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 . A Method for preparing a variant of albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof, comprising following steps:
 a. Providing a nucleic acid encoding a parent albumin having at least 80% sequence identity to SEQ ID NO: 2;   b. Modifying the sequence of step a., to encode a variant albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof having one or more substitutions corresponding to the substitutions in SEQ ID NO: 2 selected among:
 Q417A,C,D,E,F,G,H,I,K,L,M,N,P, R,S,T,V,W,Y; 
 H440A,C,D,E,F,G, I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 A490C,D,E, F,G,H,I,K,L,M,N,P, R,S,T,V,W,Y 
 E492A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 V493A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T.W,Y: 
 D494A,C,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 E495A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 T496A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,V,W,Y; 
 P499A,C,D,E,F,G,H,I,K,L,M,N, Q,R,S,T,V,W,Y; 
 K500A,C,D,E,F,G,H,I, L,M,N, Q,R,S,T,V,W,Y; 
 E501A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 N503A,C,D,E,F,G,H,I,K,L,M, P,Q,R,S,T,V,W,Y; 
 A504C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 E505A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 T506A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S, V,W,Y; 
 H510A,C,D,F,G, I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 H535A,C,D,F,G, I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 K536A,C,D,E,F,G,H,I, L,M,N,P,Q,R,S,T,V,W,Y; 
 P537A,C,D,E,F,G,H,I,K,L,M,N, Q,R,S,T,V,W,Y; 
 K538A,C,D,E,F,G,H,I, L,M,N,P,Q,R,S,T,V,W,Y; 
 T540A,C,D,E,F,G,H,I, L,M,N,P,Q,R,S, V,W,Y; 
 K541A,C,D,E,F,G,H,I, L,M,N,P,Q,R,S,T,V,W,Y; 
 E542A,C,D,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 D550A,C,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 K573A,C,D,E,F,G,H,I, L,M,N,P,Q,R,S,T,V,W,Y; 
 K574A,C,D,E,F,G,H,I, L,M,N,P,Q,R,S,T,V,W,Y; 
 Q580A,C,D,E,F,G,H,I, K, L,M,N,P,R,S,T,V,W,Y; 
 A581C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
 A582C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; or 
 G584A,C,D,E,F,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y; 
   c. Introducing the modified sequence of step b., in a suitable host cell;   d. Growing the cells in a suitable growth medium under condition leading to expression of the variant of albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof; and   e. Recovering the variant of albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof from the growth medium;   
       wherein the variant of albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof, has an altered plasma half-life compared with the parent albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof.