Activin-actriia antagonists and uses for treating multiple myeloma

• US 9,572,865 B2
• Filed: 04/30/2012
• Issued: 02/21/2017
• 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, Kumar, Ravindra
• Primary Examiner(s): BORGEEST, CHRISTINA M
• Application Number:
  US13/460,342
• Publication Number:
  US 20130004489A1
• Time in Patent Office: 1,758 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 38/1796 for hormones for neuromediators A61K38/1787
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• 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

Abstract

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density, as well as for the treatment of multiple myeloma.

Claims

1. A method for treating multiple myeloma in a human patient, the method comprising administering to the patient an effective amount of an ActRIIa-Fc fusion protein, wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

3, and wherein the fusion protein binds to activin and/or GDF11.

2. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:

3.

3. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

2.

4. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:

2.

5. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

7.

6. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:

7.

7. The method of claim 6, wherein the N-terminus of the ActRIIa-Fc fusion protein is ILGRSETQE (SEQ ID NO:

11).

8. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

12.

9. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:

12.

10. The method of claim 1, wherein the N-terminus of the ActRIIa-Fc fusion protein is ILGRSETQE (SEQ ID NO:

11).

11. The method of claim 1, wherein the ActRIIa-Fc fusion protein comprises one or more modified amino acids selected from:

a glycosylated amino acid, a PEGylated amino acid, a farnesylated amino acid, an acetylated amino acid, a biotinylated amino acid, or an amino acid conjugated to a lipid moiety.

12. The method of claim 1, wherein the ActRIIa-Fc fusion protein is glycosylated and has a glycosylation pattern obtainable from a Chinese hamster ovary cell.

13. The method of claim 1, wherein the ActRIIa-Fc fusion protein binds to activin.

14. The method of claim 13, wherein the ActRIIa-Fc fusion protein binds to activin A.

15. The method of claim 13, wherein the ActRIIa-Fc fusion protein binds to activin B.

16. The method of claim 13, wherein the ActRIIa-Fc fusion protein binds to GDF11.

17. The method of claim 1, wherein the ActRIIa-Fc fusion protein binds to GDF11.