Method of identifying an agent that promotes bone growth or increases bone density

• US 10,071,135 B2
• Filed: 09/09/2015
• Issued: 09/11/2018
• Est. Priority Date: 11/23/2005
• Status: Active Grant

• Current Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Original Assignee: Acceleron Pharma Inc. (Merck & Co., Inc.)
• Inventors: Knopf, John, Seehra, Jasbir
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US14/849,313
• Publication Number:
  US 20160120939A1
• Time in Patent Office: 1,098 Days
• CPC Class Codes: A61K 38/00 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 Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/35 containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction

Abstract

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

Claims

1. A method of identifying an agent that promotes bone growth or increases bone density, the method comprising:

a) identifying an agent that binds to a ligand-binding domain of an ActRIIa polypeptide competitively with an activin 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 set forth in amino acid position 1-9 of SEQ ID NO:

7.

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

7.