PD-1 ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF, AND MEDICAL APPLICATION THEREOF

• US 20190309069A1
• Filed: 05/30/2019
• Published: 10/10/2019
• Est. Priority Date: 12/12/2013
• Status: Active Grant

• Current Assignee: Jiangsu Hengrui Medicine Company Limited, Shanghai Hengrui Pharmaceutical Co., Ltd. (Jiangsu Hengrui Pharmaceuticals Co., Ltd.), Suzhou Suncadia Biopharmaceuticals Co., Ltd.
• Original Assignee: Jiangsu Hengrui Medicine Company Limited, Shanghai Hengrui Pharmaceutical Co., Ltd. (Jiangsu Hengrui Pharmaceuticals Co., Ltd.)
• Inventors: YUAN, Jijun, QU, Xiangdong, LIN, Jufang, YE, Xin, CAO, Guoqing, TAO, Weikang, ZHANG, Lianshan, ZHANG, Lei, YANG, Li
• Granted Patent: US 11,365,255 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/20 characterized by taxonomic origin
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention provides a human PD-1 antibody, an antigen-binding fragment thereof, and medical use thereof, and further provides a chimeric antibody and humanized antibodies comprising a complementarity-determining region (CDR) of the antibody, a pharmaceutical composition comprising the human PD-1 antibody and the antigen-binding fragment thereof, and use of the antibody in preparing medicines for treating diseases or disorders.

Claims

1. An anti-PD1 antibody or an antigen-binding fragment thereof, comprising a light chain variable region and a heavy chain variable region, wherein the heavy chain variable region is identical to the heavy chain variable region of an antibody heavy chain having the amino acid sequence of SEQ ID NO:

11, or a variant thereof containing 1 to 10 amino acid mutation(s) in the heavy chain framework region.

2. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1, wherein the heavy chain variable region comprises the variant having a G44R amino acid mutation in the heavy chain framework region, wherein the position of the amino acid mutation is according to Kabat numbering.

3. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1, wherein the light chain variable region is identical to the light chain variable region of an antibody light chain having the amino acid sequence of in SEQ ID NO:

12 or a variant thereof, wherein the variant contains 1 to 10 amino acid mutation(s) in the light chain framework region.

4. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 3, wherein the light chain variable region comprises the variant having an A43S amino acid mutation in the light chain framework region, wherein the position of the amino acid mutation is according to Kabat numbering.

5. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 3, wherein the light chain variable region comprises amino acid residues 1-107 of SEQ ID NO:

12 or a variant thereof having an A43S amino acid mutation in the light chain framework region; and

the heavy chain variable region comprises amino acid residues 1-116 of SEQ ID NO;

11 or a variant thereof having a G44R amino acid mutation in the heavy chain framework region, wherein the positions of the amino acid mutations are according to Kabat numbering.

6. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 3, wherein the antibody further comprises a heavy chain constant region of human IgG1, IgG2, IgG3 or IgG4 or a variant thereof, and a light chain constant region of human κ

, λ

chain or a variant thereof.

7. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 6, wherein the antibody comprises a variant of a heavy chain constant region of human IgG2, IgG4 or IgG1 having no antibody-dependent cellular cytotoxicity (ADCC) function.

8. The antibody or the antigen-binding fragment thereof according to claim 6, comprising a heavy chain having the amino acid sequence of SEQ ID NO:

11 or a variant thereof, wherein the variant contains 1 to 10 amino acid mutation(s) in the heavy chain framework region.

9. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 8, wherein the heavy chain comprises the variant having a G44R amino acid mutation in the heavy chain framework region, wherein the position of the amino acid mutation is according to Kabat numbering.

10. The antibody or the antigen-binding fragment thereof according to claim 6, comprising a light chain having the amino acid sequence of SEQ ID NO:

12 or a variant thereof, wherein the variant contains 1 to 10 amino acid mutation(s) in the light chain framework region.

11. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 10, wherein the light chain comprises the variant having an A43S amino acid mutation in the light chain framework region, wherein the position of the amino acid mutation is according to Kabat numbering.

12. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 6, comprising a light chain having the amino acid sequence of SEQ ID NO:

12 or a variant thereof having an A43S amino acid mutation in the light chain framework region; and

a heavy chain having the amino acid sequence of SEQ ID NO;

11 or a variant thereof having a G44R amino acid mutation in the heavy chain framework region, wherein the positions of the amino acid mutations are according to Kabat numbering.

13. A DNA molecule encoding the antibody or the antigen-binding fragment thereof according to claim 3.

14. An expression vector comprising the DNA molecule according to claim 13.

15. A host cell transformed with the expression vector according to claim 14.

16. The host cell according to claim 15, wherein the host cell is a bacteria cell or a yeast cell.

17. A pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof according to claim 3 and a pharmaceutically acceptable excipient, diluent or carrier.

18. 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 thereof according to claim 3.

19. The method of claim 18, wherein the PD-1 mediated disease or disorder is cancer.

20. The method of claim 19, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, stomach cancer, intestinal cancer, renal cancer, melanoma and non-small cell lung cancer.