Methods for dosing an actriib antagonist and monitoring of treated patients

Abstract

In certain aspects, the present invention provides methods for dosing a patient with an ActRIIb antagonist and methods for managing patients treated with an ActRIIb antagonist. In certain aspects, the methods involve measuring one or more hematologic parameters in a patient.

1 - 45 . (canceled) 
     
     
         46 . A method of identifying functional mutants of an ActRIIb polypeptide, the method comprising:
 a. producing a combinatorial library of genes encoding variant polypeptides; and   b. evaluating the ability of each variant polypeptide to bind to activin, GDF8, and/or GDF11.   
     
     
         47 . The method of  claim 46 , wherein the library of genes is produced by enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences. 
     
     
         48 . The method of  claim 46  or  claim 47 , wherein the variant polypeptide sequences can be expressed individually. 
     
     
         49 . The method of  claim 46  or  claim 47 , wherein the variant polypeptide sequences can be expressed as a set of larger fusion proteins. 
     
     
         50 . The method of  claim 46  or  claim 47 , wherein the variant polypeptides are truncation mutants. 
     
     
         51 . The method of  claim 46  or  claim 47 , wherein the variant polypeptides are combinatorial mutants of an ActRIIb polypeptide. 
     
     
         52 . The method of  claim 46  or  claim 47 , wherein each gene in the library of genes includes at least a portion of a potential ActRIIb polypeptide sequence. 
     
     
         53 . The method of  claim 46  or  claim 47 , wherein a nucleotide sequence encoding the gene is chemically synthesized. 
     
     
         54 . The method of  claim 53 , wherein the chemically synthesized gene sequence is ligated into a vector for expression. 
     
     
         55 . The method of  claim 46  or  claim 47 , wherein the combinatorial library is produced using alanine scanning mutagenesis, linker scanning mutagenesis, saturation mutagenesis, PCR mutagenesis, or by random mutagenesis.