Interferon beta-like molecules
View Patent ↗The invention relates to a conjugate exhibiting interferon β (IFNB) activity and comprising at least one first non-polypeptide moiety covalently attached to an IFNB polypeptide, the amino acid sequence of which differs from that of wildtype human IFNB in at least one introduced and at least one removed amino acid residue comprising an attachment group for said first non-polypeptide moiety. The first non-polypeptide moiety is e.g. a polymer molecule or a sugar moiety. The conjugate finds particular use in therapy. The invention also relates to a glycosylated variant of a parent IFNB polypeptide comprising at least one in vivo glycosylation site, wherein an amino acid residue of said parent polypeptide located close to said glycosylation site has been modified to obtain the variant polypeptide having an increased glycosylation as compared to the glycosylation of the parent polypeptide.
1. A recombinant polypeptide comprising the polypeptide sequence of SEQ ID NO:56.
2. The polypeptide of claim 1 , which is glycosylated.
3. The polypeptide of claim 2 , further comprising at least one polyethylene glycol (PEG) molecule covalently attached to the polypeptide.
4. A composition comprising the polypeptide of claim 2 and a pharmaceutically acceptable diluent, carrier, or excipient.
5. The polypeptide of claim 3 , wherein one PEG molecule is covalently attached to the polypeptide.
6. The polypeptide of claim 5 , wherein the PEG molecule has a molecular weight of about 12 kiloDaltons (kDa).
7. The polypeptide of claim 5 , wherein the PEG molecule has a molecular weight of about 20 kDa.
8. The polypeptide of claim 5 , wherein the one PEG molecule is a linear PEG molecule or a branched PEG molecule.
9. The polypeptide of claim 5 , wherein the one PEG molecule is covalently attached to the N-terminus of the polypeptide.
10. A method of treating a mammal with a disease for which interferon β is a useful treatment, the method comprising administering to the mammal an effective amount of the polypeptide of claim 5 .
11. A method of treating a mammal suffering from a viral infection or viral disease, the method comprising administering to the mammal an effective amount of the polypeptide of claim 5 .
12. A method of treating a mammal suffering from a disorder characterized by an undesired cell proliferation, the method comprising administering to the mammal an effective amount of the polypeptide of claim 5 .
13. A composition comprising the polypeptide of claim 7 and a pharmaceutically acceptable diluent, carrier, or excipient.
14. A method of treating a mammal suffering from a viral infection or viral disease, the method comprising administering to the mammal an effective amount of the composition of claim 13 .
15. A method of treating a mammal suffering from a disorder characterized by an undesired cell proliferation, the method comprising administering to the mammal an effective amount of the composition of claim 13 .
16. A method of treating a mammal with a disease for which interferon β is a useful treatment, the method comprising administering to the mammal an effective amount of the composition of claim 13 .
17. The method of claim 16 , wherein the disease is multiple sclerosis.
18. The method of claim 16 , wherein the mammal is a human.
19. A recombinant nucleic acid comprising a nucleotide sequence encoding the polypeptide of claim 1 .
20. An expression vector comprising the nucleic acid of claim 19 .
21. A glycosylating host cell comprising the expression vector of claim 20 .
22. The glycosylating host cell of claim 21 , wherein the host cell is a CHO cell.
23. A cell culture composition comprising the host cell of claim 21 and a culture medium.
24. A method of making a polypeptide, the method comprising: providing a culture comprising a glycosylating host cell, the glycosylating host cell comprising a nucleotide sequence which encodes the polypeptide of claim 1 , culturing the culture under conditions which permit expression and glycosylation of the polypeptide, and recovering the polypeptide.
25. The method of claim 24 , wherein the glycosylating host cell is a CHO cell.
26. The method of claim 24 , further comprising attaching at least one PEG molecule to the polypeptide.
27. A method of treating a mammal with a disease for which interferon β is a useful treatment, the method comprising administering to the mammal an effective amount of the polypeptide of claim 1 .
28. The method of claim 27 , wherein the disease is multiple sclerosis.
29. A method of treating a mammal suffering from a viral infection or viral disease, the method comprising administering to the mammal an effective amount of the polypeptide of claim 1 .
30. The method of claim 29 , wherein the viral infection is a hepatitis or herpes viral infection and the viral disease is a hepatitis or herpes viral disease.
31. A method of treating a mammal suffering from a disorder characterized by an undesired cell proliferation, the method comprising administering to the mammal an effective amount of the polypeptide of claim 1 .