Albumin variants

Abstract

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

1 . (canceled) 
     
     
         2 . A method of altering the binding activity of a polypeptide, which is a variant of albumin, a fragment thereof or a fusion polypeptide comprising said variant albumin or fragment thereof, to FcRn as compared with the FcRn binding activity of a parent albumin, reference albumin, fragment thereof or a fusion polypeptide comprising said parent albumin, reference albumin or fragment or fusion thereof, comprising contacting FcRn with said polypeptide, wherein said polypeptide further comprises a substitution to D, E or G at a position corresponding to 111 in SEQ ID NO: 2, wherein said polypeptide has a stronger binding affinity to FcRn or longer plasma half-life than a parent albumin, reference albumin, fragment thereof or fusion polypeptide comprising said parent albumin, reference albumin or fragment or fusion thereof. 
     
     
         3 . The method of  claim 2 , wherein the substitution at the position corresponding to 111 in SEQ ID NO: 2 is to D. 
     
     
         4 . The method of  claim 2 , wherein the substitution at the position corresponding to 111 in SEQ ID NO: 2 is to E. 
     
     
         5 . The method of  claim 2 , wherein the substitution at the position corresponding to 111 in SEQ ID NO: 2 is to G. 
     
     
         6 . The method of  claim 2 , wherein the reference albumin is HSA (SEQ ID NO: 2) or a fragment thereof, or a fusion polypeptide comprising HSA or a fragment thereof. 
     
     
         7 . The method of  claim 2 , wherein the sequence identity of said polypeptide to SEQ ID NO: 2 is more than 80%, more than 90%, more than 95%, more than 96%, more than 97%, more than 98% or more than 99%. 
     
     
         8 . The method of  claim 2 , wherein said fusion comprises a fusion partner polypeptide selected from a therapeutic, prophylactic, diagnostic, imaging or other beneficial moiety. 
     
     
         9 . The method of  claim 2 , wherein said polypeptide further comprises a non-albumin moiety covalently attached to said polypeptide. 
     
     
         10 . The method of  claim 2 , wherein said polypeptide further comprises a non-albumin moiety noncovalently associated with said polypeptide. 
     
     
         11 . A method for altering the circulating half-life of a molecule comprising:
 providing a variant of albumin, a fragment thereof or a fusion polypeptide comprising said variant albumin or fragment thereof; and   a) where the molecule is a polypeptide, fusing or conjugating the molecule to said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof; or   b) where the molecule is not a polypeptide, conjugating the molecule to said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof; or   c) contacting the molecule with said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof, wherein said contacting results in a noncovalent association between said molecule and variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof;   wherein said variant of albumin, fragment thereof or fusion polypeptide comprising said variant albumin or fragment thereof comprises a substitution to D, E or G at a position corresponding to 111 in SEQ ID NO: 2, wherein said polypeptide has a stronger binding affinity to FcRn or longer plasma half-life than a parent albumin, reference albumin, fragment thereof or fusion polypeptide comprising said parent albumin, reference albumin or fragment or fusion thereof.   
     
     
         12 . The method of  claim 11 , wherein the substitution at the position corresponding to 111 in SEQ ID NO: 2 is to D. 
     
     
         13 . The method of  claim 11 , wherein the substitution at the position corresponding to 111 in SEQ ID NO: 2 is to E. 
     
     
         14 . The method of  claim 11 , wherein the substitution at the position corresponding to 111 in SEQ ID NO: 2 is to G. 
     
     
         15 . The method of  claim 11 , wherein the reference albumin is HSA (SEQ ID NO: 2) or a fragment thereof, or a fusion polypeptide comprising HSA or a fragment thereof. 
     
     
         16 . The method of  claim 11 , wherein the sequence identity of said polypeptide to SEQ ID NO: 2 is more than 80%, more than 90%, more than 95%, more than 96%, more than 97%, more than 98% or more than 99%. 
     
     
         17 . The method of  claim 11 , wherein said fusion comprises a fusion partner polypeptide selected from a therapeutic, prophylactic, diagnostic, imaging or other beneficial moiety. 
     
     
         18 . The method of  claim 11 , wherein said polypeptide further comprises a non-albumin moiety covalently attached to said polypeptide. 
     
     
         19 . The method of  claim 11 , wherein said polypeptide further comprises a non-albumin moiety noncovalently associated with said polypeptide.