US010238648B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 ,238 ,648 B2 Stinchcomb et al. ( 45 ) Date of Patent : Mar . 26 , 2019 ( 54 ) ABUSE DETERRENT ( 56 ) References Cited OPIOID /OPIOID - ANTAGONIST TRANSDERMAL PATCH U . S . PATENT DOCUMENTS ( 71 ) Applicant: BUZZZ PHARMACEUTICALS 4 ,584 ,355 A 4 / 1986 Blizzard 4 ,585 , 836 A 4 / 1986 Homan LIMITED , Dublin ( IE ) 4 , 591, 622 A 5 / 1986 Blizzard 4 ,655 ,767 A 4 / 1987 Woodard (72 ) Inventors: Audra Lynn Stinchcomb , Ruxton , MD 5 , 149 , 538 A 9 / 1992 Granger et al. (US ) ; Dana Carmel Hammell , 5 , 232 ,702 A 8 / 1993 Pfister Georgetown , KY (US ) ; Stan Lee 5 , 262 , 165 A 11 / 1993 Govil et al. 5 , 474 , 783 A 12 / 1995 Miranda Banks, Cincinnati, OH (US ); Josh 5 , 762 , 952 A 6 / 1998 Barnhart Eldridge, Miami, FL (US ) ; Miroslaw 5 , 916 , 587 A * 6 / 1999 Min .. .. A61K 9 / 7061 Jerzy Golinski, Lexington , KY (US ) 424 / 448 5 ,985 ,317 A 11 /1999 Venkateshwaran (73 ) Assignee : BUZZZ PHARMACEUTICALS 6 , 139 , 866 A 10 /2000 Chono LTD . , Dublin ( IE ) 6 ,231 , 885 B1 5 /2001 Carrara 2003 / 0060479 Al 3 / 2003 Brown 2004 /0013716 A1 * 1 / 2004 Gale .. * * * * A61K 31/ 4535 ( * ) Notice : Subject to any disclaimer, the term of this 424 / 449 patent is extended or adjusted under 35 2004 /0033254 A1* 2 / 2004 Song .. .. .. A61K 9 /7053 U . S . C . 154 ( b ) by 0 days . 424 449 2004 /0126323 A1 * 7 /2004 Shevchuk .. .. .. A61K 9 / 7069 424 / 10 . 1 ( 21 ) Appl. No. : 15 /326 ,797 2008 / 0233178 AL 9 /2008 Reidenberg et al . 2011/ 0244022 Al 10 / 2011 Cottrell et al. ( 22 ) PCT Filed : Jul. 17 , 2015 2011 /0245783 Al 10 / 2011 Stinchcomb et al . 2013 / 0251760 A1 9 / 2013 Gale et al . (86 ) PCT No. : PCT/ EP2015 / 066457 2017 /0202830 A17 / 2017 Stinchcomb et al . $ 371 ( c ) ( 1 ) , ( 2 ) Date : Jan . 17 , 2017 FOREIGN PATENT DOCUMENTS EP 1381352 B1 6 /2007 ( 87) PCT Pub . No. : WO2016 /009064 WO 2005081825 9 / 2005 WO 2014012653 1 /2014 PCT Pub . Date : Jan . 21, 2016 WO 2016009063 1 / 2016 (65 ) Prior Publication Data US 2017 /0209429 A1 Jul. 27 , 2017 OTHER PUBLICATIONS Dyson , D . H . et al ., “ Reversal of Oxymorphone Sedation by Related U . S . Application Data Naloxone , Nalmefene , and Butorphanol, ” Vet . Surg . 1990 , 19 , (60 ) Provisional application No . 62 / 187 ,473 , filed on Jul. 398 -403 1 , 2015 , provisional application No . 62 / 026 , 195 , filed Third party submission submitted in U . S . Appl. No. 15 / 326 , 784 , mailed Aug . 24 , 2017 . on Jul. 18 , 2014 . PCT International Search Report and Written Opinion completed by (51 ) Int. Cl. the ISA / EP dated Sep . 23 , 2015 and issued in connection with A61K 9 / 00 ( 2006 .01 ) PCT/ EP2015 / 066457 , 11 pages . A61K 9 / 70 ( 2006 .01 ) (Continued ) A61K 47 / 10 ( 2017 .01 ) A61K 47 / 12 ( 2006 .01 ) Primary Examiner - Michael B . Pallay A61K 47 / 14 ( 2017 .01 ) A61K 4732 ( 2006 . 01 ) ( 74 ) Attorney , Agent, or Firm — Barnes & Thornburg A61K 4738 ( 2006 .01 ) LLP A61K 31 /485 ( 2006 . 01 ) (52 ) U . S . CI. (57 ) ABSTRACT CPC . .. .. A61K 31/ 485 ( 2013 .01 ) ; A61K 9 / 0014 An abuse deterrent transdermal patch comprising a multil ( 2013 .01 ) ; A61K 9 / 7053 ( 2013 . 01 ) ; A61K aminate . The multilaminate can comprise a first layer com 9 / 7061 (2013 . 01 ) ; A61K 9 / 7069 ( 2013 .01 ) ; prising an opioid analgesic compound , or a pharmaceuti A61K 9 / 7084 ( 2013 . 01 ) ; A61K 9 / 7092 cally acceptable salt thereof, and a pharmaceutically ( 2013 .01 ) ; A61K 47 /10 ( 2013 .01 ) ; A61K 47/ 12 acceptable pressure sensitive adhesive . The multilaminate ( 2013 . 01 ) ; A61K 47 / 14 ( 2013 .01 ) ; A61K 4732 can further comprise a second layer comprising an opioid ( 2013 .01 ) ; A61K 47 /38 (2013 .01 ) antagonist, or a pharmaceutically acceptable salt thereof, ( 58 ) Field of Classification Search CPC . .. A61K 31/ 485 ; A61K 47 / 12 ; A61K 47 /32 ; and a pharmaceutically acceptable adhesive . In addition , the A61K 47 / 38 ; A61K 9 /0014 ; A61K multilaminate can further comprise a barrier layer disposed 9 /7053 ; A61K 9 / 7061; A61K 9 /7069 ; between the first and second layers . A61K 9 /7092 See application file for complete search history . 21 Claims, 24 Drawing Sheets US 10 ,238 ,648 B2 Page 2 ( 56 ) References Cited Karande , Pankaj , Enhancement of transdermal drug delivery via synergistic action of chemicals , Biochimica et Biophysica Acta , Sep . 2009 , pp . 236 -2373 , vol. 1788 , Issue 11. OTHER PUBLICATIONS Ogiso , Taro , Effect of Various Enhancers on Transdermal penetra tion of Indomethacin and Urea , and Relationship between Penetra Satas , Donatas, Handbook of pressure sensitive adhesive technol tion Parameters and Enhancement Factors , Journal of Pharmaceu ogy , book , 1989 , pp . 396 -456 , Van Nostrand Reinhold , New York , tical Sciences , Apr. 1995 , pp . 482 -488 , vol. 84 , No . 4 . U . S . A . Francoeur, Michael L . , Oleic Acid : Its Effects on Stratum Comeum Satas, Donatas, Handbook of pressure sensitive adhesive technol in Relation to ( Trans) Dermal Drug Delivery , Pharmaceutical Research , ogy , book , 1989 , pp . 508 -517 , Van Nostrand Reinhold , New York , 1990 , pp . 621 -627 , vol. 7 , No. 6 . U . S . A . ISR and Written Opinion for PCT /EP2015 / 066457 , dated Oct . 1 , Rowe, Raymond C ., Handbook of Pharmaceutical Excipients , 5th 2015 . edition , 2006 , pp . 494 - 497 , Pharmaceutical Press , Great Britian , and ISR and Written Opinion for PCT/ EP2015/ 066456 , dated Oct . 1 , the American Pharmacists Association , NW Washington D . C ., U . S . 2015 . A . Third Party Observation for PCT/ EP2015 / 066456 , submitted Nov . Pathan , Inayat Bashir, Chemical Penetration Enhancers of Trans 18 , 2016 . dermal Drug Delivery Systems, Tropical Journal of Pharmaceutical Research , Jun . 2009 , pp . 173 - 179 , vol. 8 , No. 2 . * cited by examiner U . S . Patent Mar. 26 , 2019 Sheet 1 of 24 US 10 ,238 ,648 B2 ssimi eiwinioni Permeation(ve/cm) inimene siivisinsilmini wiwinisisisi abatdibelen poesiaR A392xxx 0 10 20 30 40 50 60 70 80 Time ( h ) Fig 1 U . S . 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