Activin-actriia antagonists and uses for treating multiple myeloma

Abstract

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 - 5 . (canceled) 
     
     
         6 . A method for treating or preventing cancer related bone loss in a human patient, the method comprising administering to the patient an effective amount of an ActRIIa-Fc fusion protein, wherein the ActRIIa-Fc fusion protein is a dimer formed of two Dohpeptides that each comprise an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2 and wherein the ActRIIa-Fc fusion protein comprises three or more sialic acid moieties. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein has one or more of the following characteristics:
 i. binds to an ActRIIa ligand with a KD of at least 10-7 M; and   ii. inhibits ActRIIa signaling in a cell.   
     
     
         9 . The method of  claim 6 , wherein said ActRIIa-Fc fusion protein includes one or more modified amino acid residues selected from: a glycosylated amino acid, a PEGylated amino acid, a farnesylated amino acid, an acetylated amino acid, a biotinylated amino acid, an amino acid conjugated to a lipid moiety, and an amino acid conjugated to an organic derivatizing agent. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 6 , 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. 
     
     
         12 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         13 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein comprises thean amino acid sequence that is 95% identical toef-SEQ ID NO: 2. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         16 . The method of  claim 15 , wherein the ActRIIa-Fc fusion protein comprises between three and five sialic acid moieties. 
     
     
         17 . The method of  claim 6 , wherein the method causes less than 10% increase in the patient's skeletal muscle mass. 
     
     
         18 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein is administered so as to reach a serum concentration in the patient of at least 200 ng/mL. 
     
     
         19 . The method of  claim 18 , wherein the ActRIIa-Fc fusion protein is administered so as to reach a serum concentration in the patient of at least 1000 ng/mL. 
     
     
         20 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein has an amino acid sequence of SEQ ID NO: 7. 
     
     
         21 . The method of  claim 6 , wherein the ActRIIa-Fc fusion protein has a serum half-life of between 15 and 40 days in normal, healthy humans. 
     
     
         22 . The method of  claim 20 , wherein the ActRIIa-Fc fusion protein is administered to the patient no more frequently than once per week. 
     
     
         23 . The method of  claim 20 , wherein the ActRIIa-Fc fusion protein is administered to the patient no more frequently than once per month. 
     
     
         24 . The method of  claim 20 , wherein the ActRIIa-Fc fusion protein is administered to the patient no more frequently that once per three months. 
     
     
         25 . The method of  claim 6 , wherein the patient is receiving, or has received within one year prior to the administration of ActRIIa-Fc fusion protein, a bone anti-resorptive therapy. 
     
     
         26 . The method of  claim 25 , wherein the anti-resorptive agent is selected from the group consisting of: a bisphosphonate agent, a RANK ligand antagonist and an osteoprotegrin antagonist. 
     
     
         27 . The method of  claim 6 , further comprising administering a radiation therapy, cytotoxic agent or chemotherapeutic agent to the human patient. 
     
     
         28 . The method of  claim 6 , wherein the patient has multiple myeloma. 
     
     
         29 - 65 . (canceled)