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. An isolated or recombinant nucleic acid comprising a polynucleotide sequence which encodes a polypeptide comprising a sequence which differs in 0 to 8 amino acid positions from the sequence of SEQ ID NO:3, which polypeptide exhibits antiviral activity.
2. An isolated host cell comprising the nucleic acid of claim 1 .
3. A vector comprising the nucleic acid of claim 1 .
4. The vector of claim 3 , wherein the vector comprises a plasmid, a cosmid, a phage, or a virus.
5. The vector of claim 3 , which is an expression vector comprising the nucleic acid operably linked to a promoter.
6. An isolated host cell comprising the vector of claim 5 .
7. The host cell of claim 6 , wherein the host cell is a eukaryotic host cell.
8. The host cell of claim 6 , wherein the host cell is a bacterial host cell.
9. The host cell of claim 8 , wherein the bacterial host cell is E. coli.
10. The nucleic acid of claim 1 , wherein the antiviral activity of the encoded polypeptide is equal to or greater than the antiviral activity of huIFN-alpha 2b or huIFN-alpha 2a.
11. The nucleic acid of claim 10 , wherein the antiviral activity of the encoded polypeptide is at least two-fold greater than the antiviral activity of huIFN-alpha 2b or huIFN-alpha 2a.
12. The nucleic acid of claim 1 , wherein the encoded polypeptide further exhibits antiproliferative activity and wherein the polypeptide exhibits a ratio of antiviral activity/antiproliferative activity at least two-fold greater than the ratio of antiviral activity/antiproliferative activity exhibited by huIFN-alpha 2b or huIFN-alpha 2a.
13. The nucleic acid of claim 12 , wherein the encoded polypeptide exhibits a ratio of antiviral/antiproliferative activity at least four-fold greater than the ratio of antiviral activity/antiproliferative activity exhibited by huIFN-alpha 2b or huIFN-alpha 2a.
14. A method for preparing a recombinant polypeptide, wherein the polypeptide comprises a sequence which differs in 0 to 8 amino acid positions from the sequence of SEQ ID NO:3, which polypeptide exhibits antiviral activity, the method comprising:
providing a culture comprising a host cell, the host cell comprising an expression vector comprising a promoter operably linked to a nucleic acid, the nucleic acid comprising a polynucleotide sequence which encodes the polypeptide,
culturing the culture under conditions which permit expression of the polypeptide, and
recovering the polypeptide.
15. The method of claim 14 , wherein the host cell is a eukaryotic host cell.
16. The method of claim 14 , wherein the host cell is a bacterial host cell.
17. The method of claim 16 , wherein the bacterial host cell is E. coli.
18. The method of claim 14 , wherein the antiviral activity of the polypeptide is equal to or greater than the antiviral activity of huIFN-alpha 2b or huIFN-alpha 2a.
19. The method of claim 18 , wherein the antiviral activity of the polypeptide is at least two-fold greater than the antiviral activity of huIFN-alpha 2b or huIFN-alpha 2a.
20. The method of claim 14 , wherein the polypeptide further exhibits antiproliferative activity and wherein the polypeptide exhibits a ratio of antiviral activity/antiproliferative activity at least two-fold greater than the ratio of antiviral activity/antiproliferative activity exhibited by huIFN-alpha 2b or huIFN-alpha 2a.
21. The method of claim 20 , wherein the polypeptide exhibits a ratio of antiviral/antiproliferative activity at least four-fold greater than the ratio of antiviral activity/antiproliferative activity exhibited by huIFN-alpha 2b or huIFN-alpha 2a.