Anti-alpha V beta 6 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-10035859-B2
Application number	US-201414772512-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

Humanized antibodies and antibody fragments thereof that bind to αvβ6 are disclosed. Also disclosed are methods of using these antibodies and antibody fragments to treat or prevent αvβ6-mediated diseases such as fibrosis and cancer.

First claim

What is claimed is:

1. An antibody or antigen-binding fragment thereof that specifically binds to αvβ6, wherein the antibody or the antigen-binding fragment thereof comprises:
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:1 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:9;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:3 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:9;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:5 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:9;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:7 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:9;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:50 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:9; or
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:52 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:9.

2. An antibody or antigen-binding fragment thereof that specifically binds to αvβ6, wherein the antibody or the antigen-binding fragment thereof comprises:
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:1 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:11;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:3 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:11;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:5 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:11;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:7 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:11;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:50 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:11; or
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:52 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:11.

3. An antibody or antigen-binding fragment thereof that specifically binds to αvβ6, wherein the antibody or the antigen-binding fragment thereof comprises:
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:1 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:13;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:3 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:13;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:5 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:13;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:7 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:13;
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:50 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:13; or
a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:52 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO:13.

4. A pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof of claim 2 and a pharmaceutically acceptable carrier.

6. A pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof of claim 3 and a pharmaceutically acceptable carrier.

7. A method of treating a cancer in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 1 .

8. The method of claim 7 , wherein the cancer is a pancreatic cancer, a lung cancer, a breast cancer, a colorectal cancer, a head and neck cancer, an esophageal cancer, a skin cancer, a cervical cancer, a prostate cancer, an ovarian cancer, a kidney cancer, and an endometrial cancer.

9. A method of treating fibrosis in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 1 .

10. A method of treating acute exacerbations of idiopathic pulmonary fibrosis in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 1 .

11. A method of diagnosing an αvβ6-mediated disorder in a human subject, the method comprising:
(a) contacting a cell or tissue from the human subject with an isolated antibody or an antigen-binding fragment thereof of claim 1 ;
(b) detecting the formation of a complex between the antibody or the antigen-binding fragment thereof and the cell or tissue to determine the level of expression of αvβ6 in the cell or tissue,
wherein an increased level of αvβ6 in the cell or tissue compared to a cell or tissue from a control human subject not having the αvβ6-mediated disorder is indicative that the human subject has, or is likely to develop, the αvβ6-mediated disorder.

12. A method of treating a cancer in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 2 .

13. A method of treating a cancer in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 3 .

14. The method of claim 12 , wherein the cancer is a pancreatic cancer, a lung cancer, a breast cancer, a colorectal cancer, a head and neck cancer, an esophageal cancer, a skin cancer, a cervical cancer, a prostate cancer, an ovarian cancer, a kidney cancer, and an endometrial cancer.

15. The method of claim 13 , wherein the cancer is a pancreatic cancer, a lung cancer, a breast cancer, a colorectal cancer, a head and neck cancer, an esophageal cancer, a skin cancer, a cervical cancer, a prostate cancer, an ovarian cancer, a kidney cancer, and an endometrial cancer.

16. A method of treating fibrosis in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 2 .

17. A method of treating fibrosis in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 3 .

18. A method of treating acute exacerbations of idiopathic pulmonary fibrosis in a human subject in need thereof, comprising administering to the human subject the antibody or the antigen-binding fragment thereof of claim 2 .

19. A method of treating acute exacerbations of idio

Assignees

• Biogen Ma Inc

Inventors

• Violette Shelia M
• Weinreb Paul H
• Jones Timothy David
• Carr Francis Joseph
• Tessarz Anja Sibylle

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/56

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

• C07K16/2839 Primary

  against the integrin superfamily · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/92

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