PD-1 antibody, antigen-binding fragment thereof, and medical application thereof

1. An anti-PD-1 antibody or an antigen-binding fragment thereof, comprising a light chain variable region comprising at least one of a LCDR1, a LCDR2 and a LCDR3 having the amino acid sequences of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively; and a heavy chain variable region comprising a HCDR3 having the amino acid sequence of SEQ ID NO: 5.

2. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR1, a HCDR2 and the HCDR3 having the amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

3. A DNA molecule encoding the anti-PD-1 antibody or the antigen-binding fragment according to claim 1 .

4. A host cell transformed with an expression vector comprising the DNA molecule according to claim 3 .

5. A pharmaceutical composition comprising the anti-PD-1 antibody or the antigen-binding fragment according to claim 1 and a pharmaceutically acceptable excipient, diluent or carrier.

6. A method for treating a PD-1 mediated disease or disorder in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the antibody or the antigen-binding fragment according to claim 1 , wherein the PD-1 mediated disease or disorder is a cancer.

7. An anti-PD-1 antibody or an antigen-binding fragment thereof, comprising a light chain variable region comprising a LCDR1, a LCDR2 and a LCDR3 having the amino acid sequences of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively, and a heavy chain variable region comprising at least one of a HCDR1, a HCDR2 and a HCDR3 having the amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

8. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 7 , wherein the heavy chain variable region comprises the HCDR3 having the amino acid sequence of SEQ ID NO: 5.

9. An anti-PD-1 antibody or an antigen-binding fragment thereof, comprising a light chain variable region comprising a LCDR1, a LCDR2 and a LCDR3 having the amino acid sequences of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively; and a heavy chain variable region comprising a HCDR1, a HCDR2 and a HCDR3 having the amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

10. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 9 , wherein the antibody or the antigen-binding fragment thereof is a murine antibody or a fragment thereof.

11. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 9 , wherein the antibody or the antigen-binding fragment thereof is a chimeric antibody or a fragment thereof.

12. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 11 , wherein the chimeric antibody comprises a light chain variable region having the amino acid sequence of SEQ ID NO: 10.

13. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 11 , wherein the chimeric antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 9.

14. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 9 , wherein the antibody or the antigen-binding fragment is a humanized antibody or a fragment thereof.

15. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 14 , wherein the light chain variable region of the humanized antibody comprises a light chain FR sequence derived from a combination sequence of human germline light chains IGKV1-39 and JK4 as shown in SEQ ID NO: 14, and the light chain FR sequence comprises FR1, FR2 and FR3 of the light chain IGKV 1-39 and FR4 of the light chain JK4.

16. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 14 , wherein the humanized antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 12 or a variant thereof.

17. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 14 , wherein the heavy chain variable region of the humanized antibody further comprises a heavy chain FR sequence of human IgG1, IgG2, IgG3 or IgG4, or a variant thereof.

18. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 14 , wherein the heavy chain variable region of the humanized antibody comprises a heavy chain FR sequence derived from a combination sequence of human germline heavy chains IgHV3-7 and JH6 as shown in SEQ ID NO:13, and the heavy chain FR sequence comprises FR1, FR2 and FR3 of the heavy chain IgHV3-7 and FR4 of the heavy chain JH6.

19. The anti-PD-1 antibody or the antigen-binding fragment thereof according to claim 14 , wherein the humanized antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 11 or a variant thereof.

20. A DNA molecule encoding the anti-PD-1 antibody or the antigen-binding fragment according to claim 9 .

21. An expression vector comprising the DNA molecule according to claim 20 .

22. A host cell transformed with the expression vector according to claim 21 .

23. The host cell according to claim 22 , wherein the host cell is a bacterial cell.

24. The host cell according to claim 22 , wherein the host cell is a yeast cell.

25. A pharmaceutical composition comprising the anti-PD-1 antibody or the antigen-binding fragment according to claim 9 and a pharmaceutically acceptable excipient, diluent or carrier.

26. A method for treating a PD-1 mediated disease or disorder in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the antibody or the antigen-binding fragment according to claim 9 , wherein the PD-1 mediated disease or disorder is a cancer.

27. The method of claim 26 , wherein the cancer is breast cancer, lung cancer, stomach cancer, intestinal cancer, renal cancer, melanoma or non-small cell lung cancer.