Albumin variants
AssigneeNovozymes Biopharma DK A/S
InventorsDarrell Sleep, Andrew Plumridge, Jason Cameron, Inger Sandlie, Jan Terje Andersen, Esben Peter Friis
Life of this patent
Estimating the term…
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.
Claims18
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.
A variant of albumin, fragments thereof or fusion polypeptides comprising said variant albumin or a fragment thereof having altered plasma half-life compared with the parent albumin, fragment thereof or fusion polypeptide comprising said parent albumin or fragment thereof, comprising one or more substitutions in positions corresponding to the positions in SEQ ID NO:2 selected among:
- 573, 500, 550, 492, 580, 574, 417, 440, 464, 490, 493, 494, 495, 496, 499, 501, 503, 504, 505, 506, 510, 535, 536, 537, 538, 540, 541, 542, 575, 577, 578, 579, 581, 582 and 584, where the variant is not the variant consisting of SEQ ID NO:
- 2 with the substitution D494N, E501K, K541E, D550G,A, K573E or K574N.
A composition comprising a variant of albumin, fragments thereof or fusion polypeptide comprising said variant albumin or fragment thereof or a conjugate comprising said variant albumin, wherein the binding to FcRn is stronger than for the corresponding albumin or fragment thereof or fusion polypeptide comprising said albumin or fragment thereof or a conjugate comprising said albumin.
Dependencies are inferred from the claim text.