Claims for Patent: 8,742,101

Summary for Patent: 8,742,101

Title:	Purine nucleoside analogues for treating flaviviridae including hepatitis C
Abstract:	This invention is directed to a method for treating a host, especially a human, infected with hepatitis C, flavivirus and/or pestivirus, comprising administering to that host an effective amount of an anti-HCV biologically active pentofuranonucleoside where the pentofuranonucleoside base is an optionally substituted 2-azapurine. The optionally substituted pentofuranonucleoside, or a salt or prodrug thereof, may be administered alone or in combination with one or more optionally substituted pentofuranonucleosides or other anti-viral agents.
Inventor(s):	Storer; Richard (Folkestone, GB), Gosselin; Gilles (Montpellier, FR), Dukhan; David (Montpellier, FR), Leroy; Frederic (Jonquieres, FR)
Assignee:	Idenix Pharmaceuticals, Inc. (Cambridge, MA) Centre National de la Recherche Scientifique (Paris, FR) L\'Universite Montpellier II (Montpellier, FR)
Application Number:	12/270,795
Patent Claims:	1. A method of treating a host infected with HCV, comprising administering an effective amount of a ribofuranonucleoside of Formula (III): ##STR00069## or a pharmacologically acceptable salt thereof, wherein: R, R.sup.2*, and R.sup.3* are each independently H, mono-, di-, or triphosphate; phosphonate; or optionally substituted alkyl, lower alkyl, optionally substituted alkenyl or alkynyl, acyl, --C(O)-(alkyl), --C(O)(lower alkyl), --C(O)-(alkenyl), or --C(O)-(alkynyl); X is O; R.sup.2' is H; optionally substituted alkyl, alkenyl, or alkynyl; and Base is selected from the group consisting of: ##STR00070## wherein: each R' and R'' independently is H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, halogenated alkyl, OH, CN, N.sub.3, carboxy, C.sub.1-4 alkoxycarbonyl, NH.sub.2, C.sub.1-4 alkylamino, di(C.sub.1-4 alkyl)amino, C.sub.1-6 alkoxy, C.sub.1-6 alkylsulfonyl, or (C.sub.1-4 alkyl).sub.0-2 aminomethyl; each W is Cl, Br, I, F, halogenated alkyl, alkoxy, OH, SH, O-alkyl, S-alkyl, O-alkenyl, O-alkynyl, S-alkenyl, S-alkynyl, --OC(O)NR.sup.4R.sup.4, O-acyl, S-acyl, CN, SCN, OCN, NO.sub.2, N.sub.3, NH.sub.2, NH(alkyl), N(alkyl).sub.2, NH-cycloalkyl, NH-acyl, CONH.sub.2, CONH(alkyl), or CON(alkyl).sub.2; and each R.sup.4 is independently H, acyl, or C.sub.1-6 alkyl. 2. The method of claim 1, wherein R.sup.2' is CH.sub.3 or CF.sub.3. 3. The method of claim 1, wherein R, R.sup.2*, and R.sup.3* are each independently H, mono-, di-, or triphosphate, or phosphonate. 4. The method of claim 1, wherein each R, R.sup.2*, and R.sup.3* is H. 5. The method of claim 1, wherein each R, R.sup.2*, and R.sup.3* is independently H, acyl, or an amino acid acyl residue. 6. The method of claim 1, wherein the host is a mammal. 7. The method of claim 6, wherein the mammal is a human. 8. The method of claim 1, further comprising administering an antivirally effective amount of the compound, or a pharmaceutically acceptable salt thereof, in combination or alternation with one or more additional antivirally effective agents. 9. The method of claim 8, wherein the additional antivirally effective agent is selected from the group consisting of an interferon, ribavirin, an interleukin, an NS3 protease inhibitor, a cysteine protease inhibitor, phenanthrenequinone, a thiazolidine derivative, a thiazolidine, a benzanilide, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, gliotoxin, cerulenin, an antisense phosphorothioate oligodeoxynucleotide, an inhibitor of IRES-dependent translation, and a ribozyme. 10. The method of claim 9, wherein the additional antivirally effective agent is an interferon. 11. The method of claim 10, wherein the additional antivirally effective agent is selected from the group consisting of pegylated interferon alpha 2a, interferon alphacon-1, natural interferon, albuferon, interferon beta-1a, omega interferon, interferon alpha, interferon gamma, interferon tau, interferon delta, and interferon gamma-1b. 12. The method of claim 1, wherein the compound is in the form of a dosage unit. 13. The method of claim 12, wherein the dosage unit contains 50 to 1000 mg of the compound. 14. The method of claim 13, wherein the said dosage unit is a tablet or capsule. 15. The method of claim 1, wherein the compound is in substantially pure form. 16. The method of claim 15, wherein the compound is at least 90% by weight of the .beta.-D-isomer. 17. The method of claim 15, wherein the compound is at least 95% by weight of the .beta.-D-isomer. 18. The method of claim 15, wherein the compound is at least 90% by weight of the .beta.-L-isomer. 19. The method of claim 15, wherein the compound is at least 95% by weight of the .beta.-L-isomer. 20. A pharmaceutical composition comprising an anti-virally effective amount of a compound of Formula (III) or a pharmacologically acceptable salt thereof: ##STR00071## wherein: R, R.sup.2*, and R.sup.3* are each independently H, mono-, di-, or triphosphate; phosphonate; or optionally substituted alkyl, lower alkyl, optionally substituted alkenyl or alkynyl, acyl, --C(O)-(alkyl), --C(O)-(lower alkyl), --C(O)-(alkenyl), or --C(O)-(alkynyl); X is O; R.sup.2' is optionally substituted alkyl, alkenyl, or alkynyl; and Base is ##STR00072## wherein R' and R'' are each independently H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, halogenated alkyl, OH, CN, N.sub.3, carboxy, C.sub.1-4 alkoxycarbonyl, NH.sub.2, C.sub.1-4 alkylamino, di(C.sub.1-4 alkyl)amino, C.sub.1-6 alkoxy, C.sub.1-6 alkylsulfonyl, or (C.sub.1-4 alkyl).sub.0-2 aminomethyl; W is Cl, Br, I, F, halogenated alkyl, alkoxy, OH, SH, O-alkyl, S-alkyl, O-alkenyl, O-alkynyl, S-alkenyl, S-alkynyl, --OC(O)NR.sup.4R.sup.4, O-acyl, S-acyl, CN, SCN, OCN, NO.sub.2, N.sub.3, NH.sub.2, NH(alkyl), N(alkyl).sub.2, NH-cycloalkyl, NH-acyl, CONH.sub.2, CONH(alkyl), or CON(alkyl).sub.2; and each R.sup.4 is independently H, acyl, or C.sub.1-6 alkyl; and a pharmaceutically acceptable carrier, diluent or excipient. 21. The pharmaceutical composition of claim 20, wherein R.sup.2' is CH.sub.3 or CF.sub.3. 22. The pharmaceutical composition of claim 20, wherein R, R.sup.2*, and R.sup.3* are each independently H, mono-, di-, or triphosphate, or phosphonate. 23. The pharmaceutical composition of claim 20, wherein R, R.sup.2*, and R.sup.3* are H. 24. The pharmaceutical composition of claim 20, wherein R, R.sup.2*, and R.sup.3* are each independently H, acyl, or an amino acid acyl residue. 25. The pharmaceutical composition of claim 20, wherein the compound or salt thereof is in the form of a dosage unit. 26. The pharmaceutical composition of claim 25, wherein the dosage unit contains from about 50 to about 1000 mg of the compound. 27. The pharmaceutical composition of claim 26, wherein said dosage unit is a tablet or capsule. 28. The pharmaceutical composition of claim 20, further comprising one or more additional anti-virally effective agents. 29. The pharmaceutical composition of claim 28, wherein the additional anti-virally agent is selected from the group consisting of an interferon, ribavirin, an interleukin, an NS3 protease inhibitor, a cysteine protease inhibitor, a thiazolidine derivative, a thiazolidine, a benzanilide, phenanthrenequinone, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, gliotoxin, cerulenin, an antisense oligodeoxynucleotide, an inhibitor of IRES-dependent translation, and a ribozyme. 30. The pharmaceutical composition of claim 29, wherein the additional anti-virally effective agent is an interferon. 31. The pharmaceutical composition of claim 30, wherein the additional anti-virally effective agent is selected from the group consisting of pegylated interferon alpha 2a, interferon alphacon-1, natural interferon, albuferon, interferon beta-1a, omega interferon, interferon alpha, interferon gamma, interferon tau, interferon delta, and interferon gamma-1b. 32. The pharmaceutical composition of claim 20, wherein the compound is in substantially pure form. 33. The pharmaceutical composition of claim 32, wherein the compound is at least 90% by weight of the .beta.-D-isomer. 34. The pharmaceutical composition of claim 32, wherein the compound is at least 95% by weight of the .beta.-D-isomer. 35. The pharmaceutical composition of claim 32, wherein the compound is at least 90% by weight of the .beta.-L-isomer. 36. The pharmaceutical composition of claim 32, wherein the compound is at least 95% by weight of the .beta.-L-isomer. 37. The pharmaceutical composition of claim 20, wherein the compound is ##STR00073## 38. The method of claim 1, wherein the compound is ##STR00074##

Details for Patent 8,742,101

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Biogen Inc.	AVONEX	interferon beta-1a	For Injection	103628	05/17/1996		2023-07-25
Biogen Inc.	AVONEX	interferon beta-1a	Injection	103628	05/28/2003		2023-07-25
Biogen Inc.	AVONEX	interferon beta-1a	Injection	103628	02/27/2012		2023-07-25
Emd Serono, Inc.	REBIF	interferon beta-1a	Injection	103780	03/07/2002		2023-07-25
Emd Serono, Inc.	REBIF	interferon beta-1a	Injection	103780	12/17/2004		2023-07-25
Emd Serono, Inc.	REBIF	interferon beta-1a	Injection	103780	12/21/2012		2023-07-25