Anti-CD147 antibody

Patent metadata

Field	Value
Publication number	US-11459387-B2
Application number	US-202117499814-A
Country	US
Kind code	B2
Filing date	Oct 12, 2021
Priority date	Jul 27, 2017
Publication date	Oct 4, 2022
Grant date	Oct 4, 2022

Abstract

An object of the present invention is to provide a novel anti-CD147 antibody exhibiting potent antitumor efficacy and having excellent safety. Another object of the present invention is to provide a pharmaceutical product comprising such an antibody. Another object of the present invention is to provide a method for treating tumors using the antibody or the pharmaceutical product, for example. The present invention provides a CD147-specific antibody that activates CD147 and exhibits high antitumor efficacy. The present invention provides the anti-CD147 antibody that exhibits high antitumor efficacy independent of effector functions. The present invention provides a pharmaceutical composition comprising such an anti-CD147 antibody. The present invention provides a method for treating tumors using such an anti-CD147 antibody and/or pharmaceutical composition.

First claim

The invention claimed is:

1. An antibody against human CD147 or an antigen-binding fragment thereof comprising,
a) a CDRH1 consisting of amino acids 45 to 54 of SEQ ID NO: 135, a CDRH2 consisting of amino acids 69 to 78 of SEQ ID NO: 135, a CDRH3 consisting of amino acids 118 to 125 of SEQ ID NO: 135, a CDRL1 consisting of amino acids 44 to 54 of SEQ ID NO: 137, a CDRL2 consisting of amino acids 70 to 76 of SEQ ID NO: 137, and a CDRL3 consisting of amino acids 109 to 117 of SEQ ID NO: 137;
b) a CDRH1 consisting of amino acids 45 to 54 of SEQ ID NO: 147, a CDRH2 consisting of amino acids 69 to 78 of SEQ ID NO: 147, a CDRH3 consisting of amino acids 118 to 125 of SEQ ID NO: 147, a CDRL1 consisting of amino acids 44 to 54 of SEQ ID NO: 149, a CDRL2 consisting of amino acids 70 to 76 of SEQ ID NO: 149, and a CDRL3 consisting of amino acids 109 to 117 of SEQ ID NO: 149; or
c) a CDRH1 consisting of amino acids 45 to 54 of SEQ ID NO: 147, a CDRH2 consisting of amino acids 69 to 78 of SEQ ID NO: 147, a CDRH3 consisting of amino acids 118 to 125 of SEQ ID NO: 147, a CDRL1 consisting of amino acids 44 to 54 of SEQ ID NO: 151, a CDRL2 consisting of amino acids 70 to 76 of SEQ ID NO: 151, and a CDRL3 consisting of amino acids 109 to 117 of SEQ ID NO: 151.

2. The antibody of claim 1 , wherein the CDRH1 consists of amino acids 45 to 54 of SEQ ID NO: 135, the CDRH2 consists of amino acids 69 to 78 of SEQ ID NO: 135, the CDRH3 consists of amino acids 118 to 125 of SEQ ID NO: 135, the CDRL1 consists of amino acids 44 to 54 of SEQ ID NO: 137, the CDRL2 consists of amino acids 70-76 of SEQ ID NO: 137, and the CDRL3 consists of amino acids 109-117 of SEQ ID NO: 137.

3. The antibody of claim 1 , wherein the CDRH1 consists of amino acids 45 to 54 of SEQ ID NO: 147, the CDRH2 consists of amino acids 69 to 78 of SEQ ID NO: 147, the CDRH3 consists of amino acids 118 to 125 of SEQ ID NO: 147, the CDRL1 consists of amino acids 44 to 54 of SEQ ID NO: 149, the CDRL2 consists of amino acids 70-76 of SEQ ID NO: 149, and the CDRL3 consists of amino acids 109-117 of SEQ ID NO: 149.

4. The antibody of claim 1 , wherein the CDRH1 consists of amino acids 45 to 54 of SEQ ID NO: 147, the CDRH2 consists of amino acids 69 to 78 of SEQ ID NO: 147, the CDRH3 consists of amino acids 118 to 125 of SEQ ID NO: 147, the CDRL1 consists of amino acids 44 to 54 of SEQ ID NO: 151, the CDRL2 consists of amino acids 70-76 of SEQ ID NO: 151, and the CDRL3 consists of amino acids 109-117 of SEQ ID NO: 151.

5. The antibody of claim 1 , comprising:
a heavy chain variable region consisting of amino acids 20 to 136 of SEQ ID NO: 135, and a light chain variable region consisting of amino acids 21 to 128 of SEQ ID NO: 137.

6. The antibody of claim 1 , comprising:
a heavy chain variable region consisting of amino acids 20 to 136 of SEQ ID NO: 147, and a light chain variable region consisting of amino acids 21 to 128 of SEQ ID NO: 149.

7. The antibody of claim 1 , comprising:
a heavy chain variable region consisting of amino acids 20 to 136 of SEQ ID NO: 147, and a light chain variable region consisting of amino acids 21 to 128 of SEQ ID NO: 151.

8. The antibody of claim 1 , wherein the constant region is a human constant region.

9. The antibody of claim 1 , comprising
a heavy chain consisting of amino acids 20 to 463 of SEQ ID NO: 135, and a light chain consisting of amino acids 21 to 234 of SEQ ID NO: 137.

10. The antibody of claim 1 , comprising
a heavy chain consisting of amino acids 20 to 463 of SEQ ID NO: 147, and a light chain consisting of amino acids 21 to 234 of SEQ ID NO: 149.

11. The antibody of claim 1 , comprising
a heavy chain consisting of amino acids 20 to 463 of SEQ ID NO: 147, and a light chain consisting of amino acids 21 to 234 of SEQ ID NO: 151.

12. The antibody of claim 1 , comprising
a heavy chain consisting of amino acids 20 to 461 or amino acids 20 to 462 of SEQ ID NO: 135, and a light chain consisting of amino acids 21 to 234 of SEQ ID NO: 137.

13. The antibody of claim 1 , comprising
a heavy chain consisting of amino acids 20 to 461 or amino acids 20 to 462 of SEQ ID NO: 147, and a light chain consisting of amino acids 21 to 234 of SEQ ID NO: 149.

14. The antibody of claim 1 , comprising
a heavy chain consisting of amino acids 20 to 461 or amino acids 20 to 462 of SEQ ID NO: 147, and a light chain consisting of amino acids 21 to 234 of SEQ ID NO: 151.

15. The antibody of claim 1 , wherein the antibody possesses decreased ADCC activity or lacks ADCC activity.

16. The antibody of claim 1 , wherein the antibody possesses decreased CDC activity or lacks CDC activity.

17. The antibody of claim 1 , wherein the antibody possesses decreased ADCP activity or lacks ADCP activity.

18. A polynucleotide encoding the antibody of claim 1 .

19. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof according to claim 1 .

20. The pharmaceutical composition according to claim 19 , which is an antitumor agent.

21. The pharmaceutical composition according to claim 20 , wherein the tumor is a tumor expressing CD147.

22. The pharmaceutical composition according to claim 21 , wherein the tumor is pancreatic cancer, liver cancer, gastric cancer, colon cancer, renal cancer, breast cancer, uterine cancer, ovarian cancer, lung cancer, lymphoma, thyroid cancer, skin cancer, head and neck cancer, sarcoma, prostate cancer, bladder cancer, brain tumor, gastrointestinal stromal tumor (GIST), leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), malignant lymphoma, B-cell lymphoma, non-Hodgkin's lymphoma or diffuse large B-cell lymphoma (DLBCL).

23. An expression vector comprising the polynucleotide of claim 18 .

24. A host cell transformed with the expression vector according to claim 23 .

25. A method for producing the antibody or the antigen-binding fragment thereof, comprising a step of culturing a host cell with an expression vector comprising a nucleotide that encodes the antibody or antigen-binding fragment thereof according to claim 1 and collecting the target antibody or the antigen-binding fragment thereof from a culture supernatant.

26. A method for treating a CD147-expressing tumor, comprising administering an antibody of claim 1 to an individual with a CD147-expressing tumor.

27. The method of claim 26 , wherein the tumor is pancreatic cancer, liver cancer, gastric cancer, colon cancer, renal cancer, breast cancer, uterine cancer, ovarian cancer, lung cancer, lymphoma, thyroid cancer, skin cancer, head and neck cancer, sarcoma, prostate cancer, bladder cancer, brain tumor, gastrointestinal stromal tumor (GIST), leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CIVIL), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), malignant lymphoma, B-cell lymphoma, non-Hodgkin's lymphoma or diffuse large B-cell lymphoma (DLBCL).

28. The method of claim 26 , wherein the tumor is pancreatic cancer, liver cancer, gastric cancer, colon cancer, renal cancer, leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia (CIVIL), chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), malignant lymphoma, B-cell lymphoma, non-Hodgkin's lymphoma or diffuse large B-cell lymphoma (DLBCL).

29. An antibody-drug complex comprising t

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Fukuchi Keisuke
• Nanai Kayoko
• Amano Masato
• Yoneda Kozo
• Totoki Yusuke
• Yamamoto Shoji

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• C07K2317/24

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

• C07K2317/21

  from primates, e.g. man · CPC title