Isolated activin-binding ActRIIa polypeptide comprising the SEQ ID NO: 7 and uses for promoting bone growth
In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density.
1. An isolated activin-binding ActRIIa polypeptide comprising the amino acid sequence of SEQ ID NO:7.
2. The activin-binding ActRIIa polypeptide of claim 1 , wherein the polypeptide is at least 95% pure, with respect to protein contaminants, as determined by size exclusion chromatography.
3. The activin-binding ActRIIa polypeptide of claim 1 , wherein the polypeptide exhibits at least 10-fold selectivity in dissociation constant for activin versus Growth Differentiation Factor (GDF)-11.
4. A pharmaceutical preparation comprising the activin-binding ActRIIa polypeptide of claim 1 and at least one pharmaceutically acceptable excipient.
5. The pharmaceutical preparation of claim 4 , wherein said preparation is pyrogen free.
6. The activin-binding ActRIIa polypeptide of claim 1 , wherein the polypeptide is glycosylated.
7. The activin-binding ActRIIa polypeptide of claim 6 , wherein the amino acid sequence consists of SEQ ID NO: 7.
8. The activin-binding ActRIIa polypeptide of claim 6 , wherein the polypeptide is expressed in CHO cells.
9. The activin-binding ActRIIa polypeptide of claim 1 , wherein the amino acid sequence consists of SEQ ID NO: 7.
10. The activin-binding ActRIIa polypeptide of claim 1 , wherein the polypeptide is expressed in Chinese hamster ovary (CHO) cells.
11. An isolated polypeptide comprising SEQ ID NO:7.
12. A polypeptide according to claim 11 , wherein the polypeptide is soluble.
13. A polypeptide according to claim 12 which binds activin.
14. A polypeptide according to claim 13 which binds activin with a KD less than about 1 micromolar.
15. A polypeptide according to claim 14 which binds activin with a KD less than about 100 nanomolar.
16. A polypeptide according to claim 15 which binds activin with a KD less than about 10 nanomolar.
17. A polypeptide according to claim 16 which binds activin with a KD less than about 1 nanomolar.
18. A polypeptide according to claim 11 which is at least about 95% pure.
19. A polypeptide according to claim 18 which is at least about 98% pure.
20. A polypeptide according to claim 11 which is acetylated.
21. A polypeptide according to claim 11 which is carboxylated.
22. A polypeptide according to claim 11 which is glycosylated.
23. A polypeptide according to claim 22 , wherein the amino acid sequence consists of SEQ ID NO: 7.
24. A polypeptide according to claim 11 which is phosphorylated.
25. A polypeptide according to claim 11 which is lipidated.
26. A polypeptide according to claim 11 which is acylated.
27. A polypeptide according to claim 11 which is PEGylated.
28. A polypeptide according to claim 11 which is farnesylated.
29. A polypeptide according to claim 11 which is biotinylated.
30. A polypeptide according to claim 11 , wherein the amino acid sequence consists of SEQ ID NO: 7.