[0176] (d) inhibiting PTK7-mediated signal transduction;

[0177] (e) preventing and / or treating a disease / disorder mediated by PTK7; or

[0178] (f) Any combination of (a)-(e).

[0179] In certain embodiments, the PTK7-mediated disease / disorder is a tumor, such as a tumor expressing PTK7. In certain embodiments, the tumor is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary carcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct carcinoma, breast cancer, ovarian cancer, lung cancer (such as small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, etc.), esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

[0180] In another aspect, the present invention provides the use of the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition of the present invention in the preparation of a drug, wherein the drug is used to: inhibit cell proliferation, or prevent and / or treat and / or assist in the treatment of tumors.

[0181] In certain embodiments, the medicament is used to inhibit the proliferation of cells (eg, tumor cells) expressing PTK7.

[0182] In another aspect, the present invention provides a method for inhibiting cell proliferation, comprising contacting the cell with the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition of the present invention. In certain embodiments, the cell is a cell expressing PTK7, such as a tumor cell.

[0183] In another aspect, the present invention provides a method for preventing and / or treating and / or adjuvanting the treatment of tumors in a subject, the method comprising administering an effective amount of the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition of the present invention to a subject in need thereof.

[0184] In certain embodiments, the method further comprises administering to the subject a second therapy selected from surgery, chemotherapy, radiotherapy, immunotherapy, gene therapy, DNA therapy, RNA therapy, nanotherapy, viral therapy, adjuvant therapy, and any combination thereof. In certain embodiments, the second therapy can be applied simultaneously, separately, or sequentially with the above method.

[0185] In any of the above embodiments, the tumor involved in the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition of the present invention can be any tumor type. In certain embodiments, the tumor involved in the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition of the present invention is a PTK7-positive tumor. In certain embodiments, the tumor involved in the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition of the present invention is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary carcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct carcinoma, breast cancer, ovarian cancer, lung cancer (such as small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, etc.), esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

[0186] The antibodies or antigen-binding fragments thereof of the present invention and the pharmaceutical compositions of the present invention can be formulated into any dosage form known in the medical field, for example, tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, sterile powders for injection and concentrated solutions for injection), inhalants, sprays, etc. The preferred dosage form depends on the intended mode of administration and therapeutic use. The pharmaceutical composition of the present invention should be sterile and stable under production and storage conditions. A preferred dosage form is an injection. Such injections can be sterile injection solutions. For example, sterile injection solutions can be prepared by the following method: incorporating the necessary dose of the antibody of the present invention into an appropriate solvent, and optionally, simultaneously incorporating other desired ingredients (including but not limited to, pH regulators, surfactants, adjuvants, ionic strength enhancers, isotonic agents, preservatives, diluents, or any combination thereof), followed by filtration and sterilization. In addition, sterile injection solutions can be prepared as sterile lyophilized powders (e.g., by vacuum drying or freeze drying) for easy storage and use. Such sterile lyophilized powders can be dispersed in a suitable vehicle, such as sterile pyrogen-free water, before use.

[0187] In addition, the antibodies or antigen-binding fragments thereof of the present invention may be present in a pharmaceutical composition in a unit dosage form for ease of administration.

[0188] The antibody or its Fab of the present invention, pharmaceutical composition can be applied by any suitable method known in the art, including but not limited to, oral, oral, sublingual, eyeball, topical, parenteral, rectal, intrathecal, intracytoplasmic reticulum, inguinal, intravesical, topical (such as, powder, ointment or drops), or nasal route. However, for many therapeutic uses, preferred route of administration / mode is parenteral administration (such as intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection). Technicians should understand that route of administration and / or mode will change according to the intended purpose. In a preferred embodiment, the antibody or its Fab of the present invention, pharmaceutical composition is administered by intravenous infusion or injection.

[0189] The pharmaceutical compositions of the present invention may include a "therapeutically effective amount" or a "prophylactically effective amount" of the antibody or antigen-binding fragment thereof of the present invention. A "prophylactically effective amount" refers to an amount sufficient to prevent, prevent, or delay the onset of a disease. A "therapeutically effective amount" refers to an amount sufficient to cure or at least partially prevent the disease and its complications in a patient already suffering from the disease. The therapeutically effective amount of the antibody or antigen-binding fragment thereof of the present invention may vary depending on the severity of the disease to be treated, the overall state of the patient's own immune system, the patient's general condition such as age, weight and sex, the mode of administration of the drug, and other treatments administered simultaneously, etc.

[0190] In the present invention, the dosage regimen can be adjusted to obtain the best desired response (e.g., therapeutic or preventive response). For example, the dosage can be administered once, multiple times over a period of time, or the dosage can be reduced or increased in proportion to the urgency of the treatment situation.

[0191] In the present invention, the subject may be a mammal, such as a human.

[0192] Detection Application

[0193] The antibody or antigen-binding fragment thereof of the present invention can specifically bind to PTK7, and thus can be used to detect the presence or level of PTK7 in a sample.

[0194] Therefore, in another aspect, the present invention provides a kit comprising an antibody or antigen-binding fragment thereof of the present invention. In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention carries a detectable label. In a preferred embodiment, the kit further comprises a second antibody that specifically recognizes the antibody or antigen-binding fragment thereof of the present invention. Preferably, the second antibody further comprises a detectable label.

[0195] In the present invention, the detectable label can be any substance that can be detected by fluorescence, spectroscopy, photochemistry, biochemistry, immunology, electricity, optics or chemical means. It is particularly preferred that such labels can be suitable for immunological detection (e.g., enzyme-linked immunosorbent assay, radioimmunoassay, fluorescence immunoassay, chemiluminescence immunoassay, etc.). Such labels are well known in the art, including but not limited to enzymes (e.g., horseradish peroxidase, alkaline phosphatase, β-galactosidase, urease, glucose oxidase, etc.), radionuclides (e.g., 3H, 125I, 35S, 14C or 32P), fluorescent dyes (e.g., fluorescein isothiocyanate (FITC), fluorescein, tetramethylrhodamine isothiocyanate (TRITC), phycoerythrin (PE), Texas Red, rhodamine, quantum dots or cyanine dye derivatives (e.g., Cy7, Alexa 750)), acridinium ester compounds, magnetic beads (e.g., ), calorimetric labels such as colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, latex, etc.) beads, and biotin for binding to avidin (e.g., streptavidin) modified with the above labels. In certain embodiments, detectable labels as described above can be attached to the antibodies of the present invention via linkers of varying lengths to reduce potential steric hindrance.

[0196] In another aspect, the present invention provides a method for detecting the presence or level of PTK7 in a sample, comprising the step of using an antibody or antigen-binding fragment thereof of the present invention. In a preferred embodiment, the antibody or antigen-binding fragment thereof of the present invention also carries a detectable label. In another preferred embodiment, the method further comprises detecting the antibody or antigen-binding fragment thereof of the present invention using a reagent with a detectable label. The method can be used for diagnostic purposes, or non-diagnostic purposes (e.g., the sample is a cell sample, not a sample from a patient).

[0197] In certain embodiments, the method comprises contacting the sample with the antibody or antigen-binding fragment thereof of the present invention under conditions that allow formation of a complex between the antibody or antigen-binding fragment thereof and PTK7, and detecting formation of the complex.

[0198] In view of the low expression or non-expression of PTK7 in normal tissues, the expression or high expression in some cancers, the tumor can be diagnosed by detecting the presence or level of PTK7 in the sample. Therefore, in certain embodiments, the method is used to diagnose a tumor, such as a PTK7-positive tumor, such as uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary cancer, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct cancer, breast cancer, ovarian cancer, lung cancer (such as small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, etc.), esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

[0199] In certain embodiments, the method comprises detecting the expression level of PTK7 in a test sample from a subject, and comparing the expression level with a reference value (eg, a healthy control), wherein an increase in the expression level compared to the reference value is indicative of a tumor.

[0200] In another aspect, provided is a use of the antibody or antigen-binding fragment thereof of the present invention in preparing a kit for detecting the presence or level of PTK7 in a sample and / or diagnosing a tumor.

[0201] In another aspect, the present invention provides a diagnostic or therapeutic kit comprising the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate or multispecific antibody described in the present invention, and instructions for use.

[0202] The antibody of the present invention has a high binding affinity to PTK7, can induce efficient endocytosis after binding to cells expressing PTK7, and the antibody has good hydrophilicity, may have better quality and in vivo metabolic properties, and is suitable for coupling and other advantages. Therefore, the antibody of the present invention has the potential to be used for the prevention and / or treatment of tumors. In addition, the antibody of the present invention is a humanized antibody that can be safely administered to human subjects, reducing the risk of inducing immunogenic reactions. Therefore, the antibody of the present invention has great clinical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0204] Figure 1A :ELISA detects the binding of mouse antibodies to human PTK7 protein.

[0205] Figure 1B : ELISA detects the binding of mouse antibodies to monkey PTK7 protein.

[0206] Figure 2A : Binding assay of anti-human PTK7 chimeric and humanized antibodies to H1299 cells.

[0207] Figure 2B : Binding activity assay of anti-human PTK7 humanized antibody to human lung adenocarcinoma cell H1975.

[0208] Figure 2C : Binding activity assay of anti-human PTK7 humanized antibody to human breast cancer cells T47D.

[0209] Figure 2D :Binding activity assay of anti-human PTK7 humanized antibody to CHO-hPTK7 overexpressing cells

[0210] Figure 3 : Detection of ADCC activity of anti-human PTK7 humanized antibody.

[0211] Figure 4A : Endocytosis detection of anti-human PTK7 humanized antibody and H1299 cells.

[0212] Figure 4B : Endocytosis detection of anti-human PTK7 humanized antibody and H1975 cells.

[0213] Figure 4C : Endocytosis detection of anti-human PTK7 chimeric and humanized antibodies in T47D cells.

[0214] Figure 4D :Endocytosis detection of anti-human PTK7 humanized antibody and human pharyngeal squamous cell carcinoma cells (FADU).

[0215] Figure 5 : ELISA detection of epitope competitive binding of anti-human PTK7 humanized antibody.

[0216] Fig. 6A : Flow cytometry detection of epitope competitive binding of anti-human PTK7 humanized antibodies (labeled as Hu24, 64A10HZ and 4E12HZ).

[0217] Figure 6B : Flow cytometry detection of epitope competitive binding of anti-human PTK7 humanized antibodies (labeled as 101A6HZ and 19C12HZ). DETAILED DESCRIPTION OF THE INVENTION

[0219] definition

[0220] In the present invention, unless otherwise specified, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. In addition, the cell culture, biochemistry, nucleic acid chemistry, immunology laboratory and other operating procedures used herein are conventional procedures widely used in the corresponding fields. At the same time, in order to better understand the present invention, the definitions and explanations of the relevant terms are provided below.

[0221] As used herein, the term "antibody" is used in the broadest sense, including various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) and antibody fragments, as long as they exhibit the desired antigen binding activity. For example, an immunoglobulin molecule can be composed of two pairs of polypeptide chains (each pair having a light chain (LC) and a heavy chain (HC)). Antibody light chains can be classified as κ (kappa) and λ (lambda) light chains. Heavy chains can be classified as μ, δ, γ, α or ε, and the isotype of the antibody is defined as IgM, IgD, IgG, IgA and IgE, respectively. In the light chain and heavy chain, the variable region and the constant region are connected by a "J" region of about 12 or more amino acids, and the heavy chain also contains a "D" region of about 3 or more amino acids. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of 3 domains (CH1, CH2 and CH3). Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region consists of one domain, CL. The constant domain is not directly involved in the binding of antibodies to antigens, but exhibits a variety of effector functions, such as mediating the binding of immunoglobulins to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. The VH and VL regions can also be subdivided into highly variable regions (called complementary determining regions (CDRs)), interspersed with more conservative regions called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs arranged from the amino terminus to the carboxyl terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions (VH and VL) of each heavy chain / light chain pair form antigen binding sites, respectively. The distribution of amino acids in various regions or domains can follow the definition of Kabat, Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)), or Chothia & Lesk (1987) J. Mol. Biol. 196:901-917; Chothia et al. (1989) Nature 342:878-883.

[0222] Herein, unless the context clearly indicates otherwise, when referring to the term "antibody", it includes not only intact antibodies but also antigen-binding fragments of antibodies.

[0223] As used herein, the term "complementarity determining region" or "CDR" refers to the amino acid residues in the variable region of an antibody that are responsible for antigen binding. The precise boundaries of these amino acid residues can be defined according to various numbering systems known in the art, such as the AbM numbering system (Martin ACR, Cheetham JC, Rees AR (1989) Modelling antibody hypervariable loops: A combined algorithm. Proc Natl Acad Sci USA 86: 9268-9272) or the IMGT numbering system (Lefranc et al., Dev. Comparat. Immunol. 27: 55-77, 2003). For a given antibody, a person skilled in the art will easily identify the CDRs defined by each numbering system. Moreover, the corresponding relationship between different numbering systems is well known to those skilled in the art (for example, see Lefranc et al., Dev. Comparat. Immunol. 27: 55-77, 2003).

[0224] In the present invention, the CDRs contained in the antibodies or antigen-binding fragments thereof of the present invention can be determined according to various numbering systems known in the art. In certain embodiments, the CDRs contained in the antibodies or antigen-binding fragments thereof of the present invention are preferably determined by the IMGT, Kabat, Chothia or AbM numbering systems.

[0225] The following general rules published at www.bioinf.org.uk: Prof. Andrew CR Martin' Group can be used to define CDRs in antibody sequences, which include amino acids that specifically interact with amino acids that make up the antigenic epitope to which the antibody binds. In rare cases, this general constant feature does not occur; however, Cys residues are the most conserved feature.

[0226]

[0227]

[0228] V H The entire amino acid sequence of is generally numbered according to Kabat, while the three CDRs within the variable region may be defined according to any of the aforementioned numbering systems. H The numbering of amino acid positions in the sequence may be continuous starting from amino acid position 1 and continuing to the end of the sequence, or numbered according to Kabat. H and V LThe amino acid positions in are defined according to sequential numbering.

[0229] The numbering of amino acid positions in the heavy chain constant region can be numbered consecutively starting from amino acid position 1 and continuing sequentially to the end of the sequence, or numbered according to Eu. The amino acid sequence of the IgG1 heavy chain constant region has 330 amino acids, numbered sequentially from 1 to 330. The corresponding sequence numbered according to Eu starts with position number 118 and ends with position number 447. Unless otherwise specified, the amino acid positions of the heavy and light chains herein are defined according to sequential numbering.

[0230] As used herein, the term "framework region" or "FR" residues refers to those amino acid residues in the variable region of an antibody other than the CDR residues as defined above.

[0231] The term "antibody" is not limited to any particular method of producing the antibody. For example, it includes recombinant antibodies, monoclonal antibodies and polyclonal antibodies. The antibody can be an antibody of different isotypes, for example, IgG (e.g., IgG1, IgG2, IgG3 or IgG4 subtype), IgA1, IgA2, IgD, IgE or IgM antibody.

[0232] As used herein, the term "antigen-binding fragment" of an antibody refers to a molecule other than an intact antibody, which includes a portion of an intact antibody and binds to an antigen to which the intact antibody binds. For example, an antigen-binding fragment may be a polypeptide that is a fragment of a full-length antibody that retains the ability to specifically bind to the same antigen to which the full-length antibody binds, and / or competes with the full-length antibody for specific binding to the antigen, which is also referred to as an "antigen-binding portion". See generally, Fundamental Immunology, Ch. 7 (Paul, W., ed., 2nd edition, Raven Press, NY (1989), which is incorporated herein by reference in its entirety for all purposes. Antigen-binding fragments of antibodies can be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact antibodies. Non-limiting examples of antigen-binding fragments include Fab, Fab', Fab'-SH, F(ab')2, Fd, Fv, dAb and complementarity determining region (CDR) fragments, single-chain antibodies (e.g., scFv), chimeric antibodies, diabodies, linear antibodies, nanobodies (technology from Domantis), domain antibodies (technology from Ablynx), and polypeptides that contain at least a portion of an antibody sufficient to confer specific antigen binding ability to the polypeptide. Engineered antibody variants are reviewed in Holliger et al., 2005; Nat Biotechnol, 23: 1126-1136.

[0233] As used herein, the term "full-length antibody" means an antibody consisting of two "full-length heavy chains" or "heavy chains" and two "full-length light chains" or "light chains". Wherein, "full-length heavy chain" or "heavy chain" refers to a polypeptide chain that consists of a heavy chain variable region (VH), a heavy chain constant region CH1 domain, a hinge region (HR), a heavy chain constant region CH2 domain, and a heavy chain constant region CH3 domain in the direction from N to C; and, when the full-length antibody is an IgE isotype, optionally also includes a heavy chain constant region CH4 domain. Preferably, a "full-length heavy chain" is a polypeptide chain consisting of VH, CH1, HR, CH2 and CH3 in the direction from N to C. A "full-length light chain" or "light chain" is a polypeptide chain consisting of a light chain variable region (VL) and a light chain constant region (CL) in the direction from N to C. Two pairs of full-length antibody chains are linked together by a disulfide bond between CL and CH1 and a disulfide bond between the HRs of the two full-length heavy chains. The full-length antibody of the present invention may be from a single species, such as human; or may be a chimeric antibody or a humanized antibody. The full-length antibody of the present invention comprises two antigen-binding sites formed by a VH and a VL pair, respectively, and the two antigen-binding sites specifically recognize / bind to the same antigen.

[0234] As used herein, the term "Fd fragment" means an antibody fragment consisting of VH and CH1 domains; the term "dAb fragment" means an antibody fragment consisting of a VH domain (Ward et al., Nature 341:544-546 (1989)); the term "Fab fragment" means an antibody fragment consisting of VL, VH, CL and CH1 domains; the term "F(ab')2 fragment" means an antibody fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; the term "Fab' fragment" means a fragment obtained after reducing the disulfide bonds linking two heavy chain fragments in the F(ab')2 fragment, consisting of a complete light chain and the Fd fragment of the heavy chain (consisting of VH and CH1 domains).

[0235] As used herein, the term "Fv fragment" means an antibody fragment consisting of the VL and VH domains of a single arm of an antibody. The Fv fragment is generally considered to be the smallest antibody fragment that can form a complete antigen binding site. It is generally believed that the six CDRs confer antigen binding specificity to an antibody. However, even a variable region (e.g., a Fd fragment, which contains only three CDRs specific for an antigen) can recognize and bind to an antigen, although its affinity may be lower than that of a complete binding site.

[0236] As used herein, the term "Fc fragment" means an antibody fragment formed by the second and third constant regions of the first heavy chain of an antibody and the second and third constant regions of the second heavy chain of an antibody bound via a disulfide bond. The Fc fragment of an antibody has a variety of different functions, but does not participate in antigen binding.

[0237] As used herein, the term "scFv" refers to a single polypeptide chain comprising a VL and VH domain, wherein the VL and VH are connected by a linker (see, e.g., Bird et al., Science 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. USA 85: 5879-5883 (1988); and Pluckthun, The Pharmacology of Monoclonal Antibodies, Vol. 113, Roseburg and Moore, ed., Springer-Verlag, New York, pp. 269-315 (1994)). Such scFv molecules may have a general structure: NH2-VL-linker-VH-COOH or NH2-VH-linker-VL-COOH. Suitable prior art linkers consist of repeated GGGGS (SEQ ID NO: 133) amino acid sequences or variants thereof. For example, a linker having the amino acid sequence (GGGGS)4 (SEQ ID NO: 134) can be used, but variants thereof can also be used (Holliger et al. (1993), Proc. Natl. Acad. Sci. USA 90: 6444-6448). Other linkers that can be used in the present invention are described by Alfthan et al. (1995), Protein Eng. 8: 725-731, Choi et al. (2001), Eur. J. Immunol. 31: 94-106, Hu et al. (1996), Cancer Res. 56: 3055-3061, Kipriyanov et al. (1999), J. Mol. Biol. 293: 41-56 and Roovers et al. (2001), Cancer Immunol. In some cases, a disulfide bond may also be present between the VH and VL of the scFv.

[0238] As used herein, the term "diabody" means that its VH and VL domains are expressed on a single polypeptide chain, but with a linker that is too short to allow pairing between the two domains of the same chain, thereby forcing the domains to pair with the complementary domains of another chain and create two antigen binding sites (see, e.g., Holliger P. et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993), and Poljak RJ et al., Structure 2:1121-1123 (1994)).

[0239] Each of the above antibody fragments retains the ability to specifically bind to the same antigen that the full-length antibody binds to, and / or competes with the full-length antibody for specific binding to the antigen. In this article, those skilled in the art can use known conventional techniques to obtain an antigen-binding fragment of an antibody (e.g., the above antibody fragment) from a given antibody (e.g., an antibody provided by the invention), and screen the antigen-binding fragment of the antibody for specificity in the same manner as for a complete antibody.

[0240] As used herein, the term "multispecific antibody" refers to an antibody with multiple different antigen binding specificities, including, for example, bispecific antibodies, trispecific antibodies, and tetraspecific antibodies. "Bispecific antibodies" refer to antibodies with two different antigen binding specificities, which are conjugates formed by coupling arms of a first antibody (or a fragment thereof) and a second antibody (or a fragment thereof) or an antibody analog, wherein the coupling method includes, but is not limited to, chemical reaction, gene fusion, and enzymatic. "Multispecific antibodies" include, for example, trispecific antibodies and tetraspecific antibodies, trispecific antibodies are antibodies with three different antigen binding specificities, and tetraspecific antibodies are antibodies with four different antigen binding specificities.

[0241] As used herein, the terms "monoclonal antibody", "single antibody", and "mAb" have the same meaning and are used interchangeably, and refer to an antibody or a fragment of an antibody from a group of highly homologous antibody molecules, that is, a group of identical antibody molecules except for natural mutations that may occur spontaneously. Monoclonal antibodies have high specificity for a single epitope on an antigen. Polyclonal antibodies, relative to monoclonal antibodies, generally contain at least two or more different antibodies, and these different antibodies generally recognize different epitopes on an antigen. In addition, the modifier "monoclonal" only indicates that the antibody is characterized as being obtained from a highly homologous antibody group, and it should not be understood that the antibody needs to be prepared by any specific method.

[0242] As used herein, 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 the 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 an antibody in which the heavy and light chain variable regions are derived from a first antibody (e.g., human), while the heavy and light chain constant regions of the antibody are derived from a second antibody (e.g., mouse). For example, an antibody produced by immunizing a fully human transgenic mouse may be referred to as a chimeric antibody, which consists of a fully human variable region and a mouse constant region.

[0243] As used herein, the term "humanized antibody" refers to an antibody that can be prepared by replacing a part of a human antibody with a part of a non-human antibody prepared by immunizing a mammal other than a human. Specifically, it is known that it can be prepared by constructing a chimera with a gene encoding a human antibody constant region (Proc. Natl. Acad. Sci. (USA) (1987), vol. 84, p. 3439) -3443, Journal of Immunology (1987), Vol. 139, No. 1, p. 3521). The DNA sequence of the human constant region has been described in the prior art, and the constant region gene can be easily obtained from a known clone. Then, the DNA sequence encoding the antibody variable region can be fused to the human constant region. The isotype of the human constant region can be selected based on the desired effective function or antibody-dependent cellular toxicity activity. Suitable isotypes are IgG1, IgG3 and IgG4. Human light chain constant region, κ chain and λ chain can all be used. This humanized chimeric antibody can be expressed by conventional methods.

[0244] As used herein, the term "fully human antibody" refers to an antibody of interest that can be prepared by using mice (XenoMouse (Chemical Biology (2000), vol.7, issue 8, p.R185-6), HuMAb-Mouse (Infection and Immunity (2002), vol.70, issue 2, p.612-9), TC mouse (Biotechnology and Genetics Enginnering Revew (2002), vol.19, p.73-82) and KM mouse (Cloning Stem Cells (2002), vol.4, issue 1, p.91-102)), to which the constant region gene of human immunoglobulin is transferred, and can be produced in large quantities by isolating antibody-producing lymphocytes from mice to hybridomas. It can be prepared by phage display method (FEBS Letter (1998), vol.441, p.20-24). In this method, by using a phage in which a human antibody gene has been integrated into a circular single-stranded DNA, a fully human antibody can be expressed on the surface of the phage in the form of a fusion with the coat protein of the phage.

[0245] As used herein, the term "variant", in the context of a polypeptide (including a polypeptide), also refers to a polypeptide or peptide comprising an amino acid sequence that has been changed by introducing an amino acid residue substitution, deletion or addition. In some cases, the term "variant" also refers to a polypeptide or peptide that has been modified (i.e., by covalently linking any type of molecule to a polypeptide or peptide). For example, but not limiting, a polypeptide can be modified, such as by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protection / blocking groups, proteolytic cleavage, connection to a cell ligand or other protein, etc. Derivatized polypeptides or peptides can be produced by chemical modification using techniques known to those skilled in the art, including but not limited to specific chemical cleavage, acetylation, formylation, metabolic synthesis of tunicamycin, etc. In addition, a variant has a function similar, identical or improved to the polypeptide or peptide from which it is derived.

[0246] As used herein, the term "specific binding" refers to a non-random binding reaction between two molecules, such as an antibody and its antigen. The strength or affinity of a specific binding interaction can be measured by the equilibrium dissociation constant (K) of the interaction. D ) or half maximal effect concentration (EC 50 )express.

[0247] The specific binding properties between two molecules can be determined using methods known in the art. One method involves measuring the rate at which the antigen binding site / antigen complex forms and dissociates. The "binding rate constant" (k a or k on ) and the “dissociation rate constant” (k dis or k off ) Both can be calculated from the concentration and the actual rates of association and dissociation (see Malmqvist M, Nature, 1993, 361: 186-187). dis / k on The ratio is equal to the dissociation constant K D (See Davies et al., Annual Rev Biochem, 1990; 59: 439-473). K can be measured by any effective method. D , k on and k dis In some embodiments, the dissociation constant can be measured using bioluminescence interferometry (e.g., the ForteBio Octet method). In addition, the dissociation constant can be measured using surface plasmon resonance technology (e.g., Biacore) or Kinexa.

[0248] As used herein, the term "vector" refers to a nucleic acid delivery vehicle into which a polynucleotide can be inserted. When a vector can express the protein encoded by the inserted polynucleotide, the vector is called an expression vector. The vector can be introduced into a host cell by transformation, transduction or transfection, so that the genetic material elements it carries are expressed in the host cell. Vectors are well known to those skilled in the art, and include but are not limited to: plasmids; phagemids; cosmids; artificial chromosomes, such as yeast artificial chromosomes (YAC), bacterial artificial chromosomes (BAC) or P1-derived artificial chromosomes (PAC); bacteriophages such as lambda phage or M13 phage and animal viruses, etc. Animal viruses that can be used as vectors include but are not limited to retroviruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpes viruses (such as herpes simplex virus), poxviruses, baculoviruses, papillomaviruses, papillomaviruses (such as SV40). A vector can contain a variety of elements that control expression, including but not limited to promoter sequences, transcription initiation sequences, enhancer sequences, selection elements and reporter genes. In addition, the vector may also contain a replication initiation site.

[0249] Expression and cloning vectors contain nucleic acid sequences that enable the vector to replicate in one or more selected host cells. Typically, in cloning vectors, this sequence is one that enables the vector to replicate independently of the host chromosomal DNA, and it includes an origin of replication or an autonomous replication sequence. The term "expression vector" as used herein refers to a vector comprising a recombinant polynucleotide, which comprises an expression regulatory sequence operably linked to a nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting elements for expression; other elements for expression can be provided by a host cell or an in vitro expression system. Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses).

[0250] As used herein, the term "host cell" refers to a cell that can be used to introduce a vector, including but not limited to prokaryotic cells such as Escherichia coli or Bacillus subtilis, fungal cells such as yeast cells or Aspergillus, insect cells such as S2 Drosophila cells or Sf9, or animal cells such as fibroblasts, NS0 cells, Vero cells, Hela cells, COS cells, CHO cells (e.g., CHO-K1, CHO-S, CHO DXB11, ExpiCHO, CHO DG44 cells), ExpiCHO cells, HEK293 cells, Expi293 cells, BHK cells and MDCKII cells.

[0251] As used herein, the term "identity" is used to refer to the matching of sequences between two polypeptides or between two nucleic acids. When a position in both sequences being compared is occupied by the same base or amino acid monomer subunit (e.g., a position in each of the two DNA molecules is occupied by adenine, or a position in each of the two polypeptides is occupied by lysine), then the molecules are identical at that position. The "percent identity" between two sequences is a function of the number of matching positions shared by the two sequences divided by the number of positions compared x 100. For example, if 6 out of 10 positions in two sequences match, then the two sequences have 60% identity. For example, the DNA sequences CTGACT and CAGGTT share 50% identity (3 out of a total of 6 positions match). Typically, the comparison is made when the two sequences are aligned to produce maximum identity. Such an alignment can be achieved by using, for example, the method of Needleman et al. (1970) J. Mol. Biol. 48: 443-453, which can be conveniently performed by a computer program such as the Align program (DNAstar, Inc.). The percent identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl Biosci., 4: 11-17 (1988)), which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (J MoI Biol. 48: 444-453 (1970)) algorithm, which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using a Blossum 62 matrix or a PAM250 matrix and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

[0252] As used herein, the term "conservative substitution" means an amino acid substitution that does not adversely affect or change the expected properties of the protein / polypeptide comprising the amino acid sequence. For example, conservative substitutions can be introduced by standard techniques known in the art such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions include substitutions of amino acid residues with amino acid residues having similar side chains, such as substitutions with residues physically or functionally similar to the corresponding amino acid residues (e.g., having similar size, shape, charge, chemical properties, including the ability to form covalent bonds or hydrogen bonds, etc.). Families of amino acid residues with similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, and histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine), and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, it is preferred to substitute a corresponding amino acid residue with another amino acid residue from the same side chain family. Methods for identifying conservative amino acid substitutions are well known in the art (see, e.g., Brummell et al., Biochem. 32: 1180-1187 (1993); Kobayashi et al. Protein Eng. 12(10): 879-884 (1999); and Burks et al. Proc. Natl Acad. Set USA 94: 412-417 (1997), which are incorporated herein by reference).

[0253] The compilation of the twenty conventional amino acids involved in this article follows conventional usage. See, for example, Immunology-A Synthesis (2nd Edition, ES Golub and DR Gren, Eds., Sinauer Associates, Sunderland, Mass. (1991)), which is incorporated herein by reference. In the present invention, the terms "polypeptide" and "protein" have the same meaning and are used interchangeably. And in the present invention, amino acids are generally represented by single-letter or three-letter abbreviations known in the art. For example, alanine can be represented by A or Ala.

[0254] As used herein, the term "pharmaceutically acceptable carrier and / or excipient" refers to a carrier and / or excipient that is pharmacologically and / or physiologically compatible with the subject and the active ingredient, which is well known in the art (see, e.g., Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995), and includes, but is not limited to, pH regulators, surfactants, adjuvants, ionic strength enhancers, diluents, agents that maintain osmotic pressure, agents that delay absorption, and preservatives. For example, pH regulators include, but are not limited to, phosphate buffers. Surfactants include, but are not limited to, cationic, anionic, or nonionic surfactants, such as Tween-80. Ionic strength enhancers include, but are not limited to, sodium chloride. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid, and the like. Agents that maintain osmotic pressure include, but are not limited to, sugars, NaCl, and the like. Agents that delay absorption include, but are not limited to, monostearate and gelatin. Diluents include, but are not limited to, water, aqueous buffers (such as buffered saline), alcohols and polyols (such as glycerol), etc. Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as thimerosal, 2-phenoxyethanol, parabens, chlorobutanol, phenol, sorbic acid, etc. Stabilizers have the meanings commonly understood by those skilled in the art, and are capable of stabilizing the desired activity of the active ingredient in the drug, including, but not limited to, sodium glutamate, gelatin, SPGA, sugars (such as sorbitol, mannitol, starch, sucrose, lactose, dextran or glucose), amino acids (such as glutamic acid, glycine), proteins (such as dried whey, albumin or casein) or their degradation products (such as lactalbumin hydrolysate), etc.

[0255] As used herein, the term "prevention" refers to a method implemented in order to prevent or delay the occurrence of a disease or illness or symptom (e.g., a tumor) in a subject. As used herein, the term "treatment" refers to a method implemented in order to obtain a beneficial or desired clinical result in an individual (human or animal individual) who is showing disease symptoms or is diagnosed as having a disease ("in need") For the purposes of the present invention, beneficial or desired clinical results include, but are not limited to, alleviating symptoms, reducing the scope of the disease, stabilizing (i.e., no longer worsening) the state of the disease, delaying or slowing the development of the disease, improving or alleviating the state of the disease and alleviating symptoms (whether partially or completely), whether detectable or undetectable. In addition, "treatment" can also refer to, compared with the expected survival period (if not treated), prolonging the survival period.

[0256] As used herein, the term "subject" refers to a mammal, such as a primate mammal, such as a human. In certain embodiments, the subject (eg, human) suffers from a tumor, or has a risk of suffering from the above-mentioned disease.

[0257] As used herein, the term "effective amount" refers to an amount sufficient to obtain or at least partially obtain the desired effect. For example, an effective amount for preventing a disease (e.g., a tumor) refers to an amount sufficient to prevent, stop, or delay the occurrence of a disease (e.g., a tumor); an effective amount for treating a disease refers to an amount sufficient to cure or at least partially stop the disease and its complications in a patient already suffering from the disease. Determining such an effective amount is well within the capabilities of those skilled in the art. For example, an effective amount for therapeutic use will depend on the severity of the disease to be treated, the overall state of the patient's own immune system, the patient's general condition such as age, weight and sex, the mode of administration of the drug, and other treatments administered simultaneously, etc.

[0258] As used herein, the term "effector function" refers to those biological activities attributable to the Fc region of an antibody (a native sequence Fc region or an amino acid sequence variant Fc region), and varies with the antibody isotype. Examples of antibody effector functions include, but are not limited to, Fc receptor binding affinity, antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), downregulation of cell surface receptors (e.g., B cell receptors), B cell activation, cytokine secretion, half-life / clearance rate of antibodies and antigen-antibody complexes, and the like. Methods for altering the effector functions of antibodies are known in the art, for example, by introducing mutations in the Fc region.

[0259] As used herein, the term "antibody-dependent cell-mediated cytotoxicity (ADCC)" refers to a form of cytotoxicity in which Ig binds to Fc receptors (FcRs) present on cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, or macrophages), causing these cytotoxic effector cells to specifically bind to antigen-attached target cells and then kill the target cells by secreting cytotoxins.

[0260] As used herein, the term "antibody-mediated internalization" refers to the phenomenon that an antibody crosses a cell membrane after binding to a cell surface antigen. Internalization includes antibody-mediated internalization of a receptor (eg, PTK7).

[0261] As used herein, combination therapy includes the use of an anti-PTK7 antibody or antigen-binding fragment thereof encompassed by the invention in combination with one or more additional active therapeutic agents of a second therapy (eg, chemotherapeutic agents) or other prophylactic or therapeutic modality (eg, radiation therapy).

[0262] In such combination therapies, various active agents often have different complementary mechanisms of action, and combination therapies may result in synergistic effects. Combination therapies include therapeutic agents that affect immune responses (e.g., enhance or activate responses) and therapeutic agents that affect (e.g., inhibit or kill) tumor / cancer cells. Combination therapies can reduce the likelihood of drug-resistant cancer cells. Combination therapies can allow one or more of the reagents to be reduced in dose to reduce or eliminate adverse effects associated with one or more of the reagents. Such combination therapies can have a synergistic therapeutic or preventive effect on underlying diseases, disorders, or conditions.

[0263] As used herein, "combination" includes therapies that can be administered separately, such as separately formulated for separate administration (e.g., can be provided in a kit), and therapies that can be administered together in a single formulation (i.e., a "co-formulation"). In certain embodiments, the anti-PTK7 antibodies or antigen-binding fragments thereof of the present invention can be administered sequentially. In other embodiments, the anti-PTK7 antibodies or antigen-binding fragments thereof can be administered simultaneously. The anti-antibodies or antigen-binding fragments thereof of the present invention can be used in combination with at least one other (active) agent in any manner.

[0264] In this article, PTK7 positivity was obtained by immunohistochemistry and staining intensity evaluation by professional clinical pathologists.

[0265] The terms "cancer" and "tumor" are used interchangeably to refer to a broad class of diseases characterized by the uncontrolled growth of abnormal cells in the body. Unregulated cell division may lead to the formation of malignant tumors, or cells that invade neighboring tissues and may metastasize to distant parts of the body via the lymphatic system or bloodstream. Cancer includes both benign and malignant cancers as well as dormant tumors or micrometastases. Cancer also includes hematological malignancies.

[0266] The term "hematological malignancy" includes lymphoma, leukemia, myeloma or lymphoid malignancies, as well as spleen cancer and lymph node tumors. Exemplary lymphomas include B cell lymphomas and T cell lymphomas. B cell lymphomas include, for example, Hodgkin's lymphoma. T cell lymphomas include, for example, cutaneous T cell lymphomas. Hematological malignancies also include leukemias, such as secondary leukemia or acute lymphocytic leukemia. Hematological malignancies also include myeloma (e.g., multiple myeloma) and other hematological and / or B cell or T cell related cancers.

[0267] As used herein, the term "about" or "approximately" when used with a numerical variable generally means that the value of the variable is within the range of experimental error (eg, within a 95% confidence interval for the mean) or within a range of ±10% or wider.

[0268] Antibody

[0269] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof comprises the following complementarity determining region (CDR):

[0270] (a) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 19; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 20;

[0271] (b) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 1; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 2;

[0272] (c) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 3; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 4;

[0273] (d) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 5; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 6;

[0274] (e) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 7; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 8;

[0275] (f) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 9; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 10;

[0276] (g) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 11; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 12;

[0277] (h) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 13; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 14;

[0278] (i) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 15; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 16;

[0279] (j) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 17; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 18;

[0280] (k) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 21; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 22;

[0281] (l) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) having the amino acid sequence shown in SEQ ID NO: 23; and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) having the amino acid sequence shown in SEQ ID NO: 24; or

[0282] (m) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) of (a) to (l), and / or CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) of (a) to (l); compared with any one of the heavy chain variable region (VH) and / or light chain variable region (VL) in (a) to (l), at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) comprises a mutation, wherein the mutation refers to a substitution, deletion or addition of one or more amino acids (for example, a substitution, deletion or addition of 1, 2 or 3 amino acids); preferably, the substitution is a conservative substitution.

[0283] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (a) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 19; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 20.

[0284] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (b) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 1; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 2.

[0285] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (c) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 3; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 4.

[0286] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (d) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 5; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 6.

[0287] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (e) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 7; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 8.

[0288] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (f) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 9; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 10.

[0289] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (g) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 11; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 12.

[0290] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (h) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 13; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 14.

[0291] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (i) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 15; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 16.

[0292] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (j) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 17; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 18.

[0293] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (k) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 21; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 22.

[0294] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (l) CDR-H1, CDR-H2 and CDR-H3 contained in a heavy chain variable region (VH) having an amino acid sequence as shown in SEQ ID NO: 23; and / or CDR-L1, CDR-L2 and CDR-L3 contained in a light chain variable region (VL) having an amino acid sequence as shown in SEQ ID NO: 24.

[0295] In one aspect, the present application provides a specific PTK7 binding antibody or an antigen-binding fragment thereof, which comprises the following complementarity determining regions (CDRs): (m) CDR-H1, CDR-H2 and CDR-H3 in the heavy chain variable region (VH) in (a) to (l), and CDR-L1, CDR-L2 and CDR-L3 in the light chain variable region (VL) described in (a) to (l); compared with any one of the heavy chain variable region (VH) and / or light chain variable region (VL) in (a) to (l), at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) comprises a mutation, wherein the mutation refers to a substitution, deletion or addition of one or several amino acids (e.g., a substitution, deletion or addition of 1, 2 or 3 amino acids); preferably, the substitution is a conservative substitution.

[0296] In certain embodiments, the substitutions are conservative substitutions.

[0297] In certain embodiments, the CDRs are defined according to the IMGT, Kabat, Chothia, or AbM numbering systems.

[0298] In certain embodiments, PTK7 comprises human PTK7 and / or monkey PTK7. In certain embodiments, the monkey is a rhesus monkey (Macaca mulatta).

[0299] In certain embodiments, an antibody or antigen-binding fragment thereof of the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are defined according to the Chothia numbering system as follows:

[0300] (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 27 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0301] (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 41 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 42 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0302] (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 55 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 56 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 59 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 60 or a variant thereof;

[0303] (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 68 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0304] (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 74 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 85 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0305] (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 92 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 93 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 96 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0306] (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 27 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0307] (1h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0308] (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0309] (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 27; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0310] (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 55; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 56; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0311] (11) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as shown in SEQ ID NO: 74 or a variant thereof; CDR-H2 having an amino acid sequence as shown in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having an amino acid sequence as shown in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as shown in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as shown in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as shown in SEQ ID NO: 73 or a variant thereof; and

[0312] The variant of any one of (1a)-(1h) and (11) has one or more amino acid substitutions, deletions or additions (eg, 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0313] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows:

[0314] (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 27 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0315] (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 41 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 42 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0316] (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 55 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 56 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 59 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 60 or a variant thereof;

[0317] (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 68 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0318] (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 74 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 85 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0319] (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 92 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 93 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 96 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0320] (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 27 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0321] (1h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0322] (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0323] (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 27; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0324] (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 55; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 56; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0325] (11) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as shown in SEQ ID NO: 74 or a variant thereof; CDR-H2 having an amino acid sequence as shown in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having an amino acid sequence as shown in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as shown in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as shown in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as shown in SEQ ID NO: 73 or a variant thereof; and

[0326] The variant of any one of (1a)-(1h) and (11) has one or more amino acid substitutions, deletions or additions (eg, 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0327] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows:

[0328] (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 27; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0329] (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0330] (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 55; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 56; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60;

[0331] (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 68; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 70; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 71; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73;

[0332] (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 74; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 83; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 84; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86;

[0333] (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 92; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 93; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 94; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 95; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97;

[0334] (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 27; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 105; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 106; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107;

[0335] (1h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0336] (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 41; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0337] (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 27; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0338] (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 55; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 56; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0339] (1l) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 74; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 69; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0340] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention comprise a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 27; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 29; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 30; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0341] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 41; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0342] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 55; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 56; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 57; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 58; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0343] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 68; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 69; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0344] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 74; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 69; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 83; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 84; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 85; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 86.

[0345] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 92; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 93; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 94; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 95; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 96; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 97.

[0346] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 27; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 105; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 106; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 107.

[0347] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1h) a heavy chain variable region (VH), which comprises the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 41; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0348] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 41; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 42; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0349] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 27; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 28; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 30; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0350] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 55; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 56; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 58; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0351] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present invention comprise a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (11) a heavy chain variable region (VH), which comprises the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 74; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 69; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0352] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are defined according to the Kabat numbering system as follows:

[0353] (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having a sequence as set forth in SEQ ID NO: 33 or a variant thereof; CDR-H2 having a sequence as set forth in SEQ ID NO: 34 or a variant thereof; and CDR-H3 having a sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having a sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having a sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having a sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0354] (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 33 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0355] (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 47 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 49 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0356] (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as shown in SEQ ID NO: 61 or a variant thereof; CDR-H2 having an amino acid sequence as shown in SEQ ID NO: 62 or a variant thereof; and CDR-H3 having an amino acid sequence as shown in SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as shown in SEQ ID NO: 58 or a variant thereof; CDR-L2 having an amino acid sequence as shown in SEQ ID NO: 59 or a variant thereof; and CDR-L3 having an amino acid sequence as shown in SEQ ID NO: 60 or a variant thereof; or

[0357] (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 75 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 76 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0358] (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 87 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 88 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 85 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0359] (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 98 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 99 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 96 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0360] (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 108 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0361] (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 47 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 48 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0362] (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 47; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 48; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0363] (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 61; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 62; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0364] (21) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 75; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 76; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 70; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 71; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73;

[0365] A variant of any one of (2a)-(2i) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived; in certain embodiments, the substitutions are conservative substitutions.

[0366] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention comprise a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as shown in SEQ ID NO: 33 or a variant thereof; CDR-H2 having an amino acid sequence as shown in SEQ ID NO: 34 or a variant thereof; and CDR-H3 having an amino acid sequence as shown in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as shown in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as shown in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as shown in SEQ ID NO: 32 or a variant thereof;

[0367] (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 33 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0368] (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 47 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 49 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0369] (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as shown in SEQ ID NO: 61 or a variant thereof; CDR-H2 having an amino acid sequence as shown in SEQ ID NO: 62 or a variant thereof; and CDR-H3 having an amino acid sequence as shown in SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as shown in SEQ ID NO: 58 or a variant thereof; CDR-L2 having an amino acid sequence as shown in SEQ ID NO: 59 or a variant thereof; and CDR-L3 having an amino acid sequence as shown in SEQ ID NO: 60 or a variant thereof; or

[0370] (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 75 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 76 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0371] (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 87 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 88 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 85 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0372] (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 98 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 99 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 96 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0373] (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 108 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0374] (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 47 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 48 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0375] (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 47; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 48; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0376] (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 61; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 62; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0377] (21) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 75; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 76; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 70; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 71; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73;

[0378] A variant of any one of (2a)-(2i) has one or more amino acid substitutions, deletions or additions (eg, 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived; in certain embodiments, the substitutions are conservative substitutions.

[0379] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows:

[0380] (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 33; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 34; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0381] (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 33; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 35; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0382] (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 47; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 49; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0383] (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 61; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 62; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0384] (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 75; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 76; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 70; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 71; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73;

[0385] (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 87; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 88; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 83; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 84; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86;

[0386] (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 98; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 99; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 94; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 95; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97;

[0387] (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 108; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 35; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 105; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 106; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107;

[0388] (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 47; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 48; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0389] (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 47; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 48; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0390] (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 61; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 62; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0391] (2l) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 75; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 76; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0392] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 33; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 34; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 29; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 30; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0393] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 33; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 35; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 29; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 30; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0394] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 47; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 49; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0395] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 61; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 62; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 57; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 58; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0396] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 75; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 76; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0397] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 87; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 88; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 83; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 84; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 85; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 86.

[0398] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 98; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 99; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 94; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 95; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 96; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 97.

[0399] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 108; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 35; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 105; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 106; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 107.

[0400] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 47; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 48; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0401] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 47; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 48; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0402] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 61; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 62; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 58; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0403] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (2l) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 75; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 76; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0404] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are defined according to the IMGT numbering system as follows:

[0405] (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 36 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 38 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 39 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 40 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0406] (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 50 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 51 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 52 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 53 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 54 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0407] (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 63 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 64 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 65 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 66 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 67 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 60 or a variant thereof;

[0408] (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 77 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 82 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0409] (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 80 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 89 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 90 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 91 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0410] (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 100 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 101 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 102 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 103 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 104 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0411] (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 36 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 109 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 110 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 40 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0412] (3h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0413] (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0414] (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 36; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 38; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 39; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0415] (3k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 63; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 64; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 65; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 66; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 67; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0416] (31) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 80 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 82 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0417] The variant of any one of (3a)-(3g) and (3l) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0418] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are as follows:

[0419] (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 36 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 38 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 39 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 40 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0420] (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 50 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 51 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 52 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 53 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 54 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0421] (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 63 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 64 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 65 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 66 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 67 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 60 or a variant thereof; or

[0422] (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 77 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 82 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0423] (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 80 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 89 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 90 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 91 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0424] (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 100 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 101 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 102 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 103 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 104 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0425] (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 36 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 109 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 110 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 40 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0426] (3h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0427] (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0428] (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 36; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 38; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 39; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0429] (3k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 63; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 64; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 65; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 66; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 67; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0430] (31) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 80 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 82 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0431] The variant of any one of (3a)-(3g) and (3l) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0432] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are as follows:

[0433] (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 36; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 38; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 39; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0434] (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0435] (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 63; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 64; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 65; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 66; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 67; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60;

[0436] (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 77; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 79; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 81; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 82; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73;

[0437] (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 80; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 89; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 90; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 91; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86;

[0438] (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 100; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 101; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 102; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 103; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 104; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97;

[0439] (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 36; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 109; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 110; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107;

[0440] (3h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0441] (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 50; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 52; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 53; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0442] (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 36; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 38; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 39; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0443] (3k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 63; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 64; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 65; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 66; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 67; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0444] (3l) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 80; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 78; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 79; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 81; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 82; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0445] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 36; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 38; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 39; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0446] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 50; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 52; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 53; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0447] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 63; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 64; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 65; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 66; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 67; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0448] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 77; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 78; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 79; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 81; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 82; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0449] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 80; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 78; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 89; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 90; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 91; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 86.

[0450] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 100; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 101; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 102; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 103; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 104; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 97.

[0451] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 36; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 109; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 110; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 40; CDR-L3 having the amino acid sequence shown in SEQ ID NO: 107.

[0452] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3h) a heavy chain variable region (VH), wherein the heavy chain variable region (VH) includes the following three CDRs: CDR: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 50; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 52; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 53; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0453] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 50; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 51; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 52; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 53; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 54; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0454] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 36; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 37; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 38; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 39; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 40; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0455] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 63; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 64; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 65; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 66; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 67; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0456] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (3l) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 80; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 78; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 79; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 81; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 82; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0457] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are defined according to the AbM numbering system as follows:

[0458] (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 113 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0459] (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 115 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 116 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0460] (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 117 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 118 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 59 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 60 or a variant thereof; or

[0461] (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 119 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0462] (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 122 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 123 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 85 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0463] (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 124 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 125 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 96 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0464] (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 126 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0465] (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0466] (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0467] (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 113; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0468] (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 117; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 118; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0469] (41) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 121 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0470] The variant of any one of (4a)-(4g) and (4l) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0471] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are as follows:

[0472] (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 113 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 32 or a variant thereof;

[0473] (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 115 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 116 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 46 or a variant thereof;

[0474] (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 117 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 118 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 59 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 60 or a variant thereof;

[0475] (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 119 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0476] (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 122 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 123 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 85 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 86 or a variant thereof;

[0477] (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 124 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 125 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 96 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 97 or a variant thereof;

[0478] (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 126 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 107 or a variant thereof;

[0479] (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0480] (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0481] (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 113; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0482] (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 117; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 118; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0483] (41) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having an amino acid sequence as set forth in SEQ ID NO: 121 or a variant thereof; CDR-H2 having an amino acid sequence as set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having an amino acid sequence as set forth in SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having an amino acid sequence as set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having an amino acid sequence as set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having an amino acid sequence as set forth in SEQ ID NO: 73 or a variant thereof;

[0484] The variant of any one of (4a)-(4g) and (4l) has one or more amino acid substitutions, deletions or additions (e.g., 1, 2 or 3 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions.

[0485] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are as follows:

[0486] (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 113; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0487] (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0488] (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 117; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 118; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60;

[0489] (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 119; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 120; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 70; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 71; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73;

[0490] (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 122; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 123; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 83; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 84; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86;

[0491] (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 124; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 125; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 94; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 95; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97;

[0492] (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 126; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 105; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 106; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107;

[0493] (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0494] (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 115; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 43; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 44; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46;

[0495] (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 113; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 30; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32;

[0496] (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 117; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 118; and CDR-H3 having the amino acid sequence set forth in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence set forth in SEQ ID NO: 58; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60; or

[0497] (4l) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 121; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 120; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0498] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 113; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 29; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 30; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0499] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 115; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0500] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 117; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 118; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 57; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 58; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0501] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 119; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 120; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0502] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 122; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 123; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 83; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 84; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 85; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 86.

[0503] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 124; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 125; and CDR-H3 having the amino acid sequence shown in SEQID NO: 94; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQID NO: 95; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 96; and CDR-L3 having the amino acid sequence shown in SEQID NO: 97.

[0504] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 126; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 105; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 106; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 107.

[0505] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 115; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0506] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 115; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 116; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 43; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 44; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 45; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 46.

[0507] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 113; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 114; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 30; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 31; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 32.

[0508] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention includes a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 117; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 118; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 57; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 58; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 59; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 60.

[0509] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), and the CDRs are as follows: (4l) a heavy chain variable region (VH), wherein the heavy chain variable region (VH) comprises the following three CDRs: CDR-H1 having the amino acid sequence shown in SEQ ID NO: 121; CDR-H2 having the amino acid sequence shown in SEQ ID NO: 120; and CDR-H3 having the amino acid sequence shown in SEQ ID NO: 70; and / or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the amino acid sequence shown in SEQ ID NO: 71; CDR-L2 having the amino acid sequence shown in SEQ ID NO: 72; and CDR-L3 having the amino acid sequence shown in SEQ ID NO: 73.

[0510] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a framework region (FR) from a human immunoglobulin.

[0511] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention comprise:

[0512] (a) a VH having an amino acid sequence as shown in SEQ ID NO: 19 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 20 or a variant thereof;

[0513] (b) a VH having the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 2 or a variant thereof;

[0514] (c) a VH having an amino acid sequence as shown in SEQ ID NO: 3 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 4 or a variant thereof;

[0515] (d) a VH having an amino acid sequence as shown in SEQ ID NO: 5 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 6 or a variant thereof;

[0516] (e) a VH having an amino acid sequence as shown in SEQ ID NO: 7 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 8 or a variant thereof;

[0517] (f) a VH having an amino acid sequence as shown in SEQ ID NO: 9 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 10 or a variant thereof;

[0518] (g) a VH having the amino acid sequence of SEQ ID NO: 11 or a variant thereof and / or a VL having the amino acid sequence of SEQ ID NO: 12 or a variant thereof;

[0519] (h) a VH having an amino acid sequence as shown in SEQ ID NO: 13 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 14 or a variant thereof;

[0520] (i) a VH having an amino acid sequence as shown in SEQ ID NO: 15 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 16 or a variant thereof;

[0521] (j) a VH having an amino acid sequence as shown in SEQ ID NO: 17 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 18 or a variant thereof;

[0522] (k) a VH having an amino acid sequence as shown in SEQ ID NO: 21 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 22 or a variant thereof; or

[0523] (l) a VH having an amino acid sequence as shown in SEQ ID NO: 23 or a variant thereof and / or a VL having an amino acid sequence as shown in SEQ ID NO: 24 or a variant thereof;

[0524] The variant 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 compared to the sequence from which it is derived, or has one or more amino acid substitutions, deletions or additions (such as 1, 2, 3, 4 or 5 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions. In certain embodiments, the variants in (a)-(l) have mutations in the framework region of the antibody sequence from which it is derived. In certain embodiments, the variants are substitutions, deletions or additions of one or more amino acids (such as 1, 2, 3, 4 or 5 amino acid substitutions, deletions or additions) in the framework region of the antibody sequence from which it is derived. In certain embodiments, the variants are substitutions of one or more amino acids in the framework region of the antibody sequence from which it is derived. In certain embodiments, the substitutions are conservative substitutions in the framework region of the antibody sequence from which it is derived.

[0525] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention comprise:

[0526] (a) a VH having the amino acid sequence of SEQ ID NO: 19 and / or a VL having the amino acid sequence of SEQ ID NO: 20;

[0527] (b) a VH having the amino acid sequence of SEQ ID NO: 1 and / or a VL having the amino acid sequence of SEQ ID NO: 2;

[0528] (c) a VH having the amino acid sequence of SEQ ID NO: 3 and / or a VL having the amino acid sequence of SEQ ID NO: 4;

[0529] (d) a VH having the amino acid sequence of SEQ ID NO: 5 and / or a VL having the amino acid sequence of SEQ ID NO: 6;

[0530] (e) a VH having the amino acid sequence of SEQ ID NO: 7 and / or a VL having the amino acid sequence of SEQ ID NO: 8;

[0531] (f) a VH having the amino acid sequence of SEQ ID NO: 9 and / or a VL having the amino acid sequence of SEQ ID NO: 10;

[0532] (g) a VH having the amino acid sequence of SEQ ID NO: 11 and / or a VL having the amino acid sequence of SEQ ID NO: 12;

[0533] (h) a VH having the amino acid sequence of SEQ ID NO: 13 and / or a VL having the amino acid sequence of SEQ ID NO: 14;

[0534] (i) a VH having the amino acid sequence of SEQ ID NO: 15 and / or a VL having the amino acid sequence of SEQ ID NO: 16;

[0535] (j) a VH having the amino acid sequence of SEQ ID NO: 17 and / or a VL having the amino acid sequence of SEQ ID NO: 18;

[0536] (k) a VH having the amino acid sequence of SEQ ID NO: 21 and / or a VL having the amino acid sequence of SEQ ID NO: 22;

[0537] (l) VH having the amino acid sequence shown in SEQ ID NO: 23 and / or VL having the amino acid sequence shown in SEQ ID NO: 24.

[0538] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (a) a VH having the amino acid sequence shown in SEQ ID NO: 19 and / or a VL having the amino acid sequence shown in SEQ ID NO: 20.

[0539] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (b) a VH having the amino acid sequence shown in SEQ ID NO: 1 and / or a VL having the amino acid sequence shown in SEQ ID NO: 2.

[0540] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (c) a VH having the amino acid sequence shown in SEQ ID NO:3 and / or a VL having the amino acid sequence shown in SEQ ID NO:4.

[0541] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (d) a VH having the amino acid sequence shown in SEQ ID NO:5 and / or a VL having the amino acid sequence shown in SEQ ID NO:6.

[0542] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (e) a VH having the amino acid sequence shown in SEQ ID NO:7 and / or a VL having the amino acid sequence shown in SEQ ID NO:8.

[0543] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (f) a VH having the amino acid sequence shown in SEQ ID NO:9 and / or a VL having the amino acid sequence shown in SEQ ID NO:10.

[0544] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (g) a VH having the amino acid sequence shown in SEQ ID NO:11 and / or a VL having the amino acid sequence shown in SEQ ID NO:12.

[0545] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (h) a VH having the amino acid sequence shown in SEQ ID NO:13 and / or a VL having the amino acid sequence shown in SEQ ID NO:14.

[0546] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention include: (i) a VH having an amino acid sequence as shown in SEQ ID NO: 15 and / or a VL having an amino acid sequence as shown in SEQ ID NO: 16;

[0547] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (j) a VH having the amino acid sequence shown in SEQ ID NO:17 and / or a VL having the amino acid sequence shown in SEQ ID NO:18.

[0548] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (k) a VH having the amino acid sequence shown in SEQ ID NO: 21 and / or a VL having the amino acid sequence shown in SEQ ID NO: 22.

[0549] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (1) a VH having the amino acid sequence shown in SEQ ID NO: 23 and / or a VL having the amino acid sequence shown in SEQ ID NO: 24.

[0550] In certain embodiments, the antibody or antigen-binding fragment according to any of the above embodiments further has a feature selected from the following:

[0551] (1) With a binding of less than about 50 ng / mL, such as less than about 40 ng / mL, 30 ng / mL, 25 ng / mL, 24 ng / mL, 23 ng / mL, 22 ng / mL, 21 ng / mL, 20 ng / mL, 19 ng / mL, 18 ng / mL, 17 ng / mL, 16 ng / mL, 15 ng / mL, 14 ng / mL, 13 ng / mL, 12 ng / mL, 11 ng / mL, 10 ng / mL, 9 ng / mL, 8 ng / mL, 7 ng / mL, or an EC of less than 6 ng / mL. 50 Binds to PTK7 (such as human or monkey PTK7); preferably, the EC 50 Determined by ELISA;

[0552] (2) binds to PTK7 (such as human or monkey PTK7) with a KD of less than about 100 nM, such as less than about 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 15 nM, 10 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM or less; preferably, the KD is determined by biofilm interferometry (BLI) (e.g., ForteBio ) measured;

[0553] (3) having ADCC and CDC activities, such as inducing killing of cells expressing PTK7 (e.g., tumor cells) through ADCC and CDC; in certain embodiments, the antibody or antigen-binding fragment comprises a wild-type Fc region. In certain embodiments, the antibody or antigen-binding fragment comprises a heavy chain constant region (CH) having an amino acid sequence as shown in SEQ ID NO: 25.

[0554] Alternatively, it has no ADCC and CDC activity; In certain embodiments, the antibody or antigen-binding fragment comprises an Fc region comprising a mutation or chemical modification. In certain embodiments, the antibody or antigen-binding fragment comprises a heavy chain constant region (CH) having an amino acid sequence as shown in SEQ ID NO: 131;

[0555] (4) inducing PTK7 internalization, as detected by flow cytometry;

[0556] (5) inhibiting cell proliferation; and / or

[0557] (6) Inhibit tumor growth.

[0558] In certain embodiments, the antibody or antigen-binding fragment according to any of the above embodiments may include a constant region from or derived from a human immunoglobulin.

[0559] In certain embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises a heavy chain constant region from or derived from a human immunoglobulin (e.g., IgG1, IgG2, IgG3, or IgG4). In certain embodiments, the antibody or its antigen-binding fragment comprises a wild-type Fc region, or comprises a mutated or chemically modified Fc region, which has an altered effector function (e.g., enhanced ADCC activity) compared to the wild-type Fc region. In certain embodiments, the heavy chain of the antibody or its antigen-binding fragment comprises the amino acid sequence shown in SEQ ID NO: 25 or a variant thereof, and the variant has a substitution of up to 20 amino acids (e.g., a substitution of up to 15, a substitution of up to 10, or a substitution of up to 5 amino acids, such as a substitution of 1, 2, 3, 4, or 5 amino acids) compared to the amino acid sequence shown in SEQ ID NO: 25. In certain embodiments, the substitution is a conservative substitution.

[0560] In certain embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises the sequence set forth in SEQ ID NO:25.

[0561] In certain embodiments, the variant has 3 amino acid substitutions compared to the amino acid sequence shown in SEQ ID NO: 25. In certain embodiments, the variant has amino acid substitutions at positions corresponding to positions 117, 118 and 120 in the amino acid sequence shown in SEQ ID NO: 25. In certain embodiments, the variant has alanine substitutions at positions corresponding to positions 117, 118 and 120 in the amino acid sequence shown in SEQ ID NO: 25. In certain embodiments, the variant has a heavy chain constant region (CH) having an amino acid sequence shown in SEQ ID NO: 131.

[0562] In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain constant region (e.g., κ or λ) from or derived from a human immunoglobulin. In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises an amino acid sequence as shown in SEQ ID NO: 26 and a variant thereof, and compared with the amino acid sequence as shown in SEQ ID NO: 26, the variant has a substitution of up to 20 amino acids (e.g., a substitution of up to 15, a substitution of up to 10, or a substitution of up to 5 amino acids, such as a substitution of 1, 2, 3, 4, or 5 amino acids). In certain embodiments, the substitution is a conservative substitution.

[0563] In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises the sequence shown in SEQ ID NO:26.

[0564] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO:25 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO:26.

[0565] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO:131 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO:26.

[0566] In certain embodiments, antibodies or antigen-binding fragments thereof having a heavy chain constant region do not bind to Fc receptors (such as CD16a protein, CD32a protein, CD32b protein, and CD64 protein). Therefore, in such embodiments, antibodies or antigen-binding fragments thereof can reduce nonspecific cytotoxicity mediated by Fc receptors and improve the safety of antibodies or antigen-binding fragments thereof in subjects. In certain embodiments, antibodies or antigen-binding fragments thereof having a heavy chain constant region can bind to FcRn. Therefore, in such embodiments, antibodies or antigen-binding fragments thereof have a longer half-life in subjects. In certain embodiments, antibodies or antigen-binding fragments thereof having a heavy chain constant region can induce PTK7-mediated endocytosis. Therefore, in such embodiments, antibodies or antigen-binding fragments thereof have the potential to be used as carriers for targeted delivery of drugs, toxins, enzymes, or DNA for treatment.

[0567] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention comprise:

[0568] (a) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0569] (b) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0570] (c) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0571] (d) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0572] (e) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:3 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:4 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0573] (f) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:5 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:6 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0574] (g) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:7 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:8 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0575] (h) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:9 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:10 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0576] (i) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0577] (j) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0578] (k) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0579] (l) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0580] (m) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:21 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:22 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0581] (n) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:23 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:24 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0582] (o) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:3 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:4 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0583] (p) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:5 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:6 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0584] (q) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:7 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:8 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0585] (r) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:9 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:10 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26;

[0586] (s) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0587] (t) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0588] (u) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0589] (v) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO: 26;

[0590] (w) a heavy chain comprising a VH having the amino acid sequence of SEQ ID NO:21 and a heavy chain constant region (CH) having the amino acid sequence of SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence of SEQ ID NO:22 and a light chain constant region (CL) having the amino acid sequence of SEQ ID NO:26; or

[0591] (x) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 23 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 24 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0592] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (a) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0593] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (b) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0594] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (c) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0595] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (d) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0596] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (e) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 3 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 4 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0597] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (f) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 5 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 6 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0598] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (g) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 7 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 8 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0599] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (h) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 9 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 10 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0600] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (i) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0601] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (j) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0602] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (k) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0603] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (l) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0604] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (m) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 21 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 22 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0605] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (n) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 23 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 24 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0606] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (o) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 3 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 4 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0607] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (p) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 5 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 6 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0608] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (q) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 7 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 8 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0609] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (r) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 9 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 10 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0610] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (s) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0611] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (t) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0612] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (u) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0613] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (v) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0614] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (w) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 21 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 22 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0615] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises: (x) a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO: 23 and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence shown in SEQ ID NO: 24 and a light chain constant region (CL) having the amino acid sequence shown in SEQ ID NO: 26.

[0616] In certain embodiments, the antibodies or antigen-binding fragments thereof according to the present invention comprise a heavy chain comprising a VH having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23.

[0617] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:1.

[0618] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:3.

[0619] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:5.

[0620] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:7.

[0621] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:9.

[0622] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:11.

[0623] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:13.

[0624] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:15.

[0625] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:17.

[0626] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:19.

[0627] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:21.

[0628] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises a heavy chain comprising a VH having the amino acid sequence shown in SEQ ID NO:23.

[0629] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain, wherein the heavy chain variable region (VH) has the amino acid sequence shown in SEQ ID NO: 19 or a variant thereof, and a heavy chain constant region (CH) having the amino acid sequence shown in SEQ ID NO: 131 or a variant thereof;

[0630] Wherein, the variant 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 compared to the sequence from which it is derived, or, has one or more amino acid substitutions, deletions or additions (such as 1, 2, 3, 4 or 5 amino acid substitutions, deletions or additions) compared to the sequence from which it is derived. In certain embodiments, the substitution is a conservative substitution. In certain embodiments, the variant has mutations in the framework region of the antibody sequence from which it is derived. In certain embodiments, the variant has one or more amino acid substitutions, deletions or additions (such as 1, 2, 3, 4 or 5 amino acid substitutions, deletions or additions) in the framework region of the antibody sequence from which it is derived. In certain embodiments, the variant replaces one or more amino acids in the framework region of the antibody sequence from which it is derived. In certain embodiments, the substitution is a conservative substitution in the framework region of the antibody sequence from which it is derived.

[0631] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain comprisi...

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to PTK7, wherein: The antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (a) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 19; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 20; (b) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 1; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 2; (c) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 3; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 4; (d) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:5; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:6; (e) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:7; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:8; (f) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:9; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:10; (g) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 11; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 12; (h) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 13; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 14; (i) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 15; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 16; (j) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO: 17; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO: 18; (k) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:21; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:22; (l) CDR-H1, CDR-H2 and CDR-H3 contained in the heavy chain variable region (VH) shown in SEQ ID NO:23; and / or, CDR-L1, CDR-L2 and CDR-L3 contained in the light chain variable region (VL) shown in SEQ ID NO:24; or (m) CDR-H1, CDR-H2 and CDR-H3 contained in the following heavy chain variable region (VH), and / or CDR-L1, CDR-L2 and CDR-L3 contained in the following light chain variable region (VL), wherein, compared with the heavy chain variable region (VH) and / or light chain variable region (VL) described in any one of (a) to (l), at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) contains a mutation, and the mutation is a substitution, deletion or addition of one or more amino acids.

2. The antibody or antigen-binding fragment thereof according to claim 1, wherein The antibody or antigen-binding fragment thereof comprises: (1) the following heavy chain variable region (VH) and / or light chain variable region (VL), wherein the CDRs are defined according to the Chothia numbering system: (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 27 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 28 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof; (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 41 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 42 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof; (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 55 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 56 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 68 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 69 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 74 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 69 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 84 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 85 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 86 or a variant thereof; (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 92 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 93 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 95 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 96 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 97 or a variant thereof; (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 27 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 28 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 106 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 107 or a variant thereof; (1h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 41; CDR-H2 of SEQ ID NO: 42; CDR-H3 of SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44; CDR-L2 of SEQ ID NO: 45; CDR-L3 of SEQ ID NO: 46; (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 41; CDR-H2 of SEQ ID NO: 42; CDR-H3 of SEQ ID NO: 43; or, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44; CDR-L2 of SEQ ID NO: 45; CDR-L3 of SEQ ID NO: 46; (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 27; CDR-H2 with a sequence of SEQ ID NO: 28; CDR-H3 with a sequence of SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30; CDR-L2 with a sequence of SEQ ID NO: 31; CDR-L3 with a sequence of SEQ ID NO: 32; (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 55; CDR-H2 with a sequence of SEQ ID NO: 56; CDR-H3 with a sequence of SEQ ID NO: 57; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58; CDR-L2 with a sequence of SEQ ID NO: 59; CDR-L3 with a sequence of SEQ ID NO: 60; or, (11) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 74 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 69 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; or, (2) the following heavy chain variable region (VH) and / or light chain variable region (VL), wherein the CDRs are defined according to the Kabat numbering system: (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 33 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 34 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof; (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 33 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 35 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof; (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 47 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 49 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof; (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 61 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 62 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 75 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 76 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 87 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 88 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 84 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 85 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 86 or a variant thereof; (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 98 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 99 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 95 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 96 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 97 or a variant thereof; (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 108 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 35 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 106 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 107 or a variant thereof; (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 47 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 48 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 44 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 45 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof; (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 47; CDR-H2 of SEQ ID NO: 48; CDR-H3 of SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44; CDR-L2 of SEQ ID NO: 45; CDR-L3 of SEQ ID NO: 46; (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 61; CDR-H2 with a sequence of SEQ ID NO: 62; CDR-H3 with a sequence of SEQ ID NO: 57; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58; CDR-L2 with a sequence of SEQ ID NO: 59; CDR-L3 with a sequence of SEQ ID NO: 60; or, (21) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 75; CDR-H2 with a sequence of SEQ ID NO: 76; CDR-H3 with a sequence of SEQ ID NO: 70; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71; CDR-L2 with a sequence of SEQ ID NO: 72; CDR-L3 with a sequence of SEQ ID NO: 73; or, (3) the following heavy chain variable region (VH) and / or light chain variable region (VL), wherein the CDRs are defined according to the IMGT numbering system: (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 36 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 37 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 38 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 39 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 40 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof; (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 50 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 51 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 52 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 53 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 54 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 46 or a variant thereof; (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 63 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 64 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 65 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 66 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 67 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 77 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 78 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 81 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 82 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 80 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 78 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 89 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 90 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 91 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 86 or a variant thereof; (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 100 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 101 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 102 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 103 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 104 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 97 or a variant thereof; (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 36 or a variant thereof; CDR-H2 of SEQ ID NO: 37 or a variant thereof; CDR-H3 of SEQ ID NO: 109 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 110 or a variant thereof; CDR-L2 of SEQ ID NO: 40 or a variant thereof; CDR-L3 of SEQ ID NO: 107 or a variant thereof; (3h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 50; CDR-H2 of SEQ ID NO: 51; CDR-H3 of SEQ ID NO: 52; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 53; CDR-L2 of SEQ ID NO: 54; CDR-L3 of SEQ ID NO: 46; (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 50; CDR-H2 of SEQ ID NO: 51; CDR-H3 of SEQ ID NO: 52; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 53; CDR-L2 of SEQ ID NO: 54; CDR-L3 of SEQ ID NO: 46; (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 36; CDR-H2 of SEQ ID NO: 37; CDR-H3 of SEQ ID NO: 38; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 39; CDR-L2 of SEQ ID NO: 40; CDR-L3 of SEQ ID NO: 32; (3k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 63; CDR-H2 of SEQ ID NO: 64; CDR-H3 of SEQ ID NO: 65; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 66; CDR-L2 of SEQ ID NO: 67; CDR-L3 of SEQ ID NO: 60; or, (31) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 80 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 78 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 81 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 82 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; or, (4) the following heavy chain variable region (VH) and / or light chain variable region (VL), wherein the CDRs are defined according to the AbM numbering system: (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 113 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 114 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 31 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 32 or a variant thereof; (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 115 or a variant thereof; CDR-H2 of SEQ ID NO: 116 or a variant thereof; CDR-H3 of SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44 or a variant thereof; CDR-L2 of SEQ ID NO: 45 or a variant thereof; CDR-L3 of SEQ ID NO: 46 or a variant thereof; (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 117 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 118 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 59 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 60 or a variant thereof; (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 119 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 120 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 122 or a variant thereof; CDR-H2 of SEQ ID NO: 123 or a variant thereof; CDR-H3 of SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 84 or a variant thereof; CDR-L2 of SEQ ID NO: 85 or a variant thereof; CDR-L3 of SEQ ID NO: 86 or a variant thereof; (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 124 or a variant thereof; CDR-H2 of SEQ ID NO: 125 or a variant thereof; CDR-H3 of SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 95 or a variant thereof; CDR-L2 of SEQ ID NO: 96 or a variant thereof; CDR-L3 of SEQ ID NO: 97 or a variant thereof; (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 126 or a variant thereof; CDR-H2 of SEQ ID NO: 114 or a variant thereof; CDR-H3 of SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 106 or a variant thereof; CDR-L2 of SEQ ID NO: 31 or a variant thereof; CDR-L3 of SEQ ID NO: 107 or a variant thereof; (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 115; CDR-H2 of SEQ ID NO: 116; CDR-H3 of SEQ ID NO: 43; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44; CDR-L2 of SEQ ID NO: 45; CDR-L3 of SEQ ID NO: 46; (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 of SEQ ID NO: 115; CDR-H2 of SEQ ID NO: 116; CDR-H3 of SEQ ID NO: 43; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 of SEQ ID NO: 44; CDR-L2 of SEQ ID NO: 45; CDR-L3 of SEQ ID NO: 46; (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 113; CDR-H2 with a sequence of SEQ ID NO: 114; CDR-H3 with a sequence of SEQ ID NO: 29; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 30; CDR-L2 with a sequence of SEQ ID NO: 31; CDR-L3 with a sequence of SEQ ID NO: 32; (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 117; CDR-H2 with a sequence of SEQ ID NO: 118; CDR-H3 with a sequence of SEQ ID NO: 57; and, a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 58; CDR-L2 with a sequence of SEQ ID NO: 59; CDR-L3 with a sequence of SEQ ID NO: 60; or, (41) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 with a sequence of SEQ ID NO: 121 or a variant thereof; CDR-H2 with a sequence of SEQ ID NO: 120 or a variant thereof; CDR-H3 with a sequence of SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 with a sequence of SEQ ID NO: 71 or a variant thereof; CDR-L2 with a sequence of SEQ ID NO: 72 or a variant thereof; CDR-L3 with a sequence of SEQ ID NO: 73 or a variant thereof; Among them, the variants described in any one of (1a)-(1g), (1l), (2a)-(2i), (3a)-(3g), (3l), (4a)-(4g) and (4l) have one or more amino acid substitutions, deletions or additions compared to the sequence from which they are derived.

3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein The antibody or antigen-binding fragment thereof comprises: (a) a VH comprising the sequence shown in SEQ ID NO: 19 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 20 or a variant thereof; (b) a VH comprising the sequence shown in SEQ ID NO: 1 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 2 or a variant thereof; (c) a VH comprising the sequence shown in SEQ ID NO: 3 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 4 or a variant thereof; (d) a VH comprising the sequence shown in SEQ ID NO: 5 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 6 or a variant thereof; (e) a VH comprising the sequence shown in SEQ ID NO: 7 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 8 or a variant thereof; (f) a VH comprising the sequence shown in SEQ ID NO: 9 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 10 or a variant thereof; (g) a VH comprising the sequence shown in SEQ ID NO: 11 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 12 or a variant thereof; (h) a VH comprising the sequence shown in SEQ ID NO: 13 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 14 or a variant thereof; (i) a VH comprising the sequence shown in SEQ ID NO: 15 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 16 or a variant thereof; (j) a VH comprising the sequence shown in SEQ ID NO: 17 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 18 or a variant thereof; (k) a VH comprising the sequence shown in SEQ ID NO: 21 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 22 or a variant thereof; or (l) a VH comprising the sequence shown in SEQ ID NO: 23 or a variant thereof and / or a VL comprising the sequence shown in SEQ ID NO: 24 or a variant thereof; wherein the variant 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 compared to the sequence from which it is derived, or has one or several amino acid substitutions, deletions or additions compared to the sequence from which it is derived.

4. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein The antibody or antigen-binding fragment thereof is a murine antibody, a chimeric antibody, a humanized antibody or a fully human antibody.

5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The antibody or antigen-binding fragment thereof further comprises a constant region from or derived from a human immunoglobulin.

6. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain constant region from or derived from human immunoglobulin.

7. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The antibody or antigen-binding fragment thereof comprises a wild-type Fc region, or comprises a mutated or chemically modified Fc region having altered effector function compared to the wild-type Fc region.

8. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The light chain of the antibody or antigen-binding fragment thereof comprises a light chain constant region from or derived from human immunoglobulin.

9. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) as shown in SEQ ID NO: 25 or a variant thereof, wherein the variant has up to 20 amino acid substitutions compared to SEQ ID NO:

25.

10. The antibody or antigen-binding fragment thereof according to claim 9, wherein The variant has 3 amino acid substitutions compared to SEQ ID NO:

25.

11. The antibody or antigen-binding fragment thereof according to claim 9, wherein The variant has amino acid substitutions at positions 117, 118 and 120 corresponding to SEQ ID NO:

25.

12. The antibody or antigen-binding fragment thereof according to claim 9, wherein The variant has alanine substitutions at positions 117, 118 and 120 corresponding to SEQ ID NO:

25.

13. The antibody or antigen-binding fragment thereof according to claim 9, wherein The variant has a heavy chain constant region (CH) as shown in SEQ ID NO:

131.

14. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The antibody or antigen-binding fragment thereof comprises a light chain constant region (CL) as shown in SEQ ID NO: 26 or a variant thereof having up to 20 amino acid substitutions compared to SEQ ID NO:

26.

15. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein The antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) as shown in SEQ ID NO: 25 or 131 and a light chain constant region (CL) as shown in SEQ ID NO:

26.

16. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 15, wherein The antibody or antigen-binding fragment thereof comprises: (1) a heavy chain comprising the VH of SEQ ID NO: 19 and the heavy chain constant region (CH) of SEQ ID NO: 131, and a light chain comprising the VL of SEQ ID NO: 20 and the light chain constant region (CL) of SEQ ID NO: 26; (2) a heavy chain comprising the VH set forth in SEQ ID NO: 19 and the heavy chain constant region (CH) set forth in SEQ ID NO: 25, and a light chain comprising the VL set forth in SEQ ID NO: 20 and the light chain constant region (CL) set forth in SEQ ID NO: 26; (3) a heavy chain comprising the VH set forth in SEQ ID NO:1 and the heavy chain constant region (CH) set forth in SEQ ID NO:25, and a light chain comprising the VL set forth in SEQ ID NO:2 and the light chain constant region (CL) set forth in SEQ ID NO:26; (4) a heavy chain comprising the VH set forth in SEQ ID NO:1 and the heavy chain constant region (CH) set forth in SEQ ID NO:131, and a light chain comprising the VL set forth in SEQ ID NO:2 and the light chain constant region (CL) set forth in SEQ ID NO:26; (5) a heavy chain comprising the VH shown in SEQ ID NO:3 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:4 and the light chain constant region (CL) shown in SEQ ID NO:26; (6) a heavy chain comprising the VH set forth in SEQ ID NO:5 and the heavy chain constant region (CH) set forth in SEQ ID NO:25, and a light chain comprising the VL set forth in SEQ ID NO:6 and the light chain constant region (CL) set forth in SEQ ID NO:26; (7) a heavy chain comprising the VH shown in SEQ ID NO:7 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:8 and the light chain constant region (CL) shown in SEQ ID NO:26; (8) a heavy chain comprising the VH shown in SEQ ID NO:9 and the heavy chain constant region (CH) shown in SEQ ID NO:25, and a light chain comprising the VL sequence shown in SEQ ID NO:10 and the light chain constant region (CL) shown in SEQ ID NO:26; (9) a heavy chain comprising the VH shown in SEQ ID NO: 11 and the heavy chain constant region (CH) shown in SEQ ID NO: 25, and a light chain comprising the VL sequence shown in SEQ ID NO: 12 and the light chain constant region (CL) shown in SEQ ID NO: 26; (10) a heavy chain comprising the VH of SEQ ID NO: 13 and the heavy chain constant region (CH) of SEQ ID NO: 25, and a light chain comprising the VL of SEQ ID NO: 14 and the light chain constant region (CL) of SEQ ID NO: 26; (11) a heavy chain comprising the VH of SEQ ID NO: 15 and the heavy chain constant region (CH) of SEQ ID NO: 25, and a light chain comprising the VL of SEQ ID NO: 16 and the light chain constant region (CL) of SEQ ID NO: 26; (12) a heavy chain comprising the VH of SEQ ID NO: 17 and the heavy chain constant region (CH) of SEQ ID NO: 25, and a light chain comprising the VL of SEQ ID NO: 18 and the light chain constant region (CL) of SEQ ID NO: 26; (13) a heavy chain comprising the VH of SEQ ID NO:21 and the heavy chain constant region (CH) of SEQ ID NO:25, and a light chain comprising the VL of SEQ ID NO:22 and the light chain constant region (CL) of SEQ ID NO:26; (14) a heavy chain comprising the VH of SEQ ID NO:23 and the heavy chain constant region (CH) of SEQ ID NO:25, and a light chain comprising the VL of SEQ ID NO:24 and the light chain constant region (CL) of SEQ ID NO:26; (15) a heavy chain comprising the VH of SEQ ID NO:3 and the heavy chain constant region (CH) of SEQ ID NO:131, and a light chain comprising the VL of SEQ ID NO:4 and the light chain constant region (CL) of SEQ ID NO:26; (16) a heavy chain comprising the VH of SEQ ID NO:5 and the heavy chain constant region (CH) of SEQ ID NO:131, and a light chain comprising the VL of SEQ ID NO:6 and the light chain constant region (CL) of SEQ ID NO:26; (17) a heavy chain comprising the VH of SEQ ID NO:7 and the heavy chain constant region (CH) of SEQ ID NO:131, and a light chain comprising the VL of SEQ ID NO:8 and the light chain constant region (CL) of SEQ ID NO:26; (18) a heavy chain comprising the VH of SEQ ID NO:9 and the heavy chain constant region (CH) of SEQ ID NO:131, and a light chain comprising the VL of SEQ ID NO:10 and the light chain constant region (CL) of SEQ ID NO:26; (19) a heavy chain comprising the VH of SEQ ID NO: 11 and the heavy chain constant region (CH) of SEQ ID NO: 131, and a light chain comprising the VL of SEQ ID NO: 12 and the light chain constant region (CL) of SEQ ID NO: 26; (20) a heavy chain comprising the VH of SEQ ID NO: 13 and the heavy chain constant region (CH) of SEQ ID NO: 131, and a light chain comprising the VL of SEQ ID NO: 14 and the light chain constant region (CL) of SEQ ID NO: 26; (21) a heavy chain comprising the VH of SEQ ID NO: 15 and the heavy chain constant region (CH) of SEQ ID NO: 131, and a light chain comprising the VL of SEQ ID NO: 16 and the light chain constant region (CL) of SEQ ID NO: 26; (22) a heavy chain comprising the VH of SEQ ID NO: 17 and the heavy chain constant region (CH) of SEQ ID NO: 131, and a light chain comprising the VL of SEQ ID NO: 18 and the light chain constant region (CL) of SEQ ID NO: 26; (23) a heavy chain comprising the VH of SEQ ID NO:21 and the heavy chain constant region (CH) of SEQ ID NO:131, and a light chain comprising the VL of SEQ ID NO:22 and the light chain constant region (CL) of SEQ ID NO:26; or (24) A heavy chain comprising the VH shown in SEQ ID NO:23 and the heavy chain constant region (CH) shown in SEQ ID NO:131, and a light chain comprising the VL sequence shown in SEQ ID NO:24 and the light chain constant region (CL) shown in SEQ ID NO:

26.

17. The antibody or antigen-binding fragment thereof of claim 3, wherein the N-terminal glutamine or glutamic acid of the VH having the sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 or 23 is cyclized to form pyroglutamate or pyroglutamic acid.

18. The antibody or antigen-binding fragment thereof of claim 3 or 17, wherein the N-terminal glutamine of the VL having the sequence shown in SEQ ID NO: 12 is cyclized to form pyroglutamate or pyroglutamic acid, or the N-terminal glutamic acid of the VL having the sequence shown in SEQ ID NO: 16 is cyclized to form pyroglutamate or pyroglutamic acid.

19. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof comprises: a VH having an amino acid sequence as shown in SEQ ID NO: 19 and an N-terminal glutamic acid that is cyclized to form pyroglutamate or pyroglutamic acid, and a VL having an amino acid sequence as shown in SEQ ID NO:

20.

20. The antibody of claim 1 or 2, comprising: (a) a heavy chain comprising the sequence shown in SEQ ID NO: 135 or a variant thereof and / or a light chain comprising the sequence shown in SEQ ID NO: 112; (b) a heavy chain consisting of the sequence shown in SEQ ID NO: 135 and a light chain consisting of the sequence shown in SEQ ID NO: 112; or (c) a heavy chain comprising the sequence shown in SEQ ID NO: 135 and a light chain comprising the sequence shown in SEQ ID NO:

112.

21. The antibody of claim 1 or 2, comprising: (a) a heavy chain consisting of the sequence shown in SEQ ID NO: 136 and a light chain consisting of the sequence shown in SEQ ID NO: 112; (b) a heavy chain consisting of the sequence shown in SEQ ID NO: 137 and a light chain consisting of the sequence shown in SEQ ID NO: 112; or (c) a heavy chain consisting of the sequence shown in SEQ ID NO: 138 and a light chain consisting of the sequence shown in SEQ ID NO:

112.

22. The antibody or antigen-binding fragment thereof according to claim 1 or 2, comprising: (a) a heavy chain comprising the sequence shown in SEQ ID NO: 111 or a variant thereof and / or a light chain comprising the sequence shown in SEQ ID NO: 112; (b) a heavy chain consisting of the sequence shown in SEQ ID NO: 111 and a light chain consisting of the sequence shown in SEQ ID NO: 112; or (c) a heavy chain comprising the sequence shown in SEQ ID NO:111 and a light chain comprising the sequence shown in SEQ ID NO:

112.

23. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 22, wherein: The antibody or antigen-binding fragment thereof is selected from the group consisting of scFv, Fab, Fab', Fab'-SH, (Fab')2, Fv fragment, disulfide-linked Fv (dsFv), diabody, bispecific antibody and multispecific antibody.

24. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 23, wherein: The antibody or antigen-binding fragment thereof carries a label, a detectable label selected from an enzyme, a radionuclide, a fluorescent dye, a luminescent substance or biotin.

25. The antibody or antigen-binding fragment thereof of any one of claims 1 to 24, wherein the antibody or antigen-binding fragment thereof has a characteristic selected from the group consisting of: (1) With an EC of less than about 50 ng / mL 50 Binds to PTK7; (2) binds PTK7 with a KD of less than about 100 nM; (3) having ADCC and CDC activities, or not having ADCC and CDC activities; (4) induce PTK7 internalization; (5) inhibiting cell proliferation; and / or (6) Inhibit tumor growth.

26. An isolated nucleic acid molecule encoding the antibody or antigen-binding fragment thereof, the heavy chain and / or light chain thereof, or the heavy chain variable region and / or light chain variable region thereof according to any one of claims 1 to 25.

27. The isolated nucleic acid molecule of claim 26, comprising a nucleic acid molecule encoding the heavy chain variable region of the antibody and / or a nucleic acid molecule encoding the light chain variable region of the antibody, wherein The nucleic acid molecule encoding the antibody heavy chain variable region includes: (i) the nucleotide sequence shown in SEQ ID NO: 127, (ii) a sequence substantially identical to SEQ ID NO: 127, or (iii) a degenerate sequence of (i) or (ii); and / or, the nucleic acid molecule encoding the antibody light chain variable region comprises: (iv) the nucleotide sequence shown in SEQ ID NO: 128, (v) a sequence substantially identical to SEQ ID NO: 128, or (vi) a degenerate sequence of (iv) or (v).

28. The isolated nucleic acid molecule of claim 26 or 27, comprising a nucleic acid molecule encoding the heavy chain of the antibody, and / or a nucleic acid molecule encoding the light chain of the antibody, wherein Nucleic acid molecules encoding antibody heavy chains include: (i) the nucleotide sequence shown in SEQ ID NO: 132: (ii) a sequence substantially identical to SEQ ID NO: 132, or (iii) a degenerate sequence of (i) or (ii); and / or, a nucleic acid molecule encoding an antibody light chain, comprising: (iv) the nucleotide sequence shown in SEQ ID NO: 130: (v) a sequence substantially identical to SEQ ID NO: 130, or (vi) a degenerate sequence of (iv) or (v).

29. The isolated nucleic acid molecule of claim 26 or 27, comprising a nucleic acid molecule encoding the heavy chain of the antibody, and / or a nucleic acid molecule encoding the light chain of the antibody, wherein Nucleic acid molecules encoding antibody heavy chains include: (i) the nucleotide sequence shown in SEQ ID NO: 129: (ii) a sequence substantially identical to SEQ ID NO: 129, or (iii) a degenerate sequence of (i) or (ii); and / or, a nucleic acid molecule encoding an antibody light chain, comprising: (iv) the nucleotide sequence shown in SEQ ID NO: 130: (v) a sequence substantially identical to SEQ ID NO: 130, or (vi) a degenerate sequence of (iv) or (v).

30. A vector comprising the nucleic acid molecule according to any one of claims 27 to 29.

31. The vector according to claim 30, wherein The vector is a cloning vector or an expression vector.

32. A host cell comprising the nucleic acid molecule of any one of claims 27 to 29 or the vector of claim 30 or 31.

33. A method for preparing the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25, comprising culturing the host cell according to claim 32 under conditions that allow expression of the antibody or antigen-binding fragment thereof, and recovering the antibody or antigen-binding fragment thereof from the cultured host cell culture.

34. An antibody or antigen-binding fragment thereof obtainable by the method of claim 33.

35. A conjugate comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25 and a conjugated moiety connected thereto.

36. The conjugate according to claim 35, wherein The conjugated moiety is selected from the group consisting of a detectable label and a therapeutic agent.

37. A multispecific antibody comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25.

38. The multispecific antibody according to claim 37, wherein The multispecific antibody comprises the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25 as a first antigen-binding domain, and further comprises at least one second antigen-binding domain against other targets.

39. The multispecific antibody according to claim 38, wherein The multispecific antibody is a bispecific antibody, a trispecific antibody or a tetraspecific antibody.

40. A chimeric antigen receptor comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25, a transmembrane domain, and one or more intracellular T cell signaling domains.

41. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1 to 25, or the isolated nucleic acid molecule of any one of claims 26 to 29, or the vector of claim 30 or 31, or the host cell of claim 32, or the conjugate of claim 35 or 36, or the multispecific antibody of any one of claims 37 to 39, or the chimeric antigen receptor of claim 40 or a host cell expressing the chimeric antigen receptor, and a pharmaceutically acceptable carrier and / or excipient.

42. The pharmaceutical composition of claim 41 further comprising an additional pharmaceutically active agent.

43. The pharmaceutical composition of claim 42, wherein The additional pharmaceutically active agent is a drug having anti-tumor activity.

44. The pharmaceutical composition of claim 43, wherein The additional pharmaceutically active agent is selected from: EGFR inhibitors, BCR-ABL, FLT3, KIT or RET inhibitors, HER2 inhibitors, HER3 inhibitors, HER4 inhibitors, IGFR-1 inhibitors, mTOR inhibitors, PI3 kinase inhibitors, c-met or VEGF inhibitors, PARP inhibitors, chemotherapeutic drugs and any combination thereof.

45. The pharmaceutical composition of claim 44, wherein The antibody or antigen-binding fragment thereof and the additional pharmaceutically active agent are provided as separate components or as mixed components.

46. ​​A diagnostic or therapeutic kit comprising the antibody or antigen-binding fragment thereof of any one of claims 1-25, or the isolated nucleic acid molecule of any one of claims 26-29, or the vector of claim 30 or 31, or the host cell of claim 32, or the conjugate of claim 35 or 36, or the multispecific antibody of claim 37, 38 or 39, or the chimeric antigen receptor of claim 40 or a host cell expressing the chimeric antigen receptor, or the pharmaceutical composition of any one of claims 41-45, and optionally instructions for use.

47. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25, or the isolated nucleic acid molecule according to any one of claims 26 to 29, or the vector according to claim 30 or 31, or the host cell according to claim 32, or the conjugate according to claim 35 or 36, or the multispecific antibody according to claim 37, 38 or 39, or the chimeric antigen receptor according to claim 40 or a host cell expressing the chimeric antigen receptor, or the pharmaceutical composition according to any one of claims 41 to 45 in the preparation of a medicament for inhibiting cell proliferation or preventing and / or treating and / or adjuvanting the treatment of tumors.

48. The use according to claim 47, wherein The antibody or antigen-binding fragment thereof, isolated nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition is administered in combination with another pharmaceutically active agent simultaneously, separately or sequentially.

49. The use according to claim 48, wherein The additional pharmaceutically active agent is a drug having anti-tumor activity.

50. The use of claim 49, wherein The additional pharmaceutically active agent is selected from: EGFR inhibitors, BCR-ABL, FLT3, KIT or RET inhibitors, HER2 inhibitors, HER3 inhibitors, HER4 inhibitors, IGFR-1 inhibitors, mTOR inhibitors, PI3 kinase inhibitors, c-met or VEGF inhibitors, PARP inhibitors, chemotherapeutic drugs, and any combination thereof.

51. The use according to any one of claims 47 to 50, wherein the tumor is a PTK7-positive tumor.

52. The use of claim 51, wherein The tumor is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary carcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct carcinoma, breast cancer, ovarian cancer, lung cancer, esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

53. A method for inhibiting cell proliferation, comprising contacting the cell with the antibody or antigen-binding fragment thereof described in any one of claims 1-25, or the isolated nucleic acid molecule described in any one of claims 26-29, or the vector described in claim 30 or 31, or the host cell described in claim 32, or the conjugate described in claim 35 or 36, or the multispecific antibody described in claim 37, 38 or 39, or the chimeric antigen receptor described in claim 40 or the host cell expressing the chimeric antigen receptor, or the pharmaceutical composition described in any one of claims 41-45.

54. The method of claim 53, wherein: The cells are cells expressing PTK7.

55. The method of claim 54, wherein: The cells are tumor cells.

56. A method for preventing and / or treating and / or adjuvanting a tumor in a subject, the method comprising: An effective amount of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25, or the isolated nucleic acid molecule according to any one of claims 26 to 29, or the vector according to claim 30 or 31, or the host cell according to claim 32, or the conjugate according to claim 35 or 36, or the multispecific antibody according to claim 37, 38 or 39, or the chimeric antigen receptor according to claim 40 or the host cell expressing the chimeric antigen receptor, or the pharmaceutical composition according to any one of claims 41 to 45 is administered to a subject in need thereof.

57. The method of claim 56, further comprising administering to the subject a second therapy selected from surgery, chemotherapy, radiotherapy, immunotherapy, gene therapy, DNA therapy, RNA therapy, nanotherapy, virotherapy, adjuvant therapy, and any combination thereof.

58. The method of claim 57, wherein: The second therapy may be applied simultaneously, separately or sequentially with the method of claim 56.

59. The method of claim 56 or 57, wherein: The tumor is a PTK7-positive tumor.

60. The method of claim 59, wherein: The tumor is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary carcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct carcinoma, breast cancer, ovarian cancer, lung cancer, esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

61. A method for detecting the presence or level of PTK7 in a sample, comprising: The sample is contacted with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 25 under conditions that allow formation of a complex between the antibody or antigen-binding fragment thereof and PTK7, and the formation of the complex is detected.

62. The method of claim 61, wherein: The method is used to diagnose PTK7-positive tumors.

63. The method of claim 62, wherein: The PTK7-positive tumor is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary carcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct carcinoma, breast cancer, ovarian cancer, lung cancer, esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

64. The method of claim 63, wherein: The method comprises: detecting the expression level of PTK7 in a test sample from a subject, and comparing the expression level with a reference value, wherein an increase in the expression level compared to the reference value is an indication of a tumor.

65. Use of the antibody or antigen-binding fragment thereof of any one of claims 1-25, or the isolated nucleic acid molecule of any one of claims 26-29, or the vector of claim 30 or 31, or the host cell of claim 32, or the conjugate of claim 35 or 36, or the multispecific antibody of claim 37, 38 or 39 in the preparation of a detection kit for detecting the presence or level of PTK7 in a sample and / or diagnosing a tumor.

66. The use of claim 65, wherein The tumor is a PTK7-positive tumor.

67. The use of claim 66, wherein The tumor is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, glioblastoma, hepatobiliary carcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic bile duct carcinoma, breast cancer, ovarian cancer, lung cancer, esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, pharyngeal squamous cell carcinoma, or any combination thereof.

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