COMUNE US009744181B2CHA DA ALTAMURA TUTTA LA TOT (12 ) United States Patent (10 ) Patent No. : US 9 , 744 , 181 B2 Dahl et al. (45 ) Date of Patent: * Aug. 29 , 2017 ( 54 ) COMPOSITIONS AND METHODS FOR 3 ,682 , 930 A 8 / 1972 Bourquin et al . 3 , 994 , 974 A 11/ 1976 Murakami et al . COMBINATION ANTIVIRAL THERAPY 4 ,003 , 878 A 1 / 1977 Skaar et al . 4 ,258 , 062 A 3 / 1981 Jonas et al . (71 ) Applicant : Gilead Sciences, Inc. , Foster City , CA 4 ,355 ,032 A 10 / 1982 Verheyden et al . (US ) 4 , 384 ,005 A 5 / 1983 McSweeney 4 , 430 , 343 A 2 / 1984 lemura et al. (72 ) Inventors : Terrence C . Dahl, Sunnyvale , CA 4 ,476 , 248 A 10 / 1984 Gordon et al . 4 ,724 , 233 A 2 / 1988 De Clercq et al . ( US ) ; Mark M . Menning , San 4 , 808 ,716 A 2 / 1989 Holy et al . Francisco , CA (US ) ; Reza Oliyai, 4 , 816 , 570 A 3 / 1989 Farquhar Foster City , CA (US ) 4 , 879 , 288 A 11/ 1989 Warawa et al. 4 , 935 ,507 A 6 / 1990 Takaya et al . ( 73 ) Assignee : Gilead Sciences , Inc ., Foster City , CA 4 ,957 ,924 A 9 / 1990 Beauchamp 4 , 968 , 788 A 11/ 1990 Farquhar (US ) 5 , 047 ,407 A 9 / 1991 Belleau et al. 5 , 075 ,445 A 12 / 1991 Jarvest et al . ( * ) Notice : Subject to any disclaimer, the term of this 5 , 142 , 051 A 8 / 1992 Holy et al . patent is extended or adjusted under 35 5 , 151 , 426 A 9 / 1992 Belleau et al . U . S . C . 154 ( b ) by 0 days. 5 , 155 , 268 A 10 / 1992 Hester 5 , 177 , 064 A 1 / 1993 Bodor This patent is subject to a terminal dis 5 , 179 , 104 A 1 / 1993 Chu et al . claimer . 5 , 204 ,466 A 4 / 1993 Liotta et al. ( Continued ) ( 21) Appl . No. : 14 /523 , 783 FOREIGN PATENT DOCUMENTS ( 22 ) Filed : Oct. 24 , 2014 EP O 182 024 A2 5 / 1986 (65 ) Prior Publication Data EP 0 206 459 A2 12 / 1986 US 2015 /0111856 A1 Apr. 23, 2015 ( Continued ) Related U . S . Application Data OTHER PUBLICATIONS (63 ) Continuation of application No. 14 / 227, 653 , filed on Decision Denying Petitioner ' s Request for Rehearing for Case PTAB - IPR2014 -00885 , dated Aug . 3 , 2015 , 15 pages. Mar. 27 , 2014 , which is a continuation of application Decision Denying Petitioner ' s Request for Rehearing for Case No. 12 / 204, 174 , filed on Sep . 4 , 2008 , now Pat . No . PTAB - IPR2014 -00887 , dated Aug . 3 , 2015 , 13 pages . 8 ,716 , 264, which is a continuation of application No . Decision Denying Petitioner ' s Request for Rehearing for Case 10 / 540 ,794 , filed as application No . PTAB - IPR - 2014 -00888 , dated Aug . 3 , 2015 , 15 pages . PCT/ US2004 / 000832 on Jan . 13 , 2004 , now Joint Motion to Dismiss and Stipulation by Mylan Inc ., Mylan abandoned . Pharmaceuticals Inc ., Case No. 1 : 14 - cv - 00099 - IMF - JSK ( Dated : Oct . 30 , 2015 ) , 3 pages . ( 60 ) Provisional application No . 60/ 440 , 246 , filed on Jan . Order on Stipulation for Dismissal: Ordered , adjudged and decreed 14 , 2003, provisional application No . 60 /440 , 308 , that all claims, counterclaims or causes of action asserted in this suit by and between Gilead , Emory and Mylan are dismissed with filed on Jan . 14 , 2003 . prejudice . Signed by District Judge Irene M . Keeley on Nov . 2 , ( 51) Int . Ci. 2015 . (jss ), Case No. 1 : 14 -cv - 00099 - IMF - JSK ( Entered : Nov . 2 , A61K 9 /20 (2006 . 01 ) 2015 ), 2 pages . A6IK 31 /675 ( 2006 .01 ) ( Continued ) A61K 31 / 513 ( 2006 .01 ) Primary Examiner — Alton Pryor A61K 31/ 7076 ( 2006 .01 ) A61K 45 /06 ( 2006 .01 ) ( 74) Attorney , Agent, or Firm — Fish & Richardson P . C . A61K 31/ 683 ( 2006 .01 ) (57 ) ABSTRACT (52 ) U . S . CI. The present invention relates to therapeutic combinations of CPC . .. .. A61K 31/ 675 ( 2013 . 01 ) ; A61K 9 / 2009 [ 2 - (6 - amino - purin - 9 yl) - 1 -methyl - ethoxymethyl] - phospho (2013 .01 ) ; A61K 9 / 2013 ( 2013 .01 ) ; A61K nic acid diisopropoxycarbonyloxymethyl ester ( tenofovir 9 /2018 ( 2013 . 01 ) ; A61K 9 / 2054 ( 2013 . 01 ) ; disoproxil fumarate , Viread® ) and ( 2R , 55 , cis ) - 4 - amino - 5 A61K 9 / 2059 ( 2013 . 01 ) ; A61K 31 /513 fluoro - 1 - ( 2 hydroxymethyl- 1 , 3 -oxathiolan - 5 - yl) - ( 1H ) -py ( 2013 . 01 ) ; A61K 31/ 683 ( 2013 . 01 ) ; A61K rimidin - 2 -one (emtricitabine , EmtrivaTM , ( - ) -cis FTC ) and 31/ 7076 ( 2013 .01 ) ; A61K 45 / 06 (2013 .01 ) their physiologically functional derivatives. The combina (58 ) Field of Classification Search tions may be useful in the treatment of HIV infections, None including infections with HIV mutants bearing resistance to See application file for complete search history . nucleoside and / or non - nucleoside inhibitors . The present invention is also concerned with pharmaceutical composi References Cited tions and formulations of said combinations of tenofovir ( 56 ) disoproxil fumarate and emtricitabine , and their physiologi U . S . PATENT DOCUMENTS cally functional derivatives, as well as therapeutic methods 3 , 524 ,846 A 8 / 1970 Moffatt et al. of use of those compositions and formulations . 3 ,622 ,677 A 11/ 1971 Short et al. 30 Claims, No Drawings US 9 , 744 , 181 B2 Page 2 (56 ) References Cited 2009 /0036408 AL 2 /2009 Dahl et al. 2009 /0143314 A1 6 / 2009 Dahl et al. U . S . PATENT DOCUMENTS 2014 / 0037732 A1 2 /2014 Dahl et al. 2014 / 0213556 Al 7 / 2014 Dahl et al. 5 , 208 , 221 CA 5 / 1993 Kim et al. 2014 /0370102 Al 12 /2014 Dahl et al. 5 , 210 , 085 A 5 / 1993 Liotta et al. 2015 /0111855 AL 4 /2015 Dahl et al . 5 , 386 ,030 CA 1 / 1995 Kim et al. 5 ,432 , 172 A 7 / 1995 Kashman et al . FOREIGN PATENT DOCUMENTS 5 , 453 , 503 A 9 / 1995 Aikins et al. 5 ,466 , 806 A 11 / 1995 Belleau et al. EP 0 269 947 A 6 / 1988 5 ,476 , 938 A 12 / 1995 Vemishetti et al. 0 369 409 A1 5 / 1990 5 ,486 ,520 A 1 / 1996 Belleau et al . EP 0 382 526 A2 8 / 1990 5 , 506 , 347 A 4 / 1996 Erion et al . EP 0 481 214 A1 4 / 1992 5 , 512 , 596 A 4 / 1996 Kim et al. EP 0 482 657 A2 4 / 1992 5 , 514 , 557 A 5 / 1996 Moghaddam EP 0 595 635 5 / 1994 5 ,514 , 798 A 5 / 1996 Bischofberger et al. EP 0 632 048 AL 1 / 1995 5 , 519 ,021 A 5 / 1996 Payne et al . EP 0 647 649 AL 4 / 1995 5 , 538 , 975 A 7 / 1996 Dionne EP 0 694 547 A2 1 / 1996 5 , 587 , 480 A 12 / 1996 Belleau et al. EP 1 256 585 AL 11 / 2002 5 ,618 ,820 A 4 / 1997 Dionne EP 1 332 757 A1 8 / 2003 5 ,618 , 964 A 4 / 1997 Cheng et al. GB 942 152 A 11 / 1963 5 ,627 , 186 A 5 / 1997 Cameron et al . GB 1 523 865 A 9 / 1978 5 ,663 , 159 A 9 / 1997 Starrett , Jr. et al . GB 2 111 043 A 6 / 1983 5 ,696 , 254 A 12 / 1997 Mansour et al. 10 - 511682 11 / 1998 5 , 733 , 788 A 3 / 1998 Bischofberger JP 2001 -502718 2 / 2001 5 , 744 ,596 A 4 / 1998 Mansour et al. WO WO 88 / 05438 7 / 1988 5 , 756 , 706 A 5 / 1998 Mansour et al. WO WO 91/ 19721 Al 12 / 1991 5 , 763 ,606 A 6 / 1998 Mansour et al. WO WO 92 /01698 2 / 1992 5 , 792 , 756 A 8 / 1998 Starrett , Jr . et al. Wo WO 92 / 09611 Al 6 / 1992 5 ,798 , 340 A 8 / 1998 Bischofberger et al . WO WO 92 / 13869 8 / 1992 5 ,814 ,639 A 9 / 1998 Liotta et al. WO WO 92 / 14743 A2 9 / 1992 5 , 859 , 021 A 1 / 1999 Cameron et al. WO WO 93 / 03027 Al 2 / 1993 5 , 905 , 082 A 5 / 1999 Roberts et al . WO WO 94 / 03466 2 / 1994 5 ,914 ,331 A 6 / 1999 Liotta et al . WO WO 94 / 03467 A2 2 / 1994 5 , 922 ,695 A 7 / 1999 Arimilli et al. WO WO 95 /07919 3 / 1995 5 ,935 , 946 A 8 / 1999 Munger , Jr. et al . WO WO 95 / 07920 AL 3 / 1995 5 , 977 ,089 A 11/ 1999 Arimilli et al . WO WO 95 / 32957 Al 12 / 1995 6 , 043 , 230 A 3 / 2000 Arimilli et al. WO WO 96 / 30025 3 / 1996 6 ,057 , 305 A 5 /2000 Holy et al . WO WO 96 / 18605 Al 6 / 1996 6 , 069 , 249 A 5 / 2000 Arimilli et al . WO WO 98 / 04569 A1 2 / 1998 6 , 069 , 252 A 5 / 2000 Liotta et al . WO WO 98 / 18477 5 / 1998 6 , 113 , 920 A 9 / 2000 Maye et al. WO WO 99 / 25352 A1 5 / 1999 6 , 114 , 343 A 9 / 2000 Liotta et al . WO WO 99 /61026 12 / 1999 6 , 121, 315 A 9 / 2000 Nair et al . WO WO 00 / 16755 3 / 2000 6 ,180 , 639 B1 1 / 2001 Coates et al. WO WO 00 / 25797 A1 5 / 2000 6 , 194 , 391 B1 2 / 2001 Schinazi et al . WO WO 00 /64427 A2 11 / 2000 6 ,312 ,662 B1 11/ 2001 Erion et al . WO WO 01/ 64221 Al 9 /2001 6 , 417 , 191 B1 7 / 2002 Barry et al. wo WO 02 / 08241 A2 1 / 2002 6 ,639 ,071 B2 10 / 2003 Thompson et al . WO WO 02 / 062123 A2 8 / 2002 RE38 , 333 E 11/ 2003 Arimilli et al. WO WO 02 /068058 A2 9 / 2002 6 ,642 ,245 B1 11/ 2003 Liotta et al. WO WO 02 / 070518 AL 9 / 2002 6 ,703 , 396 B1 3 / 2004 Liotta et al .