Methods for increasing thermogenic adipocytes

Patent metadata

Field	Value
Publication number	US-2022017639-A1
Application number	US-202117186072-A
Country	US
Kind code	A1
Filing date	Feb 26, 2021
Priority date	Jun 8, 2009
Publication date	Jan 20, 2022
Grant date	—

Abstract

In certain aspects, the present invention provides compositions and methods for increasing thermogenic adipocytes (e.g., brown adipocytes or other UCP-1 expressing adipocytes) by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, anti-Nodal, anti-activin, and anti-GDF11 antibodies. A variety of metabolic and other disorders may be treated by causing an increase in thermogenic adipocytes.

First claim

1 - 10 . (canceled)

11 . A method for increasing thermogenic adipocytes in a patient in need thereof, the method comprising administering an effective amount of a polypeptide comprising an amino acid sequence that is at least 95% identical to the sequence of amino acids 29-109 of SEQ ID NO: 2, wherein administration of the polypeptide increases SIRT-1 and/or PGC-1α mRNA levels in adipocytes of the treated patient.

12 . The method of claim 11 , wherein the polypeptide is a fusion protein comprising a portion heterologous to ActRIIB.

13 . The method of claim 12 , wherein the polypeptide is fused to a constant domain of an immunoglobulin.

14 . The method of claim 12 , wherein the polypeptide is fused to an Fc portion of an immunoglobulin.

15 . The method of claim 14 , wherein the immunoglobulin is a human IgG1.

16 . The method of claim 11 , wherein the polypeptide is a dimer.

17 . The method of claim 11 , wherein the polypeptide comprises the sequence of SEQ ID NO: 5.

18 . The method of claim 11 , wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to the sequence of amino acids 29-109 of SEQ ID NO: 2.

19 . The method of claim 11 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of amino acids 25-131 of SEQ ID NO: 2.

20 . The method of claim 19 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of amino acids 25-131 of SEQ ID NO: 2.

21 . The method of claim 20 , wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to the sequence of amino acids 25-131 of SEQ ID NO: 2.

22 . The method of claim 11 , wherein administration of the polypeptide increases SIRT-1 mRNA levels in adipocytes of the treated patient.

23 . The method of claim 11 , wherein administration of the polypeptide increases PGC-1α mRNA levels in adipocytes of the treated patient.

24 . The method of claim 11 , wherein administration of the polypeptide increases SIRT-1 and PGC-1α mRNA levels in adipocytes of the treated patient.

25 . The method of claim 11 , wherein administration of the compound promotes uncoupling protein-1 (UCP-1) expression in adipocytes of the treated patient.

26 . The method of claim 11 , wherein the polypeptide comprises the sequence of SEQ ID NO: 6.

Assignees

• Acceleron Pharma Inc

Inventors

• Knopf John
• Seehra Jasbir
• Kumar Ravindra

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C12N5/0653

  Adipocytes; Adipose tissue · CPC title

• C12N2501/16

  Activin; Inhibin; Mullerian inhibiting substance · CPC title

• C12N5/0667

  Adipose-derived stem cells [ADSC]; Adipose stromal stem cells · CPC title