Anti-PTK7 antibody and its use

Abstract

This disclosure relates to anti-PTK7 antibodies or their antigen-binding fragments, nucleic acid molecules encoding them, and their use in the preparation of antibody-drug conjugates, and further relates to antibody-drug conjugates comprising antibodies or their antigen-binding fragments, as well as methods for their preparation and use. In certain embodiments, CDR1, CDR2, and CDR3 contained in the heavy chain variable region (VH), and / or CDR1, CDR2, and CDR3 contained in the light chain variable region (VL), are defined by Kabat, Chothia, or IMGT numbering systems.

Claims

1. An antibody or its antigen-binding fragment that can specifically bind to PTK7, (a) The following three heavy chain variable region (VH) complementarity determination regions (CDR): (i) VH CDR1 having a sequence of CDR1 contained in VH as shown in Sequence ID No. 20, 21 or 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., one or two amino acid substitutions, deletions or additions) compared to the sequence of CDR1 contained in VH, (ii) VH CDR2 having a sequence of CDR2 contained in VH as shown in Sequence ID No. 20, 21 or 22, or a sequence having one or more amino acid substitutions, deletions or additions (e.g., one or two amino acid substitutions, deletions or additions) compared to the sequence of CDR2 contained in VH, and (iii) VH CDR3 having a sequence of CDR3 contained in VH as shown in Sequence ID No. 20, 21, or 22, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one amino acid substitution, deletion, or addition) compared to the sequence of CDR3 contained in VH. And / or (b) The following three light chain variable region (VL) CDRs: (iv) A VL CDR1 having a sequence of CDR1 contained in the VL shown in SEQ ID NOs: 19, 23, 24, or 25, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to the sequence of CDR1 contained in the VL, (v) VL CDR2 having a sequence of CDR2 contained in a VL as shown in SEQ ID NOs. 19, 23, 24, or 25, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to the sequence of CDR2 contained in the VL, and (vi) A VL CDR3 having a sequence of CDR3 contained in a VL as shown in SEQ ID NO: 19, 23, 24, or 25, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to the sequence of CDR3 contained in the VL, Preferably, the substitution in any one of (i) to (vi) is a conservative substitution, and Preferably, the CDR1, CDR2, and CDR3 included in the heavy chain variable region (VH), and / or the CDR1, CDR2, and CDR3 included in the light chain variable region (VL), are defined by the Kabat, Chothia, or IMGT numbering system. An antibody or its antigen-binding fragment that can specifically bind to PTK7.

2. The sequence of CDR1, CDR2, and CDR3 included in the VH shown in Sequence ID No. 20, 21, or 22, and / or The sequence includes CDR1, CDR2, and CDR3 contained in the VL shown in sequence numbers 19, 23, 24, or 25, and Preferably, the antibody or antigen-binding fragment according to claim 1, wherein the CDR1, CDR2, and CDR3 contained in the heavy chain variable region (VH) and / or the CDR1, CDR2, and CDR3 contained in the light chain variable region (VL) are defined by the Kabat, Chothia, or IMGT numbering system.

3. (1) (a) The following three heavy chain variable region (VH) CDRs: (i) VH CDR1 consisting of the sequence shown in SEQ ID NO: 1, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 1; (ii) VH CDR2 consisting of the sequence shown in SEQ ID NO: 2, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 2, and (iii) VH CDR3 consisting of the sequence shown in SEQ ID NO: 3, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one amino acid substitution, deletion, or addition) compared to SEQ ID NO:

3. And / or (b) The following three light chain variable region (VL) CDRs: (iv) VL CDR1 consisting of the sequence shown in SEQ ID NO: 4, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 4, (v) VL CDR2 consisting of the sequence shown in SEQ ID NO: 5, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 5, and (vi) VL CDR3 comprising the sequence shown in SEQ ID NO: 6, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 6, Preferably, the substitution in any one of (i) to (vi) is a conservative substitution, Preferably, the VH of the antibody or its antigen-binding fragment comprises VH CDR1 shown in SEQ ID NO: 1, VH CDR2 shown in SEQ ID NO: 2, and VH CDR3 shown in SEQ ID NO: 3, and / or the VL of the antibody or its antigen-binding fragment comprises VL CDR1 shown in SEQ ID NO: 4, VL CDR2 shown in SEQ ID NO: 5, and VL CDR3 shown in SEQ ID NO:

6. Preferably, the VH of the antibody or its antigen-binding fragment comprises VH CDR1 shown in SEQ ID NO: 1, VH CDR2 shown in SEQ ID NO: 2, and VH CDR3 shown in SEQ ID NO: 3, and the VL of the antibody or its antigen-binding fragment comprises VL CDR1 shown in SEQ ID NO: 4, VL CDR2 shown in SEQ ID NO: 5, and VL CDR3 shown in SEQ ID NO:

6. or (2) (a) The following three heavy chain variable region (VH) CDRs: (i) VH CDR1 consisting of the sequence shown in SEQ ID NO: 7, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 7; (ii) VH CDR2 consisting of the sequence shown in SEQ ID NO: 8, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 8, and (iii) VH CDR3 consisting of the sequence shown in SEQ ID NO: 9, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one amino acid substitution, deletion, or addition) compared to SEQ ID NO:

9. And / or (b) The following three light chain variable region (VL) CDRs: (iv) VL CDR1 consisting of the sequence shown in SEQ ID NO: 10, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 10, (v) VL CDR2 consisting of the sequence shown in SEQ ID NO: 11, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 11, and (vi) VL CDR3 comprising the sequence shown in SEQ ID NO: 12, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 12, Preferably, the substitution in any one of (i) to (vi) is a conservative substitution, Preferably, the VH of the antibody or its antigen-binding fragment comprises VH CDR1 shown in SEQ ID NO: 7, VH CDR2 shown in SEQ ID NO: 8, and VH CDR3 shown in SEQ ID NO: 9, and / or the VL of the antibody or its antigen-binding fragment comprises VL CDR1 shown in SEQ ID NO: 10, VL CDR2 shown in SEQ ID NO: 11, and VL CDR3 shown in SEQ ID NO:

12. Preferably, the VH of the antibody or its antigen-binding fragment comprises VH CDR1 shown in SEQ ID NO: 7, VH CDR2 shown in SEQ ID NO: 8, and VH CDR3 shown in SEQ ID NO: 9, and the VL of the antibody or its antigen-binding fragment comprises VL CDR1 shown in SEQ ID NO: 10, VL CDR2 shown in SEQ ID NO: 11, and VL CDR3 shown in SEQ ID NO:

12. or (3) (a) The following three heavy chain variable region (VH) CDRs: (i) VH CDR1 consisting of the sequence shown in SEQ ID NO: 13, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 13; (ii) VH CDR2 consisting of the sequence shown in SEQ ID NO: 14, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 14, and (iii) VH CDR3 consisting of the sequence shown in SEQ ID NO: 15, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one amino acid substitution, deletion, or addition) compared to SEQ ID NO:

15. And / or (b) The following three light chain variable region (VL) CDRs: (iv) VL CDR1 consisting of the sequence shown in SEQ ID NO: 16, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 16, (v) VL CDR2 consisting of the sequence shown in SEQ ID NO: 17, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 17, and (vi) VL CDR3 comprising the sequence shown in SEQ ID NO: 18, or a sequence having one or more amino acid substitutions, deletions, or additions (e.g., one or two amino acid substitutions, deletions, or additions) compared to SEQ ID NO: 18, Preferably, the substitution in any one of (i) to (vi) is a conservative substitution, Preferably, the VH of the antibody or its antigen-binding fragment comprises VH CDR1 shown in SEQ ID NO: 13, VH CDR2 shown in SEQ ID NO: 14, and VH CDR3 shown in SEQ ID NO: 15, and / or the VL of the antibody or its antigen-binding fragment comprises VL CDR1 shown in SEQ ID NO: 16, VL CDR2 shown in SEQ ID NO: 17, and VL CDR3 shown in SEQ ID NO:

18. Preferably, the VH of the antibody or its antigen-binding fragment includes VH CDR1 shown in SEQ ID NO: 13, VH CDR2 shown in SEQ ID NO: 14, and VH CDR3 shown in SEQ ID NO: 15, and the VL of the antibody or its antigen-binding fragment includes VL CDR1 shown in SEQ ID NO: 16, VL CDR2 shown in SEQ ID NO: 17, and VL CDR3 shown in SEQ ID NO:

18. The antibody or antigen-binding fragment according to claim 1.

4. (a) Heavy chain variable region (VH) containing an amino acid sequence selected from the following: (i) The sequence shown in Sequence ID No. 20, (ii) A sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2, 3, 4, or 5 amino acid substitutions, deletions or additions) compared to the sequence shown in Sequence ID No. 20, or (iii) A sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 20, and (b) Light chain variable region (VL) containing an amino acid sequence selected from the following: (iv) Sequence shown in sequence number 19, (v) A sequence having one or more amino acid substitutions, deletions or additions (e.g., 1, 2, 3, 4, or 5 amino acid substitutions, deletions or additions) compared to the sequence shown in Sequence ID No. 19, or (vi) A sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 19, Preferably, the substitution in (ii) or (v) is a conservative substitution, Preferably, the antibody or its antigen-binding fragment A heavy chain variable region (VH) comprising the sequence shown in SEQ ID NO: 20, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in SEQ ID NO: 20, and a light chain variable region (VL) comprising the sequence shown in SEQ ID NO: 19, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in SEQ ID NO: 19, and Preferably, the antibody or its antigen-binding fragment VH having the sequence shown in sequence number 20 and VL having the sequence shown in sequence number 19, The antibody or antigen-binding fragment according to any one of claims 1 to 3.

5. The antibody or its antigen-binding fragment is humanized, Preferably, the antibody or its antigen-binding fragment further comprises a framework region of human immunoglobulin. Preferably, the antibody or its antigen-binding fragment further comprises a heavy chain framework region of human immunoglobulin (e.g., a heavy chain framework region included in the amino acid sequence encoded by a human heavy chain germline antibody gene) and / or a light chain framework region of human immunoglobulin (e.g., a light chain framework region included in the amino acid sequence encoded by a human light chain germline antibody gene), and Preferably, the heavy chain framework region and / or light chain framework region include, if necessary, one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) reverse mutations from human-derived residues to mouse-derived residues. The antibody or antigen-binding fragment according to any one of claims 1 to 4.

6. The antibody or its antigen-binding fragment (1) A heavy chain variable region (VH) comprising the sequence shown in Sequence ID No. 21, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 21, and a light chain variable region (VL) comprising the sequence shown in Sequence ID No. 23, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No.

23. (2) A heavy chain variable region (VH) comprising the sequence shown in Sequence ID No. 21, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 21, and a light chain variable region (VL) comprising the sequence shown in Sequence ID No. 24, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No.

24. (3) A heavy chain variable region (VH) comprising the sequence shown in Sequence ID No. 22, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 22, and a light chain variable region (VL) comprising the sequence shown in Sequence ID No. 23, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No.

23. (4) A heavy chain variable region (VH) comprising the sequence shown in SEQ ID NO: 22, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in SEQ ID NO: 22, and a light chain variable region (VL) comprising the sequence shown in SEQ ID NO: 24, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in SEQ ID NO: 24, or (5) A heavy chain variable region (VH) comprising the sequence shown in Sequence ID No. 22, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 22, and a light chain variable region (VL) comprising the sequence shown in Sequence ID No. 25, or a sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the sequence shown in Sequence ID No. 25, Preferably, the antibody or its antigen-binding fragment (1) VH having the sequence shown in sequence number 21, and VL having the sequence shown in sequence number 23, (2) VH having the sequence shown in sequence number 21, and VL having the sequence shown in sequence number 24, (3) VH having the sequence shown in sequence number 22, and VL having the sequence shown in sequence number 23, (4) VH having the sequence shown in sequence number 22 and VL having the sequence shown in sequence number 24, or (5) A VH having the sequence shown in sequence number 22 and a VL having the sequence shown in sequence number 25, The antibody or antigen-binding fragment according to any one of claims 1 to 5.

7. The antibody or its antigen-binding fragment further comprises a constant region derived from human immunoglobulin, Preferably, the heavy chain of the antibody or its antigen-binding fragment includes a heavy chain constant region derived from human immunoglobulin (e.g., IgG1, IgG2, IgG3, or IgG4), and Preferably, the light chain of the antibody or its antigen-binding fragment includes a constant light chain region derived from human immunoglobulin (e.g., κ or λ). An antibody or antigen-binding fragment according to any one of claims 1 to 6.

8. The antibody or its antigen-binding fragment is a monoclonal antibody, mouse antibody, rabbit antibody, humanized antibody, fully human antibody, chimeric antibody (e.g., human-mouse chimeric antibody), bispecific antibody, polyspecific antibody, single-chain antibody, dAb, complementarity-determining region fragment, Fv, single-chain Fv (scFv), Fd, Fab, Fab', and F(ab'). ２ Selected from, and Preferably, the monoclonal antibody includes a non-CDR region, and the non-CDR region is derived from a species other than mouse, such as a human antibody. The antibody or antigen-binding fragment according to any one of claims 1 to 7.

9. The antibody or its antigen-binding fragment is 1.0 × 10 －８ K less than or equal to M Ｄ An antibody or antigen-binding fragment according to any one of claims 1 to 8, which binds to human or monkey PTK7.

10. The antibody or antigen-binding fragment according to any one of claims 1 to 9, wherein the antibody or antigen-binding fragment does not cross-react with mouse PTK7.

11. A nucleic acid molecule comprising a nucleic acid sequence encoding an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, its heavy chain and / or light chain, or its heavy chain variable region and / or light chain variable region, or an isolated nucleic acid molecule encoding an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, its heavy chain and / or light chain, or its heavy chain variable region and / or light chain variable region.

12. A vector comprising the isolated nucleic acid molecule described in claim 11.

13. A host cell comprising the nucleic acid molecule described in claim 11 or the vector described in claim 12.

14. Use of the antibody or antigen-binding fragment according to any one of claims 1 to 10 in the preparation of an antibody-drug conjugate, or in the preparation of a kit for diagnosing a disease, in particular a PTK7-mediated disease or disorder, or in the preparation of a pharmaceutical product for the prevention and / or treatment of a disease, in particular a PTK7-mediated disease or disorder.

15. A composition comprising an antibody or antigen-binding fragment according to any one of claims 1 to 10, an isolated nucleic acid molecule according to claim 11, a vector according to claim 12, or a host cell according to claim 13, Preferably, the composition comprises an antibody or antigen-binding fragment according to any one of claims 1 to 10, and optionally other antibodies, such as an anti-PD-1 antibody, an anti-PDL-1 antibody, and / or an anti-CTLA-4 antibody.

16. Equation (I): 【Chemistry 25】 An antibody-drug conjugate or a pharmaceutically acceptable salt thereof shown in the formula, Q １ -L １ -L ２ -L ３ It is a linker, Ab is an antibody or antigen-binding fragment according to any one of claims 1 to 10, and Q in the linker via the S atom in the antibody or antigen-binding fragment. １ It is coupled with T is a drug unit or a diagnostic reagent unit, and is coupled to L in the linker via an N atom or an O atom in the drug unit or the diagnostic reagent unit ３ and m is a number from 1 to 12, for example, m is a number from 3 to 9, for example, approximately 4 or approximately 8. Q １ The following: 【Chemistry 26】 Selected from, L １ is, -L １ａ -C (=O)-, and in the formula, L １ａ These are selected from alkylene, polyethylene glycol group, alkenylene, alkylylene, alicylidene, aliphatic heterocyclylene, arylene, heteroarylene, substituted alkylene, substituted polyethylene glycol group, substituted alkenylene, substituted alkylylene, substituted alicylidene, substituted aliphatic heterocyclylene, substituted arylene, and substituted heteroarylene. L ２ is a polypeptide residue or a substituted polypeptide residue, and L ３ teeth, 【Chemistry 27】 That is, Antibody-drug conjugates or pharmaceutically acceptable salts thereof.

17. L ２ and / or L ３ The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 16, which may be substituted with a polysarcosine residue, a glycosylated polyethylene glycol fragment, a substituted polysarcosine residue, or a substituted glycosylated polyethylene glycol fragment.

18. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 16, wherein the polypeptide residue comprises an amino acid selected from phenylalanine, isoleucine, leucine, tryptophan, valine, methionine, tyrosine, alanine, threonine, histidine, serine, glutamine, arginine, lysine, asparagine, glutamic acid, proline, citrulline, aspartic acid, and glycine.

19. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 18, wherein the polypeptide residue is selected from phenylalanine-lysine (Phe-Lys), valine-alanine (Val-Ala), valine-citrulline (Val-Cit), glutamate-valine-alanine (Glu-Val-Ala), glutamate-valine-citrulline (Glu-Val-Cit), valine-lysine (Val-Lys), alanine-alanine-alanine (Ala-Ala-Ala), alanine-alanine-asparagine (Ala-Ala-Asn), and glycine-glycine-phenylalanine-glycine (Gly-Gly-Phe-Gly).

20. L １ａ ga- (CH ２ ) ｎ１ - and n1 is a number from 1 to 10, for example, a number from 1 to 8, a number from 1 to 6, or a number from 1 to 4, according to claim 16, an antibody-drug conjugate or a pharmaceutically acceptable salt thereof.

21. L ３ However, it may be substituted with a polysarcosine residue, a glycosylated polyethylene glycol fragment, a substituted polysarcosine residue, or a substituted glycosylated polyethylene glycol fragment. 【Chemistry 28】 The polysarcosine residue is linked to the benzene ring via a structural unit -X-, The aforementioned structural unit -X- is 【Chemistry 29】 And, The substituted polysarcosine residue, 【Transformation 30】 In the formula, n² is a number between 4 and 18, for example, a number between 4 and 12, and R is C １ ~C ６ Alkyl, C １ ~C ６ Cycloalkyl, and C １ ~C ６ Selected from alkoxy, and The substituted glycosylated polyethylene glycol fragment 【Chemistry 31】 In this formula, n3 is a number between 4 and 18, for example, a number between 4 and 12. The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 17.

22. The aforementioned drug unit, (i) Microtubule protein inhibitors, e.g., monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), tubulosin or its analogues (e.g., tubulosin A, tubulosin B, tubulosin D, tubulosin H, tubulosin U and tubulosin V), eribulin or its analogues, vinblastine or its analogues (e.g., vincristine, vindesine, vinblastine and DAVLBH), and Aur0101; (ii) Camptothecin topoisomerase inhibitors such as SN38, exatecan, and berotecan, and (iii) Immune activators such as TLR7 / 8 agonists and STING agonists Selected from, The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 16.

23. Q １ -L １ -L ２ -L ３ -Tが、The following: 【Chemistry 32】 【Transformation 33】 An antibody-drug conjugate or a pharmaceutically acceptable salt thereof, selected from the above.

24. The antibody-drug conjugate is 【Transformation 34】 【Chemistry 35】 【Transformation 36】 Selected from, where m and Ab are as defined in claim 16, The antibody-drug conjugate or pharmaceutically acceptable salt thereof according to claim 16.

25. A method for preparing an antibody-drug conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 16 to 24, 【Chemistry 37】 The steps are: reducing Ab to obtain Ab', The process includes the step of coupling Ab' with a compound represented by formula L-D to obtain an antibody-drug conjugate represented by formula (I), In the formula, Ab, Q １ , L １ , L ２ , L ３ A method in which , T, and m are as defined in any one of claims 16 to 24.

26. A pharmaceutical composition comprising an antibody-drug conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 16 to 24, and one or more pharmaceutically acceptable carriers and / or additives.

27. Use of an antibody-drug conjugate or a pharmaceutically acceptable salt thereof according to any one of claims 16 to 24, or a pharmaceutical composition according to claim 26, in the preparation of a pharmaceutical for the prevention and / or treatment of a disease, particularly a PTK7-mediated disease or disorder, or in the preparation of a pharmaceutical for the treatment and / or prevention of a tumor, or in the preparation of a kit for the diagnosis of a disease, particularly a PTK7-mediated disease or disorder.

28. The use according to claim 27, wherein the PTK7-mediated disease or disorder is a cancer accompanied by high expression of PTK7.

29. The tumor is selected from lung cancer, urethral cancer, colorectal cancer, prostate cancer, ovarian cancer, pancreatic cancer, breast cancer, bladder cancer, stomach cancer, gastrointestinal stromal tumor, cervical cancer, esophageal cancer, squamous cell carcinoma, peritoneal cancer, liver cancer, hepatocellular carcinoma, colon cancer, rectal cancer, colorectal cancer, endometrial cancer, uterine cancer, salivary gland cancer, kidney cancer, vulvar cancer, thyroid cancer, penile cancer, leukemia, malignant lymphoma, plasmacytoma, myeloma, and sarcoma, and Preferably, the use according to claim 27, wherein the tumor is selected from lung cancer, breast cancer, colorectal cancer, esophageal cancer, cervical cancer, head and neck squamous cell carcinoma, and ovarian cancer.

30. A kit comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 10, an isolated nucleic acid molecule according to claim 11, a vector according to claim 12, a host cell according to claim 13, an antibody-drug conjugate or pharmaceutically acceptable salt thereof according to any one of claims 16 to 24, or a pharmaceutical composition according to claim 26.

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