Follistatin fusion proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-9919030-B2
Application number	US-201514622459-A
Country	US
Kind code	B2
Filing date	Feb 13, 2015
Priority date	Jun 26, 2008
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

In certain aspects, the present invention provides methods for dosing a patient with a follistatin antagonist and methods for managing patients treated with a follistatin antagonist.

First claim

I claim:

1. A follistatin fusion protein comprising a first amino acid sequence and a second amino acid sequence, wherein the first amino acid sequence comprises a sequence that is at least 90% identical to SEQ ID NO: 17 or that is at least 90% identical to a mature form of SEQ ID NO: 17, and wherein the second amino acid sequence comprises an immunoglobulin Fc domain; wherein the fusion protein comprises a linker between the first amino acid sequence and the second amino acid sequence; and wherein the linker comprises three glycines.

2. The follistatin fusion protein of claim 1 , wherein the first amino acid sequence comprises a sequence that is at least 95% identical to SEQ ID NO: 17, or that is at least 95% identical to a mature form of SEQ ID NO: 17.

3. The follistatin fusion protein of claim 1 , wherein the immunoglobulin Fc domain is selected from the group consisting of: an IgG1 Fc domain, an IgG2 Fc domain, an IgG3 Fc domain and an IgG4 Fc domain.

4. The follistatin fusion protein of claim 1 , wherein the linker further comprises a threonine.

5. The follistatin fusion protein of claim 4 , wherein the linker is 4 amino acids in length.

6. The follistatin fusion protein of claim 5 , wherein the first amino acid sequence comprises the amino acid sequence of SEQ ID NO: 17.

7. The follistatin fusion protein of claim 6 , wherein the immunoglobulin Fc domain is an IgG2 Fc domain.

8. The follistatin fusion protein of claim 5 , wherein the first amino acid sequence comprises a mature form of the amino acid sequence of SEQ ID NO: 17.

9. The follistatin fusion protein of claim 1 , wherein the linker is 4 amino acids in length.

10. The follistatin fusion protein of claim 1 , wherein the first amino acid sequence comprises a sequence that is at least 97% identical to SEQ ID NO: 17 or that is at least 97% identical to a mature form of SEQ ID NO: 17.

11. The follistatin fusion protein of claim 10 , wherein the linker is 50 or more amino acids in length.

12. The follistatin fusion protein of claim 11 , wherein the immunoglobulin Fc domain is an IgG1 Fc domain.

13. The follistatin fusion protein of claim 12 , wherein the first amino acid sequence comprises the amino acid sequence of SEQ ID NO: 17.

14. The follistatin fusion protein of claim 12 , wherein the first amino acid sequence comprises a mature form of the amino acid sequence of SEQ ID NO: 17.

15. The follistatin fusion protein of claim 11 , wherein the first amino acid sequence comprises the amino acid sequence of SEQ ID NO: 17.

16. The follistatin fusion protein of claim 11 , wherein the first amino acid sequence comprises a mature form of the amino acid sequence of SEQ ID NO: 17.

17. The follistatin fusion protein of claim 1 , wherein the first amino acid sequence comprises the amino acid sequence of SEQ ID NO: 17 or a mature form of SEQ ID NO: 17.

18. The follistatin fusion protein of claim 1 , wherein the first amino acid sequence comprises an N-terminal follistatin domain (FSND) having the amino acid sequence of SEQ ID NO: 18.

19. The follistatin fusion protein of claim 18 , wherein the first amino acid sequence comprises a first follistatin domain (FSD1) having the amino acid sequence of SEQ ID NO: 20.

20. The follistatin fusion protein of claim 18 , wherein the first amino acid sequence comprises a second follistatin domain (FSD2) having the amino acid sequence of SEQ ID NO: 19.

21. The follistatin fusion protein of claim 1 , wherein the linker is 50 or more amino acids in length.

22. The follistatin fusion protein of claim 1 , wherein the immunoglobulin Fc domain is an IgG2 Fc domain.

23. A pharmaceutical composition comprising the fusion protein of claim 1 .

Assignees

• Acceleron Pharma Inc

Inventors

• Sherman Matthew L

Classifications

• G01N33/721

  Haemoglobin · CPC title

• G01N2333/47

  Assays involving proteins of known structure or function as defined in the subgroups · CPC title

• G01N33/80 Primary

  involving blood groups or blood types {or red blood cells (white blood cells G01N33/56972)} · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61K38/22

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35) · CPC title