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

Patent metadata

Field	Value
Publication number	US-11365255-B2
Application number	US-201916426001-A
Country	US
Kind code	B2
Filing date	May 30, 2019
Priority date	Dec 12, 2013
Publication date	Jun 21, 2022
Grant date	Jun 21, 2022

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.

First claim

It is claimed:

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 anti-PD1 antibody or the antigen-binding fragment thereof specifically binds to a human or cynomolgus PD1 polypeptide, and wherein the heavy chain variable region comprises complementarity determining regions (CDRs) comprising the amino acid sequences of the corresponding CDRs of the antibody heavy chain of SEQ ID NO: 11, and wherein the light chain variable region comprises CDRs comprising the amino acid sequences of the corresponding CDRs of the antibody light chain of SEQ ID NO: 12.

2. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1 ,
(i) wherein the light chain variable region comprises the amino acid sequence of amino acids 1-107 of SEQ ID NO: 12 or the light chain variable region comprises the amino acid sequence of amino acids 1-107 of SEQ ID NO: 12 but for the replacement of the amino acid at position 43 (alanine) with serine (A43S), wherein the positions of the amino acid replacement is according to Kabat numbering; and
(ii) wherein the heavy chain variable region comprises the amino acid sequence of amino acids 1-116 of SEQ ID NO: 11 or the heavy chain variable region comprises the amino acid sequence of amino acids 1-116 of SEQ ID NO: 11 but for the replacement of the amino acid at position 44 (glycine) with arginine (G44R), wherein the positions of the amino acid replacement is according to Kabat numbering.

3. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody further comprises a light chain constant region of human κ or λ chain and a heavy chain constant region of human IgG1, human IgG2, human IgG3, human IgG4, or a variant of the heavy chain constant region selected from the group consisting of: (a) a variant of the heavy chain constant region of a human IgG1 in which one or more of the amino acids at positions 297, 234, and 235, as according to EU numbering, have been replaced by alanine; (b) a variant of the heavy chain constant region of a human IgG4 in which the amino acid at position 235, as according to EU numbering, has been replaced by glutamic acid; or (c) a variant of the heavy chain constant region of a human IgG4 in which the amino acids at positions 234 and 235, as according to EU numbering, have been replaced by alanine.

4. The anti-PD1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 12 or a light chain having the amino acid sequence of SEQ ID NO: 12 but for the replacement of the amino acid at position 43 (alanine) with serine (A43S); and a heavy chain having the amino acid sequence of SEQ ID NO: 11 or a heavy chain having the amino acid sequence of SEQ ID NO: 11 but for the replacement of the amino acid at position 44 (glycine) with arginine (G44R), wherein the positions of the amino acid replacements are according to Kabat numbering.

5. A DNA molecule encoding the antibody or the antigen-binding fragment thereof according to claim 1 .

6. An expression vector comprising the DNA molecule according to claim 5 .

7. A host cell transformed with the expression vector according to claim 6 .

8. The host cell according to claim 7 , wherein the host cell is a bacteria cell or a yeast cell.

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

10. A method for treating cancer in a human subject, the method comprising administering to the subject an effective amount of the antibody according to claim 1 to block binding of PD-1 to PD-L1 in the subject.

11. The method of claim 10 , 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.

12. An anti-PD-1 antibody or an antigen-binding fragment thereof, comprising a light chain variable region and a heavy chain variable region, wherein the anti-PD-1 antibody or the antigen-binding fragment thereof specifically binds to a human or cynomolgus PD-1 polypeptide, wherein the light chain variable region comprises the amino acid sequence of amino acids 1-107 of SEQ ID NO: 12 and wherein the heavy chain variable region comprises the amino acid sequence of amino acids 1-116 of SEQ ID NO: 11.

Assignees

• Suzhou Suncadia Biopharmaceuticals Co Ltd
• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Yuan Jijun
• Qu Xiangdong
• Lin Jufang
• Ye Xin
• Cao Guoqing
• Tao Weikang
• Zhang Lianshan
• Zhang Lei
• Yang Li

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title

• C07K2317/20

  characterized by taxonomic origin · CPC title

• A61K39/395 Primary

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title