IP Library › Granted Patent US 12,240,887
Granted Patent B2
US 12,240,887 · App. 17/687,934 · Granted Mar 4, 2025

Variant ActRIIB proteins and uses thereof

Inventors: Ravindra Kumar (Cambridge, MA); Asya Grinberg (Cambridge, MA); Erik M. Vogan (Cambridge, MA)
Assignee: Acceleron Pharma Inc.
C07K14/71A61P21/00A61K38/00C07K2319/30
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Quick Facts
Patent No.
US 12,240,887
App. No.
17/687,934
Granted
Mar 4, 2025
Kind
B2
Abstract

In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of red blood cells or a tissue, such as bone, cartilage, muscle, fat, and/or neuronal tissue. The present invention also provides methods of screening compounds that modulate activity of an ActRIIB protein and/or an ActRIIB ligand. The compositions and methods provided herein are useful in treating diseases associated with abnormal activity of an ActRIIB protein and/or an ActRIIB ligand.

Claims (19)

1. An ActRIIB polypeptide comprising an amino acid sequence that is at least 90% identical to amino acids 20-134 of SEQ ID NO: 2, wherein the polypeptide comprises a glutamic acid at the position corresponding to position 55 of SEQ ID NO: 2, and wherein the ActRIIB polypeptide maintains inhibition of activin A and GDF11, and demonstrates less potent inhibition of BMP9, compared to a wild type ActRIIB polypeptide.

2. The polypeptide of claim 1 , wherein the ActRIIB polypeptide is a fusion protein further comprising an Fc polypeptide domain.

3. The polypeptide of claim 2 , wherein the fusion protein further comprises a linker domain positioned between the ActRIIB polypeptide and the Fc polypeptide domain.

4. The polypeptide of claim 3 , wherein the linker domain is selected from the group consisting of TGGG (SEQ ID NO: 265), TGGGG (SEQ ID NO: 263), SGGGG (SEQ ID NO: 264), GGGGS (SEQ ID NO: 267), GGG (SEQ ID NO: 261), GGGG (SEQ ID NO: 262, and SGGG (SEQ ID NO: 266).

5. The polypeptide of claim 3 , wherein the linker domain comprises GGG.

6. The polypeptide of claim 2 , wherein the fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 5.

7. The polypeptide of claim 2 , wherein the fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 6.

8. The polypeptide of claim 2 , wherein the fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 12.

9. The polypeptide of claim 2 , wherein the fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 34.

10. The polypeptide of claim 2 , wherein the fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 36.

11. The polypeptide of claim 2 , wherein the fusion protein is encoded by a nucleic acid sequence that is at least 90% identical to the nucleic acid sequence of SEQ ID NO: 35.

12. The polypeptide of claim 1 , wherein the ActRIIB polypeptide is a homodimer protein.

13. The polypeptide of claim 1 , wherein the ActRIIB polypeptide is a heterodimer protein.

14. The polypeptide of claim 13 , wherein the heterodimer comprises a second ActRIIB polypeptide, wherein the first ActRIIB polypeptide comprises a different amino acid sequence compared to the second ActRIIB polypeptide.

15. The polypeptide of claim 14 , wherein the second ActRIIB polypeptide is a wild-type ActRIIB extracellular domain polypeptide.

16. The polypeptide of claim 1 , wherein the ActRIIB polypeptide is glycosylated and has a glycosylation pattern obtainable from expression of the polypeptide in a CHO cell.

17. A pharmaceutical composition comprising the ActRIIB polypeptide of claim 1 , and a pharmaceutically acceptable carrier.

18. An ActRIIB polypeptide comprising an amino acid sequence that is at least 90% identical to amino acids 29-109 of SEQ ID NO: 2, wherein the polypeptide comprises a glutamic acid at the position corresponding to position 55 of SEQ ID NO: 2, and wherein the ActRIIB polypeptide maintains inhibition of activin A and GDF11, and demonstrates less potent inhibition of BMP9, compared to a wild type ActRIIB polypeptide.

19. An ActRIIB polypeptide comprising an amino acid sequence that is at least 90% identical to amino acids 25-131 of SEQ ID NO: 2, wherein the polypeptide comprises a glutamic acid at the position corresponding to position 55 of SEQ ID NO: 2, and wherein the ActRIIB polypeptide maintains inhibition of activin A and GDF11, and demonstrates less potent inhibition of BMP9, compared to a wild type ActRIIB polypeptide.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2022
From: KUMAR, RAVINDRA; GRINBERG, ASYA; VOGAN, ERIC M.
To: ACCELERON PHARMA INC.
Reel/Frame 059611/0199 →
Continuity (3)
Continuation 16340048
Provisional Application 62404718 · Oct 5, 2016
Related Publication 20220306724A1 · Sep 29, 2022
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