Claims for Patent: 9,339,510

Summary for Patent: 9,339,510

Title:	Azepane derivatives and methods of treating hepatitis B infections
Abstract:	Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
Inventor(s):	Hartman; George D. (Landsdale, PA), Kuduk; Scott (Harleysville, PA)
Assignee:	NOVIRA THERAPEUTICS, INC. (Doylestown, PA)
Application Number:	14/856,761
Patent Claims:	1. A method of treating an HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a compound of Formula Va: ##STR00750## or a pharmaceutically acceptable salt thereof; wherein each R.sup.1 is, independently at each occurrence, halo, OH, --C.sub.1-C.sub.6 alkyl, or --O--C.sub.1-C.sub.6 alkyl, wherein the alkyl groups are optionally substituted 1-3 times with halo or OH; each R.sup.2 is, independently at each occurrence, halo, OH, --C.sub.1-C.sub.6 alkyl, or --O--C.sub.1-C.sub.6 alkyl, wherein the alkyl groups are optionally substituted 1-3 times with halo or OH; x is 2 or 3; Cy is ##STR00751## and R.sup.11 is, independently at each occurrence, --OH, halo, --C.sub.1-C.sub.6 alkyl, --OC(O)CH.sub.3, or --H.sub.2PO.sub.4, wherein n and m are 1, 2, or 3, and at least one R.sup.11 is ##STR00752## 2. The method of claim 1, further comprising administering to the individual at least one additional therapeutic agent selected from the group consisting of a HBV polymerase inhibitor, immunomodulatory agents, pegylated interferon, viral entry inhibitor, viral maturation inhibitor, BAY 41-4109, reverse transcriptase inhibitor, a cyclophilin/TNF inhibitor, a TLR-agonist, and an HBV vaccine, and a combination thereof. 3. The method of claim 2, wherein the therapeutic agent is a reverse transcriptase inhibitor, and is at least one of Zidovudine, Didanosine, Zalcitabine, ddA, Stavudine, Lamivudine, Abacavir, Emtricitabine, Entecavir, Apricitabine, Atevirapine, ribavirin, acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir, Tenofovir, Adefovir, cidofovir, Efavirenz, Nevirapine, Delavirdine, and Etravirine. 4. The method of claim 2, wherein the therapeutic agent is a TLR agonist, and wherein the TLR agonist is a TLR-7 agonist selected from the group consisting of SM360320 (9-benzyl-8-hydroxy-2-(2-methoxy-ethoxy)adenine) and AZD 8848 (methyl[3-({[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl][- 3-(4-morpholinyl)propyl]amino}methyl)phenyl]acetate). 5. The method of claim 2, wherein the therapeutic agent is an interferon selected from the group consisting of interferon alpha (IFN-.alpha.), interferon beta (IFN-.beta.), interferon lambda (IFN-.lamda.), and interferon gamma (IFN-.gamma.). 6. The method of claim 5, wherein the interferon is interferon-alpha-2a, interferon-alpha-2b, or interferon-alpha-n1. 7. The method of claim 6, wherein the interferon-alpha-2a or interferon-alpha-2b is pegylated. 8. The method of claim 6, wherein the interferon-alpha-2a is pegylated interferon-alpha-2a (PEGASYS). 9. The method of claim 1, further comprising administering to the individual at least one HBV vaccine, a nucleoside HBV inhibitor, an interferon or any combination thereof. 10. The method of claim 9, wherein the HBV vaccine is selected from the group consisting of RECOMBIVAX HB, ENGERIX-B, ELOVAC B, GENEVAC-B, and SHANVAC B. 11. A method of treating an HBV infection in an individual in need thereof, comprising reducing the HBV viral load by administering to the individual a therapeutically effective amount of a compound alone or in combination with a reverse transcriptase inhibitor; and further administering to the individual a therapeutically effective amount of HBV vaccine; wherein the compound is a compound of Formula Va: ##STR00753## or a pharmaceutically acceptable salt thereof; wherein each R.sup.1 is, independently at each occurrence, halo, OH, --C.sub.1-C.sub.6 alkyl, or --O--C.sub.1-C.sub.6 alkyl, wherein the alkyl groups are optionally substituted 1-3 times with halo or OH; each R.sup.2 is, independently at each occurrence, halo, OH, --C.sub.1-C.sub.6 alkyl, or --O--C.sub.1-C.sub.6 alkyl, wherein the alkyl groups are optionally substituted 1-3 times with halo or OH; x is 2 or 3; Cy is ##STR00754## and R.sup.11 is, independently at each occurrence, --OH, halo, --C.sub.1-C.sub.6 alkyl, --OC(O)CH.sub.3, or --H.sub.2PO.sub.4, wherein n and m are 1, 2, or 3, and at least one R.sup.11 is ##STR00755## 12. The method of claim 1 further comprising monitoring the HBV viral load of the subject, and wherein the method is carried out for a period of time such that the HBV virus is undetectable. 13. The method of claim 1, wherein each R.sup.1 is, independently at each occurrence, halo. 14. The method of claim 1, wherein each R.sup.2 is, independently at each occurrence, halo or --C.sub.1-C.sub.6 alkyl, wherein the alkyl is optionally substituted 1-3 times with halo. 15. The method of claim 1, wherein the compound is selected from: ##STR00756## or a pharmaceutically acceptable salt thereof. 16. The method of claim 1, wherein the compound is ##STR00757## or a pharmaceutically acceptable salt thereof. 17. The method of claim 11, wherein each R.sup.1 is, independently at each occurrence, halo. 18. The method of claim 11, wherein each R.sup.2 is, independently at each occurrence, halo or --C.sub.1-C.sub.6 alkyl, wherein the alkyl is optionally substituted 1-3 times with halo. 19. The method of claim 11, wherein the compound is selected from: ##STR00758## or a pharmaceutically acceptable salt thereof. 20. The method of claim 11, wherein the compound is ##STR00759## or a pharmaceutically acceptable salt thereof.

Details for Patent 9,339,510

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Llc	RECOMBIVAX, RECOMBIVAX HB	hepatitis b vaccine (recombinant)	Injection	101066	July 23, 1986	9,339,510	2034-01-16
Glaxosmithkline Biologicals	ENGERIX-B	hepatitis b vaccine (recombinant)	Injection	103239	August 28, 1989	9,339,510	2034-01-16
Pharmaand Gmbh	PEGASYS	peginterferon alfa-2a	Injection	103964	October 16, 2002	9,339,510	2034-01-16
Pharmaand Gmbh	PEGASYS	peginterferon alfa-2a	Injection	103964	January 07, 2004	9,339,510	2034-01-16
Pharmaand Gmbh	PEGASYS	peginterferon alfa-2a	Injection	103964	September 29, 2011	9,339,510	2034-01-16
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	June 04, 2004	9,339,510	2034-01-16
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	June 13, 2008	9,339,510	2034-01-16