Compositions and Methods of Use for Treating Metabolic Disorders

Abstract

Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

1 . A dimer comprising two covalently joined polypeptides, wherein the two polypeptides each comprise a contiguous amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 1,
 wherein the two polypeptides each comprise at least one of the following pairs of substitutions of the corresponding amino acids in SEQ ID NO: 1:   i) D5T/S and R21N;   ii) R16N and H18T/S;   iii) S23N and E25T/S;   iv) S50N and F52T/S or F52N and A54T/S;   v) R53N and A55T/S;   vi) S64N and H66T/S;   vii) K91N and D93T/S or D93N and G95T/S;   viii) T94N and V96T/S or V96N and L98T/S;   ix) S97N and Q99T/S; and   x) A106N and D108T/S,   
     
     
         2 .- 9 . (canceled) 
     
     
         10 . The dimer of  claim 1 , wherein the two polypeptides each comprise a signal sequence at the N-terminus. 
     
     
         11 . The dimer of  claim 10 , wherein the signal sequence is IgK signal sequence. 
     
     
         12 . The dimer of  claim 10 , wherein the signal sequence is conjugated to the polypeptide via a linker. 
     
     
         13 . The dimer of  claim 12 , wherein the linker is a cleavable linker. 
     
     
         14 . The dimer of  claim 1 , wherein at least one of the two polypeptides is fused to a heterologous polypeptide. 
     
     
         15 . The dimer of  claim 14 , wherein the heterologous polypeptide is serum albumin, maltose binding protein, or immunoglobulin Fc polypeptide. 
     
     
         16 . The dimer of  claim 15 , wherein the heterologous polypeptide is serum albumin, and the serum albumin is human serum albumin, cyno serum albumin or bovine serum albumin. 
     
     
         17 . The dimer of  claim 15 , wherein the heterologous polypeptide is immunoglobulin Fc polypeptide. 
     
     
         18 . The dimer of  claim 14 , wherein the heterologous polypeptide is conjugated to N-terminus of the polypeptide. 
     
     
         19 . The dimer of  claim 14 , wherein the heterologous polypeptide is conjugated to C-terminus of the polypeptide. 
     
     
         20 .- 24 . (canceled) 
     
     
         25 . The dimer of  claim 1 , wherein the dimer is N-glycosylated. 
     
     
         26 .- 28 . (canceled) 
     
     
         29 . A nucleic acid molecule encoding at least one of the polypeptides of  claim 1 . 
     
     
         30 . (canceled) 
     
     
         31 . A vector comprising the nucleic acid molecule of  claim 29 . 
     
     
         32 . (canceled) 
     
     
         33 . A host cell that expresses the dimer of  claim 1 . 
     
     
         34 . A host cell comprising the nucleic acid molecule of  claim 29 . 
     
     
         35 . A pharmaceutical composition, comprising the dimer of  claim 1 , and a pharmaceutically acceptable diluent, carrier or excipient. 
     
     
         36 . The pharmaceutical composition of  claim 35 , further comprising at least one additional prophylactic or therapeutic agent. 
     
     
         37 .- 39 . (canceled) 
     
     
         40 . A sterile container comprising the pharmaceutical composition of  claim 35 . 
     
     
         41 . The sterile container of  claim 40 , wherein the sterile container is a syringe. 
     
     
         42 . A kit comprising the sterile container of  claim 40 . 
     
     
         43 . A method of making the dimer of  claim 1 , the method comprising:
 culturing a host cell expressing at least one of the polypeptides of  claim 1 ; and   purifying the expressed dimer.   
     
     
         44 . A method of treating or preventing a body weight disorder or a glucose metabolism disorder in a subject, the method comprising administering to the subject the dimer of  claim 1 , wherein the dimer is administered in an amount effective in treating or preventing the body weight disorder or the glucose metabolism disorder in the subject. 
     
     
         45 .- 50 . (canceled) 
     
     
         51 . The method of  claim 44 , wherein the glucose metabolism disorder is diabetes mellitus. 
     
     
         52 . The method of  claim 44 , wherein the subject is human. 
     
     
         53 . The method of  claim 44 , wherein the subject is obese. 
     
     
         54 .- 55 . (canceled)