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, or a fusion polypeptide comprising said variant albumin, the method comprising:
 providing a nucleic acid encoding a variant albumin having at least 98% sequence identity to SEQ ID NO: 2 along the length of said variant albumin to a host cell; wherein said variant albumin has one or more substitutions corresponding to the substitutions in SEQ ID NO: 2 selected from K500A,C,D,E,F,G,H,L,M,N,Q,S,T,V,W, or Y; and   expressing a protein product of said nucleic acid to yield said variant albumin, or fusion polypeptide comprising said variant albumin;   wherein said variant albumin or fusion polypeptide comprising said variant albumin has an altered plasma half-life compared to an albumin having the sequence of SEQ ID NO: 2 or fusion polypeptide comprising said albumin having the sequence of SEQ ID NO: 2.   
     
     
         3 . The method of  claim 2 , further comprising growing the host cell in a growth medium and recovering the variant albumin or fusion polypeptide comprising said variant albumin from said growth medium or host cell. 
     
     
         4 . The method of  claim 2 , wherein said variant of albumin, or fusion polypeptide comprising said variant albumin has a shorter serum half-life than an albumin having the sequence of SEQ ID NO: 2 or fusion polypeptide comprising said albumin having the sequence of SEQ ID NO: 2. 
     
     
         5 . The method of  claim 2 , further comprising modifying said nucleic acid to further comprise one or more alterations that generate a thiol group on the surface of said variant albumin. 
     
     
         6 . The method of  claim 2 , wherein said variant albumin has a sequence identity to SEQ ID NO: 2 of more than 98% along the length of said variant albumin, and wherein said variant albumin is at least 100 amino acids in length. 
     
     
         7 . A nucleic acid encoding a variant albumin having at least 98% sequence identity to SEQ ID NO: 2, wherein said variant albumin has a substitution corresponding to K500A,C,D,E,F,G,H,L,M,N,Q,S,T,V,W, or Y. 
     
     
         8 . A composition comprising a variant albumin that has at least 95% sequence identity to SEQ ID NO: 2 along the length of said variant albumin, and further comprising a substitution corresponding to K500A,C,G,E,F,H,I,K,L,M,N,P,Q,R,S,T,V,W, or Y, wherein the binding of said variant albumin to FcRn is weaker than the binding of an albumin having the sequence of SEQ ID NO: 2, and wherein said composition further comprises a therapeutic or diagnostic moiety fused to the variant albumin, conjugated thereto, or associated therewith. 
     
     
         9 . The composition of  claim 8 , further comprising a therapeutic or diagnostic moiety genetically fused thereto. 
     
     
         10 . The composition of  claim 8 , further comprising a therapeutic or diagnostic moiety chemically conjugated thereto. 
     
     
         11 . The composition of  claim 8 , further comprising a therapeutic or diagnostic moiety non-covalently associated therewith. 
     
     
         12 . The composition of  claim 10 , further comprising one or more excipients. 
     
     
         13 . The composition of  claim 11 , further comprising one or more excipients. 
     
     
         14 . The composition of  claim 12 , further comprising one or more excipients. 
     
     
         15 . A method of altering the circulating half-life of a therapeutic or diagnostic moiety, comprising fusing or conjugating the moiety to a variant albumin that has at least 95% sequence identity to SEQ ID NO: 2 along the length of said variant albumin, and wherein said variant albumin further comprises a substitution corresponding to K500A,C,G,E,F,H,I,K,L,M,N,P,Q,R,S,T,V,W, or Y; wherein the binding of said variant albumin to FcRn is altered relative to the binding of an albumin having the sequence of SEQ ID NO: 2. 
     
     
         16 . A method of providing to a subject in need thereof a therapeutic or diagnostic moiety, wherein the moiety is fused or conjugated to a variant albumin that has at least 95% sequence identity to SEQ ID NO: 2 along the length of said variant albumin, and wherein said variant albumin further comprises a substitution corresponding to K500A,C,G,E,F,H,I,K,L,M,N,P,Q,R,S,T,V,W, or Y; wherein the binding of said variant albumin to FcRn is altered relative to the binding of an albumin having the sequence of SEQ ID NO: 2.