Method for promoting bone growth using activin-actriia antagonists

Patent metadata

Field	Value
Publication number	US-11129873-B2
Application number	US-201816054107-A
Country	US
Kind code	B2
Filing date	Aug 3, 2018
Priority date	Nov 23, 2005
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density.

First claim

We claim:

1. A method of identifying an agent that inhibits bone resorption, the method comprising: a) identifying an agent that binds to a ligand-binding domain of an ActRIIa polypeptide competitively with an activin or ActRIIa antagonist polypeptide; and b) evaluating the effect of the agent on bone tissue.

2. The method of claim 1 , wherein the agent is selected from the group consisting of non-peptidyl organic molecules, peptides, polypeptides, peptidomimetics, sugars, hormones, and nucleic acid molecules.

3. The method of claim 1 , wherein the agent is identified by a biochemical method.

4. The method of claim 1 , wherein the agent is identified by a mechanism based assay.

5. The method of claim 1 , wherein the agent is evaluated in a cell-based assay.

6. The method of claim 1 , wherein the agent is evaluated in an in vivo assay.

7. The method of claim 1 , wherein the ActRIIa polypeptide comprises the amino acid sequence of SEQ ID NO: 2.

8. The method of claim 1 , wherein the ActRIIa polypeptide comprises the amino acid sequence of SEQ ID NO: 3.

9. The method of claim 1 , wherein the ActRIIa polypeptide comprises the amino acid sequence of SEQ ID NO: 7.

10. The method of claim 1 , wherein the ActRIIa polypeptide comprises the amino acid sequence of SEQ ID NO: 12.

11. The method of claim 1 , wherein the N-terminus of the ActRIIa polypeptide is ILGRSETQE (SEQ ID NO: 11).

12. The method of claim 1 , wherein the ActRIIa polypeptide consists of the amino acid sequence of SEQ ID NO: 7.

Assignees

• Acceleron Pharma Inc

Inventors

• Knopf John
• Seehra Jasbir

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K38/179 Primary

  for growth factors; for growth regulators · CPC title

• A61P35/04

  specific for metastasis · CPC title

• C07K14/71

  for growth factors; for growth regulators · CPC title

• C07K14/575 Primary

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695) · CPC title