Antibodies and their use

Abstract

This disclosure relates to anti-PTK7 (protein tyrosine kinase 7) antibodies, their antigen-binding fragments, and antibody-drug conjugates (ADCs) derived therefrom, anti-TROP2 (trophoblast cell surface antigen 2) antibodies, their antigen-binding fragments, and antibody-drug conjugates (ADCs) derived therefrom, and anti-PTK7 / TROP2 (e.g., multispecific or bispecific) antibodies or their antigen-binding fragments, and antibody-drug conjugates (ADCs) derived therefrom, and their uses.

Description

Technical Field

[0001] Claim of Priority This application claims priority to PCT / CN2023 / 083324 filed on March 23, 2023, PCT / CN2023 / 113943 filed on August 21, 2023, and PCT / CN2023 / 125451 filed on October 19, 2023. The entire contents of the above applications are incorporated herein by reference.

[0002] Technical Field The present disclosure relates to antibodies, antigen-binding fragments thereof, and antibody-drug conjugates (ADCs) derived therefrom.

Background Art

[0003] Cancer is currently one of the diseases with the highest mortality rate in humans. According to the statistical data of the World Health Organization, in 2012, the number of cancer cases and deaths worldwide reached 14 million and 8.2 million respectively. In China, the number of newly diagnosed cancer cases is 3.07 million, and the number of deaths is 2.2 million. Due to the recent clinical and commercial success of anti-cancer antibodies, great interest has been shown in antibody-based therapies.

[0004] There is a need to develop antibodies for use in various antibody-based therapies for treating cancer.

Summary of the Invention

[0005] The present disclosure relates to anti-PTK7 antibodies, anti-TROP2 antibodies, and / or anti-PTK7 / TROP2 antibodies, antigen-binding fragments thereof, and their uses.

[0006] In one aspect, the present disclosure is an antibody or an antigen-binding fragment thereof that binds to PTK7 (protein tyrosine kinase 7), A heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR1, the VH CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR2, and the VH CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR3, and A light chain variable region (VL) comprising CDR1, 2, and 3, wherein the VL CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR1, the VL CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR2, and the VL CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR3. The amino acid sequences of the above-selected VH CDR1, 2, and 3, and the amino acid sequences of the above-selected VL CDR1, 2, and 3, relate to an antibody or its antigen-binding fragment, which is one of the following. (1) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 4 to 6, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (2) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 7 to 9, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 10 to 12, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 16-18, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (6) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 19 to 21, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (7) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (8) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 25-27, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (9) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 28-30, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (10) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 31 to 33, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (11) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 34-36, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (12) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 37-39, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (13) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (14) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (15) The amino acid sequences of the above-selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 86-88, respectively, and the amino acid sequences of the above-selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively, and (16) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 89 to 91, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0007] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 4 to 6, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

[0008] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 7 to 9, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

[0009] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 10 to 12, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

[0010] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 13 to 15, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

[0011] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 16-18, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1-3, respectively.

[0012] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 19 to 21, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

[0013] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 22 to 24, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0014] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 86 to 88, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0015] In some embodiments, based on Chothia's definition, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 25 to 27, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0016] In some embodiments, based on the definition of Chothia, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 28 to 30, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0017] In some embodiments, based on the definition of Chothia, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 31 to 33, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0018] In some embodiments, based on the definition of Chothia, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 34 to 36, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0019] In some embodiments, based on Chothia's definition, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 37 to 39, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0020] In some embodiments, based on Chothia's definition, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 40 to 42, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0021] In some embodiments, based on the definition of Chothia, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 43 to 45, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0022] In some embodiments, based on Chothia's definition, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 89 to 91, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0023] In some embodiments, the antibody or its antigen-binding fragment specifically binds to human PTK7, monkey PTK7, or canine PTK7.

[0024] In some embodiments, the antibody or its antigen-binding fragment is a human antibody or its antigen-binding fragment, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

[0025] In some embodiments, the antibody or its antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

[0026] In one embodiment, the disclosure relates to nucleic acids comprising polynucleotides that encode a polypeptide including the following: (1) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 4 to 6, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (2) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 25 to 27, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (3) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which, when the VL forms a pair with a VH containing the respective amino acid sequences shown in SEQ ID NO: 46, binds to PTK7. (4) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 7 to 9, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (5) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 28 to 30, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (6) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which, when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 47, binds to PTK7. (7) An immunoglobulin heavy chain or fragment thereof comprising a VH containing complementarity-determining regions (CDRs) 1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 10 to 12, wherein the VH forms a pair with a light chain variable region (VL) each containing the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (8) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 31 to 33, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (9) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NOs. 48, and binds to PTK7. (10) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 13 to 15, wherein the VH forms a pair with a light chain variable region (VL) comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (11) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 34 to 36, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (12) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 49, and binds to PTK7. (13) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 16 to 18, wherein the VH forms a pair with a light chain variable region (VL) comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (14) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 37 to 39, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (15) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NOs. 50, and binds to PTK7. (16) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 19 to 21, wherein the VH forms a pair with a light chain variable region (VL) comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (17) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 40 to 42, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (18) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NOs. 51, and binds to PTK7. (19) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 22 to 24, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (20) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 43 to 45, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (21) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 1 to 3, wherein the VL binds to PTK7 when paired with a VH containing the amino acid sequences shown in SEQ ID NOs. 52. (22) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 86 to 88, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (23) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 89 to 91, wherein the VH forms a pair with a light chain variable region (VL) each containing the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (24) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each VL binds to PTK7 when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 92.

[0027] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, which comprises a VL containing an immunoglobulin light chain or fragment thereof, which comprises CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

[0028] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin heavy chain or fragment thereof, and a VH comprising CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 4-6, respectively.

[0029] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, which comprises an immunoglobulin heavy chain or fragment thereof, and includes a VH comprising CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 7 to 9.

[0030] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 10 to 12.

[0031] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 13-15, respectively.

[0032] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, which comprises a VH containing an immunoglobulin heavy chain or fragment thereof, which comprises CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 16-18, respectively.

[0033] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 19-21, respectively.

[0034] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 22-24, respectively.

[0035] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 25-27.

[0036] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 28-30, respectively.

[0037] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 31-33, respectively.

[0038] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 34-36.

[0039] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 37-39, respectively.

[0040] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, which comprises a VH containing an immunoglobulin heavy chain or fragment thereof, which comprises CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 40 to 42.

[0041] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 43 to 45.

[0042] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 86-88, respectively.

[0043] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 89 to 91.

[0044] In some embodiments, when VH is paired with VL, it specifically binds to human PTK7, monkey PTK7, or canine PTK7, or when VL is paired with VH, it specifically binds to human PTK7, monkey PTK7, or canine PTK7.

[0045] In some embodiments, the immunoglobulin heavy chain or fragment thereof is a human immunoglobulin heavy chain or fragment thereof (for example, a human IgG1 heavy chain or fragment thereof, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 heavy chain or fragment thereof), and the immunoglobulin light chain or fragment thereof is a human immunoglobulin light chain or fragment thereof.

[0046] In some embodiments, the nucleic acid encodes a single-stranded variable fragment (scFv), a single-arm antibody, a multispecific antibody (e.g., a bispecific antibody), or a chimeric antigen receptor (CAR).

[0047] In some embodiments, the nucleic acid is cDNA.

[0048] In one embodiment, this disclosure relates to a vector comprising one or more nucleic acids described herein.

[0049] In one embodiment, the present disclosure relates to a vector comprising two of the nucleic acids described herein, wherein the vector encodes the VL region and the VH region that bind together to PTK7.

[0050] In one embodiment, the disclosure relates to a pair of vectors, each comprising one of the nucleic acids described herein, wherein the pair of vectors encode a pair of VL and VH regions that bind together to PTK7.

[0051] In one embodiment, this disclosure relates to a cell comprising a vector described herein, or a pair of vectors described herein.

[0052] In some embodiments, the above cells are CHO cells.

[0053] In one embodiment, this disclosure relates to a cell comprising one or more nucleic acids described herein.

[0054] In one embodiment, the present disclosure relates to a cell comprising two of the nucleic acids described herein.

[0055] In some embodiments, the two nucleic acids encode a pair of VL and VH regions that bind together to PTK7.

[0056] In one embodiment, the present disclosure relates to a method for producing an antibody or an antigen-binding fragment thereof, wherein the method is (a) Culturing any one of the cells described herein under conditions sufficient to produce the antibody or antigen-binding fragment, (b) The method includes recovering the antibody or antigen-binding fragment produced by the cells.

[0057] In one embodiment, the present disclosure relates to an antibody or antigen-binding fragment thereof that binds to PTK7, The present invention relates to an antibody or its antigen-binding fragment, comprising a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) containing an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following: (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0058] In some embodiments, VH includes the sequence of sequence number 46, and VL includes the sequence of sequence number 53.

[0059] In some embodiments, VH includes the sequence of sequence number 47, and VL includes the sequence of sequence number 53.

[0060] In some embodiments, VH includes the sequence of sequence number 48, and VL includes the sequence of sequence number 53.

[0061] In some embodiments, VH includes the sequence of sequence number 49, and VL includes the sequence of sequence number 53.

[0062] In some embodiments, VH includes the sequence of sequence number 50, and VL includes the sequence of sequence number 53.

[0063] In some embodiments, VH includes the sequence of sequence number 51, and VL includes the sequence of sequence number 53.

[0064] In some embodiments, VH includes the sequence of sequence number 52, and VL includes the sequence of sequence number 53.

[0065] In some embodiments, VH includes the sequence of sequence number 92, and VL includes the sequence of sequence number 53.

[0066] In one embodiment, the present disclosure relates to an antibody or antigen-binding fragment thereof that binds to PTK7, The present invention relates to an antibody or its antigen-binding fragment, comprising a heavy chain variable region (VH) containing VH CDR1, VH CDR2, and VH CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and a light chain variable region (VL) containing VL CDR1, VL CDR2, and VL CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0067] In some embodiments, the antibody or its antigen-binding fragment specifically binds to human PTK7, monkey PTK7, or canine PTK7.

[0068] In some embodiments, the antibody or its antigen-binding fragment is a human antibody or its antigen-binding fragment, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

[0069] In some embodiments, the antibody or antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

[0070] In one embodiment, the present disclosure relates to an antibody or antigen-binding fragment thereof that binds to TROP2 (trophotrophoblast cell surface antigen 2), A heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR1, the VH CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR2, and the VH CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR3, and A light chain variable region (VL) comprising CDR1, 2, and 3, wherein the VL CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR1, the VL CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR2, and the VL CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR3. The amino acid sequences of the above-selected VH CDR1, 2, and 3, and the amino acid sequences of the above-selected VL CDR1, 2, and 3, relate to an antibody or its antigen-binding fragment, which is one of the following. (1) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 57-59, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (2) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the above-selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively, and the amino acid sequences of the above-selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively, and (4) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0071] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 57 to 59, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0072] In some embodiments, based on Kabat's definition, the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 60 to 62, respectively, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0073] In some embodiments, based on the definition of Chothia, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 66 to 68, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0074] In some embodiments, based on the definition of Chothia, the above VH includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 69 to 71, respectively, and the above VL includes CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

[0075] In some embodiments, the antibody or its antigen-binding fragment specifically binds to human TROP2, monkey TROP2, or canine TROP2.

[0076] In some embodiments, the antibody or its antigen-binding fragment is a human antibody or its antigen-binding fragment, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

[0077] In some embodiments, the antibody or its antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

[0078] In one embodiment, the disclosure relates to nucleic acids comprising polynucleotides that encode a polypeptide including the following: (1) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 57 to 59, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (2) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 66 to 68, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (3) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which, when the VL forms a pair with a VH containing the respective amino acid sequences shown in SEQ ID NO: 73, binds to TROP2. (4) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 60 to 62, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (5) An immunoglobulin heavy chain or fragment thereof comprising heavy chain variable regions (VH) comprising complementarity-determining regions (CDR) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 69 to 71, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (6) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each VL binds to TROP2 when paired with a VH containing the amino acid sequence shown in SEQ ID NO: 74.

[0079] (7) In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin light chain or fragment thereof, comprising a VL comprising CDR1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs: 1 to 3.

[0080] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 57-59, respectively.

[0081] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 60-62, respectively.

[0082] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 66-68, respectively.

[0083] In some embodiments, the nucleic acid comprises a polynucleotide encoding a polypeptide, comprising an immunoglobulin heavy chain or fragment thereof, comprising a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 69 to 71.

[0084] In some embodiments, when VH forms a pair with VL, it specifically binds to human TROP2, monkey TROP2, or canine TROP2, or when VL forms a pair with VH, it specifically binds to human TROP2, monkey TROP2, or canine TROP2.

[0085] In some embodiments, the immunoglobulin heavy chain or fragment thereof is a human immunoglobulin heavy chain or fragment thereof (for example, a human IgG1 heavy chain or fragment thereof, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 heavy chain or fragment thereof), and the immunoglobulin light chain or fragment thereof is a human immunoglobulin light chain or fragment thereof.

[0086] In some embodiments, the nucleic acid encodes a single-stranded variable fragment (scFv), a single-arm antibody, a multispecific antibody (e.g., a bispecific antibody), or a chimeric antigen receptor (CAR).

[0087] In some embodiments, the nucleic acid is cDNA.

[0088] In one embodiment, this disclosure relates to a vector comprising one or more nucleic acids described herein.

[0089] In one embodiment, the present disclosure relates to a vector comprising two of the nucleic acids described herein, wherein the vector encodes the VL region and the VH region that bind together to TROP2.

[0090] In one embodiment, the disclosure relates to a pair of vectors, each vector comprising one of the nucleic acids described herein, wherein the pair of vectors encode a pair of VL and VH regions that bind together to TROP2.

[0091] In one embodiment, this disclosure relates to a cell comprising a vector described herein, or a pair of vectors described herein.

[0092] In some embodiments, the above cells are CHO cells.

[0093] In one embodiment, this disclosure relates to a cell comprising one or more nucleic acids described herein.

[0094] In one embodiment, the present disclosure relates to a cell comprising two of the nucleic acids described herein.

[0095] In some embodiments, the two nucleic acids encode a pair of VL and VH regions that bind together to TROP2.

[0096] In one embodiment, the present disclosure relates to a method for producing an antibody or an antigen-binding fragment thereof, wherein the method is (c) Culturing any of the cells described herein under conditions sufficient to produce the antibody or antigen-binding fragment, (d) The method includes recovering the antibody or antigen-binding fragment produced by the cells.

[0097] In one embodiment, the present disclosure relates to an antibody or antigen-binding fragment thereof that binds to TROP2, The present invention relates to an antibody or its antigen-binding fragment, comprising a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) containing an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following: (1) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, and (2) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

[0098] In some embodiments, VH includes the sequence of sequence number 73, and VL includes the sequence of sequence number 53.

[0099] In some embodiments, VH includes the sequence of sequence number 74, and VL includes the sequence of sequence number 53.

[0100] In one embodiment, the present disclosure relates to an antibody or antigen-binding fragment thereof that binds to TROP2, The present invention relates to an antibody or its antigen-binding fragment, comprising a heavy chain variable region (VH) containing VH CDR1, VH CDR2, and VH CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and a light chain variable region (VL) containing VL CDR1, VL CDR2, and VL CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, and (2) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

[0101] In some embodiments, the antibody or its antigen-binding fragment specifically binds to human TROP2, monkey TROP2, or canine TROP2.

[0102] In some embodiments, the antibody or its antigen-binding fragment is a human antibody or its antigen-binding fragment, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

[0103] In some embodiments, the antibody or antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

[0104] In one embodiment, the present disclosure relates to an anti-PTK7 / TROP2 antibody (e.g., a bispecific antibody) or an antigen-binding fragment thereof, comprising a first antigen-binding domain that specifically binds to the epitope of PTK7 and a second antigen-binding domain that specifically binds to the epitope of TROP2.

[0105] In some embodiments, the first antigen-binding domain comprises a first heavy chain variable region (VH1) and a first light chain variable region (VL1), and the second antigen-binding domain comprises a second heavy chain variable region (VH2) and a second light chain variable region (VL2).

[0106] In some embodiments, the first heavy chain variable region (VH1) includes complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH1 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR1, the VH1 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR2, and the VH1 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR3, and The first light chain variable region (VL1) described above includes CDR1, 2, and 3, wherein the VL1 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR1, the VL1 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR2, and the VL1 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR3. The amino acid sequences of the selected VH1 CDR1, 2, and 3, and the amino acid sequences of the selected VL1 CDR1, 2, and 3, are one of the following: (1) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 4 to 6, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (2) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 7 to 9, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 10 to 12, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 16-18, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (6) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 19 to 21, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (7) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (8) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (9) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (10) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 31 to 33, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (11) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 34 to 36, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (12) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 37 to 39, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (13) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (14) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (15) The amino acid sequences of the above-selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 86 to 88, respectively, and the amino acid sequences of the above-selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, and (16) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 89 to 91, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0107] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0108] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0109] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0110] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0111] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16-18, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0112] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0113] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0114] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0115] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0116] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 31 to 33, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0117] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34-36, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0118] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 37 to 39, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0119] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0120] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0121] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 86 to 88, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0122] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 89 to 91, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0123] In some embodiments, the second heavy chain variable region (VH2) comprises CDR1, 2, and 3, wherein the VH2 CDR1 region comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR1, the VH2 CDR2 region comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR2, and the VH2 CDR3 region comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR3, and The second light chain variable region (VL2) described above includes CDR1, 2, and 3, wherein the VL2 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR1, the VL2 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR2, and the VL2 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR3. The amino acid sequences of the selected VH2 CDR1, 2, and 3, and the amino acid sequences of the selected VL2 CDR1, 2, and 3, are one of the following: (1) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54-56, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (2) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the above-selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively, and the amino acid sequences of the above-selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively, and (6) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0124] In some embodiments, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0125] In some embodiments, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0126] In some embodiments, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0127] In some embodiments, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0128] In some embodiments, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0129] In some embodiments, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0130] In some embodiments, (1) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 4-6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54-56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (2) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 16-18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54-56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (6) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (7) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22-24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54-56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (8) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (9) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (10) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (11) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (12) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 16-18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57-59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (13) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (14) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22-24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57-59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (15) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (16) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (17) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (18) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (19) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 16-18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60-62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (20) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (21) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22-24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60-62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (22) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25-27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (23) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28-30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (24) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 31-33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (25) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 34-36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (26) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 37-39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (27) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40-42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (28) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43-45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (29) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25-27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (30) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (31) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (32) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 34-36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (33) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 37-39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (34) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (35) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43-45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (36) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25-27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69-71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (37) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28-30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69-71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (38) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (39) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 34-36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69-71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (40) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 37-39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69-71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (41) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (42) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (43) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 86-88, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54-56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (44) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 89 to 91, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (45) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 86-88, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57-59, respectively; the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively; and (46) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 89 to 91, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0131] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 46, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0132] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 47, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0133] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 48, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0134] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 49, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0135] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 50, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0136] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 51, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0137] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 52, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0138] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 46, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0139] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 47, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0140] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 48, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0141] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 49, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0142] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 50, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0143] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 51, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0144] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 52, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0145] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 46, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0146] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 47, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0147] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 48, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0148] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 49, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0149] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 50, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0150] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 51, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0151] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 52, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0152] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 92, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0153] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 92, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0154] In some embodiments, VH1 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VH sequence, and VL1 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0155] In some embodiments, the VH2 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VH sequence, and the VL2 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 72, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (3) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

[0156] In some embodiments, VH1 includes VH1 CDR1, VH1 CDR2, and VH1 CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and VL1 includes VL1 CDR1, VL1 CDR2, and VL1 CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0157] In some embodiments, VH2 includes VH2 CDR1, VH2 CDR2, and VH2 CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and VL2 includes VL2 CDR1, VL2 CDR2, and VL2 CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 72, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (3) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

[0158] In some embodiments, the first antigen-binding domain specifically binds to human PTK7, monkey PTK7, or canine PTK7, and / or the second antigen-binding domain specifically binds to human TROP2, monkey TROP2, or canine TROP2.

[0159] In some embodiments, the first antigen-binding domain is a human antigen-binding domain or a humanized antigen-binding domain, and / or the second antigen-binding domain is a human antigen-binding domain or a humanized antigen-binding domain.

[0160] In some embodiments, the first antigen-binding domain is a single-stranded variable fragment (scFV), and / or the second antigen-binding domain is an scFv.

[0161] In some embodiments, the first light chain variable region and the second light chain variable region are the same.

[0162] In one embodiment, the present disclosure relates to an antibody or an antigen-binding fragment thereof that cross-competes with any one of the antibodies or antigen-binding fragments thereof described herein.

[0163] In some embodiments, the antibody or its antigen-binding fragment includes a fragment crystallizable region (Fc region).

[0164] In some embodiments, the Fc region exhibits increased complement-dependent cytotoxicity (CDC) or antibody-dependent cytotoxicity (ADCC).

[0165] In one embodiment, the present disclosure relates to a chimeric antigen receptor (CAR) comprising any one of the antibodies or antigen-binding fragments thereof described herein.

[0166] In one embodiment, the present disclosure relates to an antibody-drug conjugate comprising one of the antibodies or antigen-binding fragments thereof described herein, covalently bound to a therapeutic agent.

[0167] In some embodiments, the therapeutic agent is a cytotoxic agent or a cell proliferation inhibitor.

[0168] In some embodiments, the therapeutic agent is MMAE or MMAF.

[0169] In some embodiments, the above therapeutic agent is selected from the following. [ka]

[0170] In some embodiments, the therapeutic agent is linked to the antibody or its antigen-binding fragment via a linker. In some embodiments, the linker has the following structure. [ka]

[0171] In some embodiments, the antibody-drug conjugate has the following structure. [ka]

[0172] In some embodiments, n = 1, 2, 3, 4, 5, 6, 7, or 8, and in some embodiments, "Ab" represents an antibody or its antigen-binding fragment as described herein.

[0173] In one embodiment, the present disclosure relates to a method for treating a subject having cancer, the method comprising administering a therapeutically effective amount of a composition comprising one of the antibodies or antigen-binding fragments thereof described herein, one of the CARs described herein, or one of the antibody-drug conjugates described herein.

[0174] In some embodiments, the subject has a solid tumor.

[0175] In some embodiments, the cancers are colon cancer, triple-negative breast cancer (TNBC), lung cancer, non-small cell lung cancer (NSCLC), esophageal cancer, pancreatic cancer, colorectal cancer, ovarian cancer (OVCA), or bladder cancer.

[0176] In some embodiments, the subjects are further treated with an effective amount of anti-4-1BB antibody, anti-OX40 antibody, anti-PD-1 antibody, anti-CTLA4 antibody, anti-CD40 antibody, or anti-PD-L1 antibody.

[0177] In one embodiment, the present disclosure relates to a method for reducing the rate of tumor growth, the method comprising contacting tumor cells with an effective amount of a composition comprising one of the antibodies or antigen-binding fragments thereof described herein, one of the CARs described herein, or one of the antibody-drug conjugates described herein.

[0178] In one embodiment, the present disclosure relates to a method for killing tumor cells, the method comprising contacting the tumor cells with an effective amount of a composition comprising any one of the antibodies or antigen-binding fragments thereof described herein, any one of the CARs described herein, or any one of the antibody-drug conjugates described herein.

[0179] In one embodiment, the present disclosure relates to a method for increasing an immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising one of the antibodies or antigen-binding fragments thereof described herein, one of the CARs described herein, or one of the antibody-drug conjugates described herein.

[0180] In one embodiment, the present disclosure relates to a pharmaceutical composition comprising one of the antibodies or antigen-binding fragments thereof described herein and a pharmaceutically acceptable carrier.

[0181] In one embodiment, the present disclosure relates to a pharmaceutical composition comprising one of the antibody-drug conjugates described herein and a pharmaceutically acceptable carrier.

[0182] In some embodiments, the drug-antibody ratio (DAR) is approximately 4 or 8.

[0183] As used herein, the term “cancer” means cells capable of autonomous proliferation. Examples of such cells include cells in an abnormal state or condition characterized by rapid proliferation. The term means cancerous growth, e.g., tumors, oncogenic processes, metastatic tissues, and malignant transformed cells, tissues, or organs, regardless of the type of tissue change or stage of invasiveness. Malignancies of various organ systems, e.g., respiratory, cardiovascular, renal, reproductive, hematologic, nervous, liver, gastrointestinal, and endocrine systems, as well as most colon cancers, renal cell carcinoma, prostate cancer and / or testicular tumors, non-small cell lung cancer, and small intestine cancer. “Spontaneously occurring” cancers include any cancer that is not experimentally induced by transplanting cancer cells into a subject, e.g., spontaneously occurring cancers, cancers caused by exposure of a patient to a carcinogen, cancers resulting from transgenic oncogene insertions or tumor suppressor gene knockouts, and cancers caused by infections, e.g., viral infections. The term "carcinoma" is recognized in the art and refers to a malignant tumor of epithelial or endocrine glandular tissue. This term also includes carcinosarcoma, which is a malignant tumor composed of cancerous and sarcomatous tissue. "Adenocarcinoma" refers to a carcinoma of glandular origin, or a carcinoma in which tumor cells form recognizable glandular structures. The term "sarcoma" is recognized in the art and refers to a malignant tumor of mesenchymal origin. The term "hematopoietic neoplastic disease" includes diseases involving hematopoietic hyperplasia / neoplastic cells. Hematopoietic neoplastic diseases may originate from the bone marrow, lymphoid system, or erythrocyte lineage, or their progenitor cells.

[0184] As used herein, the term “antibody” means any antigen-binding molecule that contains at least one (e.g., 1, 2, 3, 4, 5, or 6) complementarity-determining regions (CDRs) (e.g., any of three CDRs derived from an immunoglobulin light chain or any of three CDRs derived from an immunoglobulin heavy chain) and is capable of specifically binding to an epitope. Non-limiting examples of antibodies include monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), single-chain antibodies, chimeric antibodies, human antibodies, and humanized antibodies. In some embodiments, antibodies may contain the Fc region of a human antibody. The term antibody also includes derivatives, such as bispecific antibodies, single-chain antibodies, diabodies, linear antibodies, and multispecific antibodies formed from antibody fragments.

[0185] As used herein, the term “antigen-binding fragment” means a portion of a full-length antibody, the portion of which is specifically capable of binding to an antigen. In some embodiments, the antigen-binding fragment contains at least one variable domain (e.g., a variable domain in the heavy chain or a variable domain in the light chain). Non-limiting examples of antibody fragments include, for example, Fab, Fab', F(ab')2, and Fv fragments.

[0186] As used herein, the term “human antibody” means an antibody encoded by endogenous nucleic acids present in humans (e.g., rearranged human immunoglobulin heavy or light chain loci). In some embodiments, human antibodies are recovered from humans or produced in human cell culture media (e.g., in human hybridoma cells). In some embodiments, human antibodies are produced in non-human cells (e.g., mouse or hamster cell lines). In some embodiments, human antibodies are produced in bacterial or yeast cells. In some embodiments, human antibodies are produced in transgenic non-human animals (e.g., cattle) containing unarranged or rearranged human immunoglobulin loci (e.g., heavy or light chain human immunoglobulin loci).

[0187] As used herein, the term “chimeric antibody” means an antibody containing sequences present in at least two different antibodies (e.g., antibodies derived from two different mammalian species, such as human and mouse antibodies). Non-limiting examples of chimeric antibodies include antibodies containing variable domain sequences (e.g., all or part of the light chain and / or heavy chain variable domain sequences) of a non-human (e.g., mouse) antibody, as well as constant domains of a human antibody. Further examples of chimeric antibodies are described herein and are well known in the art.

[0188] As used herein, the term “humanized antibody” means a non-human antibody that contains minimal sequences derived from non-human (e.g., mouse) immunoglobulin and sequences derived from human immunoglobulin. In non-limiting examples, a humanized antibody is a human antibody (recipient antibody) in which residues in the hypervariable (e.g., CDR) region of the recipient antibody are replaced by residues in the hypervariable (e.g., CDR) region of a non-human antibody (e.g., donor antibody), such as a mouse, rat, or rabbit antibody having desired specificity, affinity, and capability. In some embodiments, Fv framework residues of human immunoglobulin are replaced by corresponding non-human (e.g., mouse) immunoglobulin residues. In some embodiments, the humanized antibody may contain residues not found in the recipient antibody or donor antibody. These modifications can further refine the performance of the antibody. In some embodiments, the humanized antibody contains substantially all, at least one, and typically two, variable domains, with all or substantially all of the hypervariable loop (CDR) corresponding to the hypervariable loop of a non-human (e.g., mouse) immunoglobulin, and all or substantially all of the framework region being a human immunoglobulin sequence. The humanized antibody may also contain an immunoglobulin constant region (Fc), typically at least a portion of the constant region of a human immunoglobulin. The humanized antibody can be produced using molecular biological methods well known in the art. Non-limiting examples of methods for producing the humanized antibody are described herein.

[0189] As used herein, the term “single-chain antibody” means a single polypeptide containing at least two immunoglobulin variable domains (e.g., variable domains of mammalian immunoglobulin heavy or light chains) that are specifically capable of binding to an antigen. Non-limiting examples of single-chain antibodies are described herein.

[0190] As used herein, the term "multimeric antibody" means an antibody containing four or more (e.g., six, eight, or ten) immunoglobulin variable domains.

[0191] As used herein, the terms “subject” and “patient” are used interchangeably throughout the specification and refer to animals, humans, or non-humans to which treatment according to the methods of the present invention is provided. Veterinary and non-veterinary uses are conceived by the present invention. Human patients may be adult humans or young humans (e.g., humans under 18 years of age). In addition to humans, patients include, but are not limited to, mice, rats, hamsters, guinea pigs, rabbits, ferrets, cats, dogs, and primates. Examples include non-human primates (e.g., monkeys, chimpanzees, gorillas, etc.), rodents (e.g., rats, mice, gerbils, hamsters, ferrets, rabbits), rabbits, pigs (e.g., pigs, miniature pigs), equids, canids, felines, bovines, and other domestic, livestock, and zoo animals.

[0192] As used herein, when referring to an antibody, the terms "specifically binding" and "specifically binds" mean that the antibody generally interacts more preferably with its target molecule (e.g., PTK7) than with some other molecules, because the interaction depends on the presence of a specific structure (i.e., an antigenic determinant or epitope) on the target molecule; in other words, the reagent recognizes and binds to molecules containing a specific structure, rather than all molecules in general. An antibody that specifically binds to a target molecule may be called a target-specific antibody. For example, an antibody that specifically binds to the PTK7 molecule may be called a PTK7-specific antibody or an anti-PTK7 antibody. Similarly, an antibody that specifically binds to both the PTK7 molecule and the TROP2 molecule may be called an anti-PTK7 / TROP2 antibody.

[0193] As used herein, the term “bispecific antibody” means an antibody that binds to two different epitopes. Epitopes may be present on the same antigen or on different antigens.

[0194] As used herein, the term “multispecific antibody” means an antibody that binds to two or more different epitopes. Epitopes can be present on the same antigen or on different antigens. A multispecific antibody may be, for example, a bispecific antibody or a tripspecific antibody. In some embodiments, a multispecific antibody binds to two, three, four, five, or six different epitopes.

[0195] As used herein, the terms “polypeptide,” “peptide,” and “protein” are used interchangeably and mean polymers of at least two amino acids of any length.

[0196] As used herein, the terms “polynucleotide,” “nucleic acid molecule,” and “nucleic acid sequence” are used interchangeably and mean, but are not limited to, polymers of nucleotides of any length, of at least two nucleotides, including, but not limited to, DNA, RNA, DNA / RNA hybrids, and modifications thereof.

[0197] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art. Methods and materials for use in the present invention are described herein, but other suitable methods and materials well known in the art may also be used. Materials, methods, and examples are illustrative and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references referenced herein are incorporated by reference in their entirety. In case of any conflict, this specification, including definitions, shall prevail.

[0198] Other features and advantages of the present invention will become apparent from the following detailed description and drawings, as well as from the claims. [Brief explanation of the drawing]

[0199] [Figure 1A] List the Kabat CDR sequences of anti-PTK7 antibodies. [Figure 1B] List the Kabat CDR sequences of anti-TROP2 antibodies. [Figure 2A] List the Chothia CDR sequences of anti-PTK7 antibodies. [Figure 2B] The Chothia CDR sequences of anti-TROP2 antibodies are listed below. [Figure 3] The sequences of the heavy chain variable region and light chain variable region of the anti-PTK7 antibody and the anti-TROP2 antibody, and their antigen-binding fragments, are listed below. [Figure 4-1] Some of the amino acid sequences discussed in this disclosure are listed below. [Figure 4-2] Same as above [Figure 5]Shows the tumor volumes of mouse xenografts with MDA-MB-468 cells in different groups treated with the ADCs described herein. Sacituzumab govitecan and hu24-ADC were used as positive controls. [Figure 6] Shows the tumor volumes of mouse xenografts with patient-derived breast tumor fragments in different groups treated with the ADCs described herein. [Figure 7] Shows the tumor volumes of mouse xenografts with patient-derived lung tumor fragments in different groups treated with the ADCs described herein. [Figure 8] Shows the tumor volumes of mouse xenografts with patient-derived pancreatic tumor fragments in different groups treated with the ADCs described herein. [Figure 9] Shows the tumor volumes of mouse xenografts with patient-derived colorectal tumor fragments in different groups treated with the ADCs described herein. [Figure 10] Shows the tumor volumes of mouse xenografts with patient-derived colorectal tumor fragments in different groups treated with the ADCs described herein. [Figure 11] Shows the results of the binding activities of the antibodies in NCI-H1975 cells (A) and NUGC-4 cells (B). [Figure 12] Shows the in vitro killing activities of the ADCs in NCI-H1975 cells (A) and NUGC-4 cells (B).

Mode for Carrying Out the Invention

[0200] A bispecific antibody or an antigen-binding fragment thereof is an artificial protein that can simultaneously bind to two different epitopes (e.g., on two different antigens). In some embodiments, the bispecific antibody or an antigen-binding fragment thereof can have two arms. Each arm can have one heavy-chain variable region and one light-chain variable region and can form an antigen-binding domain (or antigen-binding region). In some embodiments, the bispecific antibody has a common light chain.

[0201] This disclosure provides examples of antibodies that bind to PTK7, TROP2, and / or both PTK7 and TROP2 (PTK7 / TROP2), their antigen-binding fragments, and antibody-drug conjugates derived from these antibodies. This disclosure also relates to anti-PTK7 / TROP2 antibodies that specifically bind to PTK7 and TROP (e.g., bispecific antibodies or their antigen-binding fragments), and antibody-drug conjugates derived from these anti-PTK7 / TROP2 antibodies.

[0202] PTK7 and TROP2 Protein tyrosine kinase 7 (PTK7) is a highly conserved member of the pseudokinase family of receptor tyrosine kinases. The lack of observable kinase activity across species is likely explained by substitutions at residues typically conserved in the kinase domain. Genetic and biochemical studies have demonstrated the crucial function of PTK7 in non-standard Wnt signaling, with PTK7-deficient embryos exhibiting severe developmental impairment in in-planar cell polarity. Evidence also exists for additional, possibly context-dependent, functions of PTK7 in vascular endothelial growth factor (VEGF), semaphorin / plexin, and standard Wnt signaling pathways. Oncogenic functions of PTK7 have been described in colon, lung, and esophageal cancers, and PTK7 promotes cell survival and chemotherapy resistance in acute myeloid leukemia.

[0203] PTK7 is highly expressed in breast cancer, correlates with poor prognosis, and is associated with tumor metastasis and progression in TNBC. Co-expression analysis of PTK7 in TNBC cell lines and gain-of-function / loss-of-function studies revealed that PTK7 is involved in EGFR / Akt signaling regulation and is associated with extracellular matrix organizing and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14, and SDC1. Gain-of-function / loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. A mouse model with PTK7 knockdown cells further demonstrated that PTK7 deficiency inhibits TNBC tumor progression in vivo.

[0204] For a detailed review of PTK7 and its function, please refer to Damelin M, et al., A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Sci Transl Med. 2017 Jan 11, 9(372):eaag2611.doi:10.1126 / scitranslmed.aag2611.PMID:28077676; Xiang et al., Biomator Res. 2022 Dec 5;26(1):74.doi:10.1186 / s40824-022-00328-9; Cui et al., Front. Oncol., 22 July 2021, Sec. Breast Cancer, Volume 11-2021; and Kim et al., Int J Mol Sci. 2022 Oct These can be found in 13;23(20):12195.doi:10.3390 / ijms232012195, and the entirety of each of these is incorporated by reference.

[0205] Trophoblastic cell surface antigen 2 (TROP2) is a glycoprotein that spreads across the epithelial membrane surface and plays a role in cell self-renewal, proliferation, and transformation. Encoded by the TACSTD2 gene, TROP2 is a 35 kDa protein consisting of a large extracellular domain, a single transmembrane domain, and a short intracellular tail, which is the functionally dominant part of the protein.

[0206] Under physiological conditions, TROP2 plays a crucial role in embryonic development, placental tissue formation, embryo implantation, stem cell proliferation, and organ development. Low basal levels of TROP2 expression are found on the surface of several normal epithelial tissues, including skin and oral mucosa. TROP2 can promote tumor growth, and its overexpression is commonly seen in many types of malignant epithelial tumors.

[0207] Trop2 expression is linked to the expression of several oncogenic transcription factors (e.g., CREB1, nuclear factor NFκB, and HOXA) through a positive feedback relationship. 10 Trop2 expression is regulated by [specific factors]. Trop2 expression can be upregulated by inactivation of several transcription factors (e.g., HNF4A, TP63 / TP53L, ERG, HNF1A / TCF-1, and FOXP3). Overexpression of TROP2 accelerates the cancer cell cycle and drives cancer growth. Knocking out the TACSTD2 gene inhibits tumor cell proliferation, further supporting the role of TROP2 in tumorigenesis.

[0208] TROP2 has been elucidated as a signaling molecule for intracellular calcium and is known to function in various cellular signaling pathways associated with tumorigenesis. Expression of TROP2 as a calcium signaling molecule mobilizes calcium from internal stores. Increased intracellular calcium levels activate MAPK, leading to increased levels of phosphorylated ERK1 and ERK2. ERK1 and ERK2 are important mediators of cell cycle progression, angiogenesis, cell proliferation, cell invasion, and metastasis. Intracellular calcium also activates the NFκB pathway, which is involved in stimulating cell proliferation, and the RAF pathway, which is essential for the upregulation of FOXM1, one of the most commonly overexpressed genes in human solid tumors.

[0209] In addition to stimulating calcium release and MAPK signaling, TROP2 is also involved in several other pro-oncogenic signaling pathways, leading to tumor cell growth and proliferation. Activation of cyclins E and D further accelerates cell cycle progression. Modification of the Notch, Hedgehog, and Wnt pathways may inhibit proper stem cell proliferation and differentiation. TROP2 signaling has also been shown to be β-catenin dependent. Direct interaction between β-catenin and the intracellular domain of TROP2 via β-catenin signaling enhances stem cell-like properties of cancer cells (e.g., self-renewal and transformation). Attenuation of IGF-1 receptor signaling by TROP2 promotes cancer growth and malignancy, particularly in lung cancer.

[0210] For detailed reviews of TROP2 and its function, see Zaman S, Jadid H, Denson AC, Gray JE. Targeting Trop-2 in solid tumors: future prospects. Onco Targets Ther. 2019;12:1781-1790.doi:10.2147 / OTT.S162447; Shvartsur A, Bonavida B. Trop2 and its overexpression in cancers: regulation and clinical / therapeutic implications. Genes Cancer. 2015;6(3-4):84-105.doi:10.18632 / genesandcancer.40; Strop P, Tran TT, Dorywalska M, et al. RN927C, a site-specific Trop-2 antibody-drug conjugate (ADC) with enhanced stability, is highly efficacious in preclinical solid tumor models. Mol Cancer These can be found in Ther. 2016;15(11):2698-2708.doi:10.1158 / 1535-7163.MCT-16-0431; and Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9(48):28989-29006.doi:10.18632 / oncotarget.25615, and the entirety of each of these is incorporated by reference.

[0211] This disclosure provides several anti-PTK7 antibodies, anti-TROP2 antibodies, and anti-PTK7 / TROP2 (e.g., multispecific or bispecific) antibodies, their antigen-binding fragments, and methods of using these anti-PTK7 antibodies, anti-TROP2 antibodies, and / or anti-PTK7 / TROP2 antibodies and antigen-binding fragments to inhibit tumor growth, treat cancer, and treat autoimmune diseases.

[0212] Anti-PTK7 antibody and antigen-binding fragments This disclosure provides antibodies and antigen-binding fragments that specifically bind to PTK7 (e.g., human PTK7, monkey PTK7, or canine PTK7). The antibodies and antigen-binding fragments described herein are capable of binding to PTK7. These antibodies may be agonists or antagonists. In some embodiments, these antibodies may increase the immune response. In some embodiments, these antibodies may block PTK7 activity, for example, by reducing the frequency of tumor initiation cells (TICs) or by inhibiting angiogenesis and immune cell stimulation.

[0213] This disclosure provides, for example, anti-PTK7 antibodies 1A7, 1A11, 1F2, 2A5, 2D11, 2F5, 3C4, 3E6, their chimeric antibodies, and their human antibodies or humanized antibodies.

[0214] CDR sequences for 1A7 antibodies and antibodies derived from 1A7 (e.g., human antibodies or humanized antibodies) include the CDRs of the heavy chain variable domain, SEQ ID NOs: 4, 5, 6, and the CDRs of the light chain variable domain, SEQ ID NOs: 1, 2, 3, as defined by Kabat numbering. CDRs can also be defined by the Chothia system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NOs: 25, 26, 27, and the CDR sequences of the light chain variable domain are shown in SEQ ID NOs: 1, 2, 3.

[0215] As the CDR sequences of the 1A11 antibody and antibodies derived from 1A11 (e.g., human antibodies or humanized antibodies), there are the CDRs of the heavy chain variable domain defined by Kabat numbering, SEQ ID NO: 86, 87, 88, and the CDRs of the light chain variable domain, SEQ ID NO: 1, 2, 3. The CDRs can also be defined by the Chothia system. Under the Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NO: 89, 90, 91, and the CDR sequences of the light chain variable domain are shown in SEQ ID NO: 1, 2, 3.

[0216] As the CDR sequences of the 1F2 antibody and antibodies derived from 1F2 (e.g., human antibodies or humanized antibodies), there are the CDRs of the heavy chain variable domain defined by Kabat numbering, SEQ ID NO: 7, 8, 9, and the CDRs of the light chain variable domain, SEQ ID NO: 1, 2, 3. The CDRs can also be defined by the Chothia system. Under the Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NO: 28, 29, 30, and the CDR sequences of the light chain variable domain are shown in SEQ ID NO: 1, 2, 3.

[0217] As the CDR sequences of the 2A5 antibody and antibodies derived from 2A5 (e.g., human antibodies or humanized antibodies), there are the CDRs of the heavy chain variable domain defined by Kabat numbering, SEQ ID NO: 10, 11, 12, and the CDRs of the light chain variable domain, SEQ ID NO: 1, 2, 3. The CDRs can also be defined by the Chothia system. Under the Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NO: 31, 32, 33, and the CDR sequences of the light chain variable domain are shown in SEQ ID NO: 1, 2, 3.

[0218] CDR sequences for 2D11 antibodies and antibodies derived from 2D11 (e.g., human antibodies or humanized antibodies) include the CDRs of the heavy chain variable domain, SEQ ID NOs: 13, 14, 15, and the CDRs of the light chain variable domain, SEQ ID NOs: 1, 2, 3, as defined by Kabat numbering. CDRs can also be defined by the Chothia system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NOs: 34, 35, 36, and the CDR sequences of the light chain variable domain are shown in SEQ ID NOs: 1, 2, 3.

[0219] CDR sequences for 2F5 antibodies and antibodies derived from 2F5 (e.g., human antibodies or humanized antibodies) include the CDRs of the heavy chain variable domain, SEQ ID NOs: 16, 17, 18, and the CDRs of the light chain variable domain, SEQ ID NOs: 1, 2, 3, as defined by Kabat numbering. CDRs can also be defined by the Chothia system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NOs: 37, 38, 39, and the CDR sequences of the light chain variable domain are shown in SEQ ID NOs: 1, 2, 3.

[0220] CDR sequences for 3C4 antibodies and 3C4-derived antibodies (e.g., human antibodies or humanized antibodies) include the CDRs of the heavy chain variable domain, SEQ ID NOs: 19, 20, 21, and the CDRs of the light chain variable domain, SEQ ID NOs: 1, 2, 3, as defined by Kabat numbering. CDRs can also be defined by the Chothia system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NOs: 40, 41, 42, and the CDR sequences of the light chain variable domain are shown in SEQ ID NOs: 1, 2, 3.

[0221] CDR sequences for 3E6 antibodies and antibodies derived from 3E6 (e.g., human antibodies or humanized antibodies) include the CDRs of the heavy chain variable domain, SEQ ID NOs. 22, 23, and 24, and the CDRs of the light chain variable domain, SEQ ID NOs. 1, 2, and 3, as defined by Kabat numbering. CDRs can also be defined by the Chothia system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in SEQ ID NOs. 43, 44, and 45, and the CDR sequences of the light chain variable domain are shown in SEQ ID NOs. 1, 2, and 3.

[0222] The amino acid sequence of the heavy chain variable region of the 1A7 antibody is shown in SEQ ID NO: 46. The amino acid sequence of the light chain variable region of the 1A7 antibody is shown in SEQ ID NO: 53.

[0223] The amino acid sequence of the heavy chain variable region of the 1A11 antibody is shown in SEQ ID NO: 92. The amino acid sequence of the light chain variable region of the 1A11 antibody is shown in SEQ ID NO: 53.

[0224] The amino acid sequence of the heavy chain variable region of the 1F2 antibody is shown in SEQ ID NO: 47. The amino acid sequence of the light chain variable region of the 1F2 antibody is shown in SEQ ID NO: 53.

[0225] The amino acid sequence of the heavy chain variable region of the 2A5 antibody is shown in SEQ ID NO: 48. The amino acid sequence of the light chain variable region of the 2A5 antibody is shown in SEQ ID NO: 53.

[0226] The amino acid sequence of the heavy chain variable region of the 2D11 antibody is shown in SEQ ID NO: 49. The amino acid sequence of the light chain variable region of the 2D11 antibody is shown in SEQ ID NO: 53.

[0227] The amino acid sequence of the heavy chain variable region of the 2F5 antibody is shown in SEQ ID NO: 50. The amino acid sequence of the light chain variable region of the 2F5 antibody is shown in SEQ ID NO: 53.

[0228] The amino acid sequence of the heavy chain variable region of the 3C4 antibody is shown in SEQ ID NO: 51. The amino acid sequence of the light chain variable region of the 3C4 antibody is shown in SEQ ID NO: 53.

[0229] The amino acid sequence of the heavy chain variable region of the 3E6 antibody is shown in SEQ ID NO: 52. The amino acid sequence of the light chain variable region of the 3E6 antibody is shown in SEQ ID NO: 53.

[0230] The amino acid sequences for the heavy chain variable region and light chain variable region of the modified antibody are also provided. In some embodiments, the heavy chain variable region is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs. 46-52 and 92. In some embodiments, the light chain variable region is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO. 53. The heavy chain variable region sequence can be paired with a corresponding light chain variable region sequence, which together bind to PTK7.

[0231] Humanization percentage refers to the percentage of identity of a heavy chain or light chain variable region sequence compared to a human antibody sequence in the International Immunogenetic Information System (IMGT) database. In some embodiments, the humanization percentage exceeds 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or 95%. Detailed descriptions of methods for determining the humanization percentage and methods for determining top hits are well known in the art, for example, in Jones, et al. “The INNs and outs of antibody nonproprietary names.” MAbs. Vol.8. No.1. Taylor & Francis, 2016, which is incorporated herein by reference in its entirety. Higher humanization percentages often have various advantages, such as being safer and more effective in humans, more likely to be accepted by human subjects, and / or less likely to have side effects. In some embodiments, the variable region is entirely human, derived from, for example, human heavy chain immunoglobulin loci (e.g., a combination of human IGHV, human IGHD, and human IGHJ genes) and / or human kappa chain immunoglobulin loci (e.g., a combination of human IGKV and human IGKJ genes).

[0232] Furthermore, in some embodiments, the antibodies or antigen-binding fragments described herein may also contain one, two, or three heavy chain variable region CDRs selected from the group consisting of SEQ ID NOs: 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, 86-88, and 89-91, and / or one, two, or three light chain variable region CDRs selected from the group consisting of SEQ ID NOs: 1-3.

[0233] In some embodiments, the antibody may have a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the CDR1 region contains or comprises an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VH CDR1; the CDR2 region contains or comprises an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VH CDR2; and the CDR3 region contains or comprises an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VH CDR3. In some embodiments, the antibody may have a light chain variable region (VL) comprising CDR1, 2, and 3, wherein the CDR1 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VL CDR1; the CDR2 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VL CDR2; and the CDR3 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VL CDR3. The amino acid sequences of the selected VH CDR1, 2, and 3, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in Figure 1A (Kabat's CDR) and Figure 2A (Chothia's CDR).

[0234] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0235] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9

[0236] In some embodiments, the antibody or antigen-binding fragments described herein may contain one, two, or three heavy chain variable domains of the CDRs of SEQ ID NO: 10 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, SEQ ID NO: 11 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, or SEQ ID NO: 12 having 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0237] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15

[0238] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18

[0239] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 19 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, SEQ ID NO: 20 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, or SEQ ID NO: 21 having 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0240] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO: 24, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0241] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0242] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 28, SEQ ID NO: 29, or SEQ ID NO: 30, all of which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0243] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 33, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0244] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO: 36, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0245] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 37, SEQ ID NO: 38, and SEQ ID NO: 39, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0246] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 40 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, SEQ ID NO: 41 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, or SEQ ID NO: 42 having 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0247] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 43, SEQ ID NO: 44, and SEQ ID NO: 45, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0248] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 86, SEQ ID NO: 87, and SEQ ID NO: 88, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0249] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 89 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, SEQ ID NO: 90 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, or SEQ ID NO: 91 having 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0250] In some embodiments, the antibody or antigen-binding fragments described herein may contain one, two, or three light chain variable domains of the CDRs of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3

[0251] Insertions, deletions, and substitutions can be located within the CDR sequence or at one or both ends of the CDR sequence. In some embodiments, the CDR is determined based on the Kabat numbering scheme. In some embodiments, the CDR is determined based on the Chothia numbering scheme. In some embodiments, the CDR is determined based on a combination of the Kabat and Chothia numbering schemes.

[0252] This disclosure also provides an antibody or antigen-binding fragment thereof that binds to PTK7. The antibody or antigen-binding fragment thereof contains a heavy chain variable region (VH) comprising or consisting of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to a selected VH sequence, and a light chain variable region (VL) comprising or consisting of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to a selected VL sequence. In some embodiments, the selected VH sequence is SEQ ID NO: 46, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is SEQ ID NO: 47, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is SEQ ID NO: 48, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is SEQ ID NO: 49, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is SEQ ID NO: 50, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. In some embodiments, the selected VH sequence is sequence number 52, and the selected VL sequence is sequence number 53. In some embodiments, the selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0253] This disclosure also provides antibodies or antigen-binding fragments thereof that are competitive with the antibodies described herein. In some embodiments, the antibodies or antigen-binding fragments may bind to the same epitopes as the antibodies described herein.

[0254] This disclosure also provides nucleic acids comprising polynucleotides encoding polypeptides containing an immunoglobulin heavy chain or an immunoglobulin light chain. The immunoglobulin heavy chain or immunoglobulin light chain contains a CDR as shown in Figure 1A or Figure 2A, or has the sequence shown in Figure 3. When a polypeptide pairs with a corresponding polypeptide (e.g., a corresponding heavy chain variable region or a corresponding light chain variable region), the paired polypeptide binds to PTK7 (e.g., human PTK7).

[0255] Anti-PTK7 antibodies and antigen-binding fragments may also be antibody variants (including derivatives and conjugates) of antibodies or antibody fragments, as well as multispecific (e.g., bispecific) antibodies or antibody fragments. Additional antibodies provided herein include polyclonal, monoclonal, multispecific (multimer, e.g., bispecific), human antibodies, chimeric antibodies (e.g., human-mouse chimeric), single-chain antibodies, intracellularly produced antibodies (i.e., intrabodies), and their antigen-binding fragments. Antibodies or their antigen-binding fragments may be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. In some embodiments, the antibody or its antigen-binding fragment is an IgG antibody or its antigen-binding fragment.

[0256] Antibody fragments are suitable for use in the provided manner, insofar as they retain the desired affinity and specificity of the full-length antibody. Therefore, an antibody fragment that binds to PTK7 retains its ability to bind to PTK7. An Fv fragment is an antibody fragment containing a complete antigen recognition and binding site. This region consists of a dimer in which one heavy chain variable domain and one light chain variable domain are closely associated, which can essentially be covalent, for example, in scFv. In this configuration, the three CDRs of each variable domain interact to define the antigen-binding site on the surface of the VH-VL dimer. Together, the six CDRs, or subsets thereof, confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific CDRs) can have the ability to recognize and bind to an antigen, though usually with lower affinity than the entire binding site.

[0257] In some embodiments, the antibodies or antigen-binding fragments described herein recognize endogenous PTK7 or recombinant PTK7. In some embodiments, the antibodies or antigen-binding fragments described herein recognize human PTK7. In some embodiments, the antibodies or antigen-binding fragments described herein recognize monkey PTK7. In some embodiments, the antibodies or antigen-binding fragments described herein recognize canine PTK7.

[0258] Anti-TROP2 antibody and antigen-binding fragment This disclosure provides antibodies and antigen-binding fragments that specifically bind to TROP2 (e.g., human TROP2, monkey TROP2, or canine TROP2). The antibodies and antigen-binding fragments described herein are capable of binding to TROP2. These antibodies may be agonists or antagonists. In some embodiments, these antibodies can increase the immune response. In some embodiments, these antibodies can inhibit TROP2 activity, such as stimulation of calcium release and activation of the MAPK signaling pathway.

[0259] This disclosure provides, for example, anti-TROP2 antibodies 18E9, 18F12, 6F7, their chimeric antibodies, and their human antibodies or humanized antibodies.

[0260] CDR sequences for 18E9 antibodies and antibodies derived from 18E9 (e.g., human antibodies or humanized antibodies) include the CDRs of the heavy chain variable domain, sequence numbers 57, 58, and 59, and the CDRs of the light chain variable domain, sequence numbers 1, 2, and 3, as defined by Kabat numbering. CDRs can also be defined by the Chothia system. Under Chothia numbering, the CDR sequences of the heavy chain variable domain are shown in sequence numbers 66, 67, and 68, and the CDR sequences of the light chain variable domain are shown in sequence numbers 1, 2, and 3.

[0261] Similarly, the CDR sequences of 18F12 antibodies and antibodies derived from 18F12 include the heavy chain variable domain CDRs, SEQ ID NOs. 60, 61, and 62, and the light chain variable domain CDRs, SEQ ID NOs. 1, 2, and 3, as defined by Kabat. Under Chothia numbering, the heavy chain variable domain CDR sequences are shown as SEQ ID NOs. 69, 70, and 71, and the light chain variable domain CDRs are shown as SEQ ID NOs. 1, 2, and 3.

[0262] The CDR sequences of 6F7 antibodies and antibodies derived from 6F7 include the heavy chain variable domain CDRs, SEQ ID NOs. 54, 55, and 56, and the light chain variable domain CDRs, SEQ ID NOs. 1, 2, and 3, as defined by Kabat numbering. Under Chothia numbering, the heavy chain variable domain CDR sequences are shown in SEQ ID NOs. 63, 64, and 65, and the light chain variable domain CDRs are shown in SEQ ID NOs. 1, 2, and 3.

[0263] The amino acid sequence of the heavy chain variable region of the 18E9 antibody is shown in SEQ ID NO: 73. The amino acid sequence of the light chain variable region of the 18E9 antibody is shown in SEQ ID NO: 53.

[0264] The amino acid sequence of the heavy chain variable region of the 18F12 antibody is shown in SEQ ID NO: 74. The amino acid sequence of the light chain variable region of the 18F12 antibody is shown in SEQ ID NO: 53.

[0265] The amino acid sequence of the heavy chain variable region of the 6F7 antibody is shown in SEQ ID NO: 72. The amino acid sequence of the light chain variable region of the 6F7 antibody is shown in SEQ ID NO: 53.

[0266] The amino acid sequences for the heavy chain variable region and light chain variable region of the modified antibody are also provided. In some embodiments, the heavy chain variable region is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to either one of SEQ ID NOs. 73 and 74. In some embodiments, the light chain variable region is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO. 53. The heavy chain variable region sequence can form a pair with the corresponding light chain variable region sequence, which together bind to TROP2.

[0267] Humanization percentage refers to the percentage of identity of a heavy chain or light chain variable region sequence compared to a human antibody sequence in the International Immunogenetic Information System (IMGT) database. In some embodiments, the humanization percentage exceeds 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or 95%. Detailed descriptions of methods for determining the humanization percentage and methods for determining top hits are well known in the art, for example, in Jones, et al. “The INNs and outs of antibody nonproprietary names.” MAbs. Vol.8. No.1. Taylor & Francis, 2016, which is incorporated herein by reference in its entirety. Higher humanization percentages often have various advantages, such as being safer and more effective in humans, more likely to be accepted by human subjects, and / or less likely to have side effects. In some embodiments, the variable region is entirely human, derived from, for example, human heavy chain immunoglobulin loci (e.g., a combination of human IGHV, human IGHD, and human IGHJ genes) and / or human kappa chain immunoglobulin loci (e.g., a combination of human IGKV and human IGKJ genes).

[0268] Furthermore, in some embodiments, the antibodies or antigen-binding fragments described herein may also contain one, two, or three heavy chain variable region CDRs selected from the group consisting of SEQ ID NOs. 54-56, SEQ ID NOs. 57-59, SEQ ID NOs. 60-62, SEQ ID NOs. 63-65, SEQ ID NOs. 66-68, and SEQ ID NOs. 69-71, and / or one, two, or three light chain variable region CDRs selected from the group consisting of SEQ ID NOs. 1-3.

[0269] In some embodiments, the antibody may have a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the CDR1 region contains or comprises an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VH CDR1; the CDR2 region contains or comprises an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VH CDR2; and the CDR3 region contains or comprises an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VH CDR3. In some embodiments, the antibody may have a light chain variable region (VL) comprising CDR1, 2, and 3, wherein the CDR1 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VL CDR1; the CDR2 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VL CDR2; and the CDR3 region comprises or consists of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to the amino acid sequence of the selected VL CDR3. The amino acid sequences of the selected VH CDR1, 2, and 3, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in Figure 1B (Kabat's CDR) and Figure 2B (Chothia's CDR).

[0270] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 54, SEQ ID NO: 55, and SEQ ID NO: 56, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0271] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 65, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0272] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 57, SEQ ID NO: 58, and SEQ ID NO: 59, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0273] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 60 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, SEQ ID NO: 61 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, or SEQ ID NO: 62 having 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0274] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, or SEQ ID NO: 68, which have 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0275] In some embodiments, the antibody or antigen-binding fragments described herein may contain heavy chain variable domains containing one, two, or three CDRs of SEQ ID NO: 69 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, SEQ ID NO: 70 having 0, 1, or 2 amino acid insertions, deletions, or substitutions, or SEQ ID NO: 71 having 0, 1, or 2 amino acid insertions, deletions, or substitutions.

[0276] In some embodiments, the antibody or antigen-binding fragments described herein may contain one, two, or three light chain variable domains of the CDRs of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3

[0277] Insertions, deletions, and substitutions can be located within the CDR sequence or at one or both ends of the CDR sequence. In some embodiments, the CDR is determined based on the Kabat numbering scheme. In some embodiments, the CDR is determined based on the Chothia numbering scheme. In some embodiments, the CDR is determined based on a combination of the Kabat and Chothia numbering schemes.

[0278] This disclosure also provides an antibody or antigen-binding fragment thereof that binds to TROP2. The antibody or antigen-binding fragment thereof contains a heavy chain variable region (VH) comprising or consisting of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to a selected VH sequence, and a light chain variable region (VL) comprising or consisting of an amino acid sequence that is at least 80%, 85%, 90%, or 95% identical to a selected VL sequence. In some embodiments, the selected VH sequence is SEQ ID NO: 72, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is SEQ ID NO: 73, and the selected VL sequence is SEQ ID NO: 53. In some embodiments, the selected VH sequence is SEQ ID NO: 74, and the selected VL sequence is SEQ ID NO: 53.

[0279] This disclosure also provides antibodies or antigen-binding fragments thereof that are competitive with the antibodies described herein. In some embodiments, the antibodies or antigen-binding fragments may bind to the same epitopes as the antibodies described herein.

[0280] This disclosure also provides nucleic acids comprising polynucleotides encoding polypeptides containing an immunoglobulin heavy chain or an immunoglobulin light chain. The immunoglobulin heavy chain or immunoglobulin light chain contains a CDR as shown in Figure 1B or Figure 2B, or has the sequence shown in Figure 3. When a polypeptide forms a pair with a corresponding polypeptide (e.g., a corresponding heavy chain variable region or a corresponding light chain variable region), the paired polypeptide binds to TROP2 (e.g., human TROP2, monkey TROP2, or canine TROP2).

[0281] Anti-TROP2 antibodies and antigen-binding fragments may also be antibody variants (including derivatives and conjugates) of antibodies or antibody fragments, as well as multispecific (e.g., bispecific) antibodies or antibody fragments. Additional antibodies provided herein include polyclonal, monoclonal, multispecific (multimer, e.g., bispecific), human antibodies, chimeric antibodies (e.g., human-mouse chimeric), single-chain antibodies, intracellularly produced antibodies (i.e., intrabodies), and their antigen-binding fragments. Antibodies or their antigen-binding fragments may be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. In some embodiments, the antibody or its antigen-binding fragment is an IgG antibody or its antigen-binding fragment.

[0282] Antibody fragments are suitable for use in the provided manner, insofar as they retain the desired affinity and specificity of the full-length antibody. Therefore, an antibody fragment that binds to TROP2 retains its ability to bind to TROP2. An Fv fragment is an antibody fragment containing a complete antigen recognition and binding site. This region consists of a dimer in which one heavy chain variable domain and one light chain variable domain are closely associated, which can essentially be covalent, for example, in scFv. In this configuration, the three CDRs of each variable domain interact to define the antigen-binding site on the surface of the VH-VL dimer. Together, the six CDRs, or subsets thereof, confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific CDRs) can have the ability to recognize and bind to an antigen, though usually with lower affinity than the entire binding site.

[0283] In some embodiments, the antibodies or antigen-binding fragments described herein recognize endogenous TROP2 or recombinant TROP2. In some embodiments, the antibodies or antigen-binding fragments described herein recognize human TROP2. In some embodiments, the antibodies or antigen-binding fragments described herein recognize monkey TROP2. In some embodiments, the antibodies or antigen-binding fragments described herein recognize canine TROP2.

[0284] Anti-PTK7 / TROP2 multispecific antibody and antigen-binding fragment This disclosure provides a multispecific (e.g., bispecific) antibody and its antigen-binding fragment that specifically bind to PTK7 / TROP2 (e.g., human PTK7 / TROP2). In one embodiment, this disclosure provides an anti-PTK7 / TROP2 multispecific (e.g., bispecific) antibody or its antigen-binding fragment comprising a first antigen-binding domain that specifically binds to PTK7 and a second antigen-binding domain that specifically binds to TROP2.

[0285] In some embodiments, the first antigen-binding domain comprises a first heavy chain variable region (VH1) and a first light chain variable region (VL1), and the second antigen-binding domain comprises a second heavy chain variable region (VH2) and a second light chain variable region (VL2).

[0286] In some embodiments, the first heavy chain variable region (VH1) includes complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH1 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR1, the VH1 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR2, and the VH1 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR3, and The first light chain variable region (VL1) described above includes CDR1, 2, and 3, wherein the VL1 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR1, the VL1 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR2, and the VL1 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR3. The amino acid sequences of the selected VH1 CDR1, 2, and 3, and the amino acid sequences of the selected VL1 CDR1, 2, and 3, are one of the following: (1) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 4 to 6, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (2) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 7 to 9, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 10 to 12, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 13 to 15, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 16-18, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (6) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 19 to 21, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (7) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (8) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (9) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (10) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 31 to 33, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (11) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 34 to 36, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (12) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 37 to 39, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (13) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (14) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (15) The amino acid sequences of the above-selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 86 to 88, respectively, and the amino acid sequences of the above-selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, and (16) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 89 to 91, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0287] In some embodiments, the second heavy chain variable region (VH2) comprises CDR1, 2, and 3, wherein the VH2 CDR1 region comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR1, the VH2 CDR2 region comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR2, and the VH2 CDR3 region comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR3, and The second light chain variable region (VL2) described above includes CDR1, 2, and 3, wherein the VL2 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR1, the VL2 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR2, and the VL2 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR3. The amino acid sequences of the selected VH2 CDR1, 2, and 3, and the amino acid sequences of the selected VL2 CDR1, 2, and 3, are one of the following: (1) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54-56, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively. (2) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the above-selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66-68, respectively, and the amino acid sequences of the above-selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1-3, respectively, and (6) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0288] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0289] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0290] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0291] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0292] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16-18, the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54-56, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3.

[0293] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0294] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0295] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0296] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0297] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0298] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34-36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0299] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37-39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63-65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0300] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40-42, the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63-65, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3.

[0301] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0302] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0303] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0304] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0305] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0306] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16-18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57-59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0307] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0308] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0309] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0310] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0311] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0312] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34-36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66-68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0313] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37-39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66-68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0314] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40-42, the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66-68, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3.

[0315] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0316] In some embodiments, the amino acid sequences of selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4-6, respectively; the amino acid sequences of selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1, respectively; and the amino acid sequences of selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0317] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0318] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0319] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0320] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16-18, the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60-62, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3.

[0321] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0322] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 22 to 24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3.

[0323] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0324] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0325] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

[0326] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34-36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69-71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0327] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37-39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69-71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1-3, respectively.

[0328] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 40 to 42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0329] In some embodiments, the amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively.

[0330] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 46, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0331] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 47, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0332] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 48, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0333] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 49, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0334] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 50, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0335] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 51, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0336] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 52, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0337] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 46, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0338] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 47, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0339] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 48, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0340] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 49, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0341] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 50, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0342] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 51, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0343] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 52, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0344] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 46, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0345] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 47, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0346] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 48, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0347] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 49, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0348] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 50, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0349] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 51, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0350] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 52, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 74, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0351] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 92, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 72, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0352] In some embodiments, the first heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 92, the first light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53, the second heavy chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 73, and the second light chain variable region includes a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to sequence number 53.

[0353] In some embodiments, VH1 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VH sequence, and VL1 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0354] In some embodiments, the VH2 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VH sequence, and the VL2 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 72, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (3) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

[0355] In some embodiments, VH1 includes VH1 CDR1, VH1 CDR2, and VH1 CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and VL1 includes VL1 CDR1, VL1 CDR2, and VL1 CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

[0356] In some embodiments, VH2 includes VH2 CDR1, VH2 CDR2, and VH2 CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and VL2 includes VL2 CDR1, VL2 CDR2, and VL2 CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 72, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (3) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

[0357] In some embodiments, the first antigen-binding domain specifically binds to human PTK7, mouse PTK7, monkey PTK7, or canine PTK7, and / or the second antigen-binding domain specifically binds to human TROP2, mouse TROP2, monkey TROP2, or canine TROP2.

[0358] In some embodiments, the first antigen-binding domain is a human antigen-binding domain or a humanized antigen-binding domain, and / or the second antigen-binding domain is a human antigen-binding domain or a humanized antigen-binding domain.

[0359] In some embodiments, the first antigen-binding domain is a single-stranded variable fragment (scFV), and / or the second antigen-binding domain is an scFv.

[0360] In some embodiments, the first light chain variable region and the second light chain variable region are the same.

[0361] In some embodiments, knobs-into-holes mutations were introduced into the Fc region of bispecific antibodies to reduce the possibility of mispairing between the two heavy chains. Exemplary bispecific antibodies obtained include 3C4-6F7, 3C4-18E9, 3C4-18F12, 3E6-6F7, 3E6-18E9, and 3E6-18F12 (Figure 5). The sequence of the human IgG1 constant region with the knob mutation is shown in SEQ ID NO: 84, and the sequence of the human IgG1 constant region with the hole mutation is shown in SEQ ID NO: 85.

[0362] In some embodiments, an anti-PTK7 / TROP2 antibody or an antibody fragment thereof comprises a combination of an anti-PTK7 antigen-binding domain and an anti-TROP2 antigen-binding domain, as shown in Figures 1A to 3.

[0363] In some embodiments, 1A7-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1A7 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1A7. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1A7. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0364] In some embodiments, 1A11-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1A11 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain comprises the CDR of 1A11. In some embodiments, the second anti-TROP2 antigen-binding domain comprises the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain comprises the VH and VL of 1A11. In some embodiments, the second anti-TROP2 antigen-binding domain comprises the VH and VL of 6F7.

[0365] In some embodiments, 1F2-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1F2 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1F2. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1F2. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0366] In some embodiments, 2A5-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2A5 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2A5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2A5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0367] In some embodiments, 2D11-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2D11 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2D11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2D11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0368] In some embodiments, 2F5-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2F5 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2F5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2F5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0369] In some embodiments, 3C4-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 3C4 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 3C4. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 3C4. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0370] In some embodiments, 3E6-6F7 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 3E6 and a second anti-TROP2 antigen-binding domain derived from 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 3E6. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 6F7. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 3E6. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 6F7.

[0371] In some embodiments, 1A7-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1A7 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1A7. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1A7. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0372] In some embodiments, 1A11-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1A11 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1A11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1A11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0373] In some embodiments, 1F2-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1F2 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1F2. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1F2. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0374] In some embodiments, 2A5-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2A5 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2A5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2A5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0375] In some embodiments, 2D11-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2D11 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2D11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2D11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0376] In some embodiments, 2F5-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2F5 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2F5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2F5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0377] In some embodiments, 3C4-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 3C4 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 3C4. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 3C4. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0378] In some embodiments, 3E6-18E9 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 3E6 and a second anti-TROP2 antigen-binding domain derived from 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 3E6. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18E9. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 3E6. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18E9.

[0379] In some embodiments, 1A7-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1A7 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1A7. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1A7. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18F12.

[0380] In some embodiments, 1F2-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 1F2 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 1F2. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 1F2. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18F12.

[0381] In some embodiments, 2A5-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2A5 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2A5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2A5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18F12.

[0382] In some embodiments, 2D11-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2D11 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2D11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2D11. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18F12.

[0383] In some embodiments, 2F5-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 2F5 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 2F5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 2F5. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18F12.

[0384] In some embodiments, 3C4-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 3C4 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the CDR of 3C4. In some embodiments, the second anti-TROP2 antigen-binding domain includes the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain includes the VH and VL of 3C4. In some embodiments, the second anti-TROP2 antigen-binding domain includes the VH and VL of 18F12.

[0385] In some embodiments, 3E6-18F12 refers to an anti-PTK7 / TROP2 antibody containing a first anti-PTK7 antigen-binding domain derived from 3E6 and a second anti-TROP2 antigen-binding domain derived from 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain comprises the CDR of 3E6. In some embodiments, the second anti-TROP2 antigen-binding domain comprises the CDR of 18F12. In some embodiments, the first anti-PTK7 antigen-binding domain comprises the VH and VL of 3E6. In some embodiments, the second anti-TROP2 antigen-binding domain comprises the VH and VL of 18F12.

[0386] In some embodiments, 3C4-6F7 contains a knob mutation in the heavy chain constant region of 3C4 and a hole mutation in the heavy chain constant region of 6F7. In some embodiments, the sequence of the light chain constant region is shown in SEQ ID NO: 83, the human IgG1 constant region with the knob mutation is shown in SEQ ID NO: 84, and the human IgG1 constant region with the hole mutation is shown in SEQ ID NO: 85.

[0387] In some embodiments, anti-PTK7 / TROP2 antibodies are bispecific antibodies. Bispecific antibodies can be produced by recombining the interface between a pair of antibody molecules to maximize the proportion of heterodimers recovered from recombinant cell culture. For example, the interface may contain at least a portion of the CH3 domain of the antibody's constant domain. In this method, one or more smaller amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g., tyrosine or tryptophan). By replacing the larger amino acid side chains with smaller ones (e.g., alanine or threonine), a compensatory "cavity" of the same or similar size as the larger side chain is created at the interface of the second antibody molecule. This provides a mechanism to increase the yield of heterodimers compared to other unwanted end products such as homodimers. This method is described, for example, in WO 96 / 27011, which is incorporated in its entirety by reference.

[0388] Any of the anti-PTK7 / TROP2 antibodies or their antigen-binding fragments described herein may be conjugated with a stabilizing molecule (e.g., a molecule that increases the half-life of the antibody or its antigen-binding fragment in a subject or in solution). Non-limiting examples of stabilizing molecules include polymers (e.g., polyethylene glycol) or proteins (e.g., serum albumin, such as human serum albumin). Conjugation with a stabilizing molecule can increase the half-life of the anti-PTK7 / TROP2 antibody or antigen-binding fragment or extend its biological activity in vitro (e.g., in tissue culture or when stored as a pharmaceutical composition) or in vivo (e.g., in humans).

[0389] Anti-PTK7 / TROP2 antibodies or their antigen-binding fragments can also exist in various forms. Many different formats of bispecific antibodies or their antigen-binding fragments are well known in the art, for example, as described in Suurs, et al., “A review of bispecific antibodies and antibody constructs in oncology and clinical challenges,” Pharmacology & Therapeutics (2019), which is incorporated herein by reference in its entirety.

[0390] In some embodiments, the anti-PTK7 / TROP2 antibody is BiTe, (scFv)2, nanobody, nanobody-HSA, DART, TandAb, scDiabody, scDiabody-CH3, scFv-CH-CL-scFv, HSAbody, scDiabody-HAS, or tandem-scFv. In some embodiments, the anti-PTK7 / TROP2 antibody is VHH-scAb, VHH-Fab, Dual scFab, F(ab')2, Diabody, crossMab, DAF(2in1), DAF(4in1), DutaMab, DT-IgG, Knob-in-hole common light chain, Knob-in-hole assembly, Charge pair, Fab arm exchange, SEEDbody, LUZ-Y, Fcab, κλ-body, Orthogonal Fab, DVD-IgG, IgG(H)-scFv, scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH These include IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, Triplebody, Mini-antibody, Minibody, TriBi Minibody, scFv-CH3 KIH, Fab-scFv, F(ab')2-scFv2, scFv-KIH, Fab-scFv-Fc, Tetravalent HCAb, scDiabody-Fc, Diabody-Fc, Tandem scFv-Fc, Intrabody, Dock and Lock, lmmTAC, IgG-IgG conjugate, Cov-X-Body, or scFv1-PEG-scFv2.

[0391] In some embodiments, the anti-PTK7 / TROP2 antibody may be TrioMab. In TrioMab, the two heavy chains originate from different species, and their different sequences limit heavy-light chain pairing.

[0392] In some embodiments, the anti-PTK7 / TROP2 antibody has two distinct heavy chains and one common light chain. Heterodimerization of the heavy chains can be based on knob-into-hole or some other heavy chain pairing technique.

[0393] In some embodiments, CrossMAb technology can be used to produce bispecific anti-PTK7 / TROP2 antibodies. CrossMAb technology can enhance correct light chain association in bispecific heterodimeric IgG antibodies, enabling the generation of various bispecific antibody formats, including bivalent (1+1), trivalent (2+1), and tetravalent (2+2) bispecific antibodies, as well as non-Fc tandem antigen-binding fragment (Fab) based antibodies. These formats can be derived from any existing antibody pair using domain crossover without requiring recognition of a common light chain, post-translational processing / extracorporeal chemical assembly, or the introduction of a series of mutations to enhance correct light chain association. This method is described in Klein et al., “The use of CrossMAb technology for the generation of bi- and multispecific antibodies.” MAbs. Vol.8. No.6. Taylor & Francis, 2016, and is incorporated in its entirety by reference. In some embodiments, the CH1 in the heavy chain is exchanged with the CL domain in the light chain.

[0394] Anti-PTK7 / TROP2 antibodies can be duobody antibodies. The Fab exchange mechanism naturally present in IgG4 antibodies is mimicked in a controlled manner in IgG1 antibodies, a mechanism called controlled Fab exchange. This format can ensure specific pairing between heavy and light chains.

[0395] In the bivariable domain antibody (DVD-Ig), additional VH and variable light chain (VL) domains are added to each N-terminus for bispecific targeting. This format is similar to IgG-scFv, but the added binding domains bind individually to the corresponding N-terminus of each heavy chain, instead of the scFv.

[0396] In scFv-IgG, two scFv molecules are linked to the C-terminus of the heavy chain (CH3). The scFv-IgG format has two distinct divalent binding sites and is therefore also called tetravalent. There is no problem with heavy-light chain pairing in scFv-IgG.

[0397] In some embodiments, the anti-PTK7 / TROP2 antibody may have an IgG-IgG format. Two intact IgG antibodies are conjugated by chemically bonding the C-terminuses of their heavy chains.

[0398] Anti-PTK7 / TROP2 antibodies can also be available in a Fab-scFv-Fc format. In the Fab-scFv-Fc format, a light chain, a heavy chain, and a third chain containing the Fc region and scFv are assembled. This ensures efficient preparation and purification.

[0399] In some embodiments, the anti-PTK7 / TROP2 antibody may be a TF (transfer-forming) antibody. Three Fab fragments are linked by disulfide crosslinks. Two fragments target tumor-associated antigens (TAAs), and one fragment targets a hapten. The TF format does not have an Fc region.

[0400] ADAPTIR has two scFvs bound to both sides of a certain Fc region. It discards the intact IgG that serves as the basis for its construct, but preserves the Fc region, extending its half-life and facilitating purification.

[0401] Biaffinity retargeting (DART) involves two peptide chains linking opposite fragments (i.e., VLA to VHB and VLB to VHA), and a sulfur bond fusing them together at the C-terminus. In DART, the sulfur bond can improve stability compared to BiTE.

[0402] In DART-Fc, the Fc region is bound to DART. This can be generated by assembling three chains (two via disulfide bonds, similar to DART). One chain contains half of the Fc region, which dimerizes with the third chain, expressing only the Fc region. The addition of the Fc region extends the half-life, resulting in a longer effective concentration and avoiding consecutive IV injections.

[0403] In tetravalent DART, four peptide chains are assembled. Essentially, two DART molecules are created by half of the Fc region and then dimerized. This format has divalent bonds to both targets, and therefore, it is a tetravalent molecule.

[0404] A tandem diabody (TandAb) contains two diabodies. Each diabody consists of a VHA and a VLB fragment, and another VHA and a VLB fragment, associated by covalent bonds. The two diabodies are linked by a peptide chain. This can improve stability compared to a diabody composed of two scFvs. It has two divalent bonding sites.

[0405] The scFv-scFv-toxin comprises a toxin and two scFvs containing a stabilizing linker. This can be used for the specific delivery of the payload.

[0406] In some embodiments, the anti-PTK7 / TROP2 antibody is a bispecific antibody. In some embodiments, the bispecific antibody in this disclosure is designed to be 1+1 (monovalent for each target) and has an IgG1 subtype structure. This allows for reduced binding activity to cells with low levels of PTK7 and TROP2 expression, and increased binding activity to cells that co-express PTK7 and TROP2, thereby achieving improved targeting function.

[0407] In some embodiments, the anti-PTK7 / TROP2 antibody or its antigen-binding fragment has a light chain constant region that is at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 83, and a heavy chain constant region that is at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to either one of SEQ ID NOs: 84 and 85.

[0408] In some embodiments, the anti-PTK7 / TROP2 antibody contains a KIH mutation. In some embodiments, the anti-PTK7 / TROP2 antibody contains a first antigen-binding domain that specifically binds to PTK7 and a second antigen-binding domain that specifically binds to TROP2. In some embodiments, the first antigen-binding domain contains a heavy chain (knob heavy chain) containing one or more knob mutations, and the second antigen-binding domain contains a heavy chain (hole heavy chain) containing one or more hole mutations. In some embodiments, the first antigen-binding domain contains a heavy chain (hole heavy chain) containing one or more hole mutations, and the second antigen-binding domain contains a heavy chain (knob heavy chain) containing one or more knob mutations. In some embodiments, the anti-PTK7 / TROP2 antibody comprises a knob heavy chain containing a constant region that is at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 84. In some embodiments, the anti-PTK7 / TROP2 antibody comprises a hole heavy chain containing a constant region that is at least 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 85.

[0409] Antibody and antigen-binding fragments This disclosure provides anti-PTK7 antibodies, anti-TROP2 antibodies, and / or anti-PTK7 / TROP2 antibodies, as well as antigen-binding fragments thereof.

[0410] Generally, antibodies (also called immunoglobulins) consist of two classes of polypeptide chains: a light chain and a heavy chain. Antibodies in this disclosure, in principle, can be intact four-immunoglobulin chain antibodies containing two heavy chains and two light chains. The heavy chains of an antibody can be any isotype, including IgM, IgG, IgE, IgA, or IgD, or a subisotype, including IgG1, IgG2, IgG2a, IgG2b, IgG3, IgG4, IgE1, IgE2, etc. The light chains can be κ-light chains or λ-light chains. An antibody may contain two identical copies of light chains and two identical copies of heavy chains. Each heavy chain, containing one variable domain (or variable region, VH) and multiple constant domains (or constant regions), binds to each other via disulfide bonds within its constant domains, forming the "stem" of the antibody. Each light chain, containing one variable domain (or variable region, VL) and one constant domain (or constant region), is bonded to a heavy chain via a disulfide bond. The variable region of each light chain is aligned with the variable region of the heavy chain to which it is bonded. The variable regions of both the light and heavy chains contain three hypervariable regions sandwiched between more conserved framework regions (FRs).

[0411] The hypervariable region, known as the complementarity-determining region (CDR), forms a loop containing the antibody's antigen-binding surface. The four framework regions are largely adapted to the β-sheet structure, and the CDRs form linked loops, sometimes even forming part of the β-sheet structure. The CDRs of each chain are held in close proximity to the framework regions and, together with the CDRs of other chains, contribute to the formation of the antigen-binding region.

[0412] Methods for identifying the CDR region of an antibody by analyzing its amino acid sequence are well-known, and several definitions of CDRs are commonly used. Kabat's definition is based on sequence variability, while Chothia's definition is based on the location of the structural loop region. These methods and definitions are, for example, found in Martin, “Protein sequence and structure analysis of antibody variable domains,” Antibody Engineering, Springer Berlin Heidelberg, 2001. 422-439, Abhinandan, et al. “Analysis and improvements to Kabat and structurally correct numbering of antibody variable domains,” Molecular Immunology 45.14(2008):3832-3839, Wu, T. and Kabat, EA(1970) J. Exp. Med. 132:211-250, Martin et al., Methods Enzymol. 203:121-53(1991), Morea et al., Biophys Chem. 68(1-3):9-16(Oct. 1997), Morea et al., J Mol Biol. 275(2):269-94(Jan. 1998), Chothia This is described in et al., Nature 342(6252):877-83 (Dec. 1989), and Ponomarenko and Bourne, BMC Structural Biology 7:64 (2007), the entirety of each of these works is incorporated herein by reference.

[0413] CDRs are important for recognizing the epitopes of antigens. As used herein, an “epitope” is the smallest portion of a target molecule that can be specifically bound by the antigen-binding domain of an antibody. The minimum size of an epitope can be about 3, 4, 5, 6, or 7 amino acids, but these amino acids do not need to be in a continuous linear sequence of the primary structure of the antigen, as epitopes can depend on the three-dimensional structure of the antigen based on the secondary and tertiary structures of the antigen.

[0414] In some embodiments, the antibody is an intact immunoglobulin molecule (e.g., IgG1, IgG2a, IgG2b, IgG3, IgM, IgD, IgE, IgA). The IgG subclasses (IgG1, IgG2, IgG3, and IgG4) are highly conserved, differing in their constant regions, particularly the hinge and upper CH2 domain. The sequences and differences of IgG subclasses are well known in the art, and are described, for example, in Vidarsson, et al., “IgG subclasses and allotypes: from structure to effector functions.” Frontiers in immunology 5(2014); Irani, et al., “Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases.” Molecular immunology 67.2(2015):171-182; and Shakib, Farouk, ed. The human IgG subclasses: molecular analysis of structure, function and regulation. Elsevier, 2016, each of which is incorporated herein by reference.

[0415] Antibodies can also be immunoglobulin molecules derived from any species (e.g., humans, rodents, mice, camelids). Antibodies disclosed herein include, but are not limited to, polyclonal, monoclonal, monospecific, multispecific antibodies, and chimeric antibodies containing an immunoglobulin-binding domain fused to another polypeptide. The terms “antigen-binding domain” or “antigen-binding fragment” refer to any portion of an antibody that retains the specific binding activity of an intact antibody, i.e., any portion of an antibody that is specifically capable of binding to an epitope on the target molecule of an intact antibody. This includes, for example, Fab, Fab', F(ab')2, and variants of these fragments. Thus, in some embodiments, an antibody or its antigen-binding fragment may be any polypeptide containing, for example, scFv, Fv, Fd, dAb, bispecific antibodies, bispecific scFv, diabodies, linear antibodies, single-chain antibody molecules, multispecific antibodies formed from antibody fragments, and a binding domain that is an antibody-binding domain, or a binding domain homologous thereto. Non-limiting examples of antigen-binding domains include, for example, the heavy and / or light chain CDRs of an intact antibody, the heavy and / or light chain variable regions of an intact antibody, the full-length heavy or light chain of an intact antibody, or individual CDRs derived from either the heavy or light chain of an intact antibody.

[0416] In some embodiments, antigen-binding fragments can form part of a chimeric antigen receptor (CAR). In some embodiments, the chimeric antigen receptor is a fusion of single-stranded variable fragments (scFv) described herein, fused to the CD3ζ transmembrane and endodomains. In some embodiments, the chimeric antigen receptor also includes intracellular signaling domains derived from various costimulatory protein receptors (e.g., CD28, 41BB, ICOS). In some embodiments, the chimeric antigen receptor includes multiple signaling domains, e.g., CD3z-CD28-41BB, or CD3z-CD28-OX40, for increased potency. Thus, in one aspect, the disclosure further provides cells (e.g., T cells) expressing the chimeric antigen receptor described herein.

[0417] In some embodiments, the scFv has one heavy chain variable domain and one light chain variable domain. In some embodiments, the scFv has two heavy chain variable domains and two light chain variable domains.

[0418] A single-stranded Fv (scFv) or antibody fragment contains the VH and VL domains (or regions) of the antibody, and these domains are located within a single polypeptide chain. Generally, scFv polypeptides further contain a polypeptide linker between the VH and VL domains, which allows the scFv to form a desirable structure for antigen binding.

[0419] The Fab fragment contains variable and constant domains of the light chain, as well as a variable domain and a first constant domain (CH1) of the heavy chain. The F(ab')2 antibody fragment contains a pair of Fab fragments, generally commonally linked near the carboxyl terminus by a hinge cysteine ​​between them. Other chemical linkages of antibody fragments are well known in the art.

[0420] A diabody is a small antibody fragment containing two antigen-binding sites, and this fragment contains VH (VH and VL) attached to VL within the same polypeptide chain. By using a linker that is too short to allow pairing between two domains on the same chain, the domains can be paired with complementary domains on another chain, thereby generating two antigen-binding sites.

[0421] Linear antibodies contain a pair of tandem Fd segments (VH-CH1-VH-CH1) that, together with a complementary light chain polypeptide, form a pair of antigen-binding regions. Linear antibodies may be bispecific or monospecific.

[0422] A single-arm antibody may have a heavy chain and a light chain, as well as a heavy chain fragment containing the CH2 and CH3 domains of IgG. In some embodiments, a single-arm antibody is an antibody having only one of the two antigen-binding arms in a typical antibody. In some embodiments, a single-arm antibody includes an antigen-binding arm (e.g., VH+CH1 and VL+CL) and Fc.

[0423] The antibodies and antibody fragments of this disclosure can be modified within the Fc region to provide a desired effector function or serum half-life. In some embodiments, the Fc region can be modified to silence or reduce complement-dependent cell injury (CDC) or antibody-dependent cell injury (ADCC). In some embodiments, the Fc region can be modified to increase complement-dependent cell injury (CDC) or antibody-dependent cell injury (ADCC).

[0424] Antibody multimerization can be achieved by spontaneous aggregation of antibodies or by chemical or recombinant conjugation techniques known in the art. For example, a certain percentage of purified antibody preparations (e.g., one purified IgG molecule) spontaneously form protein aggregates containing antibody homodimers and other higher-order antibody multimers.

[0425] Alternatively, antibody homodimers can be formed by chemical bonding techniques well known in the art. For example, antibody polymers can be formed using heterobifunctional crosslinking agents, including but not limited to SMCC (4-(maleimidomethyl)cyclohexane-1-carboxylic acid succinimidyl) and SATA (S-acetylthioacetate N-succinimidyl). Exemplary procedures for forming antibody homodimers are described in Ghetie et al. (Proc. Natl. Acad. Sci. USA 94:7509-7514, 1997). Antibody homodimers can be converted to Fab'2 homodimers by pepsin digestion. Another method for forming antibody homodimers is to use the autophilic T15 peptide, as described in Zhao et al. (J. Immunol. 25:396-404, 2002).

[0426] In some embodiments, multispecific antibodies are bispecific antibodies. Bispecific antibodies can be produced by recombining the interface between a pair of antibody molecules to maximize the proportion of heterodimers recovered from recombinant cell culture. For example, the interface may contain at least a portion of the CH3 domain of the antibody's constant domain. In this method, one or more smaller amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g., tyrosine or tryptophan). By replacing the larger amino acid side chains with smaller ones (e.g., alanine or threonine), a compensatory "cavity" of the same or similar size as the larger side chain is created at the interface of the second antibody molecule. This provides a mechanism to increase the yield of heterodimers compared to other unwanted end products such as homodimers. This method is described, for example, in WO 96 / 27011, which is incorporated in its entirety by reference.

[0427] Examples of bispecific antibodies include crosslinked or "heterocomplex" antibodies. For example, one antibody in a heterocomplex can be coupled to avidin and the other to biotin. Heterocomplex antibodies can also be produced using any convenient crosslinking method. Suitable crosslinking agents and techniques are well known in the art and are disclosed in U.S. Patent No. 4,676,980, which is incorporated herein by reference in its entirety.

[0428] Methods for generating bispecific antibodies from antibody fragments are also well known in the art. For example, bispecific antibodies can be prepared using chemical bonding. Brennan et al. (Science 229:81, 1985) describe a procedure in which an intact antibody is cleaved by proteolysis to generate F(ab')2 fragments. These fragments are reduced in the presence of sodium arsenite, a dithiol complexing agent, to stabilize adjacent dithiols and prevent intermolecular disulfide formation. The resulting Fab' fragments are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab'TNB derivatives is then reconverted to a Fab'thiol by reduction with mercaptoethylamine and mixed with an equimolar amount of another Fab'TNB derivative to form a bispecific antibody.

[0429] In some embodiments, bispecific antibodies targeting PTK7 and TROP2 can be generated using the antibody or antigen-binding fragment sequences described herein (e.g., CDR or VH / VL sequences).

[0430] Any antibody or antigen-binding fragment described herein can be conjugated with a stabilizing molecule (e.g., a molecule that increases the half-life of the antibody or its antigen-binding fragment in a subject or in solution). Non-limiting examples of stabilizing molecules include polymers (e.g., polyethylene glycol) or proteins (e.g., serum albumin such as human serum albumin). Conjugation with a stabilizing molecule can increase the half-life of the antibody or antigen-binding fragment or extend its biological activity, either in vitro (e.g., in tissue culture medium or when stored as a pharmaceutical composition) or in vivo (e.g., in humans).

[0431] This disclosure also provides an antibody or an antigen-binding fragment thereof that cross-competes with any antibody or antigen-binding fragment described herein. Cross-competition assays are well known in the art and are described, for example, in Moore et al., “Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein.” Journal of virology 70.3(1996):1863-1872, which is incorporated herein by reference in its entirety. In one embodiment, this disclosure also provides an antibody or an antigen-binding fragment thereof that binds to the same epitope or region as any antibody or antigen-binding fragment described herein. Epitope-binding assays are well known in the art and are described, for example, in Estep et al., “High throughput solution-based measurement of antibody-antigen affinity and epitope binning.” MAbs. Vol.5. No.2. Taylor & Francis, 2013, which is incorporated herein by reference in its entirety.

[0432] To measure the percentage of identity between two amino acid sequences or two nucleic acid sequences, the sequences are aligned for optimal comparison (for example, gaps may be introduced in one or both of the first and second amino acid or nucleic acid sequences to ensure optimal alignment for comparison, and non-homologous sequences may be ignored). Subsequently, amino acid residues or nucleotides at the corresponding amino acid or nucleotide positions are compared. If a position in the first sequence is occupied by the same amino acid residue or nucleotide at the corresponding position in the second sequence, the molecules are identical at that position. The percentage of identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps that need to be introduced to optimally align the two sequences and the length of each gap. For example, sequence comparison and measurement of the percentage of identity between two sequences can be performed using a Blossum62 scoring matrix with a gap penalty 12, a gap extension penalty 4, and a frameshift gap penalty 5.

[0433] Antibody-drug conjugates (ADCs) In some embodiments, the antibodies, antigen-binding fragments thereof, or multispecific antibodies (e.g., bispecific antibodies) described herein can be optionally conjugated with a therapeutic agent using a linker to form an antibody-drug conjugate. The antibody-drug conjugate, comprising the antibody or antigen-binding fragment thereof, can be covalently or noncovalently bound to the therapeutic agent. In some embodiments, the therapeutic agent is a cytotoxic or cell proliferation inhibitor (e.g., monomethyl auristatin E, monomethyl auristatin F, camptothecin, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxyanthracene, meitansinoids (such as DM-1 and DM-4), zione, mitoxantrone, mitramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, epirubicin, and cyclophosphamide, as well as its analogues). In some embodiments, the therapeutic agent is MMAE or MMAF.

[0434] The definitions of specific functional groups and chemical terms are described in detail below. For the purposes of this invention, chemical elements are identified based on the Periodic Table, CAS edition, Handbook of Chemistry and Physics, 75th edition, inside cover, and specific functional groups are defined as generally described herein. Furthermore, general principles of organic chemistry, as well as specific functional groups and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modem Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987.

[0435] All ranges cited herein are inclusive unless explicitly stated otherwise. When a range of values ​​is listed, it is intended to include each value and subrange within that range. For example, "C1-6" is intended to include C1, C2, C3, C4, C5, C6, C1-6, C1-5, C1-4, C1-3, C1-2, C2-6, C2-5, C2-4, C2-3, C3-6, C3-5, C3-4, C4-6, C4-5, and C5-6.

[0436] Any compound or any formula describing and explaining the compounds of this disclosure may have one or more chiral centers. The present invention encompasses all stereoisomers of the compounds herein or any formula describing and explaining the compounds of the present invention. All chiral centers present in any compound or any formula describing and explaining the compounds of the present invention may independently have (R) or (S) configurations. When the bond to the chiral carbon is depicted as a straight line in the structural formula, or when the compound name is written without a (R) or (S) chiral designation for the chiral carbon, it is understood that both the (R) and (S) configurations of each chiral carbon, and therefore each enantiomer or diastereomer and mixtures thereof, are encompassed in the formula or name.

[0437] This disclosure includes all possible enantiomers and diastereomers, as well as mixtures of two or more stereoisomers, e.g., mixtures of enantiomers and / or diastereomers in any proportion. Thus, enantiomers are subject to this disclosure in the form of enantiomerically pure forms, both levorotatory and dextrorotatory anticellar forms, in racemic forms, and in mixtures of two enantiomers in any proportion. In the case of cis / trans isomerism, this disclosure includes both cis and trans forms, as well as mixtures of these forms in any proportion. Preparation of individual stereoisomers can be carried out, as necessary, by separation of mixtures by conventional methods such as chromatography or crystallization, by the use of stereochemically homogeneous starting materials for synthesis, or by stereoselective synthesis. Optionally, derivatization can also be performed before separation of stereoisomers. Separation of mixtures of stereoisomers can be carried out as an intermediate step in the synthesis of the compound, or on the final racemic product. Absolute stereochemistry can be determined, if necessary, by X-ray crystallography of crystalline products or intermediates derivatized with reagents containing stereocenters of known configurations. Alternatively, absolute stereochemistry can be determined by vibrational circular dichroism (VCD) spectroscopy.

[0438] Unless otherwise specified, the structures described herein include compounds that differ only in the presence of one or more isotopically enriched atoms, in other words, compounds in which one or more atoms are replaced by atoms having the same atomic number but with an atomic mass or mass number different from the atomic mass or mass number that is dominant in nature. These compounds are referred to as “isotope variants.” This disclosure is intended to encompass all pharmaceutically acceptable isotopic variants of the compounds of the present invention, or any formulations that describe and explain the compounds of the present invention. Examples of isotopes suitable for inclusion in the compounds of the present invention include, but are not limited to, isotopes of hydrogen (e.g., 2H (i.e., D) and 3H), isotopes of carbon (e.g., 11C, 13C, and 14C), isotopes of chlorine (e.g., 36Cl), isotopes of fluorine (e.g., 18F), isotopes of iodine (e.g., 123I, 125I), isotopes of nitrogen (e.g., 13N, 15N), isotopes of oxygen (e.g., 15O, 17O, and 18O), isotopes of phosphorus (e.g., 32P), and isotopes of sulfur (e.g., 35S). Specific isotopic variants of the compounds, or any formulas that describe and explain the compounds of this disclosure, such as those incorporating radioisotopes, may be useful in tissue distribution studies of drugs and / or substrates. In particular, compounds having the described structures that differ only in that hydrogen is replaced with a heavier isotope, such as deuterium (2H, or D), may be useful in several situations because they may offer certain therapeutic advantages, such as improved metabolic stability, extended half-life in the body, or reduced dose requirements. The compounds of this disclosure, or any isotopic variants of the compounds of this disclosure, can generally be prepared by art known to those skilled in the art, or by processes similar to those described in the accompanying examples and synthesis, using appropriate isotope-labeled reagents instead of previously used unlabeled reagents.

[0439] The compounds provided herein are described with reference to both general formulas and specific compounds. Furthermore, all compounds of this disclosure may exist in numerous different forms or derivatives within the scope of this disclosure. These include, for example, pharmaceutically acceptable salts, tautomers, stereoisomers, racemic mixtures, positional isomers, prodrugs, solvated forms, different crystalline forms or polymorphs, and active metabolites.

[0440] As used herein, the term “pharmaceutically acceptable salt” includes, unless otherwise specified, salts that retain the biological efficacy of the free acid / base form of a particular compound and are not biologically or otherwise undesirable. Pharmaceutically acceptable salts may include salts formed with inorganic bases or acids and organic bases or acids. Where a compound of the Disclosure contains one or more acidic or basic groups, the Disclosure also includes the corresponding pharmaceutically acceptable salts thereof. Thus, compounds of the Invention containing acidic groups such as carboxyl groups can exist in the form of salts and can be used in accordance with the Invention, for example, as alkali metal salts, alkaline earth metal salts, aluminum salts, or ammonium salts. More non-limiting examples of these salts include lithium salts, sodium salts, potassium salts, calcium salts, magnesium salts, barium salts, or salts with ammonia or organic amines such as ethylamine, ethanolamine, diethanolamine, triethanolamine, piperidine, N-methylglutamine, or amino acids. These salts can be readily obtained, for example, by reacting a compound having an acidic group with a suitable base, such as lithium hydroxide, sodium hydroxide, sodium propoxide, potassium hydroxide, potassium ethoxide, magnesium hydroxide, calcium hydroxide, or barium hydroxide. Other base salts of the compounds of this disclosure include, but are not limited to, copper(I), copper(II), iron(II), iron(III), manganese(II), and zinc salts. Compounds of this disclosure containing one or more basic groups, such as protonable groups, can exist in the form of salts and can be used according to the present invention in the form of addition salts with inorganic or organic acids.Examples of suitable acids include hydrogen chloride, hydrogen bromide, hydrogen iodide, phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, sulfoacetic acid, trifluoroacetic acid, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, carbonic acid, formic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, malic acid, embonic acid, mandelic acid, sulfamic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid, taurocholic acid, glutaric acid, stearic acid, glutamic acid, or aspartic acid, and other acids known to those skilled in the art. The salts formed include, among others, hydrochlorides, chlorides, hydrobroms, bromides, iodides, sulfates, phosphates, methanesulfons (mesylates), tosylates, carbonates, bicarbonates, formates, acetates, sulfoacetates, triflates, oxalates, malons, maleates, succinates, tartrates, malates, emponates, mandelates, fumarates, lactates, citrates, glutarates, stearates, aspartates, and glutamates. The stoichiometry of the salts formed from the compounds of this disclosure may further be an integer multiple of 1 or a non-integer multiple.

[0441] Compounds of the present disclosure containing a basic nitrogen-containing group can be quaternized using reagents such as methyl, ethyl, isopropyl, and C1-4 alkyl halides such as tert-butyl chloride, bromide, and iodide; diC1-4 alkyl sulfates such as dimethyl, diethyl, and diamyl sulfate; C10-18 alkyl halides such as decyl, dodecyl, lauryl, myristyl, and stearyl chloride, bromide, and iodide; and aryl C1-4 alkyl halides such as benzyl chloride and phenethyl bromide.

[0442] Where the compounds of this disclosure contain both acidic and basic groups in their molecules, this disclosure also includes internal salts or betaines (amphoteric ions) in addition to the salt forms described above. Each salt can be obtained by conventional methods known to those skilled in the art, for example, by contacting them with organic or inorganic acids or bases in a solvent or dispersant, or by anion exchange or cation exchange with other salts. This disclosure also includes all salts of the compounds of this disclosure that are not suitable for direct use in pharmaceuticals due to their poor physiological compatibility, but can be used, for example, as intermediates in chemical reactions or in the preparation of pharmaceutically acceptable salts. For a more appropriate review of salts, see Stahl and Wermuth, Handbook of Pharmaceutical Salts: Properties, Selection, and Use (Wiley-VCH, 2002).

[0443] Any formula describing and explaining a compound or a compound of the disclosure and its pharmaceutically acceptable salts may exist in both non-solvated and solvated forms. As used herein, the term “solvate” refers to a molecular complex comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable solvent molecules. For example, the term “hydrate” is used when the solvent is water.

[0444] The pharmaceutically acceptable solvates provided herein may include those in which the crystallization solvent is isotope-substituted, such as D2O, d6-acetone, and d6-DMSO.

[0445] Linker (binding compound) In some embodiments, the therapeutic agent is conjugated via a linker (or binding compound). As used herein, the terms “linker” or “binding compound” refer to a compound that can form a ligand-drug conjugate by conjugating a ligand (e.g., an antibody, its antigen-binding fragment, or an antigen-binding protein construct (e.g., a bispecific antibody)) and a therapeutic agent (e.g., any of the therapeutic agents described herein) with the groups of the ligand compound and the therapeutic agent compound, respectively, for example, by a coupling reaction.

[0446] In some embodiments, the linkers described herein are compounds having the following formula or pharmaceutically acceptable salts, solvates, stereoisomers, or isotopic variants thereof. [ka] Equation (I), In the formula, Q represents a junction that can be coupled to a ligand via a bond selected from the group consisting of carbonyl, thioether, amide, disulfide, and hydrazone bonds, and L represents a linker that can bind Q to a therapeutic agent.

[0447] In some embodiments, the joint portion (Q in formula (I)) has the following structure. [ka]

[0448] In some embodiments, the linker portion (L in formula (I)) has the following formula. [ka] In the formula, L1 is a polypeptide residue consisting of 3 to 8 amino acid residues, including at least one amino acid residue having a side-chain carboxyl group, such as a glutamic acid residue or an aspartic acid residue, where "-COOH" indicates the carboxyl group of the C-terminal amino acid residue of the polypeptide residue. L2 is either absent or a monodentate, bidentate, or tridentate hydrophilic group attached to the side chain carboxyl group on the amino acid residue of polypeptide residue L1, and L2 has the structure -NHC(RL2a)(RL2b)(RL2c), where RL2a, RL2b, and RL2c are independently selected from the group consisting of H, -(CH2O)(CH2CH2O)m(CH2)pC(O)OH, and -(CH2O)(CH2CH2O)m(CH2)pC(O)NHRL2d, and RL2d is H or a C1-6 alkyl group optionally substituted with 1 to 6 hydroxyl groups, and each m is independently 0 to 10, preferably 0 to 4, for example 0, 1, 2, 3, or 4, and particularly preferably m is 0, and each p is independently 1 to 4, for example 1, 2, 3, or 4, and [ka] This indicates the N-terminal side of the polypeptide residue covalently bonded to the junction Q.

[0449] In some embodiments, polypeptide residue L1 is NH-Glu-Val-Ala-COOH. In some embodiments, the hydrophilic group L2 has the following structure. [ka] In the formula, "*" indicates a site covalently bonded to polypeptide residue L1, such as the side chain of the Glu residue in NH-Glu-Val-Ala-COOH.

[0450] In some embodiments, the linker described herein is a compound having the following structure. [ka]

[0451] In some embodiments, the linker is a VC linker. Details of the linker used in ADCs can be found, for example, in Su, Z. et al. “Antibody-drug conjugates: Recent advances in linker chemistry.” Acta Pharmaceutica Sinica B (2021), which is incorporated in its entirety by reference.

[0452] Therapeutic drugs In some embodiments, the antibodies described herein, their antigen-binding fragments, or therapeutic agents conjugated to multispecific antibodies (e.g., bispecific antibodies) are described below.

[0453] In some embodiments, the therapeutic agents described herein are cytotoxic agents. In some embodiments, the cytotoxic agent is a camptothecin compound, its analogue, or derivative. In some preferred embodiments, the camptothecin compound is a compound having the following structure. [ka] In the formula, X is selected from the group consisting of -CH2-, O, and S, and Y is selected from the group consisting of H, D, and F.

[0454] In some embodiments, the therapeutic agent is (S)-4-amino-9-ethyl-9-hydroxy-1,9,12,15-tetrahydro-13H-pyrano[3',4':6,7]indolidino[1,2-b]thiopyrano[4,3,2-de]quinoline-10,13(2H)-dione) (CPT-1). The structure of CPT-1 is shown below. [ka]

[0455] In some embodiments, the therapeutic agent is (S)-4-amino-9-ethyl-9-hydroxy-1,9,12,15-tetrahydro-13H-pyrano[4,3,2-de]pyrano[3',4':6,7]indolidino[1,2-b]quinoline-10,13(2H)-dione (CPT-2). The structure of CPT-2 is shown below. [ka]

[0456] In some embodiments, the therapeutic agent is CPT3. The structure of CPT-3 is shown below. [ka]

[0457] In some embodiments, the therapeutic agent is (S)-4-amino-9-ethyl-5-fluoro-9-hydroxy-1,9,12,15-tetrahydro-13H-pyrano[4,3,2-de]pyrano[3',4':6,7]indolidino[1,2-b]quinoline-10,13(2H)-dione (CPT-4). The structure of CPT-4 is shown below. [ka]

[0458] In some embodiments, the therapeutic agent is an auristatin, such as auristatin E (also known in the art as a derivative of drastatin-10), or a derivative thereof. Auristatin can be, for example, an ester formed of auristatin E with a keto acid. For example, auristatin E can react with paraacetylbenzoic acid or benzoylvaleric acid to produce AEB and AEVB, respectively. Other typical auristatins include AFP, MMAF, and MMAE. The synthesis and structure of exemplary auristatins are described in U.S. Patent Publication No. 2003-0083263, International Patent Publication No. WO 04 / 010957, and International Patent Publication No. WO U.S. Patent Nos. 02 / 088172, and U.S. Patent Nos. 7,498,298, 6,884,869, 6,323,315, 6,239,104, 6,034,065, 5,780,588, 5,665,860, 5,663,149, 5,635,483, 5,599,902, 5,554,725, 5,530,097, 5, These are described in Patent Nos. 521,284, 5,504,191, 5,410,024, 5,138,036, 5,076,973, 4,986,988, 4,978,744, 4,879,278, 4,816,444, and 4,486,414, each of which is incorporated herein by reference for all purposes.

[0459] Auristatin has been shown to interfere with microtubule dynamics, as well as nuclear and cell division, and has been shown to possess anticancer activity. Auristatin can bind to tubulin and exert cytotoxic or cell proliferation inhibitory effects in cancer cells. Numerous well-known assays exist in the art that can be used to measure whether auristatin or the resulting antibody-drug conjugate exerts cell proliferation inhibitory or cytotoxic effects in desired cells.

[0460] In some embodiments, the therapeutic agent is a chemotherapeutic agent. Examples of chemotherapeutic agents include thiotepa and cyclosphosphamide (CYTOXAN). TMAlkylating agents such as ); alkyl sulfonates such as busulfan, improsulfan, and biposulfan; aziridines such as benzodopa, carbocone, metsuredopa, and uredopa; ethyleneimines and methylamelamamines such as altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide, and trimethylolomelamamine; chlorambucil, chlornafadin, colophosphamide, estramustine, ifosfamide, mechloretamine, mechloretamine oxide hydrochloride, melphalan, nobenbitin, f Nitrogen mustards such as enesterine, prednimastine, trophosphamide, and uracil mustard; nitrosoureas such as carmastine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimustine; acrasinomycin, actinomycin, anthramycin, azaserine, bleomycin, kactinomycin, calicheamicin, carabicin, carminomycin, cardinophiline, chromomycin, dactinomycin, daunorubicin, detrubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin, epi Antibiotics such as rubicin, esorubicin, idarubicin, marcelomycin, mitomycin, mycophenolic acid, nogaramycin, olibomycin, peplomycin, potophyllomycin, puromycin, keramycin, rhodorubicin, streptonigrin, streptozocin, tubercidine, ubenimex, dinostatin, and zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, and trimethrexate; fludarabine, 6-mercaptopri Purine analogs such as thiamiprine and thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, phloxuridine, and 5-FU; androgens such as carsterone, dromostanolone propionate, epithiostanol, mepitiostane, and testolactone; anti-adrenal agents such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as folinic acid; acegraton; aldofamide glycoside; aminolevulinic acid; amsacrine;Best Love Sil; Bisanthren; Edatrexate; Defofamine; Demecoltin; Diadiquan; Elfomitin; Elliptinium acetate; Etoglucide; Gallium nitrate; Hydroxyurea; Lentinan; Ronidamin; Mitoguazone; Maitoxantrone; Mopidamol; Nitracrine; Pentostatin; Fenamet; Pirarubicin; Podophyllic acid; 2-Ethylhydrazide; Procarbazine; PSK 7; Lazoxane; Schizophyllan; Spirogermanium; Tenuazonic acid; Triadiquan; 2,2',2''-Trichlorotriethylamine; Urethane; Vindesine; Dacarbazine; Mannomustine; Mitobronitol; Mitractol; Pipobroman; Gacitosine; Arabinoside ("Ara-C"); Cyclophosphamide; Taxanes, e.g., Paclitaxel (TAXOL®, Bristol-Myers Examples include Squibb Oncology (Princeton, New Jersey), doxetaxel (TAXOTERE®, Rhone-Poulenc Rorer, Antony, France), chlorambucil, gemcitabine, 6-thioguanine, platinum analogs such as cisplatin or carboplatin, vinblastine, platinum, etoposide (VP-16), ifosfamide, mitomycin C, mitoxantrone, vincristine, vinorelbine, navelbine, novantrone, teniposide, daunomycin, aminopterin, xeloda, ibandronate, CPT-11, topoisomerase inhibitor RFS 2000, difluoromethylornithine (DMFO); retinoic acid; esperamicin; capecitabine; and any pharmaceutically acceptable salts, acids, or derivatives of the above. This definition includes, for example, tamoxifen, raloxifen, aromatase inhibitor 4(5)imidazole, 4-hydroxytamoxifen, trioxyfen, keoxyfen, LY117018, onapristone, and toremifene (Fareston); as well as antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin;Furthermore, anti-hormonal agents that modulate or inhibit hormonal activity in tumors, such as anti-estrogen agents containing any of the pharmaceutically acceptable salts, acids, or derivatives mentioned above, are also included. A detailed description of chemotherapeutic agents can be found, for example, in US20180193477A1, which is incorporated in its entirety by reference.

[0461] Linker therapeutic compound In some embodiments, a linker (e.g., any of the linkers described herein) and a therapeutic agent (e.g., any of the therapeutic agents described herein) can be linked to form a "linker-therapeutic agent" compound.

[0462] In some embodiments, the linker therapeutic compound has the following structure. [ka]

[0463] In some embodiments, the linker therapeutic compound has the following structure. [ka]

[0464] In some embodiments, an antibody ("Ab"), for example, an antibody described herein, its antigen-binding fragment, or an antigen-binding protein construct (e.g., a bispecific antibody), can be linked to a linker therapeutic compound (e.g., any of the linker therapeutic compounds described herein) to generate an antibody-drug conjugate. In some embodiments, the antibody-drug conjugate has the following structure. [ka] In the formula, n = 1, 2, 3, 4, 5, 6, 7, or 8.

[0465] The drug load is expressed by the number of drug moieties per antibody in the ADC molecule. For some antibody-drug conjugates, the drug load can be limited by the number of binding sites on the antibody. For example, when the binding is cysteinethiol, as in certain exemplary embodiments described herein, the drug load can range from 0 to 8 drug moieties per antibody. In certain embodiments, a high drug load, e.g., p ≥ 5, may cause aggregation, insolubility, toxicity, or cell permeability of a particular antibody-drug conjugate. In certain embodiments, the average drug load for an antibody-drug conjugate is in the range of 1 to about 8, about 2 to about 6, or about 3 to about 5. In fact, it has been shown that for a particular antibody-drug conjugate, the optimal ratio of drug moieties per antibody can be about 4. In some embodiments, the drug-antibody ratio (DAR) of the ADCs described herein is about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, or about 9.0.In some embodiments, the DAR of the ADC described herein is approximately 3.5 to approximately 4.5, approximately 3.6 to approximately 4.5, approximately 3.7 to approximately 4.5, approximately 3.8 to approximately 4.5, approximately 3.9 to approximately 4.5, approximately 4.0 to approximately 4.5, approximately 4.1 to approximately 4.5, approximately 4.2 to approximately 4.5, approximately 4.3 to approximately 4.5, approximately 4.4 to approximately 4.5, approximately 3.5 to approximately 4.4, and approximately 3.6 ~approximately 4.4, approximately 3.7~approximately 4.4, approximately 3.8~approximately 4.4, approximately 3.9~approximately 4.4, approximately 4.0~approximately 4.4, approximately 4.1~approximately 4.4, approximately 4.2~approximately 4.4, approximately 4.3~approximately 4.4, approximately 3.5~approximately 4.3, approximately 3.6~approximately 4.3, approximately 3.7~approximately 4.3, approximately 3.8~approximately 4.3, approximately 3.9~approximately 4.3, approximately 4.0~approximately 4.3, approximately 4.1~approximately 4.3, approximately 4.2~approx. 4.3, approx. 3.5~approx. 4.2, approx. 3.6~approx. 4.2, approx. 3.7~approx. 4.2, approx. 3.8~approx. 4.2, approx. 3.9~approx. 4.2, approx. 4.0~approx. 4.2, approx. 4.1~approx. 4.2, approx. 3.5~approx. 4.1, approx. 3.6~approx. 4.1, approx. 3.7~approx. 4.1, approx. 3.8~approx. 4.1, approx. 3.9~approx. 4.1, approx. 4.0~approx. 4.1, approx. 3.5~approx. 4. The average DAR in the composition is approximately 0, 3.6 to 4.0, 3.7 to 4.0, 3.8 to 4.0, 3.9 to 4.0, 3.5 to 3.9, 3.6 to 3.9, 3.7 to 3.9, 3.8 to 3.9, 3.5 to 3.8, 3.6 to 3.8, 3.7 to 3.8, 3.5 to 3.7, 3.6 to 3.7, or 3.5 to 3.6. In some embodiments, the average DAR in the composition is approximately 1 to 2, 2 to 3, 3 to 4, 3 to 5, 4 to 5, 5 to 6, 6 to 7, or 7 to 8.

[0466] In some embodiments, the DAR of the ADC described herein is approximately 7.5 to 8.5, approximately 7.6 to 8.5, approximately 7.7 to 8.5, approximately 7.8 to 8.5, approximately 7.9 to 8.5, approximately 8.0 to 8.5, approximately 8.1 to 8.5, approximately 8.2 to 8.5, approximately 8.3 to 8.5, approximately 8.4 to 8.5, approximately 7.5 to 8.4, and approximately 7.6. ~approximately 8.4, approximately 7.7~approximately 8.4, approximately 7.8~approximately 8.4, approximately 7.9~approximately 8.4, approximately 8.0~approximately 8.4, approximately 8.1~approximately 8.4, approximately 8.2~approximately 8.4, approximately 8.3~approximately 8.4, approximately 7.5~approximately 8.3, approximately 7.6~approximately 8.3, approximately 7.7~approximately 8.3, approximately 7.8~approximately 8.3, approximately 7.9~approximately 8.3, approximately 8.0~approximately 8.3, approximately 8.1~approximately 8.3, approximately 8.2~approx. 8.3, approx. 7.5~approx. 8.2, approx. 7.6~approx. 8.2, approx. 7.7~approx. 8.2, approx. 7.8~approx. 8.2, approx. 7.9~approx. 8.2, approx. 8.0~approx. 8.2, approx. 8.1~approx. 8.2, approx. 7.5~approx. 8.1, approx. 7.6~approx. 8.1, approx. 7.7~approx. 8.1, approx. 7.8~approx. 8.1, approx. 7.9~approx. 8.1, approx. 8.0~approx. 8.1, approx. 7.5~approx. 8. 0, approximately 7.6-8.0, approximately 7.7-8.0, approximately 7.8-8.0, approximately 7.9-8.0, approximately 7.5-7.9, approximately 7.6-7.9, approximately 7.7-7.9, approximately 7.8-7.9, approximately 7.5-7.8, approximately 7.6-7.8, approximately 7.7-7.8, approximately 7.5-7.7, approximately 7.6-7.7, or approximately 7.5-7.6.

[0467] In some embodiments, the anti-PTK7 ADC, anti-TROP2 ADC, and / or PTK7 / TROP2 ADC described herein can effectively inhibit the proliferation of cancer cells in vitro at concentrations of less than 10 μg / mL, less than 3.33 μg / mL, less than 1.11 μg / mL, less than 0.37 μg / mL, less than 0.12 μg / mL, less than 0.04 μg / mL, or less than 0.01 μg / mL. In some embodiments, the anti-PTK7 ADC, anti-TROP2 ADC, and / or anti-PTK7 / TROP2 ADC described herein can inhibit the proliferation of cancer cells in vivo (e.g., lung cancer, gastric cancer, or skin cancer) in xenograft mouse models at dose levels of less than 10 mg / kg, 9 mg / kg, 8 mg / kg, 7 mg / kg, 6 mg / kg, 5 mg / kg, 4 mg / kg, 3 mg / kg, 2 mg / kg, 1.5 mg / kg, or less than 1 mg / kg.

[0468] Antibody and ADC characteristics In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, can inhibit the binding between PTK7 and PTK7 ligand (e.g., Wnt ligand). In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, can inhibit the binding between TROP2 and TROP2 ligand (e.g., neuregulin 1, an ErbB3 ligand). In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, can inhibit the binding between PTK7 and PTK7 ligand and the binding between TROP2 and TROP2 ligand.

[0469] The antibodies or antigen-binding fragments thereof, or ADCs derived therefrom, described in this specification can be agonists or antagonists. In some embodiments, by binding to PTK7, the antibody can inhibit the PTK7 signaling pathway. In some embodiments, by binding to TROP2, the antibody can inhibit the TROP2 signaling pathway. In some embodiments, by binding to PTK7 and TROP2, the antibody can inhibit the PTK7 signaling pathway and the TROP2 pathway. In some embodiments, the antibody can upregulate or downregulate the immune response.

[0470] In some embodiments, the antibody (or antigen-binding fragment thereof), or ADC derived therefrom, specifically binds to PTK7 (e.g., human PTK7, monkey PTK7 (e.g., rhesus monkey, cynomolgus monkey), dog PTK7, mouse PTK7) with a dissociation rate (koff) of less than 0.1 s -1 less than 0.01 s -1 less than 0.001 s -1 less than 0.0001 s -1 less than 0.00001 s -1 less than 0.000001 s -1 less than, or 0.0000001 s -1 less than. In some embodiments, the dissociation rate (koff) is greater than 0.01 s -1 greater than 0.001 s -1 greater than 0.0001 s -1 greater than 0.00001 s -1 greater than 0.000001 s -1 greater than 0.0000001 s -1 greater than, or 0.00000001 s -1 greater than.

[0471] [[ID=​​​Less than 0.001s -1 Less than 0.0001s -1 Less than 0.00001s -1 Less than 0.000001s -1 Less than, or 0.0000001s -1 It binds specifically at a dissociation rate (koff) of less than 0.01s. In some embodiments, the dissociation rate (koff) is 0.01s. -1 Super, 0.001s -1 Super, 0.0001s -1 Super, 0.00001s -1 Super, 0.000001s -1 Super, 0.0000001s -1 Greater than, or 0.00000001s -1 It's incredible.

[0472] In some embodiments, the kinetic velocity (kon) of PTK7 or TROP2 is 1 × 10⁻⁶ 2 / Ms super, 1×10 3 / Ms super, 1×10 4 / Ms super, 1×10 5 / Ms greater than, or 1 × 10⁻⁶ 6 It is greater than / Ms. In some embodiments, the motor velocity (kon) is 1 × 10⁻⁶. 5 / Ms less than 1 × 10 6 Less than / Ms, or 1 × 10 7 It is less than / Ms.

[0473] Affinity can be estimated from the quotient of the velocity constant (KD = koff / kon). In some embodiments, the KD of PTK7 or TROP2 is 1 × 10⁻⁶ -6 Less than M, 1 x 10 -7 Less than M, 1 x 10 -8 Less than M, 1 x 10 -9 Less than M, 1 x 10 -10 Less than M, 1 x 10 -11 Less than M, 1 x 10 -12 Less than M, 1 x 10 -13 Less than M, or 1 × 10 -14It is less than M. In some embodiments, KD is 50nM, 30nM, 20nM, 15nM, 10nM, 9nM, 8nM, 7nM, 6nM, 5nM, 4nM, 3nM, 2nM, or less than 1nM. In some embodiments, KD is 1 × 10⁻¹⁶ -7 Super M, 1×10 -8 Super M, 1×10 -9 Super M, 1×10 -10 Super M, 1×10 -11 Super M, 1×10 -12 Super M, 1×10 -13 Super M, 1×10 -14 It is greater than M.

[0474] Common techniques for measuring the affinity of an antibody to an antigen include, for example, ELISA, RIA, and surface plasmon resonance (SPR). In some embodiments, the antibody binds to human PTK7 (SEQ ID NO: 75), monkey PTK7, canine PTK7 (SEQ ID NO: 76), and / or mouse PTK7. In some embodiments, the antibody does not bind to human PTK7, monkey PTK7, canine PTK7, and / or mouse PTK7.

[0475] In some embodiments, the antibody binds to human TROP2, monkey TROP2, canine TROP2, and / or mouse TROP2. In some embodiments, the antibody does not bind to human TROP2, monkey TROP2, canine TROP2, and / or mouse TROP2.

[0476] In some embodiments, the antibody binds to human PTK7 and TROP2 (PTK7 / TROP2), monkey PTK7 / TROP2, canine PTK7 / TROP2, and / or mouse PTK7 / TROP2. In some embodiments, the antibody does not bind to human PTK7 / TROP2, monkey PTK7 / TROP2, canine PTK7 / TROP2, and / or mouse PTK7 / TROP2.

[0477] In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, are added to NUGC-4 cells (Cobioer, catalog number: CBP60493) or LN229 cells (ATCC, catalog number: CRL-2611) to test the endocytosis ratio. In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, have an endocytosis ratio greater than 5%, greater than 10%, greater than 15%, greater than 20%, greater than 25%, greater than 30%, greater than 35%, greater than 40%, greater than 45%, greater than 50%, greater than 55%, greater than 60%, greater than 65%, greater than 70%, greater than 75%, greater than 80%, greater than 85%, greater than 90%, greater than 91%, greater than 92%, greater than 93%, greater than 94%, greater than 95%, greater than 96%, greater than 97%, or greater than 98%.

[0478] In some embodiments, thermal stability is measured. Antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, may have a Tm of 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or greater than 95°C. In some embodiments, Tm is 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or less than 95°C.

[0479] In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, can bind to the same epitope of PTK7, TROP2, and / or PTK7 / TROP2. In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, can bind to different epitopes of PTK7, TROP2, and / or PTK7 / TROP2.

[0480] In some embodiments, the ADCs described herein have a mean drug-antibody ratio (DAR) greater than 3, greater than 3.2, greater than 3.4, greater than 3.6, greater than 3.8, greater than 4, greater than 4.2, greater than 4.4, or greater than 4.6, as determined by HPLC. In some embodiments, the ADCs described herein have a mean DAR less than 3, less than 3.2, less than 3.4, less than 3.6, less than 3.8, less than 4, less than 4.2, less than 4.4, or less than 4.6, as determined by HPLC.

[0481] In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, have a tumor growth inhibition percentage (TGI%) greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or 200%. In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, have a tumor growth inhibition percentage less than 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or 200%. TGI% can be measured, for example, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days after the start of treatment, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months after the start of treatment. As used herein, the tumor growth inhibition rate (TGI%) is calculated using the following formula. TGI(%)=[1-(Ti-T0) / (Vi-V0)]×100 Ti is the mean tumor volume in the treatment group on day i. T0 is the mean tumor volume in the treatment group on day 0. Vi is the mean tumor volume in the control group on day i. V0 is the mean tumor volume in the control group on day 0.

[0482] In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, are PTK7 antagonists. In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, reduce PTK7 signaling in target cells expressing PTK7.

[0483] In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, are TROP2 antagonists. In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, reduce TROP2 signaling in target cells expressing TROP2.

[0484] In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, are PTK7 and TROP2 (PTK7 / TROP2) antagonists. In some embodiments, the antibodies or antigen-binding fragments thereof described herein, or ADCs derived therefrom, reduce PTK7 and TROP2 (PTK7 / TROP2) signaling in target cells expressing PTK7 and TROP2 (PTK7 / TROP2).

[0485] In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, can enhance the function of APCs (e.g., DC cells), for example, by inducing the surface expression of costimulatory molecules and MHC molecules, inducing the production of pro-inflammatory cytokines, and / or enhancing T cell triggering function.

[0486] In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, can bind to tumor cells expressing PTK7. In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, can bind to tumor cells expressing TROP2. In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, can bind to tumor cells expressing both PTK7 and TROP2. In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, can induce complement-dependent cell-mediated cytotoxicity (CDC) and / or antibody-dependent cell-mediated cytotoxicity (ADCC), thereby killing tumor cells.

[0487] In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, have a functional Fc region. In some embodiments, the effector function of the functional Fc region is antibody-dependent cell-mediated cytotoxicity (ADCC). In some embodiments, the effector function of the functional Fc region is phagocytosis. In some embodiments, the effector functions of the functional Fc region are ADCC and phagocytosis.

[0488] In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, can induce complement-dependent cell-mediated cytotoxicity (CDC).

[0489] In some embodiments, the Fc region is human IgG1, human IgG2, human IgG3, or human IgG4. In some embodiments, the antibody is a human IgG1 antibody optionally having the SI mutation, LALA mutation, N297A mutation, YTE mutation, and / or FLAA mutation. In some embodiments, the antibody is a human IgG4 antibody optionally having the SI mutation, LALA mutation, N297A mutation, YTE mutation, and / or FLAA mutation.

[0490] In some embodiments, the antibodies or antigen-binding fragments described herein, or ADCs derived therefrom, do not have a functional Fc region. For example, the antibodies or antigen-binding fragments are Fab, Fab', F(ab')2, and Fv fragments. In some embodiments, the Fc region has LALA mutations (L234A and L235A mutations according to EU numbering) or LALA-PG mutations (L234A, L235A, and P329G mutations according to EU numbering). In some embodiments, the Fc region has FLAA mutations (F234A and L235A according to EU numbering). In some embodiments, Fc has SI mutations (S239D and I332E mutations according to EU numbering). In some embodiments, Fc has the N297A mutation according to EU numbering. In some embodiments, Fc has YTE mutations (M252Y, S254T, and T256E according to EU numbering).

[0491] Method for producing anti-PTK7 antibody, anti-TROP2 antibody, and / or anti-PTK7 / TROP2 antibody. Isolated fragments of human PTK7 and / or human TROP2 can be used as immunogens to generate antibodies using standard techniques for the preparation of polyclonal and monoclonal antibodies. Polyclonal antibodies can be produced in animals by multiple injections (e.g., subcutaneous or intraperitoneal injection) of the antigen peptide or protein. In some embodiments, the antigen peptide or protein is injected with at least one adjuvant. In some embodiments, the antigen peptide or protein can be conjugated with a drug that is immunogenic in the immunized species. Animals may be injected with the antigen peptide or protein two or more times (e.g., two, three, or four times).

[0492] Full-length polypeptides or proteins can be used, or their antigen peptide fragments can be used as immunogens. The protein antigen peptide contains at least eight (e.g., at least 10, 15, 20, or 30) amino acid residues of the PTK7 or TROP2 amino acid sequence and includes an epitope of the protein such that the antibody produced against the peptide forms a specific immune complex with the protein. As described above, the full-length sequences of human PTK7 (SEQ ID NO: 75) and TROP2 are well known in the art. In some embodiments, Fc-tagged or His-tagged human PTK7 protein or human TROP2 protein is used as an immunogen.

[0493] Immunogens are typically used for antibody preparation by immunizing a suitable target (e.g., a human or transgenic animal expressing at least one human immunoglobulin locus). A suitable immunogenic preparation may contain, for example, recombinantly expressed or chemically synthesized polypeptides (e.g., fragments of human PTK7 or human TROP2). The preparation may further contain an adjuvant, such as a Freund complete or incomplete adjuvant, or a similar immunostimulant.

[0494] Polyclonal antibodies can be prepared as described above by immunizing a suitable target with the PTK7 polypeptide or TROP2 polypeptide, or their antigenic peptide (e.g., a part of PTK7 or TROP2), as an immunogen. The antibody titer in the immunized target can be monitored over time using standard techniques such as enzyme-linked immunosorbent assay (ELISA) with immobilized PTK7 or TROP2 polypeptide or peptide. If desired, the antibody molecule can be isolated from a mammal (e.g., from blood) and further purified by well-known techniques such as protein A chromatography or protein G chromatography to obtain the IgG fraction. At an appropriate time after immunization, for example, when the titer of specific antibodies is at its maximum, antibody-producing cells can be obtained from the target organism and used to prepare monoclonal antibodies using standard techniques such as the hybridoma technique originally described by Kohler et al. (Nature 256:495-497, 1975), the human B-cell hybridoma technique (Kozbor et al., Immunol. Today 4:72, 1983), the EBV-hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp.77-96, 1985), or the trioma technique. Techniques for producing hybridomas are well known (generally, see Current Protocols in Immunology, 1994, Coligan et al. (Eds.), John Wiley & Sons, Inc., New York, NY). For example, hybridoma cells that produce monoclonal antibodies can be detected by screening hybridoma culture supernatants for antibodies that bind to a target polypeptide or epitope using a standard ELISA assay.

[0495] Variants of antibodies or antigen-binding fragments described herein can be prepared by introducing appropriate nucleotide changes into the DNA encoding a human antibody, a humanized antibody, or a chimeric antibody, or an antibody or antigen-binding fragment described herein, or by peptide synthesis. Such variants include, for example, deletions, insertions, or substitutions of residues within the amino acid sequence that produces the antigen-binding site or antigen-binding domain of the antibody. In a population of such variants, some antibodies or antigen-binding fragments exhibit increased affinity for target proteins, such as PTK7 or TROP2. Any combination of deletions, insertions, and / or combinations can be realized in an antibody or antigen-binding fragment with increased binding affinity to the target. Antibodies or antigen-binding fragments can be modified, or novel post-translational modifications can be introduced, by changing the amino acids introduced into the antibody or antigen-binding fragment, such as changing the number of glycosylation sites (e.g., increasing or decreasing them), changing the type of glycosylation sites (e.g., altering the amino acid sequence so that different sugars are bound by enzymes present in the cell), or introducing novel glycosylation sites.

[0496] The antibodies disclosed herein may be derived from any species of animal, including mammals. Non-limiting examples of natural antibodies include antibodies derived from humans, primates (e.g., monkeys and apes), cattle, pigs, horses, sheep, camelids (e.g., camels and llamas), chickens, goats, and rodents (e.g., rats, mice, hamsters, and rabbits), including transgenic rodents genetically modified to produce human antibodies.

[0497] Examples of human antibodies and humanized antibodies include antibodies having variable and constant regions derived from (or having the same amino acid sequence as) human germline immunoglobulin sequences. Examples of human antibodies include amino acid residues within the CDR that are not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-directed mutagenesis in vitro, or somatic mutations in vivo).

[0498] Humanized antibodies typically have a human framework (FR) into which a non-human CDR has been transplanted. Therefore, humanized antibodies have one or more amino acid sequences introduced from a non-human source. These non-human amino acid residues are often called “import” residues, and are typically obtained from the “import” variable domain. Humanization can essentially be carried out by substituting, for example, a rodent CDR or CDR sequence with the corresponding sequence of a human antibody. These methods are described, for example, in Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); and Verhoeyen et al., Science, 239:1534-1536 (1988), each of which is incorporated herein by reference in its entirety. Thus, a “humanized” antibody is a chimeric antibody in which a portion considerably smaller than the intact human V domain is substituted with the corresponding sequence derived from a non-human species. In practice, humanized antibodies are typically mouse antibodies in which several CDR residues and several FR residues are substituted with residues derived from similar sites within the human antibody.

[0499] The selection of human VH and VL domains used in the production of humanized antibodies is crucial for reducing immunogenicity. Following the so-called "best-fit" method, the V domain sequence of a mouse antibody is screened against an entire library of known human domain sequences. The human sequence that most closely matches the mouse sequence is then recognized as the human FR for humanized antibodies (Sims et al., J.Immunol., 151:2296 (1993); Chothia et al., J.Mol.Biol., 196:901 (1987)).

[0500] Furthermore, it is important to humanize antibodies while maintaining high specificity and affinity for antigens, as well as other desirable biological properties. To achieve this goal, humanized antibodies can be prepared by analytical processes of parental sequences and various conceptual humanization products using three-dimensional models of parental and humanized sequences. Three-dimensional immunoglobulin models are generally available and well known to those skilled in the art. Computer programs are available that can illustrate and display the possible three-dimensional structures of selected candidate immunoglobulin sequences. By observing these displays, it is possible to analyze the roles that residues can play in the functionalization of candidate immunoglobulin sequences, i.e., the residues that affect the candidate immunoglobulin's ability to bind to its antigen. In this way, FR residues can be selected and combined from recipient and import sequences to achieve desired antibody properties, such as increased affinity for the target antigen.

[0501] Typically, amino acid sequence variants of human, humanized, or chimeric anti-PTK7 antibodies, anti-TROP2 antibodies, or anti-PTK7 / TROP2 antibodies contain amino acid sequences that have at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with the sequences present in the light or heavy chain of the original antibody.

[0502] In some embodiments, mice having humanized heavy chain immunoglobulin loci and humanized κ chain immunoglobulin loci (e.g., RenMab TMAntibodies are generated using mice. A heavy chain immunoglobulin locus is a chromosomal region containing the gene for the heavy chain of an antibody. Examples of loci include the human IGHV (variable) gene, the human IGHD (variability) gene, the human IGHJ (binding) gene, and the mouse heavy chain constant domain gene. A κ chain immunoglobulin locus is a chromosomal region containing the gene encoding the light chain (κ chain) of an antibody. Examples of κ chain immunoglobulin loci include the human IGKV (variable) gene, the human IGKJ (binding) gene, and the mouse light chain constant domain gene. RenMab TM A detailed description of the mouse can be found in PCT / CN2020 / 075698 or US20200390073A1, which are incorporated herein by reference in their entirety.

[0503] In some embodiments, mice having humanized heavy chain immunoglobulin loci and humanized κ chain immunoglobulin loci (e.g., RenLite TM Antibodies are generated using mice. A heavy chain immunoglobulin locus is a chromosomal region containing the gene for the heavy chain of an antibody. Examples of loci include the human IGHV (variable) gene, the human IGHD (diversity) gene, the human IGHJ (binding) gene, and the mouse heavy chain constant domain gene. A κ chain immunoglobulin locus is a chromosomal region containing the gene encoding a common light chain. Examples of κ chain immunoglobulin loci include the human IGKV (variable) gene, the human IGKJ (binding) gene, and the mouse light chain constant domain gene. RenLite TM A detailed description of the mouse can be found in PCT / CN2021 / 097652, which is incorporated herein by reference in its entirety.

[0504] The antibodies produced by mice have a fully human VH, a fully human VL, and a mouse constant region. In some embodiments, the human VH and human VL are linked to a human IgG constant region (e.g., IgG1, IgG2, IgG3, and IgG4).

[0505] Identity or homology to the original sequence is typically the percentage of amino acid residues present in a candidate sequence that is identical to a sequence present in a human, humanized, or chimeric anti-PTK7 antibody or fragment, anti-TROP2 antibody or fragment, or anti-PTK7 / TROP2 antibody or fragment, after aligning the sequences, introducing gaps where necessary, and achieving the maximum percentage sequence identity, without considering conservative substitutions as part of the sequence identity.

[0506] Further modifications can be made to anti-PTK7 antibodies or antigen-binding fragments, anti-TROP2 antibodies or antigen-binding fragments, or anti-PTK7 / TROP2 antibodies or antigen-binding fragments. For example, cysteine ​​residues can be introduced into the Fc region to enable interchain disulfide bond formation within this region. Homodimeric antibodies thus produced may have some kind of extended in vitro and / or in vivo half-life. For example, homodimeric antibodies with extended in vitro and / or in vivo half-lives can also be prepared using heterobifunctional crosslinking agents described by Wolff et al. (Cancer Res. 53:2560-2565, 1993). Alternatively, antibodies with a double Fc region can be recombinant (see, for example, Stevenson et al., Anti-Cancer Drug Design 3:219-230, 1989).

[0507] In some embodiments, covalent modifications can be added to anti-PTK7 antibodies, anti-TROP2 antibodies, or anti-PTK7 / TROP2 antibodies or their antigen-binding fragments. These covalent modifications can be added by chemical or enzymatic synthesis, or by enzymatic or chemical cleavage. Other types of covalent modifications of the antibody or antibody fragment are introduced into the molecule by reacting the targeted amino acid residue of the antibody or fragment with an organic derivatizing agent that can react with a selected side chain or an N or C-terminal residue.

[0508] In some embodiments, antibody variants are provided having carbohydrate structures lacking fucose (directly or indirectly) bound to the Fc region. For example, the amount of fucose in such antibodies may be 1% to 80%, 1% to 65%, 5% to 65%, or 20% to 40%. The amount of fucose is determined by calculating the average amount of fucose in the glycans located at Asn297 relative to the total of all sugar structures (e.g., complexes, hybrids, and high-mannose structures) bound to Asn297, measured, for example, by MALDI-TOF mass spectrometry as described in WO 2008 / 077546. Asn297 refers to the asparagine residue located at position 297 in the Fc region (Eu numbering of Fc region residues, or position 314 in Kabat numbering), however, Asn297 may also be located approximately ±3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to minor sequence variations in the antibody. Such fucosylated mutants may have improved ADCC function. In some embodiments, to reduce glycan heterogeneity, the Fc region of the antibody can be further recombined, and asparagine at position 297 can be replaced with alanine (N297A).

[0509] In some embodiments, to enhance production efficiency by avoiding Fab-arm exchange, the Fc region of the antibody is further recombined, replacing serine at position 228 (EU numbering) of IgG4 with proline (S228P). A detailed description of the S228 mutation is, for example, found in Silva et al. "The S228P mutation prevents in vivo and in vitro IgG4 Fab-arm exchange as demonstrated using a combination of novel quantitative immunoassays and physiological matrix preparation." Journal of Biological Chemistry 290.9(2015):5462-5469, which is incorporated in its entirety by reference.

[0510] Recombination vectors This disclosure also provides recombinant vectors (e.g., expression vectors) containing isolated polynucleotides disclosed herein (e.g., polynucleotides encoding polypeptides disclosed herein), host cells into which the recombinant vectors have been introduced (i.e., such host cells contain polynucleotides and / or the polynucleotide-containing vectors), and the production of recombinant antibody polypeptides or fragments thereof by recombinant technology.

[0511] As used herein, “vector” is any construct that, when introduced into a host cell, can deliver one or more polynucleotides of interest to the host cell. An “expression vector” can deliver and express one or more polynucleotides of interest as encoded polypeptides within the host cell into which the expression vector has been introduced. Thus, within the expression vector, the polynucleotides of interest are positioned for expression within the vector by being operably bound to regulatory elements such as promoters, enhancers, and / or poly-A tails, either within the vector or in the host cell genome, at, near, or adjacent to the integration site of the polynucleotides of interest, so that the polynucleotides of interest are translated within the host cell into which the expression vector has been introduced.

[0512] Vectors can be introduced into host cells by methods well known in the art, such as electroporation, chemical transfection (e.g., DEAE-dextran), transformation, transfection, and infection and / or transduction (e.g., by recombinant viruses). Therefore, non-limiting examples of vectors include viral vectors (that can be used to generate recombinant viruses), naked DNA or RNA, plasmids, cosmids, phage vectors, and DNA or RNA expression vectors associated with cationic condensers.

[0513] In some embodiments, polynucleotides disclosed herein (e.g., polynucleotides encoding polypeptides disclosed herein) are introduced using a viral expression system (e.g., a smallpox or other poxvirus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (deficient) replicable virus or a non-replicable virus. In the latter case, viral replication generally occurs only in complementary viral packaging cells. Suitable systems include, for example, Fisher-Hoch et al., 1989, Proc. Natl. Acad. Sci. USA 86:317-321; Flexner et al., 1989, Ann. NYAcad Sci. 569:86-103; Flexner et al., 1990, Vaccine, 8:17-21; U.S. Patent Nos. 4,603,112, 4,769,330, and 5,017,487; WO 89 / 01973; U.S. Patent No. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91 / 02805; Berkner-Biotechniques, 6:616-627, 1988; Rosenfeld et al. This is disclosed in al., 1991, Science, 252:431-434; Kolls et al., 1994, Proc. Natl. Acad. Sci. USA, 91:215-219; Kass-Eisler et al., 1993, Proc. Natl. Acad. Sci. USA, 90:11498-11502; Guzman et al., 1993, Circulation, 88:2838-2848; and Guzman et al., 1993, Cir. Res., 73:1202-1207. Techniques for incorporating DNA into such expression systems are well known to those skilled in the art. DNA may also be “naked,” as described, for example, in Ulmer et al., 1993, Science, 259:1745-1749 and Cohen, 1993, Science, 259:1691-1692. The uptake of naked DNA can be increa...

Claims

1. An antibody that binds to PTK7 (protein tyrosine kinase 7) or an antigen-binding fragment thereof, A heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR1, the VH CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR2, and the VH CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR3, and A light chain variable region (VL) comprising CDR1, 2, and 3, wherein the VL CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR1, the VL CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR2, and the VL CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR3. An antibody or its antigen-binding fragment wherein the amino acid sequences of the selected VH CDR1, 2, and 3, and the amino acid sequences of the selected VL CDR1, 2, and 3, are one of the following: (1) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (2) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (3) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (4) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (5) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 16 to 18, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (6) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (7) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 22 to 24, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (8) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (9) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 28 to 30, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (10) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (11) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 34 to 36, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (12) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 37 to 39, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (13) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 40 to 42, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (14) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 43 to 45, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (15) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 86 to 88, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, and (16) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 89 to 91, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

2. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 4 to 6, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

3. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 7 to 9, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

4. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 10 to 12, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

5. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 13 to 15, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3.

6. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 16 to 18, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

7. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 19 to 21, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs: 1 to 3, respectively.

8. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 22 to 24, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

9. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 86 to 88, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

10. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 25 to 27, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

11. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 28 to 30, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3.

12. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 31 to 33, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

13. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 34 to 36, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

14. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 37 to 39, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

15. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 40 to 42, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

16. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 43 to 45, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3.

17. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 1, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 89 to 91, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

18. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, wherein the antibody or antigen-binding fragment thereof specifically binds to human PTK7, monkey PTK7, or canine PTK7.

19. The antibody or antigen-binding fragment according to any one of claims 1 to 18, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

20. The antibody or antigen-binding fragment according to any one of claims 1 to 19, wherein the antibody or antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

21. A nucleic acid containing a polynucleotide that codes for a polypeptide including the following: (1) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs: 4 to 6, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO: 53, and binds to PTK7. (2) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively containing the amino acid sequences shown in SEQ ID NOs. 25 to 27, wherein the VH forms a pair with a light chain variable region (VL) containing the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (3) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 46, and binds to PTK7. (4) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 7 to 9, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (5) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which contain the amino acid sequences shown in SEQ ID NOs. 28 to 30, wherein the VH forms a pair with a light chain variable region (VL) which contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (6) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 47, and binds to PTK7. (7) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 10 to 12, wherein the VH forms a pair with a light chain variable region (VL) each comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (8) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 31 to 33, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (9) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 48, and binds to PTK7. (10) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 13 to 15, wherein the VH forms a pair with a light chain variable region (VL) each comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (11) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 34 to 36, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (12) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 49, and binds to PTK7. (13) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 16 to 18, wherein the VH forms a pair with a light chain variable region (VL) each comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (14) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 37 to 39, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (15) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 50, and binds to PTK7. (16) An immunoglobulin heavy chain or fragment thereof comprising a VH comprising complementarity-determining regions (CDRs) 1, 2, and 3, each comprising the amino acid sequences shown in SEQ ID NOs. 19 to 21, wherein the VH forms a pair with a light chain variable region (VL) each comprising the amino acid sequences shown in SEQ ID NOs. 53, and binds to PTK7. (17) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 40 to 42, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (18) An immunoglobulin light chain or fragment thereof comprising a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 51, and binds to PTK7. (19) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 22 to 24, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (20) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively containing the amino acid sequences shown in SEQ ID NOs. 43 to 45, wherein the VH binds to PTK7 when paired with a light chain variable region (VL) containing the amino acid sequences shown in SEQ ID NOs. 53, and (21) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL binds to PTK7 when paired with a VH containing the amino acid sequences shown in SEQ ID NO:

52. (22) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 86 to 88, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to PTK7. (23) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively containing the amino acid sequences shown in SEQ ID NOs. 89 to 91, wherein the VH binds to PTK7 when paired with a light chain variable region (VL) containing the amino acid sequences shown in SEQ ID NOs. 53, and (24) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL binds to PTK7 when paired with a VH containing the amino acid sequences shown in SEQ ID NO:

92.

22. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VL including CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs: 1 to 3.

23. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH including CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs: 4 to 6.

24. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH including CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 7 to 9.

25. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH including CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 10 to 12.

26. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof includes VH, which includes CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 13 to 15.

27. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof includes VH comprising CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 16 to 18.

28. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof includes VH comprising CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 19 to 21.

29. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH including CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 22 to 24.

30. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof includes VH comprising CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 25 to 27.

31. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide, which includes an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH including CDR1, 2, and 3, which each contain the amino acid sequences shown in SEQ ID NOs. 28 to 30.

32. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 31 to 33.

33. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 34 to 36.

34. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 37 to 39.

35. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 40 to 42.

36. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH including CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 43 to 45.

37. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH including CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 86 to 88.

38. The nucleic acid according to claim 21, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 89 to 91.

39. The nucleic acid according to any one of claims 21 to 38, wherein when VH forms a pair with VL, it specifically binds to human PTK7, monkey PTK7, or canine PTK7, or when VL forms a pair with VH, it specifically binds to human PTK7, monkey PTK7, or canine PTK7.

40. The nucleic acid according to any one of claims 21 to 39, wherein the immunoglobulin heavy chain or fragment thereof is a human immunoglobulin heavy chain or fragment thereof (for example, a human IgG1 heavy chain or fragment thereof, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 heavy chain or fragment thereof), and the immunoglobulin light chain or fragment thereof is a human immunoglobulin light chain or fragment thereof.

41. The nucleic acid according to any one of claims 21 to 40, wherein the nucleic acid encodes a single-stranded variable fragment (scFv), a single-arm antibody, a multispecific antibody (e.g., a bispecific antibody), or a chimeric antigen receptor (CAR).

42. The nucleic acid according to any one of claims 21 to 41, wherein the nucleic acid is cDNA.

43. A vector comprising one or more nucleic acids as described in any one of claims 21 to 42.

44. A vector comprising two nucleic acids according to any one of claims 21 to 42, wherein the vector encodes the VL region and the VH region that bind together to PTK7.

45. A pair of vectors, each vector comprising one of the nucleic acids described in any one of claims 21 to 42, wherein the pair of vectors encode the VL region and the VH region together which bind to PTK7.

46. A cell comprising the vector according to claim 43 or 44, or the pair of vectors according to claim 45.

47. The cell according to claim 46, wherein the cell is a CHO cell.

48. A cell comprising one or more nucleic acids as described in any one of claims 21 to 42.

49. A cell comprising two nucleic acids according to any one of claims 21 to 42.

50. The cell according to claim 49, wherein the two nucleic acids encode a pair of VL and VH regions that bind together to PTK7.

51. A method for producing an antibody or an antigen-binding fragment thereof, wherein the method is: (a) Culturing the cells according to any one of claims 46 to 50 under conditions sufficient for the cells to produce the antibody or the antigen-binding fragment, (b) Recovering the antibody or antigen-binding fragment produced by the cells, method.

52. An antibody that binds to PTK7 or an antigen-binding fragment thereof, An antibody or antigen-binding fragment comprising a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) containing an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

53. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 46 and VL comprises the sequence of SEQ ID NO:

53.

54. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 47 and VL comprises the sequence of SEQ ID NO:

53.

55. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 48 and VL comprises the sequence of SEQ ID NO:

53.

56. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 49 and VL comprises the sequence of SEQ ID NO:

53.

57. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 50 and VL comprises the sequence of SEQ ID NO:

53.

58. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 51 and VL comprises the sequence of SEQ ID NO:

53.

59. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 52 and VL comprises the sequence of SEQ ID NO:

53.

60. The antibody or antigen-binding fragment thereof according to claim 52, wherein VH comprises the sequence of SEQ ID NO: 92 and VL comprises the sequence of SEQ ID NO:

53.

61. An antibody that binds to PTK7 or an antigen-binding fragment thereof, An antibody or its antigen-binding fragment comprising a heavy chain variable region (VH) containing VH CDR1, VH CDR2, and VH CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of a selected VH sequence, and a light chain variable region (VL) containing VL CDR1, VL CDR2, and VL CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

62. The antibody or antigen-binding fragment thereof according to any one of claims 52 to 61, wherein the antibody or antigen-binding fragment thereof specifically binds to human PTK7, monkey PTK7, or canine PTK7.

63. The antibody or antigen-binding fragment according to any one of claims 52 to 62, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

64. The antibody or antigen-binding fragment according to any one of claims 52 to 63, wherein the antibody or antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

65. An antibody that binds to TROP2 (trophoblast cell surface antigen 2) or an antigen-binding fragment thereof, A heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR1, the VH CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR2, and the VH CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH CDR3, and A light chain variable region (VL) comprising CDR1, 2, and 3, wherein the VL CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR1, the VL CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR2, and the VL CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL CDR3. An antibody or its antigen-binding fragment wherein the amino acid sequences of the selected VH CDR1, 2, and 3, and the amino acid sequences of the selected VL CDR1, 2, and 3, are one of the following: (1) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (2) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, and (4) The amino acid sequences of the selected VH CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively, and the amino acid sequences of the selected VL CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

66. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 65, wherein the VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 57 to 59, and the VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

67. Based on the definition of Kabat, the antibody or antigen-binding fragment thereof according to claim 65, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 60 to 62, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

68. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 65, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 66 to 68, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

69. Based on the definition of Chothia, the antibody or antigen-binding fragment thereof according to claim 65, wherein VH comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 69 to 71, and VL comprises CDR1, 2, and 3 having the amino acid sequences shown in SEQ ID NOs. 1 to 3, respectively.

70. The antibody or antigen-binding fragment thereof according to any one of claims 65 to 69, wherein the antibody or antigen-binding fragment thereof specifically binds to human TROP2, monkey TROP2, or canine TROP2.

71. The antibody or antigen-binding fragment according to any one of claims 65 to 70, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

72. The antibody or antigen-binding fragment according to any one of claims 65 to 71, wherein the antibody or antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

73. A nucleic acid containing a polynucleotide that codes for a polypeptide including the following: (1) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 57 to 59, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (2) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 66 to 68, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (3) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL forms a pair with a VH containing the amino acid sequences shown in SEQ ID NO: 73, and binds to TROP2. (4) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) comprising complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs. 60 to 62, wherein the VH forms a pair with a light chain variable region (VL) which each contains the amino acid sequences shown in SEQ ID NO. 53, and binds to TROP2. (5) An immunoglobulin heavy chain or fragment thereof comprising a heavy chain variable region (VH) containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively containing the amino acid sequences shown in SEQ ID NOs. 69 to 71, wherein the VH binds to TROP2 when paired with a light chain variable region (VL) containing the amino acid sequences shown in SEQ ID NO. 53, and (6) An immunoglobulin light chain or fragment thereof comprising a VL containing complementarity-determining regions (CDRs) 1, 2, and 3, respectively, which each contain the amino acid sequences shown in SEQ ID NOs: 1 to 3, wherein the VL binds to TROP2 when paired with a VH containing the amino acid sequences shown in SEQ ID NO:

74.

74. The nucleic acid according to claim 73, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VL containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs: 1 to 3.

75. The nucleic acid according to claim 73, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 57 to 59.

76. The nucleic acid according to claim 73, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH including CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 60 to 62.

77. The nucleic acid according to claim 73, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 66 to 68.

78. The nucleic acid according to claim 73, wherein the nucleic acid comprises a polynucleotide encoding a polypeptide containing an immunoglobulin light chain or a fragment thereof, and the immunoglobulin light chain or fragment thereof comprises a VH containing CDR1, 2, and 3, each containing the amino acid sequences shown in SEQ ID NOs. 69 to 71.

79. The nucleic acid according to any one of claims 73 to 78, wherein when VH forms a pair with VL, it specifically binds to human TROP2, monkey TROP2, or canine TROP2, or when VL forms a pair with VH, it specifically binds to human TROP2, monkey TROP2, or canine TROP2.

80. The nucleic acid according to any one of claims 73 to 79, wherein the immunoglobulin heavy chain or fragment thereof is a human immunoglobulin heavy chain or fragment thereof (for example, a human IgG1 heavy chain or fragment thereof, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 heavy chain or fragment thereof), and the immunoglobulin light chain or fragment thereof is a human immunoglobulin light chain or fragment thereof.

81. The nucleic acid according to any one of claims 73 to 80, wherein the nucleic acid encodes a single-stranded variable fragment (scFv), a single-arm antibody, a multispecific antibody (e.g., a bispecific antibody), or a chimeric antigen receptor (CAR).

82. The nucleic acid according to any one of claims 73 to 81, wherein the nucleic acid is cDNA.

83. A vector comprising one or more nucleic acids as described in any one of claims 73 to 82.

84. A vector comprising two nucleic acids according to any one of claims 73 to 82, wherein the vector encodes the VL region and the VH region that bind together to TROP2.

85. A pair of vectors, each vector comprising one of the nucleic acids described in any one of claims 73 to 82, wherein the pair of vectors encode the VL region and the VH region together which bind to TROP2.

86. A cell comprising the vector according to claim 83 or 84, or the pair of vectors according to claim 85.

87. The cell according to claim 86, wherein the cell is a CHO cell.

88. A cell comprising one or more nucleic acids as described in any one of claims 73 to 82.

89. A cell comprising two nucleic acids according to any one of claims 73 to 82.

90. The cell according to claim 89, wherein the two nucleic acids encode a pair of VL and VH regions that bind together to TROP2.

91. A method for producing an antibody or an antigen-binding fragment thereof, wherein the method is: (a) Culturing the cells according to any one of claims 86 to 90 under conditions sufficient for the cells to produce the antibody or the antigen-binding fragment, (b) Recovering the antibody or antigen-binding fragment produced by the cells, Methods that include...

92. An antibody that binds to TROP2 or an antigen-binding fragment thereof, An antibody or antigen-binding fragment comprising a heavy chain variable region (VH) containing an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) containing an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (2) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

93. The antibody or antigen-binding fragment thereof according to claim 92, wherein VH comprises the sequence of SEQ ID NO: 73 and VL comprises the sequence of SEQ ID NO:

53.

94. The antibody or antigen-binding fragment thereof according to claim 92, wherein VH comprises the sequence of SEQ ID NO: 74 and VL comprises the sequence of SEQ ID NO:

53.

95. An antibody that binds to TROP2 or an antigen-binding fragment thereof, An antibody or its antigen-binding fragment comprising a heavy chain variable region (VH) containing VH CDR1, VH CDR2, and VH CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of a selected VH sequence, and a light chain variable region (VL) containing VL CDR1, VL CDR2, and VL CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (2) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

96. The antibody or antigen-binding fragment thereof according to any one of claims 92 to 95, wherein the antibody or antigen-binding fragment thereof specifically binds to human TROP2, monkey TROP2, or canine TROP2.

97. The antibody or antigen-binding fragment according to any one of claims 92 to 96, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof, a single-chain variable fragment (scFv), a single-arm antibody, and / or a multispecific antibody (e.g., a bispecific antibody).

98. The antibody or antigen-binding fragment according to any one of claims 92 to 97, wherein the antibody or antigen-binding fragment is a human IgG1 antibody or its antigen-binding fragment, a human IgG2 antibody or its antigen-binding fragment, or a human IgG4 antibody or its antigen-binding fragment.

99. An anti-PTK7 / TROP2 antibody or its antigen-binding fragment, comprising a first antigen-binding domain that specifically binds to the epitope of PTK7 and a second antigen-binding domain that specifically binds to the epitope of TROP2.

100. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 99, wherein the first antigen-binding domain comprises a first heavy chain variable region (VH1) and a first light chain variable region (VL1), and the second antigen-binding domain comprises a second heavy chain variable region (VH2) and a second light chain variable region (VL2).

101. The first heavy chain variable region (VH1) includes complementarity-determining regions (CDRs) 1, 2, and 3, wherein the VH1 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR1, the VH1 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR2, the VH1 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH1 CDR3, and the first light chain variable region (VL1) includes CDRs 1, 2, and 3, wherein the VL1 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR1, the VL1 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL1 CDR2, and the VL1 CDR3 region includes the selected VL1 It contains an amino acid sequence that is at least 80% identical to the amino acid sequence of CDR3, The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100, wherein the amino acid sequences of the selected VH1 CDR1, 2, and 3, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are one of the following. (1) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (2) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (3) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (4) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (5) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16 to 18, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (6) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (7) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 22 to 24, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (8) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (9) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 28 to 30, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (10) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (11) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34 to 36, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (12) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37 to 39, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (13) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40 to 42, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (14) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 43 to 45, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (15) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 86 to 88, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, and (16) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 89 to 91, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

102. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100 or claim 101.

103. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100 or claim 101.

104. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

105. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

106. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16 to 18, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

107. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

108. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 22 to 24, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100 or claim 101.

109. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

110. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 28 to 30, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

111. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100 or claim 101.

112. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34 to 36, respectively, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100 or claim 101.

113. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37 to 39, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, as described in claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

114. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40 to 42, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

115. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 43 to 45, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to claim 100 or claim 101.

116. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 86 to 88, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

117. The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 89 to 91, and the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively, according to claim 100 or claim 101, an anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof.

118. The second heavy chain variable region (VH2) includes CDR1, 2, and 3, wherein the VH2 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR1, the VH2 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR2, and the VH2 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VH2 CDR3, and The second light chain variable region (VL2) includes CDR1, 2, and 3, wherein the VL2 CDR1 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR1, the VL2 CDR2 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR2, and the VL2 CDR3 region includes an amino acid sequence that is at least 80% identical to the amino acid sequence of the selected VL2 CDR3. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 117, wherein the amino acid sequences of the selected VH2 CDR1, 2, and 3, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are one of the following. (1) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (2) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (3) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (4) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (5) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, and (6) The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

119. The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 54 to 56, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, according to any one of claims 100 to 118, an anti-PTK7 / TROP2 antibody or its antigen-binding fragment.

120. The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 57 to 59, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, according to any one of claims 100 to 118, an anti-PTK7 / TROP2 antibody or its antigen-binding fragment.

121. The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 60 to 62, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, according to any one of claims 100 to 118, an anti-PTK7 / TROP2 antibody or its antigen-binding fragment.

122. The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, relating to the anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 118.

123. The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, according to any one of claims 100 to 118, an anti-PTK7 / TROP2 antibody or its antigen-binding fragment.

124. The amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively, and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively, according to any one of claims 100 to 118, an anti-PTK7 / TROP2 antibody or its antigen-binding fragment.

125. An anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 124, wherein the antibody is one of the following: (1) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (2) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (3) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (4) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (5) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16 to 18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (6) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (7) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 22 to 24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (8) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (9) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (10) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (11) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (12) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16 to 18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (13) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (14) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 22 to 24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (15) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 4 to 6, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (16) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 7 to 9, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (17) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 10 to 12, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (18) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 13 to 15, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (19) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 16 to 18, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (20) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 19 to 21, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (21) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 22 to 24, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 60 to 62, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (22) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (23) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (24) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (25) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34 to 36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (26) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37 to 39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (27) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40 to 42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (28) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (29) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (30) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (31) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (32) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34 to 36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (33) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37 to 39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (34) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40 to 42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (35) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (36) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs. 25 to 27, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs. 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs. 1 to 3, respectively. (37) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 28 to 30, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (38) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 31 to 33, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (39) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 34 to 36, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (40) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 37 to 39, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (41) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 40 to 42, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (42) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 43 to 45, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 69 to 71, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (43) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 86 to 88, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 54 to 56, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (44) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 89 to 91, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 63 to 65, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively. (45) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 86 to 88, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 57 to 59, respectively; the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; and (46) The amino acid sequences of the selected VH1 CDR1, 2, and 3 are shown in SEQ ID NOs: 89 to 91, respectively; the amino acid sequences of the selected VL1 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively; the amino acid sequences of the selected VH2 CDR1, 2, and 3 are shown in SEQ ID NOs: 66 to 68, respectively; and the amino acid sequences of the selected VL2 CDR1, 2, and 3 are shown in SEQ ID NOs: 1 to 3, respectively.

126. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 46, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

127. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 47, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

128. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 48, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

129. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 49, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

130. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 50, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

131. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 51, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

132. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 52, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

133. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 46, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

134. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 47, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

135. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 48, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

136. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 49, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

137. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 50, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

138. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 51, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

139. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 52, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

140. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 46, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

141. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 47, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

142. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 48, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

143. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 49, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

144. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 50, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

145. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 51, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

146. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 52, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 74, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

147. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 92, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 72, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

148. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 125, wherein the first heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 92, the first light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 53, the second heavy chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO: 73, and the second light chain variable region comprises a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to SEQ ID NO:

53.

149. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 148, wherein the VH1 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VH sequence, and the VL1 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

150. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 149, wherein the VH2 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VH sequence, and the VL2 comprises an amino acid sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 72, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (3) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

151. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 150, wherein the VH1 comprises VH1 CDR1, VH1 CDR2, and VH1 CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and the VL1 comprises VL1 CDR1, VL1 CDR2, and VL1 CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 46, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 47, and the selected VL sequence is sequence number 53. (3) The selected VH sequence is sequence number 48, and the selected VL sequence is sequence number 53. (4) The selected VH sequence is sequence number 49, and the selected VL sequence is sequence number 53. (5) The selected VH sequence is sequence number 50, and the selected VL sequence is sequence number 53. (6) The selected VH sequence is sequence number 51, and the selected VL sequence is sequence number 53. (7) The selected VH sequence is sequence number 52, the selected VL sequence is sequence number 53, and (8) The selected VH sequence is sequence number 92, and the selected VL sequence is sequence number 53.

152. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 151, wherein the VH2 comprises VH2 CDR1, VH2 CDR2, and VH2 CDR3 which are identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and the VL2 comprises VL2 CDR1, VL2 CDR2, and VL2 CDR3 which are identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence, and the selected VH sequence and the selected VL sequence are one of the following. (1) The selected VH sequence is sequence number 72, and the selected VL sequence is sequence number 53. (2) The selected VH sequence is sequence number 73, and the selected VL sequence is sequence number 53, (3) The selected VH sequence is sequence number 74, and the selected VL sequence is sequence number 53.

153. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 152, wherein the first antigen-binding domain specifically binds to human PTK7, monkey PTK7, or canine PTK7, and / or the second antigen-binding domain specifically binds to human TROP2, monkey TROP2, or canine TROP2.

154. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 153, wherein the first antigen-binding domain is a human antigen-binding domain or a humanized antigen-binding domain, and / or the second antigen-binding domain is a human antigen-binding domain or a humanized antigen-binding domain.

155. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 154, wherein the first antigen-binding domain is a single-stranded variable fragment (scFv), and / or the second antigen-binding domain is an scFv.

156. The anti-PTK7 / TROP2 antibody or antigen-binding fragment thereof according to any one of claims 100 to 155, wherein the first light chain variable region and the second light chain variable region are the same.

157. The anti-PTK7 / TROP2 antibody or antigen-binding fragment according to claims 100 to 156, wherein the antibody or antigen-binding fragment is a bispecific antibody or its antigen-binding fragment.

158. An antibody or an antigen-binding fragment that cross-competes with the antibody or antigen-binding fragment described in any one of claims 1 to 20, 52 to 72, and 92 to 157.

159. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, 52 to 72, and 92 to 157, wherein the antibody or antigen-binding fragment thereof includes a fragment crystallizable region (Fc region).

160. The antibody or antigen-binding fragment thereof according to claim 159, wherein the Fc region exhibits increased complement-dependent cytotoxicity (CDC) or antibody-dependent cytotoxicity (ADCC).

161. A chimeric antigen receptor (CAR) comprising an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 20, 52 to 72, and 92 to 157.

162. An antibody-drug conjugate comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, 52 to 72, and 92 to 157, covalently bound to a therapeutic agent.

163. The antibody-drug conjugate according to claim 162, wherein the therapeutic agent is a cytotoxic agent or a cell proliferation inhibitor.

164. The antibody-drug conjugate according to claim 162 or 163, wherein the therapeutic agent is MMAE or MMAF.

165. The therapeutic agent is selected from the following, and is an antibody-drug conjugate according to claim 162 or 163. 【Chemistry 1】

166. The antibody-drug conjugate according to claim 162 or 165, wherein the therapeutic agent is linked to the antibody or its antigen-binding fragment via a linker.

167. The linker has the following structure, the antibody-drug conjugate according to any one of claims 162, 165, and 166. 【Chemistry 2】

168. The antibody-drug conjugate according to any one of claims 162, 165 to 167, wherein the antibody-drug conjugate has the following structure. 【Transformation 3】 In the formula, n = 1, 2, 3, 4, 5, 6, 7, or 8, and "Ab" represents an antibody or its antigen-binding fragment.

169. A method for treating a subject having cancer, the method comprising administering to the subject a therapeutically effective amount of a composition comprising an antibody or antigen-binding fragment thereof as described in any one of claims 1 to 20, 52 to 72, and 92 to 157, a CAR as described in claim 161, or an antibody-drug conjugate as described in any one of claims 162 to 168.

170. The method according to claim 169, wherein the subject has a solid tumor.

171. The method according to claim 170, wherein the cancer is colon cancer, triple-negative breast cancer (TNBC), lung cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, esophageal cancer, colorectal cancer, ovarian cancer (OVCA), or bladder cancer.

172. The method according to any one of claims 169 to 171, wherein the subject is further treated with an effective amount of anti-4-1BB antibody, anti-OX40 antibody, anti-PD-1 antibody, anti-CTLA4 antibody, anti-CD40 antibody, or anti-PD-L1 antibody.

173. A method for reducing the rate of tumor growth, the method comprising contacting tumor cells with an effective amount of a composition comprising an antibody or antigen-binding fragment thereof as described in any one of claims 1 to 20, 52 to 72, and 92 to 157, a CAR as described in claim 161, or an antibody-drug conjugate as described in any one of claims 162 to 168.

174. A method for killing tumor cells, the method comprising contacting the tumor cells with an effective amount of a composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, 52 to 72, and 92 to 157, a CAR according to claim 161, or an antibody-drug conjugate according to any one of claims 162 to 168.

175. A method for increasing an immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, 52 to 72, and 92 to 157, a CAR according to claim 161, or an antibody-drug conjugate according to any one of claims 162 to 168.

176. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, 52 to 72, and 92 to 157, and a pharmaceutically acceptable carrier.

177. A pharmaceutical composition comprising an antibody-drug conjugate according to any one of claims 162 to 168 and a pharmaceutically acceptable carrier.

178. The antibody-drug conjugate according to any one of claims 162 to 168, wherein the drug-antibody ratio (DAR) is approximately 4 or 8.

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