Albumin variants
Variants of a parent albumin having altered plasma half-life compared with a parent albumin are described. Fusion polypeptides and conjugates including the variant albumin are also described. Embodiments include, but are not limited to, a polypeptide which is a variant of albumin, including one or more alterations at one or more positions corresponding to 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119 and 120 in SEQ ID NO: 2.
1. A polypeptide which is a variant of albumin, comprising one or more alterations at one or more positions corresponding to 104, 106, 108, 109, 110, and 120 in SEQ ID NO: 2 with one or more of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
2. The polypeptide according to claim 1 wherein the one or more alterations are substitution(s).
3. The polypeptide according to claim 1 , comprising a conjugatable thiol group on the polypeptide.
4. A fragment of the polypeptide according to claim 1 , wherein the polypeptide is a fragment with at least 500 amino acids.
5. A fusion polypeptide, conjugate, associate, nanoparticle, microparticle or composition comprising the polypeptide of claim 1 .
6. The polypeptide according to claim 1 , wherein the sequence identity of the polypeptide to SEQ ID NO: 2 is more than 97%.
7. The polypeptide according to claim 1 , wherein the sequence identity of the polypeptide to SEQ ID NO: 2 is more than 99%.
8. The polypeptide of claim 1 , wherein one alteration corresponds to position 104 in SEQ ID NO: 2 with one of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
9. The polypeptide of claim 1 , wherein one alteration corresponds to position 106 in SEQ ID NO: 2 with one of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
10. The polypeptide of claim 1 , wherein one alteration corresponds to position 108 in SEQ ID NO: 2 with one of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
11. The polypeptide of claim 1 , wherein one alteration corresponds to position 109 in SEQ ID NO: 2 with one of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
12. The polypeptide of claim 1 , wherein one alteration corresponds to position 110 in SEQ ID NO: 2 with one of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
13. The polypeptide of claim 1 , wherein one alteration corresponds to position 120 in SEQ ID NO: 2 with one of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y.
14. A method of making a polypeptide according to claim 1 comprising:
(a) providing a nucleic acid encoding a parent albumin comprising the sequence of SEQ ID NO: 2;
(b) modifying the sequence of step (a), to encode a polypeptide which is a variant albumin having one or more substitutions at one or more position corresponding to positions in SEQ ID NO: 2 selected from the group consisting of: 104, 106, 108, 109, 110, and 120.
15. The method of claim 14 further comprising:
(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 polypeptide; and
(e) recovering the polypeptide from the growth medium.