Methods of treatment with interferson and albumin fusion protein
Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.
1. A method of treating a patient in need of interferon, comprising the step of administering to said patient a fusion protein comprising interferon and albumin or an albumin variant, wherein (i) said fusion protein has a higher plasma stability than unfused interferon, (ii) said albumin or albumin variant is located either at the N-terminus or C-terminus of said fusion protein, and (iii) said fusion protein retains the therapeutic activity of unfused interferon.
2. The method of claim 1 , wherein said fusion protein comprises albumin.
3. The method of claim 1 , wherein said fusion protein comprises an albumin variant.
4. The method of claim 3 , wherein said albumin variant is a fragment of albumin.
5. The method of claim 3 , wherein said albumin variant has a mutation of one or more residues.
6. The method of claim 3 , wherein said albumin variant has a deletion of one or more residues.
7. The method of claim 3 , wherein said albumin variant has a mutation and a deletion of one or more residues.
8. The method of claim 3 , wherein said albumin variant has an addition of one or more residues.
9. The method of claim 1 , wherein said fusion protein comprises an N-terminal methionine.
10. The method of claim 1 , wherein said fusion protein comprises a peptide linker.
11. The method of claim 1 , wherein said fusion protein comprises a secretion signal sequence.
12. The method of claim 11 , wherein said secretion signal sequence is the natural leader sequence of interferon.
13. The method of claim 3 , wherein said interferon is fused to the N-terminal end of said albumin or albumin variant.
14. The method of claim 3 , wherein said interferon is fused to the C-terminal end of said albumin or albumin variant.
15. A method of treating a patient in need of interferon, comprising the step of administering to said patient a fusion protein comprising interferon and a mature form of albumin, wherein (i) said fusion protein has a higher plasma stability than unf used interferon, (ii) said mature form of albumin is located either at the N-terminus or C-terminus of said fusion protein, and (iii) said fusion protein retains the therapeutic activity of unfused interferon.
16. The method of claim 15 , wherein said fusion protein comprises an N-terminal methionine.
17. The method of claim 15 , wherein said fusion protein comprises a peptide linker.
18. The method of claim 15 , wherein said fusion protein comprises a secretion signal sequence.
19. The method of claim 18 , wherein said secretion signal sequence is the natural leader sequence of interferon.
20. The method of claim 15 , wherein said interferon is fused to the N-terminal end of said mature form of albumin.
21. The method of claim 20 , wherein said fusion protein comprises an N-terminal methionine.
22. The method of claim 20 , wherein said fusion protein comprises a peptide linker.
23. The method of claim 20 , wherein said fusion protein comprises a secretion signal sequence.
24. The method of claim 23 , wherein said secretion signal sequence is the natural leader sequence of interferon.
25. The method of claim 15 , wherein said interferon is fused to the C-terminal end of said mature form of albumin.
26. The method of claim 25 , wherein said fusion protein comprises an N-terminal methionine.
27. The method of claim 25 , wherein said fusion protein comprises a peptide linker.
28. The method of claim 25 , wherein said fusion protein comprises a secretion signal sequence.
29. The method of claim 28 , wherein said secretion signal sequence is the natural leader sequence of interferon.
30. The method of claim 3 , wherein said interferon is human interferon, and said albumin or an albumin variant is human albumin or a human albumin variant.
31. The method of claim 15 , wherein said interferon is human interferon, and said mature form of albumin is mature form of human albumin.