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

Patent metadata

Field	Value
Publication number	US-2016376367-A1
Application number	US-201415103758-A
Country	US
Kind code	A1
Filing date	Nov 14, 2014
Priority date	Dec 12, 2013
Publication date	Dec 29, 2016
Grant date	—

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

1 . APD-1 antibody or an antigen-binding fragment thereof, comprising:
a light chain variable region comprising at least one LCDR selected from those sequences as shown in: SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO: 8; and a heavy chain variable region comprising at least one HCDR region selected from those sequences as shown in: SEQ ID NO: 3, SEQ ID NO: 4 or SEQ ID NO: 5.

2 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR1 as shown in SEQ ID NO: 6.

3 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR2 as shown in SEQ ID NO: 7.

4 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR3 as shown in SEQ ID NO: 8.

5 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR1 as shown in SEQ ID NO: 3 .

6 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR2 as shown in SEQ ID NO: 4 .

7 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the heavy chain variable region comprises a HCDR3 as shown in SEQ ID NO: 5 .

8 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR1, a LCDR2 and a LCDR3 as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively.

9 . The 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 a HCDR3 as shown in SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

10 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the light chain variable region comprises a LCDR1, a LCDR2 and a LCDR3 as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively; and wherein the heavy chain variable region comprises a HCDR1, a HCDR2 and a HCDR3 as shown in SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively.

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

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

13 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 12 , wherein the light chain variable region sequence of the chimeric antibody is: SEQ ID NO: 10.

14 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 12 , wherein the heavy chain variable region sequence of the chimeric antibody is: SEQ ID NO: 9

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

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

17 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 15 , wherein the sequence of the humanized antibody light chain is a sequence as shown in SEQ ID NO: 12 or a variant thereof.

18 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 15 , wherein the heavy chain variable region of the humanized antibody further comprises a heavy chain FR of human IgG1, IgG2, IgG3 or IgG4, or a variant thereof.

19 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 15 , wherein the heavy chain FR sequence of the heavy chain variable region of the humanized antibody is derived from a combination sequence of human germline heavy chains IgHV3-7 and JH6 as shown in SEQ ID NO:13, comprising FR1, FR2 and FR3 of IgHV3-7 and FR4 of JH6.

20 . The PD-1 antibody or the antigen-binding fragment thereof according to claim 15 , wherein the sequence of the humanized antibody heavy chain is a sequence as shown in SEQ ID NO: 11 or a variant thereof.

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

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

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

24 . The host cell according to claim 23 , wherein the host cell is bacteria.

25 . The host cell according to claim 23 , wherein the host cell is yeast.

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

27 . 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 .

28 . The method of claim 27 , wherein the PD-1 mediated disease or disorder is a cancer.

29 . The method of claim 28 , wherein the cancer is breast cancer, lung cancer, stomach cancer, intestinal cancer, renal cancer, melanoma or non-small cell lung cancer.

Assignees

• Shanghai hengrui pharmaceutical co ltd
• Jiangsu Hengrui Medicine Co

Inventors

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

Classifications

• C07K2317/14

  Specific host cells or culture conditions, e.g. components, pH or temperature · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/24

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

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title