Activin-actriia antagonists and uses for treating multiple myeloma
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.
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.