PTK7-binding proteins and uses thereof

Abstract

The present invention relates to the field of disease treatment, and in particular to an anti-PTK7 antibody or antigen-binding fragment thereof, a nucleic acid molecule encoding the same, and a method for preparing the same. The anti-PTK7 antibody or antigen-binding fragment thereof of the present invention has high affinity binding to PTK7 and endocytosis activity, while maintaining good hydrophilicity. Therefore, the present invention further relates to the use of the antibody or antigen-binding fragment thereof in the treatment and diagnosis of disease.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of Chinese Application No. 202210998273.4, filed on August 19, 2022, and Chinese Application No. 202211260998.X, filed on October 14, 2022, the disclosures of each of which are incorporated herein by reference in their entireties. (Sequence Listing) This application contains a computer-readable sequence listing submitted herewith in XML file format, the entire contents of which are incorporated herein by reference in their entirety. The sequence listing XML file submitted herewith is entitled "14463-063-228_SEQ_LISTING.xml", was created on August 15, 2023, and is 152,208 bytes in size. [Background technology]

[0002] FIELD OF THE INVENTION The present invention is in the field of therapeutic monoclonal antibodies, and more particularly relates to antibodies against PTK7 and the use of such antibodies in the treatment and diagnosis of disease.

[0003] Description of Related Art PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family and can lack kinase activity due to mutations in the kinase domain. PTK7 was first 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 domain, and an intracellular tyrosine kinase domain, and its ligand is unknown. The extracellular segment of PTK7 can be cleaved at a second position by ADAM proteases and MT1-MMP. Protease hydrolysis allows PTK7 to generate two soluble fragments. PTK7 is an evolutionarily conserved transmembrane receptor whose functions include multiple processes from embryonic morphogenesis to epidermal wound repair. It is also a multifunctional synergistic receptor and acts as a molecular switch in the Wnt, sema-plexin (axon guidance factor, plexin protein), and VEGF signaling pathways.

[0004] PTK7 has a constant expression in normal tissues such as endometrium, ovary, and placenta, but is highly expressed in various solid tumors, including 47.4% in NSCLC (mean H-score 117.4), 45.10% in ovarian cancer (mean H-score 151), and 28.6% in TNBC (mean H-score 159.2). In esophageal cancer cases, PTK7 is expressed in over 80% of cases, and 60% are 2. + or 3 + It has been reported that PTK7 staining is positive in IHC, whereas normal esophageal tissue is negative, and high PTK7 expression is associated with poor prognosis. Cofetuzumab peridotin, an ADC drug targeting PTK7 and developed by Pfizer, showed good safety and initial efficacy in stage I clinical cases. Based on the high expression of PTK7 in various tumors and clinical validation of the safety and efficacy of targeted drugs, PTK7 is an ideal therapeutic target.

[0005] Currently, there is no antibody drug targeting PTK7 on the market.Therefore, it is urgent and necessary to develop an antibody targeting PTK7 with higher specificity, lower toxicity and side effects, better clinical therapeutic effect and more convenient administration mode, so as to provide more drug options for patients. Summary of the Invention

[0006] In this application, the present 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, can enter PTK7-expressing cells via endocytosis with high efficiency, and can be used in the corresponding therapeutic and diagnostic fields, thereby realizing the following invention.

[0007] Antibodies of the Invention In one aspect, the present invention provides a specific PTK7 binding antibody or antigen-binding fragment thereof, 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 as SEQ ID NO: 19, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 20; (b) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 1, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 2; (c) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 3, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 4; (d) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 5, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 6; (e) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 7, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 8; (f) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 9, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 10; (g) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 11, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 12; (h) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 13, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 14; (i) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 15, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 16; (j) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 17, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 18; (k) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 21, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 22; (l) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) shown as SEQ ID NO: 23, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) shown as SEQ ID NO: 24; or (m) CDR-H1, CDR-H2, and CDR-H3 contained in the heavy chain variable region (VH) described below, and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) described below; at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) contains a mutation compared to any one of the heavy chain variable regions (VH) and / or light chain variable regions (VL) of (a) to (l), where mutation refers to the substitution, deletion, or addition of one or several amino acids (e.g., substitution, deletion, or addition of 1, 2, or 3 amino acids), and preferably, the substitution is a conservative substitution.

[0008] In certain embodiments, the substitution is a conservative substitution.

[0009] In certain embodiments, the CDRs are defined according to the IMGT, Kabat, Chothia, or AbM numbering systems.

[0010] In certain embodiments, the PTK7 comprises human PTK7 and / or monkey PTK7. In certain embodiments, the monkey is a rhesus monkey (Macaca mulatta).

[0011] In certain embodiments, the antibodies or antigen-binding fragments thereof of the invention comprise 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: (1a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 27 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 32 or a variant thereof; (1b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 41 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 42 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 46 or a variant thereof; (1c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 55 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 56 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 58 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 59 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; (1d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 68 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 71 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; (1e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 74 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 84 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 85 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 86 or a variant thereof; (1f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 92 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 93 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 95 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 96 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 97 or a variant thereof; (1g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 27 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 106 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 107 or a variant thereof; (1h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 41 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 42 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (1i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 41 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 42 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (1j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 27 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 29 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 32 or a variant thereof; (1k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 55 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 56 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 57 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 58 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 59 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; or (11) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 74 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 71 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; and The variant of any one of (1a) to (1l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0012] In certain embodiments, an antibody or antigen-binding fragment thereof according to 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 as follows: (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 33 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 34 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 32 or a variant thereof; (2b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 33 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 35 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 32 or a variant thereof; (2c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 47 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 49 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (2d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 61 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 62 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 58 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 59 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; (2e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 75 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 76 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 71 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; (2f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 87 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 88 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 84 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 85 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 86 or a variant thereof; (2g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 98 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 99 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 95 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 96 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 97 or a variant thereof; (2h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 108 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 35 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 106 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 107 or a variant thereof; (2i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 47 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 48 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 46 or a variant thereof; (2j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 47 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 48 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (2k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 61 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 62 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 57 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 58 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 59 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; or (21) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 75 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 76 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 70 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 71 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; The variant of any one of (2a) to (2l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived, and in certain embodiments, the substitutions are conservative substitutions.

[0013] In a particular embodiment, an antibody or antigen-binding fragment thereof according to 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 as follows: (3a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 36 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 38 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 39 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 40 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 32 or a variant thereof; (3b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 50 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 51 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 52 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 53 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 54 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (3c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 63 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 64 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 65 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 66 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 67 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; (3d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 77 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 81 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 82 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; (3e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 80 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 89 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 90 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 91 or a variant thereof; CDR-L3 having the sequence shown as SEQ ID NO: 86 or a variant thereof; (3f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 100 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 101 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 102 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 103 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 104 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 97 or a variant thereof; (3g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 36 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 109 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 110 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 40 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 107 or a variant thereof; (3h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 50 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 51 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 52 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 53 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 54 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (3i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 50 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 51 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 52 or a variant thereof; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 53 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 54 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (3j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 36 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 38 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 39 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 40 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 32 or a variant thereof; (3k) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 63 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 64 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 65 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 66 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 67 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; or (31) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 80 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 79 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 81 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 82 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 73 or a variant thereof; The variant of any one of (3a) to (3l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0014] In a particular embodiment, an antibody or antigen-binding fragment thereof according to 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 as follows: (4a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 113 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 32 or a variant thereof; (4b) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 115 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 116 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (4c) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 117 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 118 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 57 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 58 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 59 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; (4d) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 119 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 120 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 71 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; (4e) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 122 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 123 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 83 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 84 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 85 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 86 or a variant thereof; (4f) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 124 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 125 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 94 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 95 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 96 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 97 or a variant thereof; (4g) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 126 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 105 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 106 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 107 or a variant thereof; (4h) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 115 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 116 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (4i) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 115 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 116 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 43 or a variant thereof; or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 44 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 46 or a variant thereof; (4j) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 113 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 29 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 32 or a variant thereof; (4k) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 117 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 118 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 57 or a variant thereof; and a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 58 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 59 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 60 or a variant thereof; or (41) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence set forth as SEQ ID NO: 121 or a variant thereof; CDR-H2 having the sequence set forth as SEQ ID NO: 120 or a variant thereof; and CDR-H3 having the sequence set forth as SEQ ID NO: 70 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence set forth as SEQ ID NO: 71 or a variant thereof; CDR-L2 having the sequence set forth as SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the sequence set forth as SEQ ID NO: 73 or a variant thereof; The variant of any one of (4a) to (4l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0015] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a framework region (FR) derived from a human immunoglobulin.

[0016] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises: (a) a VH having the sequence shown as SEQ ID NO: 19 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 20 or a variant thereof; (b) a VH having the sequence shown as SEQ ID NO: 1 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 2 or a variant thereof; (c) a VH having the sequence shown as SEQ ID NO: 3 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 4 or a variant thereof; (d) a VH having the sequence shown as SEQ ID NO: 5 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 6 or a variant thereof; (e) a VH having the sequence shown as SEQ ID NO: 7 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 8 or a variant thereof; (f) a VH having the sequence shown as SEQ ID NO: 9 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 10 or a variant thereof; (g) a VH having the sequence shown as SEQ ID NO: 11 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 12 or a variant thereof; (h) a VH having the sequence shown as SEQ ID NO: 13 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 14 or a variant thereof; (i) a VH having the sequence shown as SEQ ID NO: 15 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 16 or a variant thereof; (j) a VH having the sequence shown as SEQ ID NO: 17 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 18 or a variant thereof; (k) a VH having the sequence shown as SEQ ID NO: 21 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 22 or a variant thereof; or (l) a VH having the sequence shown as SEQ ID NO: 23 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 24 or a variant thereof; The variants have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which they are derived, or have one or several amino acid substitutions, deletions, or additions (such as 1, 2, 3, 4, or 5 amino acid substitutions, deletions, or additions) with respect to the sequence from which they are derived. In certain embodiments, the substitutions are conservative substitutions.

[0017] In certain embodiments, the antibody or antigen-binding fragment according to any one of the above embodiments further has a feature selected from the following: (1) an EC of less than about 50 ng / mL, for example, 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 6 ng / mL or less 50 and binds to PTK7 (such as human or monkey PTK7) at EC 50 is measured by ELISA); (2) binds to PTK7 (e.g., human or monkey PTK7) with a KD of less than about 100 nM, e.g., 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 measured by biolayer interferometry (BLI) (e.g., ForteBio Octet®)); (3) has ADCC activity and CDC activity (e.g., induces the death of cells expressing PTK7 (such as tumor cells) by ADCC and CDC); and in certain embodiments, the antibody or antigen-binding fragment comprises a wild-type Fc region. In certain embodiments, the antibody or antigen-binding fragment has a heavy chain constant region (CH) set forth as SEQ ID NO: 25. or lacks ADCC and CDC activity; in certain embodiments, the antibody or antigen-binding fragment comprises a mutation-containing Fc region or a chemically modified Fc region. In certain embodiments, the antibody or antigen-binding fragment comprises a heavy chain constant region (CH) set forth as SEQ ID NO: 131. (4) induce PTK7 internalization (measured by flow cytometry, etc.); (5) inhibiting cell proliferation; and / or (6) Inhibiting tumor growth.

[0018] In certain embodiments, the antibody or antigen-binding fragment thereof according to any one of the above embodiments may comprise a constant region from or derived from a human immunoglobulin.

[0019] In certain embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain constant region from or derived from a human immunoglobulin (such as IgG1, IgG2, IgG3, or IgG4). In certain embodiments, the antibody or antigen-binding fragment thereof comprises a wild-type Fc region, or a mutation-containing Fc region or a chemically modified Fc region that has altered effector function (such as improved ADCC activity) compared to the wild-type Fc region. In certain embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises the sequence set forth as SEQ ID NO: 25 or a variant thereof, wherein the variant has up to 20 amino acid replacements (such as 1, 2, 3, 4, or 5 amino acid replacements, such as up to 15, up to 10, or up to 5 amino acid replacements) compared to SEQ ID NO: 25. In certain embodiments, the replacements are conservative replacements.

[0020] In certain embodiments, the variant has three amino acid substitutions compared to SEQ ID NO: 25. In certain embodiments, the variant has amino acid substitutions at positions corresponding to 117, 118, and 120 of SEQ ID NO: 25. In certain embodiments, the variant has alanine substitutions at positions corresponding to 117, 118, and 120 of SEQ ID NO: 25. In certain embodiments, the variant has a heavy chain constant region (CH) shown as SEQ ID NO: 131.

[0021] In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain constant region from or derived from a human immunoglobulin (such as kappa or lambda). In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises the sequence set forth as SEQ ID NO: 26 and variants thereof, wherein the variants have up to 20 amino acid replacements (such as 1, 2, 3, 4 or 5 amino acid replacements, such as up to 15, up to 10 or up to 5 amino acid replacements) compared to SEQ ID NO: 26. In certain embodiments, the replacements are conservative replacements.

[0022] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) set forth as SEQ ID NO:25, and a light chain constant region (CL) set forth as SEQ ID NO:26.

[0023] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain constant region (CL) set forth as SEQ ID NO:26.

[0024] In certain embodiments, the antibody or antigen-binding fragment thereof having a heavy chain constant region is not bound to an Fc receptor (such as CD16a protein, CD32a protein, CD32b protein, and CD64 protein). Therefore, in such embodiments, the antibody or antigen-binding fragment thereof may reduce Fc receptor-mediated nonspecific cytotoxicity and improve the safety of the antibody or antigen-binding fragment thereof in a subject. In certain embodiments, the antibody or antigen-binding fragment thereof having a heavy chain constant region may bind to FcRn. Therefore, in such embodiments, the antibody or antigen-binding fragment thereof has a long half-life in a subject. In certain embodiments, the antibody or antigen-binding fragment thereof having a heavy chain constant region may induce PTK7-mediated endocytosis. Therefore, in such embodiments, the antibody or antigen-binding fragment thereof has potential as a vector for targeted delivery of therapeutic drugs, toxins, enzymes, or DNA.

[0025] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises: (a) a heavy chain comprising a VH set forth as SEQ ID NO: 19 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 20 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (b) a heavy chain comprising a VH set forth as SEQ ID NO: 19 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 20 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (c) a heavy chain comprising a VH set forth as SEQ ID NO: 1 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 2 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (d) a heavy chain comprising a VH set forth as SEQ ID NO: 1 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 2 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (e) a heavy chain comprising a VH set forth as SEQ ID NO: 3 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 4 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (f) a heavy chain comprising a VH set forth as SEQ ID NO: 5 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 6 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (g) a heavy chain comprising a VH set forth as SEQ ID NO: 7 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 8 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (h) a heavy chain comprising a VH set forth as SEQ ID NO: 9 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 10 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (i) a heavy chain comprising a VH set forth as SEQ ID NO: 11 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 12 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (j) a heavy chain comprising a VH set forth as SEQ ID NO: 13 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 14 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (k) a heavy chain comprising a VH set forth as SEQ ID NO: 15 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 16 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (l) a heavy chain comprising a VH set forth as SEQ ID NO: 17 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 18 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (m) a heavy chain comprising a VH set forth as SEQ ID NO: 21 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 22 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (n) a heavy chain comprising a VH set forth as SEQ ID NO: 23 and a heavy chain constant region (CH) set forth as SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 24 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (o) a heavy chain comprising a VH set forth as SEQ ID NO: 3 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 4 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (p) a heavy chain comprising a VH set forth as SEQ ID NO: 5 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 6 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (q) a heavy chain comprising a VH set forth as SEQ ID NO: 7 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 8 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (r) a heavy chain comprising a VH set forth as SEQ ID NO: 9 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 10 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (s) a heavy chain comprising a VH set forth as SEQ ID NO: 11 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 12 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (t) a heavy chain comprising a VH set forth as SEQ ID NO: 13 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 14 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (u) a heavy chain comprising a VH set forth as SEQ ID NO: 15 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 16 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (v) a heavy chain comprising a VH set forth as SEQ ID NO: 17 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 18 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (w) a heavy chain comprising a VH set forth as SEQ ID NO: 21 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 22 and a light chain constant region (CL) set forth as SEQ ID NO: 26; or (x) a heavy chain comprising a VH set forth as SEQ ID NO: 23 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth as SEQ ID NO: 24 and a light chain constant region (CL) set forth as SEQ ID NO: 26.

[0026] In certain embodiments, the antibody or antigen-binding fragment thereof according to the invention is a murine antibody, a chimeric antibody, a humanized antibody or a fully humanized antibody.

[0027] In certain embodiments, the antibody or antigen-binding fragment thereof according to any one of the above embodiments is selected from an scFv, Fab, Fab', (Fab')2, Fab'-SH, an Fv fragment, a disulfide-linked Fv (dsFv), a diabody, a bispecific antibody, and a multispecific antibody.

[0028] induced antibody Antibodies or antigen-binding fragments thereof according to the invention may be derivatized, e.g., the antibody or antigen-binding fragment thereof may be linked to another molecule (e.g., another polypeptide or protein). Typically, derivatization (e.g., marking) of an antibody or antigen-binding fragment thereof does not adversely affect its binding to PTK7 (particularly human PTK7). Thus, antibodies or antigen-binding fragments thereof according to the invention also include such derivatized forms. For example, antibodies or antigen-binding fragments thereof according to the invention may be functionally linked (by chemical coupling, genetic fusion, non-covalent binding, or other methods) to one or more other molecular groups, e.g., another antibody (such as to form a bispecific antibody), a detection reagent, a pharmaceutical reagent, and / or a protein or polypeptide (such as an avidin or polyhistidine tag) that can mediate binding of the antibody or antigen-binding fragment to another molecule.

[0029] As a derivative of an antibody, the conjugate according to the invention comprises an antibody or an antigen-binding fragment thereof and a coupling moiety according to the invention.

[0030] In certain embodiments, the coupling moiety is selected from a detectable marker. A detectable marker according to the present invention can be any substance that can be detected fluorescently, spectrally, photochemically, biochemically, immunologically, electrically, optically or chemically. Such markers are well known in the art, and examples thereof include, but are not limited to, enzymes (such as horseradish peroxidase, alkaline phosphatase, β-galactosidase, urease, and glucose oxidase), radionuclides (e.g., H, I, S, C, or P), fluorescent dyes (such as fluorescein isothiocyanate (FITC), fluorescein, tetramethylrhodamine isothiocyanate (TRITC), phycoerythrin (PE), Texas Red, rhodamine, quantum dots, and cyanine dye derivatives (such as Cy7 and Alexa 750)), acridinium ester compounds, calorimetric markers such as magnetic particles (such as Dynabeads®), gold colloids, colored glass, plastics (such as polystyrene, polypropylene, and latex), and biotin for binding the above-mentioned marker-modified avidin (such as streptavidin). In certain embodiments, such markers may be used for immunological detection (e.g., enzyme-linked immunoassays, radioimmunoassays, fluorescent immunoassays, and chemiluminescent immunoassays). In certain embodiments, the detectable marker is selected from a radioisotope, a fluorescent substance, a luminescent substance, a colored substance, or an enzyme. In certain embodiments, the above-mentioned detectable markers may be linked to the antibody or antigen-binding fragment thereof according to the invention by linkers of different lengths to reduce potential steric hindrance.

[0031] In certain embodiments, the coupling moiety is selected from a therapeutic reagent, which is preferably an anti-tumor reagent such as a cytotoxic reagent, cytokine, toxin or radionuclide.

[0032] In certain embodiments, the coupling moiety is selected from substances that can improve the biological properties of the antibody (e.g., increase serum half-life), such as polyethylene glycol (PEG), chemical groups such as methyl or ethyl, or glycosyl groups.

[0033] As one of the derivatives of antibodies, the multispecific antibody according to the invention comprises an antibody according to the invention or an antigen-binding fragment thereof.

[0034] In a particular embodiment, the multispecific antibody comprises an antibody or antigen-binding fragment thereof according to the invention as a first antigen-binding domain and further comprises at least one second antigen-binding domain directed against another target.

[0035] In certain embodiments, each antigen-binding domain of a multispecific antibody retains its original binding specificity.

[0036] In certain embodiments, the multispecific antibody is a bispecific antibody or a trispecific antibody or a tetraspecific antibody.

[0037] Antibody preparation The antibodies of the present invention can be prepared by various methods known in the art, for example, by recombinant genetic engineering techniques. For example, DNA molecules encoding the heavy and light chain genes of the antibodies of the present invention may be obtained by chemical synthesis or PCR amplification. The obtained DNA molecules are inserted into an expression vector and transfected into host cells. The transfected host cells are then cultured under specific conditions, after which the antibodies of the present invention are expressed.

[0038] Antigen-binding fragments according to the present invention can be obtained by hydrolysis of intact antibody molecules (see Morimoto et al., J. Biochem. Biophys. Methods 24:107-117 (1992) and Brennan et al., Science 229:81 (1985)). Furthermore, these antigen-binding fragments can be produced directly 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 obtained directly from host cells. Fab' fragments can also be chemically coupled to form F(ab')2 fragments (Carter et al., Bio / Technology, 10:163-167 (1992)). Furthermore, Fv, Fab or F(ab')2 fragments can also be isolated directly from recombinant host cell culture. Those skilled in the art will be aware of other techniques for preparing these antigen-binding fragments.

[0039] Thus, in another aspect, the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody or antigen-binding fragment thereof according to the present invention, or the heavy chain variable region and / or light chain variable region thereof. In certain embodiments, the nucleotide sequence can be substituted according to codon degeneracy in the art. In certain embodiments, the nucleotide sequence is codon-optimized.

[0040] In certain embodiments, the isolated nucleic acid molecule comprises a nucleic acid molecule encoding a heavy chain variable region of the antibody and / or a nucleic acid molecule encoding a light chain variable region of the antibody, The nucleic acid molecule encoding the heavy chain variable region of the antibody comprises: (i) the nucleotide sequence set forth as 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 more sequence identity compared to SEQ ID NO: 127, a sequence subject to one or more nucleotide substitutions); or (iii) a degenerate sequence of (i) or (ii); and / or The nucleic acid molecule encoding the light chain variable region of the antibody comprises (iv) the nucleotide sequence set forth as 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 more sequence identity compared to SEQ ID NO: 128, or a sequence subject to one or more nucleotide substitutions), or (vi) a degenerate sequence of (iv) or (v).

[0041] In another aspect, the invention provides a vector (such as a cloning vector or an expression vector) comprising an isolated nucleic acid molecule according to the invention. In certain embodiments, a vector according to the invention is, for example, a plasmid, cosmid, phage, or lentivirus. In certain embodiments, the vector is capable of expressing an antibody or antigen-binding fragment thereof according to the invention in a subject (e.g., a mammal, such as a human).

[0042] In a specific embodiment, a vector comprises a first nucleotide sequence encoding the heavy chain or heavy chain variable region of an antibody or antigen-binding fragment thereof according to the invention and a second nucleotide sequence encoding the light chain or light chain variable region thereof, wherein the first nucleotide sequence and the second nucleotide sequence are in the same or different vectors. When the first nucleotide sequence and the second nucleotide sequence are on different vectors, the vector according to the invention comprises a first vector having the first nucleotide sequence and a second vector having the second nucleotide sequence.

[0043] In certain embodiments, antibodies or antigen-binding fragments thereof according to the invention can be used to construct chimeric antigen receptors (CARs) comprising an extracellular antigen-binding domain (such as an scFv) that specifically binds to PTK7, a transmembrane domain, and one or more intracellular T cell signaling domains. In such embodiments, an isolated nucleic acid molecule according to the invention may comprise a nucleotide sequence encoding a chimeric antigen receptor, wherein the nucleotide sequence encoding the chimeric antigen receptor further comprises a nucleotide sequence encoding an antibody or antigen-binding fragment thereof (such as an scFv) according to the invention. In certain embodiments, an isolated nucleic acid molecule according to the invention encodes a chimeric antigen receptor comprising an antigen-binding fragment (such as an scFv) of an antibody according to the invention.

[0044] In a particular embodiment, the antibodies or antigen-binding fragments thereof according to the present invention can be used to construct chimeric antigen receptor-modified immune cells, which comprise a CAR and immune cells (such as T lymphocytes and NK cells).

[0045] In another aspect, the present invention provides a host cell comprising an isolated nucleic acid molecule according to the invention or a vector according to the invention. The host cell can be a eukaryotic cell (such as a mammalian cell, an insect cell, or a yeast cell) or a prokaryotic cell (such as 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 a specific embodiment, the host cell according to the invention is a mammalian cell, such as a CHO cell (such as CHO-K1, CHO-S, CHO DXB11, ExpiCHO, and CHO DG44).

[0046] In certain embodiments, the host cell according to the present invention may be a chimeric antigen receptor T cell (CAR-T). In such embodiments, the isolated nucleic acid molecule in the host cell may comprise a nucleotide sequence encoding a chimeric antigen receptor, and the nucleotide sequence encoding the chimeric antigen receptor further comprises a nucleotide sequence encoding an antibody or an antigen-binding fragment thereof (such as an scFv) according to the present invention. In certain embodiments, the isolated nucleic acid molecule in the host cell encodes a chimeric antigen receptor comprising an antigen-binding fragment (such as an scFv) of an antibody according to the present invention.

[0047] In another aspect, the invention provides a method for preparing an antibody or antigen-binding fragment thereof according to the invention, the method comprising culturing a host cell according to the invention under conditions permissive for expression of the antibody or antigen-binding fragment thereof, and recovering the antibody or antigen-binding fragment thereof from the cultured host cell culture.

[0048] therapeutic use In another aspect, the present invention provides a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, or multispecific antibody according to the invention, and a pharmaceutically acceptable carrier and / or excipient.

[0049] In a particular embodiment, a pharmaceutical composition according to the invention comprises an antibody or antigen-binding fragment thereof and a pharmaceutically acceptable carrier and / or excipient according to the invention.

[0050] In certain embodiments, the pharmaceutical composition may also contain an additional pharmaceutically active agent. In certain embodiments, the additional pharmaceutically active agent is a drug with anti-tumor activity. In certain embodiments, the additional pharmaceutically active agent is selected from an EGFR inhibitor, a BCR-ABL, FLT3, KIT, or RET inhibitor, a HER2 inhibitor, a HER3 inhibitor, a HER4 inhibitor, an IGFR-1 inhibitor, an mTOR inhibitor, a PI3 kinase inhibitor, a c-met or VEGF inhibitor, a PARP inhibitor, a chemotherapeutic agent, or any combination thereof. In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention and the additional pharmaceutically active agent are provided as separate or mixed components. Thus, the antibody or antigen-binding fragment thereof according to the present invention and the additional pharmaceutically active agent may be administered simultaneously, separately, or sequentially.

[0051] In certain embodiments, the antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, or multispecific antibody in the pharmaceutical composition according to the invention is sufficient to do the following (e.g., in a subject): (a) inhibit cell proliferation; (b) inhibiting tumor growth; (c) inducing and / or improving antibody-dependent cellular cytotoxicity; (d) inhibiting PTK7-mediated signaling; (e) preventing and / or treating a PTK7-mediated disease / disorder; or (f) Any combination of (a) to (e).

[0052] In certain embodiments, the PTK7-mediated disease / disorder is a tumor, such as a tumor that expresses PTK7. In certain embodiments, the tumor is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, breast cancer, ovarian cancer, lung cancer (including small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, and pharyngeal squamous cell carcinoma, or any combination thereof.

[0053] In another aspect, the present invention provides the use of an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition according to the invention in the preparation of a medicament for inhibiting cell proliferation or for preventing and / or treating tumors and / or assisting in tumor therapy.

[0054] In certain embodiments, the drug is used to inhibit the proliferation of cells (such as tumor cells) that express PTK7.

[0055] In another aspect, the invention provides a method of inhibiting cell proliferation, the method comprising contacting a cell with an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody, or pharmaceutical composition according to the invention. In a particular embodiment, the cell is a cell that expresses PTK7, such as a tumor cell.

[0056] In another aspect, the present invention provides a method for preventing and / or treating / or assisting in the treatment of a tumor in a subject, the method comprising administering to a subject in need thereof an effective amount of an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition according to the invention.

[0057] In certain embodiments, the method further comprises administering to the subject a second therapy, wherein the second therapy is selected from surgery, chemotherapy, radiation therapy, immunotherapy, gene therapy, DNA therapy, RNA therapy, nanotherapy, viral therapy, adjuvant therapy, and any combination thereof. In certain embodiments, the second therapy can be administered simultaneously, separately, or sequentially with the above-described method.

[0058] In any one of the above embodiments, the tumor involved by an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition according to the invention can be any tumor type. In a particular embodiment, the tumor involved by an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition according to the invention is a PTK7-positive tumor. In a particular embodiment, the tumor involved by an antibody or antigen-binding fragment thereof, nucleic acid molecule, vector, host cell, conjugate, multispecific antibody or pharmaceutical composition according to the invention is selected from uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, breast cancer, ovarian cancer, lung cancer (such as small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma and lung squamous cell carcinoma), esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer and pharyngeal squamous cell carcinoma, or any combination thereof.

[0059] The antibodies or antigen-binding fragments thereof according to the present invention and pharmaceutical compositions of the present invention can be prepared into any dosage form known in the medical field, such as tablets, pills, suspensions, emulsions, solutions, gels, capsules, powders, granules, elixirs, lozenges, suppositories, injections (including injections, sterile powders for injections, and concentrated solutions for injections), inhalants, and sprays. The preferred dosage form depends on the expected mode of administration and therapeutic use. The pharmaceutical compositions according to the present invention should be sterile and stable under the conditions of manufacture and storage. One preferred dosage form is an injection. Such an injection may be a sterile injection solution. For example, a sterile injection solution can be prepared by the following method: adding the required dose of the antibody according to the present invention to an appropriate solvent, optionally adding other desired ingredients (including, but not limited to, pH adjusters, surfactants, adjuvants, ionic strength enhancers, isotonicity agents, preservatives, diluents, or any combination thereof), followed by filtration sterilization. Furthermore, sterile injectable solutions can be prepared as sterile, lyophilized powders (e.g., by vacuum drying or freeze-drying) for ease of storage and use, which can be dispersed in a suitable vector, e.g., sterile, pyrogen-free water, prior to use.

[0060] Furthermore, the antibodies or antigen-binding fragments thereof according to the invention may be present in pharmaceutical compositions in unit dosage form for ease of administration.

[0061] The antibodies or antigen-binding fragments thereof, and pharmaceutical compositions according to the present invention may be administered by any suitable method known in the art, including, but not limited to, oral, buccal, sublingual, ocular, topical, parenteral, rectal, intrathecal, intraalveolar, inguinal, intravesical, specific site (e.g., powder, ointment, or drops), or intranasal administration. However, for many therapeutic applications, the preferred route / mode of administration is parenteral administration (e.g., intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection). The skilled artisan should understand that the route and / or mode of administration will vary according to the intended purpose. In a preferred embodiment, the antibodies or antigen-binding fragments thereof, and pharmaceutical compositions according to the present invention are administered by intravenous infusion or injection.

[0062] Pharmaceutical compositions according to the present invention may contain a "therapeutically effective amount" or a "prophylactically effective amount" of an antibody or antigen-binding fragment thereof according to the present invention. A "prophylactically effective amount" refers to an amount sufficient to prevent or delay the onset of a disease. A "therapeutically effective amount" refers to an amount sufficient to cure or at least partially prevent a disease and its complications in a patient suffering from the disease. The therapeutically effective amount of an antibody or antigen-binding fragment thereof according to the present invention may vary according to the following factors: the severity of the disease being treated, the overall state of the patient's immune system, the general condition of the patient, such as age, weight, and sex, the mode of drug administration, and other concurrently administered treatments.

[0063] In accordance with the present invention, dosage regimens may be adjusted to achieve the optimum response for the intended purpose (e.g., a therapeutic or prophylactic response). For example, the drug may be administered in a single dose, or the drug may be administered in multiple doses over a period of time, or the dose may be reduced or increased proportionately to the exigencies of treatment.

[0064] According to the present invention, the subject may be a mammal, such as a human.

[0065] Detection Applications The antibodies or antigen-binding fragments according to the invention specifically bind to PTK7 and are capable of detecting the presence or level of PTK7 in a sample.

[0066] Therefore, in another aspect, the present invention provides a kit comprising an antibody or antigen-binding fragment according to the present invention. In a particular embodiment, the antibody or antigen-binding fragment according to the present invention has a detectable marker. In a preferred embodiment, the kit further comprises a secondary antibody for specifically recognizing the antibody or antigen-binding fragment thereof according to the present invention. Preferably, the secondary antibody further comprises a detectable marker.

[0067] According to the present invention, a detectable marker can be any substance that can be detected by fluorescence, spectroscopy, photochemistry, biochemistry, immunology, electricity, light, or chemistry. Particularly preferably, such markers can be used for immunological detection (e.g., enzyme-linked immunoassay, radioimmunoassay, fluorescence immunoassay, and chemiluminescence immunoassay). Such markers are well known in the art, and examples thereof include, but are not limited to, enzymes (such as horseradish peroxidase, alkaline phosphatase, β-galactosidase, urease, and glucose oxidase), radionuclides (e.g., H, I, S, C, or P), fluorescent dyes (such as fluorescein isothiocyanate (FITC), fluorescein, tetramethylrhodamine isothiocyanate (TRITC), phycoerythrin (PE), Texas Red, rhodamine, quantum dots, and cyanine dye derivatives (such as Cy7 and Alexa 750)), acridinium ester compounds, calorimetric markers such as magnetic particles (such as Dynabeads®), gold colloids, colored glass, and plastics (such as polystyrene, polypropylene, and latex), and biotin for binding to the above-mentioned marker-modified avidin (such as streptavidin). In certain embodiments, the detectable markers described above may be linked to the antibodies according to the invention by linkers of different lengths to reduce potential steric hindrance.

[0068] In another aspect, the present invention provides a method for detecting the presence or level of PTK7 in a sample, the method comprising using an antibody or antigen-binding fragment thereof according to the invention. In a preferred embodiment, the antibody or antigen-binding fragment thereof according to the invention further comprises a detectable marker. In another preferred embodiment, the method further comprises detecting the antibody or antigen-binding fragment thereof according to the invention with a reagent comprising a detectable marker. The method may be suitable for diagnostic or non-diagnostic purposes (e.g., the sample is a cell sample rather than a sample from a patient).

[0069] In a particular embodiment, the method comprises contacting the sample with an antibody or antigen-binding fragment thereof according to the invention under conditions that allow the formation of a complex between the antibody or antigen-binding fragment thereof and PTK7, and detecting the formation of the complex.

[0070] Due to the low or no expression of PTK7 in normal tissues, and the high or low expression in some cancers, tumors can be diagnosed by detecting the presence or level of PTK7 in a sample. Thus, in certain embodiments, the method is used to diagnose tumors, such as PTK7-positive tumors, such as uterine cancer, testicular cancer, thyroid cancer, nasopharyngeal carcinoma, glioblastoma, leukemia, lymphoma, colon adenocarcinoma, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, breast cancer, ovarian cancer, lung cancer (such as small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma), esophageal cancer, colorectal cancer, pancreatic cancer, head and neck squamous cell carcinoma, gastric cancer, melanoma, prostate cancer, liver cancer, kidney cancer, bladder cancer, and pharyngeal squamous cell carcinoma, or any combination thereof.

[0071] In certain embodiments, the method includes detecting the expression level of PTK7 in a sample to be detected from a subject and comparing the expression level with a reference value (such as a healthy control), wherein an increase in the expression level compared to the reference value is indicative of a tumor.

[0072] In another aspect, the present invention provides the use of an antibody or antigen-binding fragment thereof according to the present invention, wherein the kit is used for detecting the presence or level of PTK7 in a sample and / or for diagnosing a tumor.

[0073] In another aspect, the present invention provides a diagnostic or therapeutic kit comprising an antibody or antigen-binding fragment thereof, a nucleic acid molecule, a vector, a host cell, a conjugate or a multispecific antibody according to the invention, and instructions for use.

[0074] The antibodies according to the present invention have high binding affinity to PTK7, can induce efficient endocytosis after binding to PTK7-expressing cells, and may have the advantages of good hydrophilicity, better quality and in vivo metabolic properties, and are suitable for coupling. Therefore, the antibodies according to the present invention have the potential to prevent and / or treat tumors. Furthermore, the antibodies according to the present invention are humanized antibodies that can be safely administered to human subjects and reduce the risk of causing an immunogenic response. Therefore, the antibodies according to the present invention have great clinical value. [Brief explanation of the drawings]

[0075] [Figure 1A] ELISA-detected murine antibody binding to human PTK7 protein.

[0076] [Figure 1B] ELISA detection of binding of mouse antibodies to monkey PTK7 protein.

[0077] [Figure 2A] Determination of binding of anti-human PTK7 chimeric and humanized antibodies to H1299 cells.

[0078] [Figure 2B] Measurement of the binding activity of anti-human PTK7 humanized antibodies to human lung adenocarcinoma H1975.

[0079] [Figure 2C] Measurement of the binding activity of anti-human PTK7 humanized antibodies to human breast cancer cells T47D.

[0080] [Figure 2D] Measurement of binding activity of anti-human PTK7 humanized antibodies to CHO-hPTK7 overexpressing cells.

[0081] [Figure 3] Detection of ADCC activity of anti-human PTK7 humanized antibody.

[0082] [Figure 4A] Endocytosis detection of anti-human PTK7 humanized antibody on H1299 cells.

[0083] [Figure 4B] Endocytosis detection of anti-human PTK7 humanized antibody on H1975 cells.

[0084] [Figure 4C] Endocytosis detection of anti-human PTK7 chimeric and humanized antibodies in T47D cells.

[0085] [Figure 4D] Endocytosis detection of anti-human PTK7 humanized antibody against human pharyngeal squamous cell carcinoma cells (FADU).

[0086] [Figure 5] ELISA detection of epitope competitive binding of anti-human PTK7 humanized antibodies.

[0087] [Figure 6A] Flow cytometry of epitope competitive binding of anti-human PTK7 humanized antibodies (designated Hu24, 64A10HZ, and 4E12HZ).

[0088] [Figure 6B] Flow cytometry of epitope competitive binding of anti-human PTK7 humanized antibodies (designated 101A6HZ and 19C12HZ). DETAILED DESCRIPTION OF THE INVENTION

[0089] definition In the present invention, unless otherwise specified, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the operation steps used in the present invention, such as cell culture, biochemistry, nucleic acid chemistry, and immunology laboratory, are all routine processes widely used in the corresponding fields. At the same time, in order to better understand the present invention, the definitions and explanations of relevant terms are provided below.

[0090] As used herein, the term "antibody" is used in the broadest sense and encompasses a variety of antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (such as bispecific antibodies), and antibody fragments, so long as they exhibit the required antigen-binding activity. For example, immunoglobulin molecules can be composed of two pairs of polypeptide chains, each pair having one light chain (LC) and one heavy chain (HC). Antibody light chains can be classified as kappa (κ) and lambda (λ) light chains. Heavy chains can be classified as μ, δ, γ, α, or ε, and antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. In light and heavy chains, the variable and constant regions are connected by a "J" region of about 12 or more amino acids, and heavy chains further include a "D" region of about 3 or more amino acids. Each heavy chain comprises a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region is composed of three domains (CH1, CH2, and CH3). Each light chain contains a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region is composed of the CL domain. The constant domains are not directly involved in the binding between an antibody and an antigen, but exhibit various effector functions, such as mediating the binding of immunoglobulins to various cells of the immune system (such as effector cells) and host tissues or factors, including the first component of the classical complement system (C1q). The VH and VL regions can also be subdivided into highly variable regions (called complementarity-determining regions (CDRs)) interspersed with more conserved regions called framework regions (FRs). Each VH and VL is composed of three CDRs and four FRs, arranged from the amino terminus to the carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions (VH and VL) of each heavy / light chain pair form the antigen-binding site, respectively.The amino acid assignments in each region or domain may follow the definitions 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.

[0091] In the present invention, unless otherwise specified, when the term "antibody" is referred to, it includes not only complete antibodies but also antigen-binding fragments of antibodies.

[0092] As used herein, the term "complementarity-determining region" or "CDR" refers to the amino acid residues responsible for antigen binding in the variable region of an antibody. 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) Modeling 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, one skilled in the art will readily identify the CDRs defined according to each numbering system. Furthermore, the correspondence between different numbering systems is well known to those skilled in the art (see, e.g., Lefranc et al., Dev. Comparat. Immunol. 27:55-77, 2003).

[0093] In the present invention, the CDRs in the antibody or antigen-binding fragment thereof according to the present invention can be determined according to various numbering systems known in the art. In certain embodiments, the CDRs in the antibody or antigen-binding fragment thereof according to the present invention are preferably determined according to the IMGT, Kabat, Chouiia, or AbM numbering system.

[0094] The following general rules, disclosed in www.bioinf.org.uk: Prof. Andrew C. Martin's Group and reproduced below, can be used to define CDRs in an antibody sequence that contain amino acids that interact specifically with amino acids that comprise the epitope in the antigen to which the antibody binds. There are rare instances where these generally consistent features do not occur; however, Cys residues are the most conserved features. [Table 1]

[0095] V H The entire amino acid sequence of V is generally numbered according to Kabat, although the three CDRs within the variable region may be defined according to any one of the aforementioned numbering schemes. H The numbering of amino acid positions in a sequence may start at amino acid position 1 and continue consecutively to the end of the sequence, or may be consecutive according to Kabat. H and V L The amino acid positions within are defined according to consecutive numbering.

[0096] The numbering of amino acid positions in the heavy chain constant domain can start at amino acid position 1 and continue consecutively to the end of the sequence, or can be consecutive according to Eu numbering. The IgG1 heavy chain constant domain amino acid sequence has 330 amino acids numbered consecutively from 1 to 330. The corresponding sequence numbered according to Eu starts at position 118 and ends at position 447. Unless otherwise specified, the amino acid positions in the heavy and light chains herein are defined according to consecutive numbering.

[0097] As used herein, the term "framework region" or "FR" residues refers to those amino acid residues in an antibody variable region other than the CDR residues as defined above.

[0098] The term "antibody" is not limited by any particular method of antibody production. It includes, for example, recombinant antibodies, monoclonal antibodies, and polyclonal antibodies. Antibodies can be of various isotypes, such as IgG (e.g., IgG1, IgG2, IgG3, or IgG4 subtypes), IgA1, IgA2, IgD, IgE, or IgM antibodies.

[0099] As used herein, an "antigen-binding fragment" of an antibody refers to a molecule other than a complete antibody, and includes a portion of the complete antibody that binds to the antigen to which the complete antibody binds. For example, an antigen-binding fragment may be a polypeptide fragment of a full-length antibody that retains the ability to specifically bind to the same antigen bound by the full-length antibody and / or competes with the full-length antibody for specific binding to the antigen, also referred to as an "antigen-binding fragment." In general, the entire text of Fundamental Immunology, Ch. 7 (Paul, W., ed., Version 2, Raven Press, NY (1989) is incorporated herein by reference 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 (such as scFv), chimeric antibodies, diabodies, linear antibodies, nanobodies (Domantis-based technology), domain antibodies (Ablynx-based technology), and similar polypeptides that comprise at least a sufficient portion of an antibody to permit antigen-specific binding ability to the polypeptide. Engineered variants of antibodies are reviewed in Holliger et al., 2005; Nat Biotechnol 23:1126-1136.

[0100] As used herein, the term "full-length antibody" refers to an antibody composed of two "full-length heavy chains" or "heavy chains" and two "full-length light chains" or "light chains." A "full-length heavy chain" or "heavy chain" refers to a polypeptide chain composed, from N- to C-terminal, 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. Furthermore, if the full-length antibody is of the IgE isotype, the full-length antibody optionally further comprises a heavy chain constant region CH4 domain. Preferably, a "full-length heavy chain" refers to a polypeptide chain composed, from N- to C-terminal, of VH, CH1, HR, CH2, and CH3. A "full-length light chain" or "light chain" refers to a polypeptide chain composed, from N- to C-terminal, of a light chain variable region (VL) and a light chain constant region (CL). The two pairs of full-length antibody chains are linked to each other by disulfide bonds between the CL and CH1 and disulfide bonds between the HRs of the two full-length heavy chains. The full-length antibody according to the present invention may be derived from a single species, for example, human. It may also be a chimeric or humanized antibody. The full-length antibody according to the present invention comprises two antigen-binding portions formed by a VH and VL pair, respectively, and the two antigen-binding portions specifically recognize / bind to the same antigen.

[0101] As used herein, the term "Fd fragment" refers to an antibody fragment consisting of the VH domain and the CH1 domain. The term "dAb fragment" refers to an antibody fragment consisting of the VH domain (Ward et al., Nature 341:544-546 (1989)). The term "Fab fragment" refers to an antibody fragment consisting of the VL, VH, CL, and CH1 domains. The term "F(ab')2 fragment" refers to an antibody fragment containing two Fab fragments linked by disulfide bonds in the hinge region. The term "Fab' fragment" refers to a fragment obtained after reducing the disulfide bond linking the two heavy chain fragments in the F(ab')2 fragment, and the resulting fragment consists of the complete Fd fragment (consisting of the VH and CH1 domains) of the light chain and the heavy chain.

[0102] As used herein, the term "Fv fragment" refers to an antibody fragment consisting of the VL and VH domains of a single arm of an antibody. An Fv fragment is generally considered to be the minimum antibody fragment that forms a complete antigen-binding site. It is generally believed that six CDRs confer antigen-binding specificity to the antibody. However, a single variable region (e.g., an Fd fragment containing only three antigen-specific CDRs) can also be used to recognize and bind to the antigen, although the affinity may be lower than that of the complete binding site.

[0103] As used herein, the term "Fc fragment" refers to an antibody fragment formed by linking the second and third constant regions of a first heavy chain of an antibody to the second and third constant regions of a second heavy chain by disulfide bonds. The Fc fragment of an antibody has a variety of different functions, but is not involved in antigen binding.

[0104] As used herein, the term "scFv" refers to a single polypeptide chain comprising a VL and a 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 Plückthun, The Pharmacology of Monoclonal Antibodies, Volume 113, edited by Roseburg and Moore, Springer-Verlag, New York, Pages 269-315 (1994)). Such scFv molecules can have the general structure: NH2-VL-linker-VH-COOH or NH2-VH-linker-VL-COOH. Suitable linkers in the prior art include a repeated GGGGS (SEQ ID NO: 133) amino acid sequence or variants thereof. For example, a linker having the amino acid sequence (GGGGS)4 (SEQ ID NO: 134) can be used, and variants thereof can also be used (Holliger, et al. (1993), Proc. Natl. Acad. Sci. USA 90:6444-6448). Other linkers useful 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 exist between the VL and VH of the scFv.

[0105] As used herein, the term "diabody" means a diabody whose VH and VL domains are expressed on a single polypeptide chain, but which uses a linker that is too short to allow pairing between the two domains on the same chain, thereby allowing pairing with the complementary domains on another chain to produce two antigen-binding moieties (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)).

[0106] Each of the above antibody fragments retains the ability to specifically bind to the same antigen bound by the full-length antibody and / or competes with the full-length antibody for specific binding to the antigen. In the present invention, a person skilled in the art can use known conventional techniques to obtain antigen-binding fragments of antibodies (such as the above-mentioned antibody fragments) from a given antibody (such as an antibody according to the present invention) and specifically screen for the antigen-binding fragments of the antibody in the same way as for the complete antibody.

[0107] As used herein, the term "multispecific antibody" refers to an antibody having a variety of different antigen-binding specificities, including, for example, bispecific antibodies, trispecific antibodies, and tetraspecific antibodies. A "bispecific antibody" refers to an antibody having two different antigen-binding specificities, in which a first antibody (or fragment thereof) and a second antibody (or fragment thereof) or antibody analog form a conjugate via coupling arms using coupling modes including, but not limited to, chemical reaction, gene fusion, and enzymatic catalysis. A "multispecific antibody" includes, for example, trispecific antibodies and tetraspecific antibodies, in which a trispecific antibody is an antibody with three different antigen-binding specificities and a tetraspecific antibody is an antibody with four different antigen-binding specificities.

[0108] As used herein, the terms "monoclonal antibody," "McAb," and "mAb" have the same meaning and are interchangeable for use and refer to an antibody or a fragment of an antibody from a population of highly homologous antibody molecules, i.e., a population of identical antibody molecules in addition to natural variations that may occur spontaneously. McAbs have high specificity for a single epitope on an antigen. Polyclonal antibodies correspond to monoclonal antibodies and generally consist of at least two or more different antibodies, which generally recognize different epitopes on the antigen. Furthermore, the modifier "monoclonal" indicates only that the characteristics of the antibody are obtained from a highly homologous antibody population, and cannot be understood to require any particular method for preparing the antibody.

[0109] As used herein, the term "chimeric antibody" refers to an antibody in which a portion of the light or / and 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 other portions of the light or / and heavy chain are derived from another antibody (which may be derived from the same or a different species or belong to the same or a different antibody class or subclass), but which still retains binding activity for a target antibody. For example, the term "chimeric antibody" can include antibodies in which the heavy and light chain variable regions are derived from a first antibody (as in humanized) and the heavy and light chain variable constant regions are derived from a second antibody (as in murine). For example, an antibody produced by immunizing a human transgenic mouse can be referred to as a chimeric antibody consisting of a human variable region and a murine constant region.

[0110] As used herein, the term "humanized antibody" refers to an antibody prepared by substituting portions of a human antibody with portions of a non-human antibody prepared by immunizing a non-human mammal. Specifically, it is known that humanized antibodies can be prepared by constructing chimeras containing genes encoding human antibody constant regions (Proc. Natl. Acad. Sci. (USA) (1987), vol. 84, pp. 3439-3443, Journal of Immunology (1987), Volume 139, Issue 1, Page 3521). DNA sequences of human constant regions have been described in the prior art, and constant region genes can be easily obtained from known clones. DNA sequences encoding antibody variable regions can then be fused to the human constant region. The isoform of the human constant region can be selected based on the desired effective function or antibody-dependent cellular cytotoxicity. Suitable isoforms are IgG1, IgG3, and IgG4. Either the κ or λ human light chain constant region can be used. Such humanized chimeric antibodies can be expressed by conventional methods.

[0111] As used herein, a "fully humanized antibody (human antibody)" refers to a mouse introduced with a human immunoglobulin constant region gene (Xeno mouse (Chemical Biology (2000), vol. 7, issue 8, pp. R185-6), HuMAb-mouse (Infection and Immunity (2002), vol. 70, issue 2, pp. 612-612), TC mouse (Biotechnology and Genetics Engineering Review (2002), vol. 19, pp. 73-82), and KM mouse (Cloning Stem Cells (2002), vol. 4, issue 1, pp. 91-102)), which can be prepared using a mouse into which a human immunoglobulin constant region gene has been introduced (e.g., a hybridoma). The target antibody can be mass-produced by isolating antibody-producing lymphocytes from the mouse into a hybridoma. This can also be prepared by phage display (FEBS Letter (1998), vol. 441, pp. 20-24). In this method, phages containing human antibody genes integrated into circular single-stranded DNA are used, and fully humanized antibodies can be expressed on the surface of the phage in a form fused with the phage coat protein.

[0112] As used herein, the term "variant" in the context of a polypeptide (including a polypeptide) also refers to a polypeptide or peptide containing an altered amino acid sequence by introducing amino acid residues for replacement, deletion, or addition. In some cases, the term "variant" also refers to a polypeptide or peptide that has been modified (i.e., by covalently attaching any type of molecule to the polypeptide or peptide). For example, but not limited to, a polypeptide can be modified by, for example, glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization with known protecting / blocking groups, proteolytic cleavage, or conjugation to a cellular ligand or other protein. Derived 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, and metabolic synthesis of chlamydomycin. Furthermore, a variant possesses similar, identical, or improved functionality as the polypeptide or peptide from which it is derived.

[0113] As used herein, the term "specific binding" refers to a non-random binding reaction between two molecules, such as the reaction between an antibody and a related antigen. The strength or affinity of a specific binding interaction is determined by the equilibrium dissociation constant (K D ) or half-maximal effective concentration (EC 50 )

[0114] The specific binding properties between two molecules can be determined using methods known in the art. One method involves measuring the rates of formation and dissociation of the antigen-binding site / antigen complex. The "association rate constant" (k a or k on ) and "dissociation rate constant" (k dis or k off ) can be calculated from the concentration and the actual association and dissociation rates (see Malmqvist M, Nature, 1993, 361:186-187). dis / k on The ratio of D(See Davies et al, Annual Rev Biochem, 1990;59:439-473). D , k on and k dis The dissociation constant can be measured using any efficient method. In certain embodiments, the dissociation constant can be measured using bioluminescence interferometry (such as the ForteBio Octet method). Additionally, the dissociation constant can be measured using surface plasmon resonance technology (such as Biacore) or Kinexa.

[0115] As used herein, the term "vector" refers to a nucleic acid delivery tool into which a polynucleotide can be inserted. If the vector allows for the expression of a protein encoded by the inserted polynucleotide, the vector is called an expression vector. A vector can be introduced into a host cell by transformation, transduction, or transfection to allow for the expression of the genetic material elements carried within the host cell. Vectors are well known to those skilled in the art and include, but are not limited to, plasmids, phagemids, coxs plasmids, artificial chromosomes such as yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), or P1-derived artificial chromosomes (PACs), bacteriophages such as λ bacteriophage or M13 bacteriophage, and animal viruses. Animal viruses that can be used as vectors include, but are not limited to, reverse transcriptase viruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpes viruses (such as herpes simplex viruses), poxviruses, baculoviruses, papilloma viruses, and papilloma vacuoles viruses (such as SV40). A vector may contain various elements that control expression, including, but not limited to, promoter sequences, transcription initiation sequences, enhancer sequences, selection elements, and reporter genes. Additionally, a vector may also contain an origin of replication site.

[0116] Expression and cloning vectors contain a nucleic acid sequence that enables the vector to replicate in one or more selected host cells. Typically, this sequence in a cloning vector enables the vector to replicate independently of the host chromosomal DNA and includes an origin of replication or an autonomously replicating sequence. As used herein, the term "expression vector" refers to a vector containing a recombinant polynucleotide, which includes an expression control sequence operatively linked to the nucleotide sequence to be expressed. An expression vector contains sufficient cis-acting elements for expression; other elements for expression can be provided by the host cell or an in vitro expression system. Expression vectors include those known in the art, such as cosmids, plasmids (such as lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses), and viruses.

[0117] As used herein, the term "host cell" refers to cells useful for introducing a vector, including, but not limited to, prokaryotic cells such as E. 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 (such as CHO-K1, CHO-S, CHO DXB11, ExpiCHO, CHO DG44 cells), ExpiCHO cells, HEK293 cells, Expi293 cells, BHK cells, and MDCKII cells.

[0118] As used herein, the term "identity" refers to the sequence match between two polypeptides or two nucleic acids. If a position in two compared sequences is occupied by the same base or amino acid monomer subunit (e.g., if each position in two DNA molecules is occupied by adenine, or each position in two polypeptides is occupied by lysine), the molecules are identical at that position. The "percent identity" between two sequences refers to a function obtained by the formula: number of matched positions common to the two sequences / number of compared positions x 100. For example, if two sequences have six matches out of ten positions, the two sequences have 60% identity. For example, the DNA sequences CTGACT and CAGGTT have a total identity of 50% (three matches out of six positions). Typically, comparisons are performed when two sequences are aligned to achieve maximum identity. Such alignments can be conveniently performed using computer programs such as the Align program (DNAstar, Inc.) described in, for example, Needleman et al. (1970) J. Mol. Biol. 48:443-453. The percentage 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 integrated into the ALIGN program (version 2.0) using a PAM120 weight residue table, a notch length penalty of 12, and a notch penalty of 4. Furthermore, the percentage identity between two amino acid sequences can be determined by the Needleman and Wunsch (J MoI Biol. 48:444-453 (1970)) algorithm in the GAP program integrated into the GCG software package (www.gcg.com) by using a Blossum 62 matrix or a PAM250 matrix and notch weights of 16, 14, 12, 10, 8, 6, or 4 and length weights of 1, 2, 3, 4, 5, or 6.

[0119] As used herein, the term "conservative substitution" refers to an amino acid substitution that does not adversely affect or alter the intended properties of the protein / polypeptide containing the amino acid sequence. For example, conservative substitutions can be introduced by standard techniques known in the art (e.g., site-directed mutagenesis and PCR-mediated mutagenesis). Conservative amino acid substitutions include replacement of an amino acid residue with an amino acid residue having a similar side chain, e.g., replacement with a residue that is physically or functionally similar to the corresponding amino acid residue (e.g., having similar size, shape, charge, chemical properties, including the ability to form covalent or hydrogen bonds). Families of amino acid residues with similar side chains have been defined in the art. These families include amino acids with basic side chains (such as lysine, arginine, and histidine), acidic side chains (such as aspartic acid and glutamic acid), uncharged polar side chains (such as glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, and tryptophan), nonpolar side chains (such as alanine, valine, leucine, isoleucine, proline, phenylalanine, and methionine), β-branched side chains (such as threonine, valine, and isoleucine), and aromatic side chains (such as tyrosine, phenylalanine, tryptophan, and histidine). Accordingly, corresponding amino acid residues are preferably replaced 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).

[0120] The compilation of the 20 conventional amino acids included herein follows conventional usage. See, for example, Immunology-A Synthesis (2nd Edition, E.S. Golub and D.R. 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 interchangeable for use. Also, in the present invention, amino acids are generally represented by one-letter or three-letter abbreviations known in the art. For example, alanine may be represented as A or Ala.

[0121] 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 active ingredient, and is well known in the art (see, e.g., Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995). Examples of suitable carriers and / or excipients include, but are not limited to, pH adjusters, surfactants, adjuvants, ionic strength enhancers, diluents, osmolality maintaining agents, absorption delaying agents, and preservatives. For example, pH adjusters 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, trichlorotert-butyl alcohol, phenol, and sorbic acid. Osmolality-maintaining agents include, but are not limited to, sugars, NaCl, and analogs thereof. Absorption-delaying agents include, but are not limited to, monostearate salts and gelatin. Diluents include, but are not limited to, water, aqueous buffer solutions (such as buffered saline), alcohols, and polyols (such as glycerol). Preservatives include, but are not limited to, various antibacterial and antifungal agents, such as thiomersalate, 2-phenoxyethanol, parabens, trichlorotributyl alcohol, phenol, and sorbic acid. Stabilizers have the meaning commonly understood by those skilled in the art and can stabilize 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, glucan, or glucose), amino acids (such as glutamic acid and glycine), proteins (such as dried whey, albumin, or casein), or their degradation products (such as lactalbumin hydrolysate).

[0122] As used herein, the term "prevention" refers to a method performed to prevent or delay the onset of a disease or disorder or condition (such as a tumor) in a subject. As used herein, the term "treatment" refers to a method performed to obtain a beneficial or desired clinical outcome in a subject (human or animal individual) exhibiting disease symptoms or diagnosed with a disease ("in need thereof"). For purposes of the present invention, beneficial or desired clinical outcomes include, but are not limited to, alleviation of symptoms, whether detectable or undetectable, narrowing of the extent of the disease, stabilization of the disease state (i.e., no longer worsening), delay or delay in the onset of the disease, improvement or palliative care of the disease state, and alleviation (partial or total). Furthermore, "treatment" can also refer to extending survival compared to desired survival (untreated).

[0123] As used herein, the term "subject" refers to a mammal, e.g., a primate mammal such as a human. In certain embodiments, the subject (such as a human) is suffering from or at risk of suffering from a tumor.

[0124] As used herein, the term "effective amount" refers to an amount sufficient to achieve or at least partially achieve a desired effect. For example, a preventatively effective amount for a disease (such as a tumor) refers to an amount sufficient to prevent or delay the onset of the disease (such as a tumor). An effective amount for treating a disease refers to an amount sufficient to cure or at least partially prevent the disease and its complications in a patient suffering from the disease. Determining such effective amounts is entirely within the capabilities of one skilled in the art. For example, an effective amount for therapeutic use depends on the severity of the disease being treated, the overall state of the patient's immune system, the patient's general condition, such as age, weight, and sex, the manner in which the drug is administered, and other treatments administered simultaneously.

[0125] As used herein, the term "effector function" refers to a biological activity of an antibody Fc region (a native-sequence Fc region or an amino acid sequence variant Fc region) that 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), down-regulation of cell surface receptors (such as B cell receptors), B cell activation, cytokine secretion, half-life / clearance of antibody and antigen-antibody complexes, and the like. Methods for altering antibody effector functions are known in the art, for example, by introducing mutations into the Fc region.

[0126] As used herein, the term "antibody-dependent cell-mediated cytotoxicity (ADCC)" refers to a form of cytotoxicity in which Ig binds to the Fc receptors (FcRs) of cytotoxic cells (such as natural killer (NK) cells, neutrophils, or macrophages), allowing these cytotoxic effector cells to specifically bind to antigen-bound target cells and subsequently secrete cytotoxins to kill the target cells.

[0127] As used herein, the term "antibody-mediated internalization" refers to the phenomenon in which an antibody crosses the cell membrane after binding to a cell surface antigen. Internalization includes antibody-mediated receptor (e.g., PTK7) internalization.

[0128] In the present invention, combination therapy includes the use of an anti-PTK7 antibody or antigen-binding fragment thereof according to the present invention in combination with one or more additional active therapeutic agents (such as chemotherapeutic agents) in a second treatment or other prophylactic or therapeutic modality (such as radiation therapy).

[0129] In such combination therapies, the various active agents often have different, complementary mechanisms of action, and the combination therapy can produce synergistic effects. The combination therapy includes a therapeutic agent that affects the immune response (e.g., enhances or activates the response) and a therapeutic agent that affects tumor / cancer cells (e.g., inhibits or kills them). The combination therapy may reduce the likelihood of developing drug-resistant cancer cells. The combination therapy may allow for a reduction in the dose of one or more of the agents to reduce or eliminate adverse effects associated with one or more of the agents. Such combination therapy may have a synergistic therapeutic or preventative effect against the underlying disease, disorder, or condition.

[0130] In the present invention, "combination" includes therapies that can be administered separately, such as therapies that are formulated separately for a single dosage (e.g., may be provided in a kit) and administered together as a single formulation (i.e., "co-formulated"). In certain embodiments, the anti-PTK7 antibodies or antigen-binding fragments thereof according to the invention can be administered sequentially. In other embodiments, the anti-PTK7 antibodies or antigen-binding fragments thereof can be administered simultaneously. The antibodies or antigen-binding fragments thereof according to the invention can be used in any combination with at least one other (active) agent.

[0131] In the present invention, PTK7 positivity is obtained from immunohistochemistry and staining intensity assessment by an expert clinician.

[0132] The terms "cancer" and "tumor" can be used interchangeably and are a major class of diseases characterized by the uncontrolled growth of abnormal cells in vivo. Uncontrolled cell division can lead to the formation of malignant tumors or cells that infiltrate adjacent tissues and can migrate to distant sites in the body via the lymphatic system or bloodstream. Cancer includes benign and malignant cancers as well as dormant tumors or micrometastases. Cancer also includes hematological malignancies.

[0133] The term "hematological malignancies" includes lymphomas, leukemias, myelomas, or lymphoid malignancies, as well as cancers of the spleen and lymph nodes. 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 lymphoma. Hematological malignancies also include leukemias, such as secondary leukemia or acute lymphocytic leukemia. Hematological malignancies also include myelomas (such as multiple myeloma) and other blood and / or B-cell or T-cell associated cancers.

[0134] As used herein, the terms "about" or "approximately," when used in conjunction with a numerical variable, generally mean that the value of the variable is within experimental error (e.g., within a 95% confidence interval of the mean) or within ±10% or more.

[0135] antibody In one aspect, the application provides a specific PTK7 binding antibody or antigen-binding fragment thereof, 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 a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 19; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 20; (b) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 1; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 2; (c) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 3; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 4; (d) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 5; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 6; (e) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 7; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 8; (f) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 9; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 10; (g) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 11; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 12; (h) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 13; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 14; (i) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 15; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 16; (j) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 17; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 18; (k) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 21; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 22; (l) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 23; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 24; or (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); at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) contains a mutation compared to any one of the heavy chain variable region (VH) and / or light chain variable region (VL) of (a) to (l), where mutation refers to the substitution, deletion, or addition of one or several amino acids (e.g., substitution, deletion, or addition of 1, 2, or 3 amino acids), and preferably, the substitution is a conservative substitution.

[0136] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, 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 a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 19; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 20.

[0137] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (b) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 1; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 2.

[0138] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (c) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 3; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 4.

[0139] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (d) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO:5; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO:6.

[0140] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (e) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO:7; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO:8.

[0141] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (f) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 9; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 10.

[0142] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (g) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 11; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 12.

[0143] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (h) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 13; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 14.

[0144] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (i) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 15; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 16.

[0145] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (j) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 17; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 18.

[0146] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (k) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 21; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 22.

[0147] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (1) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) having the amino acid sequence set forth in SEQ ID NO: 23; and / or CDR-L1, CDR-L2, and CDR-L3 contained in a light chain variable region (VL) having the amino acid sequence set forth in SEQ ID NO: 24.

[0148] In one aspect, the present application provides a specific PTK7-binding antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs): (m) CDR-H1, CDR-H2, and CDR-H3 contained in a heavy chain variable region (VH) described in any of (a) to (l), and / or CDR-L1, CDR-L2, and CDR-L3 contained in the light chain variable region (VL) described in (a) to (l), wherein at least one CDR of the heavy chain variable region (VH) and / or light chain variable region (VL) comprises a mutation compared to any one of the heavy chain variable regions (VH) and / or light chain variable regions (VL) of (a) to (l), wherein the mutation refers to the substitution, deletion, or addition of one or several amino acids (e.g., the substitution, deletion, or addition of one, two, or three amino acids), and preferably, the substitution is a conservative substitution.

[0149] In certain embodiments, the substitution is a conservative substitution.

[0150] In certain embodiments, the CDRs are defined according to the IMGT, Kabat, Chothia, or AbM numbering systems.

[0151] In certain embodiments, the PTK7 comprises human PTK7 and / or monkey PTK7. In certain embodiments, the monkey is a rhesus monkey (Macaca mulatta).

[0152] 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: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 56 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 93 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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; (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; (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; (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 (11) 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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; and The variant of any one of (1a) to (1h) and (1l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0153] 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 as follows: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 42 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 56 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 93 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 28 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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; (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; (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; (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 (11) 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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 69 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; and The variant of any one of (1a) to (1h) and (1l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0154] 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 as follows: (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; (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; (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; (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; (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; (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; (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; (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; (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; (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; (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 (11) 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: 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.

[0155] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0156] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0157] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0158] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0159] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0160] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0161] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0162] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0163] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0164] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0165] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0166] In certain embodiments, the antibody or antigen-binding fragment thereof of the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (11) 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: 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.

[0167] In certain embodiments, an antibody or antigen-binding fragment thereof according to 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 as follows: (2a) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the sequence shown as SEQ ID NO: 33 or a variant thereof; CDR-H2 having the sequence shown as SEQ ID NO: 34 or a variant thereof; and CDR-H3 having the sequence shown as SEQ ID NO: 29 or a variant thereof; and / or a light chain variable region (VL) comprising the following three CDRs: CDR-L1 having the sequence shown as SEQ ID NO: 30 or a variant thereof; CDR-L2 having the sequence shown as SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the sequence shown as SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 49 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; or (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 76 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 88 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 99 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 48 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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; (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 (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; The variant of any one of (2a) to (2i) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived, and in certain embodiments, the substitutions are conservative substitutions.

[0168] In a particular embodiment, 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), wherein the CDRs are defined as follows: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 34 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 49 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 62 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; or (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 76 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 88 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 99 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 35 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 48 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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; (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 (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; The variant of any one of (2a) to (2i) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived, and in certain embodiments, the substitutions are conservative substitutions.

[0169] In certain embodiments, an antibody or antigen-binding fragment thereof according to the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined as follows: (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; (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; (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; (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 (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; (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; (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; (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; (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; (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; (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 (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.

[0170] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0171] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0172] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0173] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0174] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0175] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0176] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0177] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0178] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0179] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0180] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0181] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0182] In a particular embodiment, an antibody or antigen-binding fragment thereof according to 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 as follows: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 39 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 53 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 64 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 66 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 67 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 90 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 91 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 101 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 103 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 104 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 110 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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; (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; (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; (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 (31) 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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; The variant of any one of (3a) to (3g) and (3l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0183] In certain embodiments, an antibody or antigen-binding fragment thereof according to the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined as follows: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 39 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 51 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 53 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 54 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 64 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 66 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 67 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; or (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 90 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 91 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 101 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 103 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 104 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 37 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 110 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 40 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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; (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; (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; (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 (31) 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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 78 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 81 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 82 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; The variant of any one of (3a) to (3g) and (3l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0184] In certain embodiments, an antibody or antigen-binding fragment thereof according to the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined as follows: (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; (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; (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; (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; (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; (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; (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; (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; (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; (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; (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 (31) 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: 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.

[0185] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0186] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0187] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0188] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0189] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0190] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0191] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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 / 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: 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.

[0192] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0193] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0194] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0195] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0196] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (31) 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: 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.

[0197] In a particular embodiment, an antibody or antigen-binding fragment thereof according to 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 as follows: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 118 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; or (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 123 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 125 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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; (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; (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; (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 (41) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 121 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; The variant of any one of (4a) to (4g) and (4l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0198] In certain embodiments, an antibody or antigen-binding fragment thereof according to the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined as follows: (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 30 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; and CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 32 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 116 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 44 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 45 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 46 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 118 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 58 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 59 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 60 or a variant thereof; or (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 123 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 84 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 85 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 86 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 125 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 95 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 96 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 97 or a variant thereof; (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 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 114 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 106 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 31 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 107 or a variant thereof; (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; (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; (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; (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 (41) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 121 or a variant thereof; CDR-H2 having the amino acid sequence set forth in SEQ ID NO: 120 or a variant thereof; and CDR-H3 having the amino acid sequence 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 the amino acid sequence set forth in SEQ ID NO: 71 or a variant thereof; CDR-L2 having the amino acid sequence set forth in SEQ ID NO: 72 or a variant thereof; CDR-L3 having the amino acid sequence set forth in SEQ ID NO: 73 or a variant thereof; The variant of any one of (4a) to (4g) and (4l) has one or several amino acid substitutions, deletions, or additions (e.g., one, two, or three amino acid substitutions, deletions, or additions) compared to the sequence from which the variant is derived. In a specific embodiment, the substitutions are conservative substitutions.

[0199] In certain embodiments, an antibody or antigen-binding fragment thereof according to the invention comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein the CDRs are defined as follows: (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; (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; (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; (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; (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; (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; (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; (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; (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; (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; (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 (41) A heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 121; 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.

[0200] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0201] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0202] In a specific embodiment, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0203] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0204] In a specific embodiment, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0205] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0206] In certain embodiments, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0207] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0208] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0209] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0210] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (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.

[0211] In certain embodiments, the antibody or antigen-binding fragment thereof according to the present invention comprises the following heavy chain variable region (VH) and / or light chain variable region (VL), and CDRs: (41) a heavy chain variable region (VH) comprising the following three CDRs: CDR-H1 having the amino acid sequence set forth in SEQ ID NO: 121; 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.

[0212] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a framework region (FR) derived from a human immunoglobulin.

[0213] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises: (a) a VH having the sequence shown as SEQ ID NO: 19 or a variant thereof and / or a VL having the sequence shown as SEQ ID NO: 20 or a variant thereof; (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; (c) a VH having the amino acid sequence shown in SEQ ID NO: 3 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 4 or a variant thereof; (d) a VH having the amino acid sequence set forth in SEQ ID NO: 5 or a variant thereof and / or a VL having the amino acid sequence set forth in SEQ ID NO: 6 or a variant thereof; (e) a VH having the amino acid sequence shown in SEQ ID NO: 7 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 8 or a variant thereof; (f) a VH having the amino acid sequence set forth in SEQ ID NO: 9 or a variant thereof and / or a VL having the amino acid sequence set forth in SEQ ID NO: 10 or a variant thereof; (g) a VH having the amino acid sequence shown in SEQ ID NO: 11 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 12 or a variant thereof; (h) a VH having the amino acid sequence shown in SEQ ID NO: 13 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 14 or a variant thereof; (i) a VH having the amino acid sequence shown in SEQ ID NO: 15 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 16 or a variant thereof; (j) a VH having the amino acid sequence shown in SEQ ID NO: 17 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 18 or a variant thereof; (k) a VH having the amino acid sequence shown in SEQ ID NO: 21 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 22 or a variant thereof; or (l) a VH having the amino acid sequence shown in SEQ ID NO: 23 or a variant thereof and / or a VL having the amino acid sequence shown in SEQ ID NO: 24 or a variant thereof; The variants have at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence from which they are derived, or have one or several amino acid substitutions, deletions, or additions (e.g., 1, 2, 3, 4, or 5 amino acid substitutions, deletions, or additions) with respect to the sequence from which they are derived. In certain embodiments, the substitutions are conservative substitutions. In certain embodiments, the variants in (a) to (l) have mutations in the antibody framework regions of the sequence from which they are derived. In certain embodiments, the variants have one or several amino acid substitutions, deletions, or additions (e.g., 1, 2, 3, 4, or 5 amino acid substitutions, deletions, or additions) in the antibody framework regions of the sequence from which they are derived. In certain embodiments, the variant is a substitution of one or several amino acids in the antibody framework region of the sequence from which the variant is derived, hi certain embodiments, the substitution is a conservative substitution in the antibody framework region of the sequence from which the variant is derived.

[0214] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises: (a) a VH having the amino acid sequence set forth in SEQ ID NO: 19 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 20; (b) a VH having the amino acid sequence set forth in SEQ ID NO: 1 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 2; (c) a VH having the amino acid sequence set forth in SEQ ID NO: 3 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 4; (d) a VH having the amino acid sequence set forth in SEQ ID NO: 5 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 6; (e) a VH having the amino acid sequence set forth in SEQ ID NO: 7 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 8; (f) a VH having the amino acid sequence set forth in SEQ ID NO: 9 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 10; (g) a VH having the amino acid sequence set forth in SEQ ID NO: 11 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 12; (h) a VH having the amino acid sequence set forth in SEQ ID NO: 13 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 14; (i) a VH having the amino acid sequence set forth in SEQ ID NO: 15 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 16; (j) a VH having the amino acid sequence set forth in SEQ ID NO: 17 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 18; (k) a VH having the amino acid sequence set forth in SEQ ID NO: 21 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 22; (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.

[0215] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (j) a VH having the amino acid sequence set forth in SEQ ID NO: 19 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 20.

[0216] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (b) a VH having the amino acid sequence set forth in SEQ ID NO:1 and / or a VL having the amino acid sequence set forth in SEQ ID NO:2.

[0217] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (c) a VH having the amino acid sequence set forth in SEQ ID NO:3 and / or a VL having the amino acid sequence set forth in SEQ ID NO:4.

[0218] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (d) a VH having the amino acid sequence set forth in SEQ ID NO:5 and / or a VL having the amino acid sequence set forth in SEQ ID NO:6.

[0219] In a specific embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (e) a VH having the amino acid sequence set forth in SEQ ID NO:7 and / or a VL having the amino acid sequence set forth in SEQ ID NO:8.

[0220] In a specific embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (f) a VH having the amino acid sequence set forth in SEQ ID NO:9 and / or a VL having the amino acid sequence set forth in SEQ ID NO:10.

[0221] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (g) a VH having the amino acid sequence set forth in SEQ ID NO:11 and / or a VL having the amino acid sequence set forth in SEQ ID NO:12.

[0222] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (h) a VH having the amino acid sequence set forth in SEQ ID NO: 13 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 14.

[0223] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (i) a VH having the amino acid sequence set forth in SEQ ID NO: 15 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 16.

[0224] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (j) a VH having the amino acid sequence set forth in SEQ ID NO: 17 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 18.

[0225] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (k) a VH having the amino acid sequence set forth in SEQ ID NO: 21 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 22.

[0226] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises (l) a VH having the amino acid sequence set forth in SEQ ID NO: 23 and / or a VL having the amino acid sequence set forth in SEQ ID NO: 24.

[0227] In certain embodiments, the antibody or antigen-binding fragment according to any one of the above embodiments further has a feature selected from the following: (1) Less than about 50ng / mL, such as about 40ng / mL, 30ng / mL, 25ng / mL, 24ng / mL, 23ng / mL, 22ng / mL, 21ng / mL, 20ng / mL, 19ng / mL, 18ng / mL , 17ng / mL, 16ng / mL, 15ng / mL, 14ng / mL, 13ng / mL, 12ng / mL, 11ng / mL, 10ng / mL, 9ng / mL, 8ng / mL, 7ng / mL, EC below 6ng / mL 50 and binds to PTK7 (such as human or monkey PTK7) at EC 50 is measured by ELISA); (2) binds to PTK7 (e.g., human or monkey PTK7) with a KD of less than about 100 nM, e.g., 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 measured by biolayer interferometry (BLI) (e.g., ForteBio Octet®)); (3) has ADCC activity and CDC activity (e.g., induces the death of cells expressing PTK7 (such as tumor cells) by ADCC and CDC); and 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 the amino acid sequence set forth in SEQ ID NO: 25. or lacks ADCC activity and CDC activity; in certain embodiments, the antibody or antigen-binding fragment comprises a mutation-containing Fc region or a chemically modified Fc region. In certain embodiments, the antibody or antigen-binding fragment comprises a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131. (4) induce PTK7 internalization (measured by flow cytometry, etc.); (5) inhibiting cell proliferation; and / or (6) Inhibiting tumor growth.

[0228] In certain embodiments, the antibody or antigen-binding fragment thereof according to any one of the above embodiments may comprise a constant region from or derived from a human immunoglobulin.

[0229] In certain embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises a heavy chain constant region from or derived from a human immunoglobulin (such as IgG1, IgG2, IgG3, or IgG4). In certain embodiments, the antibody or antigen-binding fragment thereof comprises a wild-type Fc region, or a mutation-containing Fc region or a chemically modified Fc region that has altered effector function (such as improved ADCC activity) compared to the wild-type Fc region. In certain embodiments, the heavy chain of the antibody or antigen-binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 25 or a variant thereof, wherein the variant has up to 20 amino acid replacements (such as 1, 2, 3, 4, or 5 amino acid replacements, such as up to 15, up to 10, or up to 5 amino acid replacements) compared to the amino acid sequence set forth in SEQ ID NO: 25. In certain embodiments, the replacements are conservative replacements.

[0230] In a particular embodiment, the heavy chain of the antibody or antigen-binding fragment thereof comprises the sequence shown in SEQ ID NO:25.

[0231] In certain embodiments, the variant comprises three amino acid substitutions compared to the amino acid sequence set forth in SEQ ID NO: 25. In certain embodiments, the variant comprises amino acid substitutions at positions corresponding to 117, 118, and 120 of the amino acid sequence set forth in SEQ ID NO: 25. In certain embodiments, the variant comprises alanine substitutions at positions corresponding to 117, 118, and 120 of the amino acid sequence set forth in SEQ ID NO: 25. In certain embodiments, the variant comprises a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131.

[0232] In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises a light chain constant region from or derived from a human immunoglobulin (such as kappa or lambda). In certain embodiments, the light chain of the antibody or antigen-binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 26, and variants thereof, wherein the variants have up to 20 amino acid replacements (such as 1, 2, 3, 4, or 5 amino acid replacements, such as up to 15, up to 10, or up to 5 amino acid replacements) compared to the amino acid sequence set forth in SEQ ID NO: 26. In certain embodiments, the replacements are conservative replacements.

[0233] In a particular embodiment, the light chain of the antibody or antigen-binding fragment thereof comprises the sequence set forth in SEQ ID NO:26.

[0234] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:25 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0235] In certain embodiments, the antibody or antigen-binding fragment thereof comprises a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0236] In certain embodiments, the antibody or antigen-binding fragment thereof having a heavy chain constant region is not bound to an Fc receptor (such as CD16a protein, CD32a protein, CD32b protein, and CD64 protein). Therefore, in such embodiments, the antibody or antigen-binding fragment thereof may reduce Fc receptor-mediated nonspecific cytotoxicity and improve the safety of the antibody or antigen-binding fragment thereof in a subject. In certain embodiments, the antibody or antigen-binding fragment thereof having a heavy chain constant region may bind to FcRn. Therefore, in such embodiments, the antibody or antigen-binding fragment thereof has a long half-life in a subject. In certain embodiments, the antibody or antigen-binding fragment thereof having a heavy chain constant region may induce PTK7-mediated endocytosis. Therefore, in such embodiments, the antibody or antigen-binding fragment thereof has potential as a vector for targeted delivery of therapeutic drugs, toxins, enzymes, or DNA.

[0237] In a particular embodiment, the antibody or antigen-binding fragment thereof according to the invention comprises: (a) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (b) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (c) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (d) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (e) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 3 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 4 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (f) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 5 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 6 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (g) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 7 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 8 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (h) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 10 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (i) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (j) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (k) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (l) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (m) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 21 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 22 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (n) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 23 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 24 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (o) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 3 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 4 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (p) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 5 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 6 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (q) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 7 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 8 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (r) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 9 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 10 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (s) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (t) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (u) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (v) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; (w) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 21 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 22 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26; or (x) A heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 23 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 24 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0238] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (a) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0239] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (b) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 19 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 20 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0240] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (c) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0241] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (d) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 1 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 2 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0242] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (e) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 3 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 4 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0243] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (f) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO:5 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO:6 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0244] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (g) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO:7 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO:8 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0245] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (h) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO:9 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO:10 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0246] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (i) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0247] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (j) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0248] In a specific embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (k) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0249] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (l) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 17 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 18 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0250] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (m) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 21 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 22 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0251] In certain embodiments, an antibody or antigen-binding fragment thereof according to the invention comprises (n) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 23 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 24 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0252] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (o) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 3 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 4 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0253] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (p) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO:5 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO:6 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0254] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (q) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO:7 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO:8 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0255] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (r) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO:9 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO:131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO:10 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO:26.

[0256] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (s) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 12 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0257] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (t) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 13 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 14 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0258] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (u) a heavy chain comprising a VH having the amino acid sequence set forth in SEQ ID NO: 15 and a heavy chain constant region (CH) having the amino acid sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the amino acid sequence set forth in SEQ ID NO: 16 and a light chain constant region (CL) having the amino acid sequence set forth in SEQ ID NO: 26.

[0259] In a particular embodiment, an antibody or antigen-binding fragment thereof according to the invention comprises (v) a heavy chain...

Claims

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

1. A specific PTK7 binding antibody or antigen-binding fragment thereof comprising:

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

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

5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, further comprising 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 a 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 a mutation-containing Fc region or a chemically modified Fc region that has an 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 a 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) set forth as SEQ ID NO: 25 or a variant thereof, wherein the variant comprises up to 20 amino acid substitutions compared to SEQ ID NO:

25.

10. The antibody or antigen-binding fragment thereof of claim 9, wherein the mutant has three amino acid substitutions compared to SEQ ID NO:

25.

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

25.

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

25.

13. The antibody or antigen-binding fragment thereof of claim 9, wherein the variant has a heavy chain constant region (CH) shown as 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) set forth as SEQ ID NO: 26 or a variant thereof, wherein the variant comprises up to 20 amino acid replacements 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) shown as SEQ ID NO: 25 or 131, and a light chain constant region (CL) shown as SEQ ID NO:

26.

16. (1) a heavy chain comprising a VH set forth as SEQ ID NO: 19 and a heavy chain constant region (CH) set forth as SEQ ID NO: 131, and a VL having the sequence set forth as SEQ ID NO: 20 and a light chain constant region (CL) set forth as SEQ ID NO: 26; (2) a heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 19 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 20 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (3) a heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 1 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 2 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (4) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 1 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 2 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (5) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 3 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 4 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (6) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 5 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 6 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (7) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 7 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 8 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (8) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 9 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 10 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (9) A heavy chain comprising a VH represented by SEQ ID NO: 11 and a heavy chain constant region (CH) represented by SEQ ID NO: 25, and a VL having the sequence represented by SEQ ID NO: 12) and a light chain constant region (CL) represented by SEQ ID NO: 26; (10) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 13 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 14 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (11) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 15 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 16 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (12) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 17 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 18 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (13) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 21 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 22 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (14) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 23 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 25, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 24 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (15) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 3 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 4 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (16) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 5 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 6 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (17) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 7 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 8 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (18) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 9 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 10 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (19) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 11 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 12 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (20) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 13 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 14 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (21) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 15 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 16 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (22) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 17 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 18 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; (23) A heavy chain comprising a VH having the sequence set forth in SEQ ID NO: 21 and a heavy chain constant region (CH) having the sequence set forth in SEQ ID NO: 131, and a light chain comprising a VL having the sequence set forth in SEQ ID NO: 22 and a light chain constant region (CL) having the sequence set forth in SEQ ID NO: 26; or (24) A heavy chain comprising a VH having the sequence shown as SEQ ID NO: 23 and a heavy chain constant region (CH) having the sequence shown as SEQ ID NO: 131, and a light chain comprising a VL having the sequence shown as SEQ ID NO: 24 and a light chain constant region (CL) having the sequence shown as SEQ ID NO:

26. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 15, comprising:

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 pyroglutamate or pyroglutamic acid.

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

19. The antibody or antigen-binding fragment thereof of claim 1, comprising a VH having the amino acid sequence set forth in SEQ ID NO: 19, in which the N-terminal glutamic acid is cyclized to pyroglutamate or pyroglutamic acid, and a VL having the amino acid sequence set forth in SEQ ID NO:

20.

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

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

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

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 an scFv, Fab, Fab', Fab'-SH, (Fab')2, Fv fragment, disulfide-linked Fv (dsFv), diabody, bispecific antibody, and multispecific antibody.

24. 24. The antibody or antigen-binding fragment thereof of any one of claims 1 to 23, wherein the antibody or antigen-binding fragment thereof is provided with a labeled detectable marker selected from an enzyme, a radionuclide, a fluorescent dye, a luminescent substance and biotin.

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

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

27. a nucleic acid molecule encoding a heavy chain variable region of the antibody and / or a nucleic acid molecule encoding a light chain variable region of the antibody, 27. The isolated nucleic acid molecule of claim 26, wherein the nucleic acid molecule encoding the heavy chain variable region of the antibody comprises (i) the nucleotide sequence set forth as 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 light chain variable region of the antibody comprises (iv) the nucleotide sequence set forth as SEQ ID NO: 128, (v) a sequence substantially identical to SEQ ID NO: 128, or (vi) a degenerate sequence of (iv) or (v).

28. a nucleic acid molecule encoding a heavy chain of the antibody and / or a nucleic acid molecule encoding a light chain of the antibody, 28. The isolated nucleic acid molecule of claim 26 or 27, wherein the nucleic acid molecule encoding the heavy chain of the antibody comprises (i) the nucleotide sequence set forth as 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 the nucleic acid molecule encoding the light chain of the antibody comprises (iv) the nucleotide sequence set forth as SEQ ID NO: 130, (v) a sequence substantially identical to SEQ ID NO: 130, or (vi) a degenerate sequence of (iv) or (v).

29. a nucleic acid molecule encoding the heavy chain of the antibody and / or a nucleic acid molecule encoding the light chain of the antibody, 28. The isolated nucleic acid molecule of claim 26 or 27, wherein a nucleic acid molecule encoding the heavy chain of the antibody comprises (i) the nucleotide sequence set forth as 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 the light chain of the antibody comprises (iv) the nucleotide sequence set forth as SEQ ID NO: 130, (v) a sequence substantially identical to SEQ ID NO: 130, or (vi) a degenerate sequence of (iv) or (v).

30. 30. A vector comprising the nucleic acid molecule of claim 27, 28 or 29.

31. 31. The vector of claim 30, wherein the vector is a cloning vector or an expression vector.

32. 32. A host cell comprising a nucleic acid molecule according to claim 27, 28 or 29, or a vector according to claim 30 or 31.

33. 36. A method for preparing the antibody or antigen-binding fragment thereof of any one of claims 1 to 25, comprising culturing the host cell of claim 32 under conditions permissive for 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. 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 coupling moiety linked thereto.

36. 36. The conjugate of claim 35, wherein the coupling moiety is selected from a detectable marker and a therapeutic reagent.

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

38. 38. The multispecific antibody of claim 37, wherein the multispecific antibody comprises an 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 another target.

39. 39. The multispecific antibody of 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. 41. A pharmaceutical composition comprising 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 of claim 37, 38 or 39, or the chimeric antigen receptor according to claim 40 or a host cell expressing said chimeric antigen receptor, and a pharmaceutically acceptable carrier and / or excipient.

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

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

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

45. 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. 46. ​​A diagnostic or therapeutic kit comprising 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 said chimeric antigen receptor, or the pharmaceutical composition according to any one of claims 41 to 45, and optionally instructions for use.

47. 46. ​​Use of the antibody or antigen-binding fragment thereof according to 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 claim 37, 38 or 39, or the chimeric antigen receptor of claim 40 or a host cell expressing said chimeric antigen receptor, or the pharmaceutical composition of any one of claims 41 to 45, in a medicament for inhibiting cell proliferation, or for preventing and / or treating tumors, or for aiding in tumor therapy.

48. 48. The use according to claim 47, wherein the antibody or antigen-binding fragment thereof, the isolated nucleic acid molecule, the vector, the host cell, the conjugate, the multispecific antibody or the pharmaceutical composition is administered in combination with an additional pharmaceutically active agent by simultaneous, separate or sequential administration.

49. 49. The use of claim 48, wherein the additional pharmaceutically active agent is a drug with antitumor activity.

50. 50. The use of claim 49, wherein the additional pharmaceutically active agent is selected from an EGFR inhibitor, a BCR-ABL, FLT3, KIT or RET inhibitor, a HER2 inhibitor, a HER3 inhibitor, a HER4 inhibitor, an IGFR-1 inhibitor, an mTOR inhibitor, a PI3 kinase inhibitor, a c-met or VEGF inhibitor, a PARP inhibitor, a chemotherapeutic agent, 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. 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, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, 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 and pharyngeal squamous cell carcinoma, or any combination thereof.

53. 46. ​​A method for inhibiting cell proliferation, comprising contacting said cell with the antibody or antigen-binding fragment thereof according to 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 claim 37, 38 or 39, or the chimeric antigen receptor of claim 40 or a host cell expressing said chimeric antigen receptor, or the pharmaceutical composition of any one of claims 41 to 45.

54. 54. The method of claim 53, wherein the cell is a cell that expresses PTK7.

55. 55. The method of claim 54, wherein the cell is a tumor cell.

56. 46. ​​A method for preventing and / or treating and / or assisting in the treatment of a tumor in a subject, comprising administering to said subject in need thereof 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 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 claim 37, 38 or 39, or the chimeric antigen receptor of claim 40 or a host cell expressing said chimeric antigen receptor, or the pharmaceutical composition of any one of claims 41 to 45.

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

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

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

60. 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, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, 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, and pharyngeal squamous cell carcinoma, or any combination thereof.

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

62. 62. The method of claim 61, wherein the method is used to diagnose a PTK7-positive tumor.

63. 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, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, 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, and pharyngeal squamous cell carcinoma, or any combination thereof.

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

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

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

67. 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, cerebral glioblastoma, hepatic cholangiocarcinoma, osteosarcoma, esophageal squamous cell carcinoma, intrahepatic cholangiocarcinoma, 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 and pharyngeal squamous cell carcinoma, or any combination thereof.

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