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Last Updated: April 25, 2024

Claims for Patent: 7,592,315

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Summary for Patent: 7,592,315

Title:	Peptide viral entry inhibitors
Abstract:	The present invention provides, inter alia, peptide compositions and methods for treating and preventing Flaviviridae virus (e.g., hepatitis C virus) infections.
Inventor(s):	Liu; Rong (Scotch Plains, NJ), Zhang; Rumin (Edison, NJ), Kong; Rong (Scotch Plains, NJ)
Assignee:	Schering Corporation (Kenilworth, NJ)
Application Number:	11/264,509
Patent Claims:	1. An isolated polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 81 fused to a tag selected from the group consisting of a glutathione-S-transferase (GST) tag, a hexahistidine (His6) tag, a maltose binding protein (MBP) tag, a haemagglutinin (HA) tag, a cellulose binding protein (CBP) tag and a myc tag; which is optionally (i) labeled with .sup.32P, .sup.35S, .sup.3H, .sup.99mTc .sup.123l, .sup.111In, .sup.68Ga, .sup.18F, .sup.125I, .sup.131I, .sup.113mIn, .sup.76Br, .sup.67Ga, .sup.99mTc, .sup.123I, .sup.111In or .sup.68Ga; (ii) fused to a polyethylene glycol molecule; (iii) fused to a polyethylene glycol molecule which is characterized by a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa or 40 kDa; or (iv) cyclic. 2. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier. 3. A composition comprising the polypeptide of claim 1 in association with one or more members selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa2a, interferon alfa2b , interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 4. The composition of claim 3 comprising said polypeptide in association with interferon alfa-2b. 5. The composition of claim 3 comprising said polypeptide in association with interferon alfa-2a. 6. The composition of claim 3 comprising said polypeptide in association with pegylated interferon alfa-2b. 7. The composition of claim 3 comprising said polypeptide in association with pegylated interferon alfa-2a. 8. The composition of claim 3 comprising said polypeptide in association with ribavirin. 9. A kit comprising the polypeptide of claim 1 and a member selected from the group consisting of an anti-human CD81 antibody, ribavirin, interferon alfa-2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 10. The polypeptide of claim 1 which is labeled with a member selected from the group consisting of .sup.32P, .sup.35S, .sup.3H, .sup.99mTc, .sup.123I, .sup.111In, .sup.68Ga, .sup.18F, .sup.125I, .sup.131I, .sup.113mIn, .sup.76Br, .sup.67Ga, .sup.99mTc, .sup.123I, .sup.111In and .sup.68Ga. 11. The polypeptide of claim 1 which is fused to a polyethylene glycol molecule. 12. The polypeptide of claim 11 where the polyethylene glycol molecule comprises a molecular weight selected from the group consisting of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa and 40 kDa. 13. The polypeptide of claim 1 which is cyclic. 14. The polypeptide of claim 1 consisting of the amino acid sequence set forth in SEQ ID NO: 81. 15. A polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 77; which is optionally (i) labeled with .sup.32P, .sup.35S, .sup.3H, .sup.99mTc, .sup.123I, .sup.111In, .sup.68Ga, .sup.18F, .sup.125I, .sup.131I, .sup.113mIn, .sup.76Br, .sup.67Ga, .sup.99mTc, .sup.123I, .sup.111In or .sup.68Ga; (ii) fused to a polyethylene glycol molecule; (iii) fused to a polyethylene glycol molecule which is characterized by a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa or 40 kDa; or (iv) cyclic. 16. The polypeptide of claim 15 consisting of the amino acid sequence set forth in SEQ ID NO: 77. 17. The polypeptide of claim 1 fused to a tag selected from the group consisting of a glutathione-S-transferase (GST) tag, a hexahistidine (His6) tag, a maltose binding protein (MBP) tag, a haemagglutinin (HA) tag, a cellulose binding protein (CBP) tag and a myc tag. 18. A method for making a polypeptide comprising culturing a host cell comprising a vector which comprises a polynucleotide encoding a polypeptide consisting of the amino acid sequence V-S-F-A-I-K-W-E-Y-V-L-L-L-F-L-L (SEQ ID NO: 77) or A-I-K-W-E-Y-V-L-L-L-F-L-L (SEQ ID NO: 81) under conditions in which the polynucleotide is expressed. 19. The method of claim 18 wherein the polypeptide is isolated from the culture. 20. A method for inhibiting entry of a virus which is a member of the Flaviviridae family into a cell comprising contacting the cell with an isolated polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 77 or 81; which is optionally (i) fused to a polyethylene glycol molecule; (ii) fused to a polyethylene glycol molecule which is characterized by a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa or 40 kDa; or (iii) cyclic. 21. The method of claim 20 wherein the cell is in vitro. 22. A method for treating infection of a subject with a virus which is a member of the Flaviviridae family comprising administering to said subject a therapeutically effective amount of an isolated polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 77 or 81; which is optionally (i) fused to a polyethylene glycol molecule; (ii) fused to a polyethylene glycol molecule which is characterized by a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa or 40 kDa; or (iii) cyclic. 23. The method of claim 22 wherein the subject is a human. 24. The method of claim 22 wherein the virus is hepatitis C virus. 25. The method of claim 24, wherein the host is infected with multiple hepatitis C virus genotypes. 26. The method of claim 25, wherein the host is infected with hepatitis C virus genotype 1, hepatitis C virus genotype 2 or hepatitis C virus genotype 3. 27. The method of claim 22 wherein the polypeptide is administered to the subject parenterally. 28. The method of claim 27 wherein the polypeptide is administered to the subject intramuscularly, intravenously or subcutaneously. 29. The method of claim 22 wherein said polypeptide is administered in association with one or more members selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa-2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 30. The method of claim 18 wherein said polypeptide is administered in association with one or more members selected from the group consisting of ribavirin, interferon alfa-2a, interferon alfa-2b, pegylated interferon alfa-2a and pegylated interferon alfa-2b. 31. The method of claim 22 wherein the subject is co-infected with human immunodeficiency virus. 32. The method of claim 22 wherein the polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 77. 33. The method of claim 22 wherein the polypeptide consists of the amino acid sequence set forth in SEQ TD NO: 81. 34. A method for treating infection of a subject, with a virus which is a member of the Flaviviridae family of viruses, following transplantation of a liver into said subject or transfusion of blood into said subject comprising administering to said subject a therapeutically effective amount of an isolated polypeptide consisting of the amino acid sequence set forth in SEQ ID NO: 77 or 81; which is optionally (i) fused to a polyethylene glycol molecule; (ii) fused to a polyethylene glycol molecule which is characterized by a molecular weight of 2 kDa, 5 kDa, 10 kDa, 12 kDa, 20 kDa, 30 kDa or 40 kDa; or (iii) cyclic. 35. The method claim 34 wherein the virus is hepatitis C virus. 36. The method of claim 34 wherein the polypeptide is administered in association with a member selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n3, and pegylated consensus interferon. 37. The method of claim 34 wherein the polypeptide is administered to the subject parenterally. 38. The method of claim 37 wherein the polypeptide is administered to the subject intramuscularly, intravenously or subcutaneously.

Details for Patent 7,592,315

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Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986	⤷ Try a Trial	2024-11-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132		⤷ Try a Trial	2024-11-02
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132		⤷ Try a Trial	2024-11-02
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	06/04/2004	⤷ Try a Trial	2024-11-02
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	06/13/2008	⤷ Try a Trial	2024-11-02
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

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