Activin-actriia antagonists for inhibiting germ cell maturation

Abstract

In certain aspects, the present invention provides compositions and methods for decreasing FSH levels in a patient. The patient may, for example, be diagnosed with an FSH-related disorder or desire to delay or inhibit germ cell maturation.

We claim: 
     
         1 . A method for inhibiting FSH production in a patient desiring to delay or inhibit his or her germ cell maturation, the method comprising administering an amount of ActRIIa-Fc fusion protein effective to reduce FSH activity in the subject, wherein the ActRIIa-Fc fusion protein comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:3. 
     
     
         2 . 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:3. 
     
     
         3 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO:3. 
     
     
         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 is a dimer formed of two polypeptides that each comprise an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:2. 
     
     
         6 . The method of  claim 5 , wherein each polypeptide of the dimer comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         7 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein comprises three or more sialic acid moieties. 
     
     
         8 . The method of  claim 7 , wherein the ActRIIa-Fc fusion protein is produced by expression in CHO cells. 
     
     
         9 . The method of  claim 7 , wherein the ActRIIa-Fc fusion protein comprises between three and five sialic acid moieties. 
     
     
         10 . The method of  claim 1 , wherein the ActRIIa-Fc fusion protein has an amino acid sequence of SEQ ID NO:7. 
     
     
         11 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein has a serum half-life of 25 to 32 days on average in normal, healthy humans and equivalent bioavailability when administered intravenously or subcutaneously. 
     
     
         12 . The method of  claim 11 , wherein the ActRIIa-Fc fusion protein has four sialic acid moieties per dimer.