Truncated ACTRIIB-FC fusion protein
In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of a tissue, such as bone, cartilage, muscle, fat, brown fat and/or neuronal tissue and for treating metabolic disorders such as diabetes and obesity, as well as disorders associated with any of the foregoing tissue.
1. A polypeptide selected from the group consisting of:
a. a polypeptide wherein the amino acid sequence of the polypeptide consists of the sequence of SEQ ID NO: 8;
b. a polypeptide produced by the expression in a mammalian cell of the nucleic acid of SEQ ID NO: 4; and
c. a polypeptide produced by the expression in a mammalian cell of the nucleic acid of SEQ ID NO: 6.
2. The polypeptide of claim 1 , wherein the amino acid sequence of the polypeptide consists of the sequence of SEQ ID NO: 8.
3. The polypeptide of claim 1 , wherein the polypeptide is a polypeptide produced by expression in a mammalian cell of the nucleic acid of SEQ ID NO: 4.
4. The polypeptide of claim 1 , wherein the polypeptide is a polypeptide produced by the expression in a mammalian cell of the nucleic acid of SEQ ID NO: 6.
5. The polypeptide of claim 1 , wherein the polypeptide causes a statistically significant increase in lean body mass in a mouse after four weeks of treatment twice per week at a dose level of 10 mg/kg.
6. The polypeptide of claim 5 , wherein the mean increase is at least 2 g of lean tissue mass.
7. The polypeptide of claim 1 , wherein the polypeptide causes a statistically significant decrease in fat mass in a mouse fed a high fat diet after four weeks of treatment twice per week at a dose level of 10 mg/kg.
8. The polypeptide of claim 7 , wherein the mean decrease is at least 5 g of fat mass.
9. The polypeptide of claim 1 , wherein the polypeptide causes a statistically significant decrease in serum triglyceride levels in a mouse fed a high fat diet after four weeks of treatment twice per week at a dose level of 10 mg/kg.
10. The polypeptide of claim 9 , wherein the mean decrease is at least 50 mg/dl triglycerides.
11. The polypeptide of claim 1 , wherein the polypeptide causes a statistically significant decrease in serum free fatty acid levels in a mouse fed a high fat diet after four weeks of treatment twice per week at a dose level of 10 mg/kg.
12. The polypeptide of claim 11 , wherein the mean decrease is at least 500 micromoles/dl free fatty acids.
13. The polypeptide of claim 1 , wherein the polypeptide causes a statistically significant decrease in serum insulin levels in a mouse fed a high fat diet after four weeks of treatment twice per week at a dose level of 10 mg/kg.
14. The polypeptide of claim 13 , wherein the mean decrease is at least 1 ng/ml insulin.
15. The polypeptide of claim 1 , wherein the polypeptide comprises at least one N-linked sugar.
16. The polypeptide of claim 1 , wherein the polypeptide is produced in a CHO cell.
17. The polypeptide of claim 1 , wherein the polypeptide is covalently associated with a second polypeptide of claim 1 .
18. The polypeptide of claim 1 , wherein the polypeptide is covalently associated with a second polypeptide to form a homodimer.
19. A pharmaceutical preparation comprising the polypeptide of claim 1 .