Anti-CD40 antibody, antigen binding fragment thereof and medical use thereof

Patent metadata

Field	Value
Publication number	US-11525005-B2
Application number	US-201816618006-A
Country	US
Kind code	B2
Filing date	May 31, 2018
Priority date	Jun 1, 2017
Publication date	Dec 13, 2022
Grant date	Dec 13, 2022

Abstract

Provided are an anti-CD40 antibody, an antigen binding fragment thereof, and a medical use thereof. Also provided are a chimeric antibody and a humanized antibody including a CDR region of the anti-CD40 antibody, a pharmaceutical composition including the human anti-CD40 antibody and the antigen binding fragment thereof, and an application thereof as an anti-cancer drug. In particular, provided are a humanized anti-CD40 antibody, and an application thereof in preparation of a drug to treat a CD40-mediated disease or disorder.

First claim

What is claimed is:

1. An anti-CD40 antibody or antigen binding fragment thereof, comprising a light chain variable region and a heavy chain variable region, wherein the light chain variable region of the antibody or antigen binding fragment thereof comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively; and the heavy chain variable region of the antibody or antigen binding fragment thereof comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively; the light chain variable region of the antibody or antigen binding fragment thereof comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16, respectively; and the heavy chain variable region of the antibody or antigen binding fragment thereof comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13, respectively; the light chain variable region of the antibody or antigen binding fragment thereof comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 42, SEQ ID NO: 43 and SEQ ID NO: 44, respectively; and the heavy chain variable region of the antibody or antigen binding fragment thereof comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 39, SEQ ID NO: 40 and SEQ ID NO: 41, respectively; the light chain variable region of the antibody or antigen binding fragment thereof comprises LCDR1, LCDR2, and LCDR3 having the sequence of SEQ ID NO: 50, SEQ ID NO: 51, and SEQ ID NO: 52, respectively; and the heavy chain variable region of the antibody or antigen binding fragment thereof comprises HCDR1, HCDR2, and HCDR3 having the sequence of SEQ ID NO: 47, SEQ ID NO: 48, and SEQ ID NO: 49, respectively; or the light chain variable region of the antibody or antigen binding fragment thereof comprises LCDR1, LCDR2, and LCDR3 having the sequence of SEQ ID NO: 58, SEQ ID NO: 59, and SEQ ID NO: 60, respectively; and the heavy chain variable region of the antibody or antigen binding fragment thereof comprises HCDR1, HCDR2, and HCDR3 having the sequence of SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57, respectively.

2. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is a murine antibody or a chimeric antibody.

3. The anti-CD40 antibody or antigen binding fragment thereof of claim 2 , wherein the heavy chain variable region comprises SEQ ID NO: 1, and the light chain variable region comprises SEQ ID NO. 2.

4. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is a humanized antibody or humanized antigen binding fragment thereof, or a human antibody or human antigen binding fragment thereof.

5. The anti-CD40 antibody or antigen binding fragment thereof of claim 4 , wherein the sequence of light chain framework region (FR) on the light chain variable region of the humanized antibody or humanized antigen binding fragment thereof is derived from light chain IGkV1-33 sequence of human germline as shown in SEQ ID NO: 22, or light chain IGkV2-28 sequence of human germline as shown in SEQ ID NO: 24.

6. The anti-CD40 antibody or antigen binding fragment thereof of claim 4 , wherein the antibody or antigen binding fragment thereof comprises a light chain sequence of SEQ ID NO: 18 or SEQ ID NO: 20.

7. The anti-CD40 antibody or antigen binding fragment thereof of claim 4 , wherein the antibody or antigen binding fragment thereof comprises human IgG1, IgG2, IgG3 or IgG4 constant regions.

8. The anti-CD40 antibody or antigen binding fragment thereof of claim 4 , wherein the sequence of heavy chain FR region on the heavy chain variable region of the humanized antibody or humanized antigen binding fragment thereof is derived from heavy chain IGHV1-69 sequence of human germline as shown in SEQ ID NO: 21, or heavy chain IGHV1-2 sequence of human germline as shown in SEQ ID NO: 23.

9. The anti-CD40 antibody or antigen binding fragment thereof of claim 4 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain sequence of SEQ ID NO: 17 or SEQ ID NO: 19.

10. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises SEQ ID NO: 26, and the light chain variable region comprises SEQ ID NO: 33.

11. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof comprise a heavy chain sequence of SEQ ID NO: 19, and a light chain sequence of SEQ ID NO: 20.

12. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is a multi-specific antibody.

13. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is a single chain antibody.

14. An antibody-drug conjugate, wherein the antibody-drug conjugate comprises the anti-CD40 antibody or antigen binding fragment thereof of claim 1 .

15. A pharmaceutical composition comprising the anti-CD40 antibody or antigen binding fragment thereof of claim 1 , and a pharmaceutically acceptable excipient, diluent or carrier.

16. A method for treating lymphoma, the method comprises administering to a subject a therapeutically effective dose of the pharmaceutical composition of claim 15 .

17. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively; and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

18. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16, respectively; and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13, respectively.

19. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the heavy chain variable region comprise SEQ ID NO: 30, and the light chain variable region comprise SEQ ID NO: 34.

20. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof comprise a heavy chain sequence of SEQ ID NO: 17, and a light chain sequence of SEQ ID NO: 18.

21. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 42, SEQ ID NO: 43 and SEQ ID NO: 44, respectively; and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 39, SEQ ID NO: 40 and SEQ ID NO: 41, respectively.

22. The anti-CD40 antibody or antigen binding fragment thereof of claim 1 , wherein the light chain variable region comprises LCDR1, LCDR2 and LCDR3 having the sequence of SEQ ID NO: 50, SEQ ID NO: 51 and SEQ ID NO: 52, respectively; and the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 having the sequence of SEQ ID NO: 47, SEQ ID NO: 48 and SEQ ID NO: 49, respectively.

23. The anti-CD40 antibody or antigen binding fragme

Assignees

• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Yan Shude
• Jiang Jiahua
• Hu Qiyue
• Zhang Lianshan
• Cao Guoqing
• Qian Xueming
• Teng Fei

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07K2317/31

  multispecific · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title