Anti-activin a antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2018371073-A1
Application number	US-201816128831-A
Country	US
Kind code	A1
Filing date	Sep 12, 2018
Priority date	Sep 8, 2006
Publication date	Dec 27, 2018
Grant date	—

Abstract

The disclosure provides compositions and methods relating to or derived from anti-activin A binding proteins, including antibodies. In particular embodiments, the disclosure provides fully human, humanized, and chimeric anti-activin A antibodies that bind human activin A, activin A-binding fragments and derivatives of such antibodies, and activin A-binding polypeptides comprising such fragments. Other embodiments provide nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having activin A-related disorders or conditions including cachexia related to gonadal cancer, other cancers, rheumatoid arthritis, and other diseases.

First claim

1 . An isolated antibody or antigen binding fragment thereof, comprising:
a. a light chain variable domain (VL) comprising:
i. a light chain CDR1 sequence of SEQ ID NO:11;
ii. a light chain CDR2 sequence of SEQ ID NO:12; and
iii. a light chain CDR3 sequence of SEQ ID NO:13; and
b. a heavy chain variable domain (VH) comprising:
i. a heavy chain CDR1 sequence of SEQ ID NO:62;
ii. a heavy chain CDR2 sequence of SEQ ID NO:63; and
iii. a heavy chain CDR3 sequence of SEQ ID NO:64.

2 . The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is an isolated fully human antibody that specifically binds to the cysteine knot region, amino acids C11-S33 and/or amino acids C81-E111, of activin A (SEQ ID NO:225).

3 . The isolated antibody or antigen binding fragment thereof of claim 1 , wherein said isolated antibody or antigen binding fragment possesses an in vivo biological activity of attenuating cachexia.

4 . The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody possesses an in vivo biological activity of attenuating cachexia in colon tumor-bearing mice.

5 . The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is an isolated fully human antibody that
a) specifically binds to the cysteine knot region, amino acids C11-S33 and/or amino acids C81-E111, of activin A (SEQ ID NO:225), wherein said fully human antibody inhibits the binding of activin A to activin A receptor in vitro, or b) specifically binds to the cysteine knot region, amino acids C11-S33 and/or amino acids C81-E111, of activin A (SEQ ID NO:225), wherein said fully human antibody inhibits the binding of activin A to activin A receptor in vivo, or c) specifically binds to amino acids K13-Y39 of activin A (SEQ ID NO:225), wherein said fully human antibody inhibits the binding of activin A to activin A receptor in vitro, or d) specifically binds to amino acids V82-N107 of activin A (SEQ ID NO:225), wherein said fully human antibody inhibits the binding of activin A to activin A receptor in vitro, or e) specifically binds to amino acids K13-Y39 of activin A (SEQ ID NO:225), wherein said fully human antibody inhibits the binding of activin A to activin A receptor in vivo, or f) specifically binds to amino acids V82-N107 of activin A (SEQ ID NO:225), wherein said fully human antibody inhibits the binding of activin A to activin A receptor in vivo.

6 . A pharmaceutical composition comprising a pharmaceutically acceptable composition comprising a pharmaceutically acceptable excipient and an isolated antibody or antigen binding fragment thereof, comprising:
a. a light chain variable domain (VL) comprising:
i. a light chain CDR1 sequence of SEQ ID NO:11;
ii. a light chain CDR2 sequence of SEQ ID NO:12; and
iii. a light chain CDR3 sequence of SEQ ID NO:13; and
b. a heavy chain variable domain (VH) comprising:
i. a heavy chain CDR1 sequence of SEQ ID NO:62;
ii. a heavy chain CDR2 sequence of SEQ ID NO:63; and
iii. a heavy chain CDR3 sequence of SEQ ID NO:64.

7 . The pharmaceutical composition of claim 6 , wherein the isolated antibody or antigen binding fragment possesses at least one in vivo biological activity of a human anti-activin A antibody.

8 . The pharmaceutical composition of claim 7 , wherein said biological activity is attenuation of cachexia.

9 . The pharmaceutical composition of claim 8 , wherein said biological activity is attenuation cachexia in colon tumor-bearing mice.

10 . The pharmaceutical composition of claim 7 , wherein said biological activity is amelioration of the loss of body weight in colon tumor-bearing mice.

11 . The pharmaceutical composition of claim 7 , wherein said biological activity is amelioration of the loss of body weight in a collagen-induced animal model of rheumatoid arthritis.

12 . The pharmaceutical composition of claim 7 , wherein said biological activity is amelioration of the loss of muscle mass in a collagen-induced animal model of rheumatoid arthritis.

13 . The pharmaceutical composition of claim 7 , wherein said biological activity is amelioration of the loss of fat mass in a collagen-induced animal model of rheumatoid arthritis.

14 . A method of inhibiting human activin A in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 6 .

15 . A method of attenuating cachexia in a subject, comprising administering an effective amount of the pharmaceutical composition of claim 6 .

16 . A method of ameliorating the loss of body weight in a subject, comprising administering an effective amount of the pharmaceutical composition of claim 6 .

17 . A method of ameliorating the loss of muscle mass in a subject, comprising administering an effective amount of the pharmaceutical composition of claim 6 .

18 . A method of ameliorating the loss of fat mass in a subject, comprising administering an effective amount of the pharmaceutical composition of claim 6 .

19 . An isolated polynucleotide comprising at least one sequence that encodes the antibody or antigen binding fragment thereof of claim 1 .

20 . A method of producing an antibody or antigen binding fragment thereof, comprising obtaining a cell comprising the isolated polynucleotide of claim 19 and producing the antibody or antigen binding fragment thereof.

Assignees

• Amgen Inc

Inventors

• Han Huiquan
• Chen Qing
• Kwak Keith Soo-Nyung
• Zhou Xiaolan

Classifications

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P5/06

  of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH · CPC title