Interferon-alpha polypeptides and conjugates
View Patent ↗The present invention provides interferon-alpha polypeptides and conjugates, and nucleic acids encoding the polypeptides. The invention also includes compositions comprising these polypeptides, conjugates, and nucleic acids; cells containing or expressing the polypeptides, conjugates, and nucleic acids; methods of making the polypeptides, conjugates, and nucleic acids; and methods of using the polypeptides, conjugates, and nucleic acids.
1. A method for reducing the level of a virus in the serum of a patient infected with the virus, comprising administering to the patient a polypeptide in an amount effective to reduce the level of virus in the serum compared to the level present prior to the start of treatment, wherein the polypeptide comprises a sequence which differs in 0 to 8 amino acid positions from the sequence of SEQ ID NO:12 or SEQ ID NO:10 and wherein the polypeptide exhibits antiviral activity.
2. The method of claim 1 wherein the virus is Hepatitis C Virus.
3. The method of claim 1 wherein the virus is Hepatitis B Virus.
4. A method for reducing the level of a virus in the serum of a patient infected with the virus, comprising administering to the patient a conjugate in an amount effective to reduce the level of virus in the serum compared to the level present prior to the start of treatment, wherein the conjugate comprises:
a) a polypeptide comprising a sequence which differs in 0 to 8 amino acid positions from the sequence of SEQ ID NO:12 or SEQ ID NO:10; and
b) a non-polypeptide moiety covalently attached to the polypeptide, and wherein the conjugate exhibits antiviral activity.
5. The method of claim 4 wherein the virus is Hepatitis C Virus.
6. The method of claim 4 wherein the virus is Hepatitis B Virus.
7. The method of claim 4 wherein the non-polypeptide moiety is a polymer.
8. The method of claim 7 wherein the polymer is polyethylene glycol.
9. The method of claim 8 wherein a polyethylene glycol moiety is covalently attached to a cysteine residue.
10. The method of claim 8 wherein a polyethylene glycol moiety is covalently attached to a lysine residue or to the N-terminal amino group.
11. The method of claim 8 wherein a polyethylene glycol moiety is covalently attached to a lysine residue.
12. The method of claim 8 wherein a polyethylene glycol moiety is covalently attached to the N-terminal amino group.
13. The method of claim 8 , wherein at least two polyethylene glycol moieties are attached to the polypeptide and wherein each polyethylene glycol moiety is covalently attached to a different amino acid residue of the polypeptide.
14. The method of claim 13 , wherein the at least two polyethylene glycol moieties are attached to different lysine residues.
15. The method of claim 13 , wherein one of the at least two polyethylene glycol moieties is attached to the N-terminal amino group and one of the at least two polyethylene glycol moieties is attached to a lysine residue.
16. The method of claim 4 wherein the non-polypeptide moiety is a sugar.
17. The method of claim 16 wherein the sugar is attached to an N-glycosylation site.
18. A method of treating a patient infected with Hepatitis C Virus comprising administering to the patient a pharmaceutically acceptable excipient and a therapeutically effective amount of a conjugate, wherein the conjugate comprises:
a) a polypeptide comprising a sequence which differs in 0 to 8 amino acid positions from the sequence of SEQ ID NO:12 or SEQ ID NO:10; and
b) a non-polypeptide moiety covalently attached to the polypeptide, and wherein the conjugate exhibits antiviral activity.
19. The method of claim 18 wherein the conjugate is administered by weekly subcutaneous injection.
20. The method of claim 18 wherein the conjugate is administered by subcutaneous injection every two weeks.
21. The method of claim 18 wherein the non-polypeptide moiety is a polymer.
22. The method of claim 21 wherein the polymer is polyethylene glycol.
23. The method of claim 22 wherein a polyethylene glycol moiety is covalently attached to a cysteine residue.
24. The method of claim 22 wherein a polyethylene glycol moiety is covalently attached to a lysine residue or to the N-terminal amino group.
25. The method of claim 22 wherein a polyethylene glycol moiety is covalently attached to a lysine residue.
26. The method of claim 22 wherein a polyethylene glycol moiety is covalently attached to the N-terminal amino group.
27. The method of claim 22 , wherein at least two polyethylene glycol moieties are attached to the polypeptide and wherein each polyethylene glycol moiety is covalently attached to a different amino acid residue of the polypeptide.
28. The method of claim 27 , wherein the at least two polyethylene glycol moieties are attached to different lysine residues.
29. The method of claim 27 , wherein one of the at least two polyethylene glycol moieties is attached to the N-terminal amino group and one of the at least two polyethylene glycol moieties is attached to a lysine residue.
30. The method of claim 18 wherein the non-polypeptide moiety is a sugar.
31. The method of claim 30 wherein the sugar is attached to an N-glycosylation site.