Albumin variants
The present invention relates to variants of a parent albumin, the variants having altered plasma half-life compared with the parent albumin. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.
1. A polypeptide comprising an albumin having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2 and having a substitution in Domain I of said albumin and having a substitution in Domain III of said albumin relative to the amino acid sequence set forth in SEQ ID NO: 2, wherein said albumin has an increased binding affinity to FcRn relative to the binding affinity of an albumin comprising the amino acid sequence of SEQ ID NO: 2 to FcRn, and wherein said substitution in Domain I is selected from amino acids corresponding to positions 82, 83, 111, 112, or any combination thereof of the amino acid sequence of SEQ ID NO: 2 and said substitution in Domain III is selected from amino acids corresponding to positions 425, 505, 510, 512, 524, 527, 531, 534, 569, 573, 575, or any combination thereof of the amino acid sequence of SEQ ID NO: 2.
2. The polypeptide of claim 1 comprising substitutions at amino acids corresponding to positions (a) 111 and 573; (b) 82 and 83; (c) 82 and 111; (d) 82 and 112; (e) 82 and 573; (f) 83 and 111; (g) 83 and 112; (h) 83 and 573; (i) 111 and 112; (j) 83, 111, and 573; (k) 112 and 573; (l) 82, 83, and 111; (m) 82, 83, and 112; (n) 82, 83, and 573; (o) 82, 111, and 112; (p) 82, 111, and 573; (q) 82, 112, and 573; (r) 83, 111, and 112; (s) 83, 112, and 573; (t) 111, 112, and 573; (u) 82, 83, 111, and 112; (v) 82, 83, 111, and 573; (w) 82, 83, 112, and 573; (x) 82, 111, 112, and 573; (y) 83, 111, 112, and 573; or (z) 82, 83, 111, 112, and 573 of the amino acid sequence of SEQ ID NO: 2.
3. The polypeptide of claim 1 , wherein said substitution in Domain I is selected from amino acids corresponding to positions 83 or 111 of the amino acid sequence of SEQ ID NO: 2.
4. The polypeptide of claim 1 , wherein said substitution in Domain III is at the amino acid corresponding to position 573 of the amino acid sequence of SEQ ID NO: 2.
5. The polypeptide of claim 1 , wherein said substitution in Domain I is at the amino acid corresponding to position 83 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is an asparagine, lysine or serine.
6. The polypeptide of claim 1 , wherein said substitution in Domain I is at the amino acid corresponding to position 111 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is an aspartic acid, glycine, histidine, arginine, glutamine, or glutamic acid.
7. The polypeptide of claim 1 , wherein said substitution in Domain III is at the amino acid corresponding to position 573 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a proline, tyrosine, tryptophan, histidine, phenylalanine, threonine, isoleucine, or valine.
8. The polypeptide of claim 1 , wherein said substitution in Domain III is at the amino acid corresponding to position 573 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a proline, tyrosine, or tryptophan.
9. The polypeptide of claim 1 , wherein said substitution in Domain III is at the amino acid corresponding to position 573 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a proline.
10. The polypeptide of claim 1 , wherein said polypeptide has a stronger binding affinity to FcRn and optionally, a longer plasma half-life relative to a polypeptide comprising the amino acid sequence of SEQ ID NO: 2.
11. A fusion polypeptide comprising the polypeptide of claim 1 and a fusion partner polypeptide selected from a therapeutic, prophylactic, diagnostic, imaging, or other moiety.
12. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 111 and 573 of the amino acid sequence of SEQ ID NO: 2.
13. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 83, 111, and 573 of the amino acid sequence of SEQ ID NO: 2.
14. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 82, 111, and 573 of the amino acid sequence of SEQ ID NO: 2.
15. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 111, 112, and 573 of the amino acid sequence of SEQ ID NO: 2.
16. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 82, 83, 111, and 573 of the amino acid sequence of SEQ ID NO: 2.
17. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 82, 111, 112, and 573 of the amino acid sequence of SEQ ID NO: 2.
18. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 83, 111, 112, and 573 of the amino acid sequence of SEQ ID NO: 2.
19. The polypeptide of claim 1 , comprising substitutions at amino acids corresponding to positions 82, 83, 111, 112, and 573 of the amino acid sequence of SEQ ID NO: 2.
20. The polypeptide of claim 1 , wherein said substitution in Domain I is at the amino acid corresponding to position 83 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is an asparagine.
21. The polypeptide of claim 1 , wherein said substitution in Domain I is at the amino acid corresponding to position 83 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a lysine.
22. The polypeptide of claim 1 , wherein said substitution in Domain I is at the amino acid corresponding to position 111 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a glutamic acid.
23. The polypeptide of claim 1 , wherein said substitution in Domain I is at the amino acid corresponding to position 83 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a lysine or asparagine, and said substitution in Domain III is at the amino acid corresponding to position 573 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a proline.
24. The polypeptide of claim 1 , wherein said substitutions in Domain I are at the amino acids corresponding to positions 83 and 111 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitutions are an asparagine and a glutamic acid, respectively, and said substitution in Domain III is at the amino acid corresponding to position 573 of the amino acid sequence of SEQ ID NO: 2 and wherein said substitution is a proline.