Albumin variants

Abstract

The present invention relates to variants of a parent albumin having altered plasma half-life compared with the parent albumin. The present invention also relates to fusion polypeptides and conjugates comprising said variant albumin.

1 . (canceled) 
     
     
         2 . A method of preparing a variant albumin comprising:
 providing to a host cell, a nucleic acid encoding a variant albumin having at least 90% sequence identity to SEQ ID NO: 2 along the length of said variant albumin; wherein said variant albumin has a substitution corresponding to substitutions in SEQ ID NO: 2 selected from K573A,C,D,F,G,H,I,L,M,N,P, R,S,V,W, or Y; and   generating said variant albumin from said nucleic acid.   
     
     
         3 . The method of  claim 2 , wherein said nucleic acid encodes a variant albumin having at least 95% sequence identity to SEQ ID NO: 2. 
     
     
         4 . The method of  claim 2 , wherein said nucleic acid encodes a variant albumin having at least 98% sequence identity to SEQ ID NO: 2. 
     
     
         5 . The method of  claim 2 , further comprising isolating the variant albumin from said host cell or from a media for said host cell. 
     
     
         6 . The method of  claim 2 , wherein said variant of albumin has a longer serum half-life than an albumin having the sequence of SEQ ID NO: 2. 
     
     
         7 . The method of  claim 2 , wherein said variant of albumin has an enhanced binding to FcRn relative to an albumin having the sequence of SEQ ID NO: 2. 
     
     
         8 . The method of  claim 2 , further comprising modifying said nucleic acid to include one or more alterations, which generate a thiol group on said variant albumin. 
     
     
         9 . The method of  claim 2 , wherein said variant albumin has a sequence identity to SEQ ID NO: 2 of more than 90% along the length of said variant albumin, and wherein said variant albumin is at least 100 amino acids in length. 
     
     
         10 . A nucleic acid encoding a variant albumin having at least 90% sequence identity to SEQ ID NO: 2 along the length of said variant albumin, wherein said variant albumin has a substitution corresponding to K573A,C,D,F,G,H,I,L,M,N,P, R,S, V,W, or Y. 
     
     
         11 . The nucleic acid of  claim 10 , wherein said nucleic acid encodes a variant albumin having at least 95% sequence identity to SEQ ID NO: 2. 
     
     
         12 . The nucleic acid of  claim 10 , wherein said nucleic acid encodes a variant albumin having at least 98% sequence identity to SEQ ID NO: 2. 
     
     
         13 . A method of preparing a fusion polypeptide comprising a variant albumin, the method comprising:
 providing to a host cell, a nucleic acid encoding a fusion polypeptide comprising a variant albumin having at least 90% sequence identity to SEQ ID NO: 2 along the length of said variant albumin and a second polypeptide; wherein said variant albumin has a substitution corresponding to the substitutions in SEQ ID NO: 2 selected from K573A,C,D,F,G,H,I,L,M,N,P,Q,R,S,T,V,W, or Y; and   generating said fusion polypeptide from said nucleic acid.   
     
     
         14 . The method of  claim 13 , further comprising isolating the fusion polypeptide from said host cell or from a media for said host cell. 
     
     
         15 . The method of  claim 13 , wherein said fusion polypeptide has a longer serum half-life than a fusion polypeptide comprising an albumin having the sequence of SEQ ID NO: 2. 
     
     
         16 . The method of  claim 13 , wherein said variant of albumin has enhanced binding to FcRn relative to an albumin having the sequence of SEQ ID NO: 2. 
     
     
         17 . The method of  claim 13 , further comprising modifying said nucleic acid to further comprise one or more alterations that generate a thiol group on said variant albumin. 
     
     
         18 . The method of  claim 13 , wherein said variant albumin has a sequence identity to SEQ ID NO: 2 of more than 90% along the length of said variant albumin, and wherein said variant albumin is at least 100 amino acids in length. 
     
     
         19 . The method of  claim 13 , wherein said nucleic acid encodes a variant albumin having at least 95% sequence identity to SEQ ID NO: 2. 
     
     
         20 . A nucleic acid encoding a fusion polypeptide comprising a variant albumin having at least 90% sequence identity to SEQ ID NO: 2, wherein said variant albumin has a substitution corresponding to K573A,C,D,F,G,H,I,L,M,N,P,Q,R,S,T,V,W, or Y, and a second polypeptide. 
     
     
         21 . The nucleic acid of  claim 19 , wherein said nucleic acid encodes a variant albumin having at least 95% sequence identity to SEQ ID NO: 2.