Claims for Patent: 9,505,722

Summary for Patent: 9,505,722

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. (Lansdale, PA), Kuduk; Scott (Harleysville, PA)
Assignee:	NOVIRA THERAPEUTICS, INC. (Doylestown, PA)
Application Number:	14/694,147
Patent Claims:	1. A compound of Formula V: ##STR00734## 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 group is 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 group is optionally substituted 1-3 times with halo or OH; Cy is ##STR00735## R.sup.11 is, independently at each occurrence, --OH, --C.sub.1-C.sub.6 alkyl, --OC(O)CH.sub.3, or --C.sub.3-C.sub.10 cycloalkyl; R.sup.13 and R.sup.14, together with the carbons to which they are attached, join to form a cyclopropyl ring; m is 1, 2, or 3; n is 1, 2, or 3; and x is 2 or 3. 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R.sup.1 is, independently at each occurrence, halo. 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, 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. 4. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier. 5. 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 claim 1. 6. A method of reducing the viral load associated with an HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a compound of claim 1. 7. The method of claim 5, 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, literature-described capsid assembly modulator, reverse transcriptase inhibitor, a cyclophilin/TNF inhibitor, a TLR-agonist, an HBV vaccine, and a combination thereof. 8. The method of claim 7, wherein the therapeutic agent is a reverse transcriptase inhibitor, and is at least one of Zidovudine, Didanosine, Zalcitabine, 2',3'-dideoxyadenosine, Stavudine, Lamivudine, Abacavir, Emtricitabine, Entecavir, Apricitabine, Atevirapine, ribavirin, acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir, Tenofovir, Adefovir, cidofovir, Efavirenz, Nevirapine, Delavirdine, and Etravirine. 9. The method of claim 7, wherein the therapeutic agent is a TLR agonist, and wherein the TLR agonist is 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). 10. The method of claim 7, 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.). 11. The method of claim 10, wherein the interferon is interferon-alpha-2a, interferon-alpha-2b, or interferon-alpha-n1. 12. The method of claim 10, wherein the interferon-alpha-2a or interferon-alpha-2b is pegylated. 13. The method of claim 10, wherein the interferon-alpha-2a is pegylated interferon-alpha-2a (PEGASYS). 14. The method of claim 5, further comprising administering to the individual at least one HBV vaccine, a nucleoside HBV inhibitor, an interferon or any combination thereof. 15. The method of claim 14, wherein the HBV vaccine is selected from the group consisting of RECOMBIVAX HB, ENGERIX-B, ELOVAC B, GENEVAC-B, and SHANVAC B. 16. 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 of claim 1 alone or in combination with a reverse transcriptase inhibitor; and further administering to the individual a therapeutically effective amount of HBV vaccine. 17. The method of claim 5 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. 18. The compound of claim 1, wherein each R.sup.1 is, independently at each occurrence, halo; 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 Cy is ##STR00736## R.sup.11 is, independently at each occurrence, --OH, --C.sub.1-C.sub.6 alkyl, --OC(O)CH.sub.3, or --C.sub.3-C.sub.10 cycloalkyl; m is 1, 2, or 3; n is 1 or 2; and x is 2 or 3. 19. The compound of claim 1, wherein Cy is ##STR00737## 20. The compound of claim 1, wherein n is 1 or 2.

Details for Patent 9,505,722

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	9,505,722	2034-01-16
Glaxosmithkline Biologicals	ENGERIX-B	hepatitis b vaccine (recombinant)	Injection	103239	August 28, 1989	9,505,722	2034-01-16
Pharmaand Gmbh	PEGASYS	peginterferon alfa-2a	Injection	103964	October 16, 2002	9,505,722	2034-01-16