Isolated gdf trap polypeptide

Abstract

In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

1 - 27 . (canceled) 
     
     
         28 . A packaged pharmaceutical comprising a polypeptide and a label for use in increasing red blood cell levels in a human, the polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO: 1, wherein the polypeptide comprises an acidic amino acid at the amino acid position corresponding to position 79 of SEQ ID NO: 1. 
     
     
         29 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of amino acids 29-109 of SEQ ID NO: 1. 
     
     
         30 . The packaged pharmaceutical of  claim 28 , wherein the acidic amino acid is glutamic acid. 
     
     
         31 . The packaged pharmaceutical of  claim 28 , wherein the acidic amino acid is aspartic acid. 
     
     
         32 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises 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. 
     
     
         33 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide binds to GDF11. 
     
     
         34 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide binds to myostatin. 
     
     
         35 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide binds to myostatin and GDF11. 
     
     
         36 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide inhibits signaling by GDF11 and myostatin in a cell-based assay. 
     
     
         37 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide further comprises a constant region of an immunoglobulin. 
     
     
         38 . The packaged pharmaceutical of  claim 37 , wherein the constant region is derived from an IgG heavy chain. 
     
     
         39 . The packaged pharmaceutical of  claim 38 , wherein the constant region of an immunoglobulin is an Fc domain. 
     
     
         40 . The packaged pharmaceutical of  claim 39 , wherein the polypeptide forms a homodimer. 
     
     
         41 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 28. 
     
     
         42 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 28. 
     
     
         43 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 28. 
     
     
         44 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 28. 
     
     
         45 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises the sequence of amino acids 29-109 of SEQ ID NO: 1, but wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1. 
     
     
         46 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of amino acids 25-131 of SEQ ID NO: 1. 
     
     
         47 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of amino acids 25-131 of SEQ ID NO: 1. 
     
     
         48 . The packaged pharmaceutical of  claim 28 , wherein the polypeptide comprises the sequence of amino acids 25-131 of SEQ ID NO: 1, but wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1. 
     
     
         49 . The packaged pharmaceutical of  claim 28 , wherein the label is for use in increasing red blood cell levels in a human subject that is receiving blood transfusions. 
     
     
         50 . The packaged pharmaceutical of  claim 28 , wherein the label is for use in increasing red blood cell levels in a human subject that has myelodysplastic syndrome. 
     
     
         51 . The packaged pharmaceutical of  claim 28 , wherein the label is for use in increasing red blood cell levels in a human subject that has refractory anemia with ringed sideroblasts. 
     
     
         52 . The packaged pharmaceutical of  claim 51 , wherein the refractory anemia is associated with a myelodysplastic syndrome. 
     
     
         53 . The packaged pharmaceutical of  claim 28 , wherein the label is for use in increasing red blood cell levels in a human subject that has a thalassemia. 
     
     
         54 . A method for promoting muscle growth in a subject in need thereof by administering to the subject an ActRIIB polypeptide.