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Last Updated: March 29, 2024

Claims for Patent: 9,249,173


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Summary for Patent: 9,249,173
Title:Compounds and pharmaceutical compositions for the treatment of viral infections
Abstract: Provided herein are compounds, compositions and methods for the treatment of liver disorder, including HCV and/or HBV infections. Specifically, compound and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.
Inventor(s): Sommadossi; Jean-Pierre (Cambridge, MA), Gosselin; Gilles (Montpellier, FR), Pierra; Claire (Montramaud, FR), Perigaud; Christian (Grabels, FR), Peyrottes; Suzanne (Grabels, FR)
Assignee: Idenix Pharmaceuticals, LLC (Cambridge, MA)
Application Number:14/197,078
Patent Claims:1. A method for the treatment of a host infected with a Flaviviridae virus or hepatitis B virus, comprising administering an effective treatment amount of a compound of formula: ##STR00271## or a pharmaceutically acceptable salt, a tautomeric or polymorphic form thereof, wherein: R.sup.y is optionally substituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkenyl, hydroxyalkyl, amino, heterocyclyl or heteroaryl; R.sup.a and R.sup.b are selected as follows: i) R.sup.a and R.sup.b are each independently hydrogen or optionally substituted alkyl, carboxyalkyl, hydroxyalkyl, hydroxyarylalkyl, acyloxyalkyl, aminocarbonylalkyl, alkoxycarbonylalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl or heterocyclyl; or ii) R.sup.a and R.sup.b together with the nitrogen atom on which they are substituted form a 3-7 membered heterocyclic or heteroaryl ring; and R.sup.1 is ribavirin, viramidine, valopicitabine, 2'-.beta.-methyl-cytidine, 2'-.beta.-methyl-guanosine, 2'-.beta.-methyl-uridine, 2'-.beta.-methyl-thymidine, 2'-.beta.-methyl-adenosine, 2'-.beta.-methyl-inosine, L-ddA, PSI-6130, MK-0608, resiquimod, celgosivir, lamivudine, entecavir, telbivudine, racivir, emtricitabine, clevudine, amdoxovir, or valtorcitabine.

2. The method of claim 1, wherein the virus is hepatitis C.

3. The method of claim 2, wherein the host is a human.

4. The method of claim 2 wherein the compound is ##STR00272## or a pharmaceutically acceptable salt thereof.

5. The method of claim 2, wherein said administration directs a substantial amount of said compound or pharmaceutically acceptable salt thereof to the liver of said host.

6. The method of claim 2, wherein said compound or pharmaceutically acceptable salt thereof is administered in combination or alternation with an interferon, a ribavirin, an interleukin, a NS3 protease inhibitor, a cysteine protease inhibitor, a phenanthrenequinone, a thiazolidine derivative, a thiazolidine, a benzanilide, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, a gliotoxin, a cerulenin, an antisense phosphorothioate oligodeoxynucleotide, an inhibitor of IRES-dependent translation, or a ribozyme.

7. The method of claim 5, wherein said compound or pharmaceutically acceptable salt thereof is administered in combination or alternation with an interferon, a ribavirin, an interleukin, a NS3 protease inhibitor, a cysteine protease inhibitor, a phenanthrenequinone, a thiazolidine derivative, a thiazolidine, a benzanilide, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, a gliotoxin, a cerulenin, an antisense phosphorothioate oligodeoxynucleotide, an inhibitor of IRES-dependent translation, or a ribozyme.

8. The method of claim 7, wherein the interferon is pegylated interferon alpha 2a, interferon alphacon-1, natural interferon, albuferon, interferon beta-1a, omega interferon, interferon alpha, interferon gamma, interferon tau, interferon delta or interferon .gamma.-1b.

9. The method of claim 5, wherein the host is a human.

10. The method of claim 9, wherein said administration directs a substantial amount of said compound or pharmaceutically acceptable salt thereof to the liver of said host.

11. The method of claim 1, comprising treating a human host infected with hepatitis B virus.

12. A method for the treatment of a host infected with a Flaviviridae virus or hepatitis B virus, comprising administering an effective treatment amount of a compound of formula: ##STR00273## wherein R.sup.y is hydroxyalkyl or --C(CH.sub.3).sub.2CH.sub.2OH; and R.sup.a and R.sup.b are independently hydrogen, alkyl, substituted alkyl, benzyl or substituted benzyl; and wherein optionally said compound or pharmaceutically acceptable salt thereof is administered in combination or alternation with interferon alfa-2b, Peginterferon alfa-2a, lamivudine, entecavir, telbivudine, racivir, emtricitabine, clevudine, amdoxovir, valtorcitabine, tenofovir or adefovir.

13. The method of claim 12, wherein said administration directs a substantial amount of said compound or pharmaceutically acceptable salt thereof to the liver of said host.

14. The method of claim 1, wherein the compound is administered in combination or alternation with ribavirin.

15. The method of claim 14, wherein the compound has the formula: ##STR00274## or a pharmaceutically acceptable salt, a tautomeric or polymorphic form thereof.

16. The method of claim 14, wherein the compound has the formula: ##STR00275## or a pharmaceutically acceptable salt, a tautomeric or polymorphic form thereof.

17. The method of claim 14, wherein the compound has the formula: ##STR00276## or a pharmaceutically acceptable salt, a tautomeric or polymorphic form thereof.

18. The method of claim 1, wherein the compound has the formula: ##STR00277## wherein R.sup.2 and R.sup.3 are each independently H, or R.sup.2 and R.sup.3 are linked to form a cyclic group by an alkyl, ester or carbamate linkage; or a pharmaceutically acceptable salt, a tautomeric or polymorphic form thereof.

19. The method of claim 14 having the formula: ##STR00278## wherein each R.sup.L is independently H, carbamyl, straight chained, branched or cyclic alkyl; acyl; CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonate ester, a lipid, an amino acid; an amino acid residue; or a carbohydrate; or a pharmaceutically acceptable salt, a tautomeric or polymorphic form thereof.

20. The method of claim 1, wherein the compound is selected from: ##STR00279##

21. The method of claim 20, wherein the virus is hepatitis C.

22. The method of claim 21, wherein the host is a human.

23. The method of claim 12, wherein the compound has the formula: ##STR00280## or a pharmaceutically acceptable salt thereof.

Details for Patent 9,249,173

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 2026-12-28
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2026-12-28
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2026-12-28
Biogen Inc. AVONEX interferon beta-1a For Injection 103628 05/17/1996 ⤷  Try a Trial 2026-12-28
Biogen Inc. AVONEX interferon beta-1a Injection 103628 05/28/2003 ⤷  Try a Trial 2026-12-28
Biogen Inc. AVONEX interferon beta-1a Injection 103628 02/27/2012 ⤷  Try a Trial 2026-12-28
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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