111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US008889159B2
`
`c12) United States Patent
`Cleary et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 8,889,159 B2
`*Nov. 18, 2014
`
`(54) COMPOSITIONS AND METHODS FOR
`TREATING HEPATITIS C VIRUS
`
`(71) Applicant: Gilead Pharmasset LLC, Foster City,
`CA (US)
`
`(72)
`
`Inventors: Darryl G. Cleary, Chapel Hill, NC
`(US); Charles J. Reynolds, Greenville,
`NC (US); Miriam Michelle Berrey,
`Durham, NC (US); Robert G. Hindes,
`Skillman, NJ (US); William T.
`Symonds, San Francisco, CA (US);
`Adrian S. Ray, Redwood City, CA
`(US); Hongmei Mo, Palo Alto, CA (US);
`Christy M. Hebner, Belmont, CA (US);
`Reza Oliyai, Burlingame, CA (US);
`Vahid Zia, San Carlos, CA (US);
`Dimitrios Stefanidis, Mountain View,
`CA (US); Rowchanak Pakdaman, San
`Carlos, CA (US); Melissa Jean Casteel,
`Burlingame, CA (US)
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
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`(Continued)
`
`(73) Assignee: Gilead Pharmasset LLC, Foster City,
`CA (US)
`
`CA
`CN
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 13/686,664
`
`(22) Filed:
`
`Nov. 27, 2012
`
`(65)
`
`Prior Publication Data
`
`US 2013/0136776 Al
`
`May 30,2013
`
`(63)
`
`(60)
`
`(51)
`
`(52)
`
`(58)
`
`Related U.S. Application Data
`
`No.
`application
`of
`Continuation-in-part
`PCT/US2012/055621, filed on Sep. 14, 2012, and a
`continuation-in-part of application No. 13/661,509,
`filed on Oct. 26, 2012.
`
`Provisional application No. 61/564,500, filed on Nov.
`29, 2011, provisional application No. 61/707,459,
`filed on Sep. 28, 2012.
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`Int. Cl.
`A61K 47110
`C07H 19104
`A61K 311513
`A61K 311675
`A61K 3114196
`U.S. Cl.
`CPC ............. A61K 311675 (2013.01); A61K 311513
`(2013.01); A61K 3114196 (2013.01)
`USPC ............................. 424/400; 514/86; 536/26.8
`Field of Classification Search
`None
`See application file for complete search history.
`
`FOREIGN PATENT DOCUMENTS
`
`10/2008
`2682230 A1
`1/2008
`101108870 A
`(Continued)
`
`OTHER PUBLICATIONS
`
`GS-7977 structure provided by Chembest Research Laboratories
`Ltd.
`(biochembest.com/product_detail.asp?m~2&id~ 1178
`&classid1~65&nclassid~195). (last visit for this website was made
`on Jun. 27, 2013).*
`World Health Organization (hereinafter 'WHO'), "Pharmaceutical
`excipients-an overview including considerations for paediatric dos(cid:173)
`ing," (Jun. 2010).*
`Gane, E., "Future Hepatitis C Virus Treatment: Interferon-Sparing
`Combinations," Liver International (20 11) 31(S 1 ): 62-67.
`Gane, E., "Future Treatment for Chronic Hepatitis C: IFN or
`Ribavirin-Free Regimens," Hepatol. Int (20 12) 6:16-17 (Abstract
`#TCS10-03).
`
`(Continued)
`
`Primary Examiner- Ernst V Arnold
`Assistant Examiner- Kyung Soak Chang
`(7 4) Attorney, Agent, or Firm - Sheppard Mullin Richter &
`HamptonLLP
`ABSTRACT
`(57)
`Disclosed herein are a composition and unit dosage form for
`the treatment ofhepatitis C virus (HCV) infection comprising
`GS-7977 and at least one pharmaceutically acceptable excipi(cid:173)
`ent, as well as methods for making said composition and unit
`dosage form. Also disclosed herein is a method of treating a
`subject, preferably a human, infected with hepatitis C virus,
`said method comprising administering to the subject for a
`time period an effective amount of GS-7977 and an effective
`amount of ribavirin. In one aspect, the method comprises
`administering to the subject an interferon-free treatment regi(cid:173)
`men comprising an effective amount of GS-7977 and an
`effective amount of ribavirin. In a particular aspect, the
`method is sufficient to produce an undetectable amount of
`HCV RNA in the subject for at least 12 weeks after the end of
`the time period.
`
`37 Claims, 3 Drawing Sheets
`
`IPR2018-00390
`
`Page 1 of 42
`
`I-MAK 1001
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`

`

`(56)
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`Page 2 of 42
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`I-MAK 1001
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`

`US 8,889,159 B2
`Page 3
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`212000
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`1112001
`1112001
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`12/2001
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`2004/003000 A2
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`2004/007512 A2
`2004/009020 A2
`2004/009610 A2
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`2004/014313 A2
`2004/014852 A2
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`2004/046331 A2
`2004/065367 A1
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`2007/039145 A1
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`112004
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`112004
`112004
`112004
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