Anti-alpha V beta 6 antibodies and uses thereof

• US 10,035,860 B2
• Filed: 03/14/2014
• Issued: 07/31/2018
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen MA Inc. (Biogen, Inc.)
• Inventors: Violette, Shelia M., Weinreb, Paul H., Jones, Timothy David, Carr, Francis Joseph, Tessarz, Anja Sibylle
• Primary Examiner(s): Haddad, Maher M
• Application Number:
  US14/772,863
• Publication Number:
  US 20160017042A1
• Time in Patent Office: 1,600 Days
• Field of Search: None
• CPC Class Codes: C07K 16/2839 against the integrin superfamily
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: G01N 2800/00 Detection or diagnosis of diseases
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites

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 diagnose, treat, and/or prevent αvβ6-mediated diseases such as acute tissue injury, fibrosis, and cancer.

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to α

vβ

6, 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;

or

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.

4. A pharmaceutical composition comprising the antibody or the antigen-binding fragment thereof of claim 1 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 α

vβ

6-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 α

vβ

6 in the cell or tissue,

wherein an increased level of α

vβ

6 in the cell or tissue compared to a cell or tissue from a control human subject not having the α

vβ

6-mediated disorder is indicative that the human subject has or is likely to develop the α

vβ

6-mediated disorder.

2. An antibody or antigen-binding fragment thereof that specifically binds to α

vβ

6, 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;

or

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.

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

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.

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.

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.

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.

20. A method of diagnosing an α

vβ

6-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 2;

(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 α

vβ

6 in the cell or tissue,

wherein an increased level of α

vβ

6 in the cell or tissue compared to a cell or tissue from a control human subject not having the α

vβ

6-mediated disorder is indicative that the human subject has or is likely to develop the α

vβ

6-mediated disorder.

3. An antibody or antigen-binding fragment thereof that specifically binds to α

vβ

6, 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;

or

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.

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

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.

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.

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.

19. 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 3.

21. A method of diagnosing an α

vβ

6-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 3;

(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 α

vβ

6 in the cell or tissue,

wherein an increased level of α

vβ

6 in the cell or tissue compared to a cell or tissue from a control human subject not having the α

vβ

6-mediated disorder is indicative that the human subject has or is likely to develop the α

vβ

6-mediated disorder.