`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
`AMNEAL PHARMACEUTICALS, LLC
`Petitioner
`v.
`PURDUE PHARMA L.P.,
`THE P.F. LABORATORIES, INC., and
`PURDUE PHARMACEUTICALS L.P.
`Patent Owners
`____________________
`Case IPR2016-01027
`U.S. Patent No. 9,060,976
`_____________________
`
`PATENT OWNERS’ RESPONSE TO PETITION FOR INTER PARTES
`REVIEW UNDER 35 U.S.C. § 313 AND 37 C.F.R. § 42.107
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`KASHIV1005
`IPR of Patent No. 9,492,392
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`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
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`TABLE OF CONTENTS
`
`B.
`C.
`
`D.
`
`Exhibit List ................................................................................................................. v
`Table of Abbreviations........................................................................................... xvi
`I.
`Introduction ...................................................................................................... 1
`II.
`Background ...................................................................................................... 5
`There Was a Long Felt Need For a Solution to the
`A.
`Problem of Opioid Abuse at the Time of the Invention ........................ 5
`Abuse-Deterrent OxyContin® ............................................................... 6
`The ’976 Patent ...................................................................................10
`1.
`Disclosure of the ’976 Patent ....................................................12
`2.
`Pertinent Prosecution History of the ’976 Patent .....................13
`The Prior Art Does Not Teach or Suggest a Core Combining
`Oxycodone with Magnesium Stearate and PEO .................................16
`1. McGinity ...................................................................................16
`2.
`Joshi...........................................................................................22
`3.
`Palermo .....................................................................................23
`HPE-3rd and Other Magnesium Stearate Prior Art ...................24
`4.
`Person of Ordinary Skill in the Art ................................................................26
`III.
`IV. Claim Construction ........................................................................................27
`“PEG applied onto the core matrix” ....................................................27
`A.
`“extended release” ...............................................................................27
`B.
`“abuse deterrent” .................................................................................28
`C.
`“core matrix is heated to melt at least a portion of the PEO included
`D.
`in the core matrix during preparation of the dosage form” .................31
`V. Amneal’s Obviousness Ground Fails ............................................................32
`A POSA Would Not Have Consulted McGinity To Tackle the
`A.
`Problem of Abuse Deterrence .............................................................34
`The Prior Art Taught Away from Using McGinity’s HME Process
`To Combine Oxycodone with Magnesium Stearate and PEO ............38
`
`B.
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`
`1.
`
`2.
`
`C.
`
`The Handbook of Pharmaceutical Excipients and Related
`References Teach Away From Using Magnesium Stearate .....38
`Bastin Teaches Not To Add Abuse-Deterring Gelling
`Properties to Extended-Release Formulations ..........................41
`The CPDD Paper Demonstrates That the Art Teaches Away ..42
`3.
`Joshi and Palermo Do Not Teach Modifying McGinity in a Way
`That Practices the Claimed Invention .................................................43
`D. Amneal Presented No Evidence of Motivation To Combine
`Particular Portions of the Prior Art in a Way That Practices the
`Claimed Invention ...............................................................................44
`A POSA Would Not Have Had a Reasonable Expectation of
`Successfully Practicing the Invention .................................................49
`Objective Indicia Confirm Nonobviousness .......................................54
`1.
`Commercial Success .................................................................54
`2.
`Regulatory Success ...................................................................56
`3.
`Initial Skepticism, Unexpected Results, and Subsequent
`Acclaim .....................................................................................58
`VI. Conclusion .....................................................................................................59
`
`
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`E.
`
`F.
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`TABLE OF AUTHORITIES
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`Page
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`
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`CASES
`
`Application of Mercier, 515 F.2d 1161 (C.C.P.A. 1975) ........................................ 33
`
`Astrazeneca Pharms. LP v. Handa Pharms., LLC,
`No. 08-3773, 2010 WL 4941431 (D.N.J. Nov. 30, 2010) .................................. 28
`
`Bausch & Lomb, Inc. v. Barnes-Hind/Hydrocurve, Inc.,
`796 F.2d 443 (Fed. Cir. 1986) ...................................................................... 33, 42
`
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp.,
`320 F.3d 1339 (Fed. Cir. 2003) .......................................................................... 30
`
`Catalina Mktg Int’l, Inc. v. Coolsavings.com, Inc.,
`289 F.3d 801 (Fed. Cir. 2002) ............................................................................ 29
`
`Deere & Co. v. Bush Hog, LLC,
`703 F.3d 1349 (Fed. Cir. 2012) .................................................................... 28, 29
`
`Demaco Corp. v. F. Von Langsdoff Licensing, Ltd.,
`851 F.2d 1387 (Fed. Cir. 1988) .......................................................................... 57
`
`Depuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`567 F.3d 1314 (Fed. Cir. 2009) .......................................................................... 32
`
`Electro Sci. Indus., Inc. v. Dynamic Details, Inc.,
`307 F.3d 1343 (Fed. Cir. 2002) .......................................................................... 29
`
`Glaxo Wellcome, Inc. v. Impax Labs., Inc.,
`356 F.3d 1348 (Fed. Cir. 2004) .......................................................................... 28
`
`Grain Processing Corp. v. Am. Maize-Products Co.,
`840 F.2d 902 (Fed. Cir. 1988) ............................................................................ 45
`
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`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 45
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`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
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`KSR Int’l Co.v. Teleflex Inc.,
`550 U.S. 398 (2007) .......................................................................... 32, 45, 46, 57
`
`Leo Pharm. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013) .................................................................... 32, 59
`
`Liebel-Flarsheim Co. v. Medrad, Inc.,
`358 F.3d 898 (Fed. Cir. 2004) ............................................................................ 31
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1372 (Fed. Cir. 2012) .......................................................................... 58
`
`Mitsubishi Chem. Corp. v. Barr Labs., Inc.,
`718 F. Supp. 2d 382 (S.D.N.Y. 2010) ................................................................ 55
`
`Panduit Corp. v. Dennison Mfg. Co.,
`810 F.2d 1561 (Fed. Cir. 1987) .......................................................................... 33
`
`Poly-Am., L.P. v. GSE Lining Tech., Inc.,
`383 F.3d 1303 (Fed. Cir. 2004) .......................................................................... 31
`
`Procter & Gamble Co. v. Teva Pharm. USA, Inc.,
`566 F.3d 989 (Fed. Cir. 2009) ............................................................................ 35
`
`Proveris Sci. Corp. v. Innovasystems, Inc.,
`739 F.3d 1367 (Fed. Cir. 2014) .......................................................................... 30
`
`Tec Air, Inc. v. Denso Mfg. Mich., Inc.,
`192 F.3d 1353 (Fed. Cir. 1999) .......................................................................... 42
`
`Unigene Labs., Inc. v. Apotex Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) .................................................................... 32, 37
`
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`Exhibit No. Description
`
`EXHIBIT LIST
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
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`2001.
`
`2002.
`2003.
`2004.
`2005.
`
`2006.
`
`2007.
`2008.
`2009.
`
`2010.
`
`2011.
`
`2012.
`2013.
`2014.
`
`2015.
`
`2016.
`
`
`
`Interference No. 106,004, Acura Pharmaceuticals, Inc. Request for
`Adverse Judgment, June 30, 2014
`File history of ’324 application, PTO, Miscellaneous Action, April 7, 2014
`Interference No. 106,004, BPAI, Judgment, July 3, 2014
`File history of ’324 application, Applicants, IDS, June 5, 2013
`File history of ’324 application, PTO, List of References Cited by
`Applicant and Considered by Examiner, July 9, 2013
`File history of ’324 application, PTO, List of References Cited by
`Applicant and Considered by Examiner, May 12, 2015
`Expert declaration of Steven Byrn, Ph.D.
`OxyContin® labeling (revised August 2015)
`File history of ’324 application, Applicants, Communication (comments
`on notice of allowance), May 18, 2015
`File history of 13/349,449 (application that issued as the ’888 patent),
`Applicants, Amendment, October 1, 2012
`File history of 14/728,601, PTO, Notice of Allowance and Examiner-
`Initiated Interview Summary, March 10, 2016, including references cited
`therein
`CPDD Paper
`(Intentionally omitted)
`Cicero et al., A tale of 2 ADFs: differences in the effectiveness of abuse-
`deterrent formulations of oxymorphone and oxycodone extended-release
`drugs, PAIN 157 (2016), 1232–38
`Timeline of Selected FDA Activities and Significant Events Addressing
`Opioid Misuse and Abuse, FDA, available at http://www.fda.gov/
` downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM332288.pdf
`(last visited August 11, 2016)
`OxyContin® labeling (revised April 2013)
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`Determination that the OXYCONTIN Oxycodone Hydrochloride Drug
`Products Covered by New Drug Application 20553 Were Withdrawn
`From Sale for Reasons of Safety or Effectiveness, FDA (Apr. 16, 2013)
`Levina et al., The Influence of Excipients on Drug Release from
`Hydroxypropyl Methylcellulose Matrices, J. PHARM. SCI. 93:11 (NOV.
`2004), 2746-54
`Vázquez, et al., Influence of technological variables on release of drugs
`from hydrophilic matrices, DRUG DEVEL. & INDUS. PHARM. 18:11-12
`(1992), 1355-1375
`“core,” Random House Webster’s College Dictionary (2001), 297
`File history of ’324 application, Applicants, IDS, January 5, 2015 (listing
`WO 02/087558)
`File history of ’324 application, PTO, List of References Cited by
`Applicant and Considered by Examiner, May 12, 2015 (listing WO
`02/087558)
`Joshi International Publication No. WO 02/087558
`Biographical information for authors of CPDD Paper
`Development and Regulation of Abuse-Deterrent Opioid Medications,
`Transcript of Public Meeting, FDA, Oct. 30, 2014.
`(Intentionally omitted)
`Excerpt from NDA for OxyContin®, 10, 15, 20, 30, 40 mg dosage
`strengths
`Excerpt from NDA for OxyContin®, 60, 80 mg dosage strengths
`PolyOxTM Water-Soluble Resins, Dow Chemical (March 2002)
`Letter from National Association of Attorneys General to FDA, March 11,
`2013
`Scheirs et al., Characterizing the solid-state thermal oxidation of
`poly(ethylene oxide) powder, POLYMER 32:11 (1991), 2014-19
`Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and
`Labeling (Draft Guidance), FDA (Jan. 2013)
`Throckmorton, The Science of Abuse-Deterrence – Progress Toward
`Creating Safer Opioids, FDA VOICE (April 16, 2013)
`
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`
`2017.
`
`2018.
`
`2019.
`
`2020.
`2021.
`
`2022.
`
`2023.
`2024.
`2025.
`
`2026.
`2027.
`
`2028.
`2029.
`2030.
`
`2031.
`
`2032.
`
`2033.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
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`
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`File History Of 14/733,659, PTO, Notice Of Allowance And Examiner-
`Initiated Interview Summary, August 1, 2016, including references cited
`therein
`HPE-3rd table of contents (highlighting gelling agents)
`HPE-3rd table of contents (highlighting lubricants)
`HPE-3rd table of contents (highlighting plasticizers)
`Chlorpheniramine maleate and oxycodone hydrochloride, Merck Index
`13th ed. (2001)
`Excerpt of trial transcript from Purdue Pharma L.P. et al. v. Amneal
`Pharmaceuticals, LLC, 13-cv-03372-SHS (July 18, 2014) (Maurin)
`U.S. Patent No. 5,549,912
`Expert Declaration of Eric M. Gaier, Ph.D.
`(Intentionally omitted)
`(Intentionally omitted)
`IPSOS Healthcare. “A Strategic Market Study to Understand the Position
`of Butrans® in the Continuous Pain Universe,” Dec. 17, 2014.
`Endo Pharmaceuticals, "Endo Pharmaceuticals Announces Reformulated
`Version of OPANA® ER with INTAC® Technology Designed to be
`Crush-Resistant Accounts for more than 90 Percent of OPANA ER Total
`Prescription Volume," news release, Sept. 6, 2012, available at
`http://www.prnewswire.com/news-releases/endo-pharmaceuticals-
`announces-reformulated-version-of-opana-er-with-intac-technology-
`designed-to-be-crush-resistant-accounts-for-more-than-90-percent-of-
`opana-er-total-prescription-volume-168750546.html.
`Theodore J. Cicero, Matthew S. Ellis, and Zachary A. Kasper, "A tale of 2
`ADFs: differences in the effectiveness of abuse-deterrent formulations of
`oxymorphone and oxycodone extended-release drugs," PAIN 157 (2016):
`1232-1238.
`U.S. Food and Drug Administration, "FDA Statement: Original Opana ER
`Relisting Determination," news release, May 10, 2013, available at
`http://www.fda.gov/Drugs/DrugSafety/ucm351357.htm.
`
`- vii -
`
`
`2034.
`
`2035.
`2036.
`2037.
`2038.
`
`2039.
`
`2040.
`2041.
`2042.
`2043.
`2044.
`
`2045.
`
`2046.
`
`2047.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`Roger Chou et al, “Clinical Guidelines for the Use of Chronic Opioid
`Therapy in Chronic Noncancer Pain,” Journal of Pain 10, no. 2 (2009),
`113–130.
`US Food and Drug Administration, Orange Book: Approved Drug
`Products with Therapeutic Equivalence Evaluations, available at
`http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm
`(Intentionally omitted)
`U.S. Food and Drug Administration, “FDA approves abuse-deterrent
`labeling for reformulated OxyContin,” news release, Apr. 16, 2013,
`available at
`http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm34
`8252.htm.
`Endo Pharmaceuticals, “Endo Announces Commercial Availability of
`Opana® ER (oxymorphone HCl) Extended-Release and Opana®
`(oxymorphone HCl) Immediate-Release Tablets CII,” news release, July
`24, 2006, available at http://www.prnewswire.com/news-releases/endo-
`announces-commercial-availability-of-opanar-er-oxymorphone-hcl-
`extended-release-and-opanar-oxymorphone-hcl-immediate-release-tablets-
`cii-56976772.html.
`Stephen F. Butler, Theresa A. Cassidy, Howard Chilcoat, Ryan A. Black,
`Craig Landau, Simon H. Budman, and Paul M. Coplan, “Abuse Rates and
`Routes of Administration of Reformulated Extended-Release Oxycodone:
`Initial Findings From a Sentinel Surveillance Sample of Individuals
`Assessed for Substance Abuse Treatment,” The Journal of Pain 14, no. 4
`(2013): 354.
`Actavis Inc., “Actavis Launches Oxymorphone Hydrochloride Extended-
`Release Rablets, CII in the U.S.,” news release, Jul. 20, 2011, available at
`http://www.prnewswire.com/news-releases/actavis-launches-
`oxymorphone-hydrochloride-extended-release-tablets-cii-in-the-us-
`125909248.html.
`Letter from Robert Barto, Vice President, Regulatory Affairs, Endo
`Pharmaceuticals, to Division of Dockets Management, Food and Drug
`Administration (Aug. 10, 2012), (available at
`https://assets.documentcloud.org/documents/2086687/endo-
`pharmaceuticals-inc-citizen-petition.pdf).
`
`- viii -
`
`
`2048.
`
`2049.
`
`2050.
`2051.
`
`2052.
`
`2053.
`
`2054.
`
`2055.
`
`
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`KASHIV1005
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`[ERO monthly TRx and Sales by product Jan 1992 - Jun
`2016_072916.xlsx]
`Purdue Pharma L.P., “OxyContin® (oxycodone hydrochloride controlled-
`release) Tablets, CII,” 2010, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022272lbl.pdf
`Purdue Pharma L.P., “Butrans (buprenorphine) Transdermal System for
`transdermal administration CIII,” 2010, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021306s000lbl.
`Endo Pharmaceuticals, “OPANA® ER (oxymorphone hydrochloride)
`Extended-Release tablets, CII,” 2011, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201655lbl.pdf
`Janssen Pharmaceuticals, Inc., “NUCYNTA® ER (tapentadol) extended-
`release oral tablets C-II,” 2011, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200533s000lbl.
`Ortho-McNeil-Janssen Pharmaceuticals, Inc., “DURAGESIC® CII
`(Fentanyl Transdermal System),” 2009, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019813s044lbl
`new.pdf
`Purdue Pharma L.P., “HYSINGLA ER (hydrocodone bitartrate) extended-
`release tablets, for oral use, CII,” 2014, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206627s000lbl.
`Zogenix Inc., “Zohydro™ ER (hydrocodone bitartrate) Extended-Release
`Capsules, CII,” 2013, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202880s000lbl.
`Alpharma Branded Products Division, “Kadian CII (morphine sulfate
`extended-release) Capsules,” 2007, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020616s025lbl.
`Neuromed Pharmaceuticals Inc., “EXALGO (hydromorphone
`hydrochloride) extended release tablets, CII,” 2010, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021217lbl.pdf
`
`- ix -
`
`
`2056.
`
`2057.
`
`2058.
`
`2059.
`
`2060.
`
`2061.
`
`2062.
`
`2063.
`
`2064.
`
`2065.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`King Pharmaceuticals, Inc., “EMBEDA™ (morphine sulfate and
`naltrexone hydrochloride) Extended Release Capsules for oral use – CII,”
`2009, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022321s000lbl.
`Cipher Pharms Inc., “Tramadol hydrochloride extended-release capsules,”
`2010, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022370s000lbl.
`Mallinckrodt Brand Pharmaceuticals, Inc., “XARTEMIS XR (oxycodone
`hydrochloride and acetaminophen) Extended-Release Tablets, for oral use,
`CII,” 2014, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204031s000lbl.
`King Pharmaceuticals, Inc., “AVINZA® (morphine sulfate) extended-
`release capsules, for oral use, CII,” 2012, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021260s015lbl.
`Purdue Pharma L.P., “MS CONTIN® (morphine sulfate controlled-
`release) Tablets CII,” 2010, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019516s034lbl.
`PriCara, a unit of Ortho-McNeil, Inc., “ULTRAM® ER (tramadol HCI)
`Extended-Release Tablets,” 2008, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021692s005s0
`07lbl.pdf
`Mallinckrodt, Inc., “METHADOSE- methadone hydrochloride tablet,”
`2014, available at
`https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6059a68d-
`5434-4a0e-9f53-b793c3dc8630
`Roxane Laboratories, Inc., “DOLOPHINE® (methadone hydrochloride)
`tablets, for oral use, CII,” 2012, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/006134s031lbl.
`
`- x -
`
`
`2066.
`
`2067.
`
`2068.
`
`2069.
`
`2070.
`
`2071.
`
`2072.
`
`2073.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
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`Xanodyne pharmaceuticals, inc., “oramorph sr (Morphine Sulfate) tablet,”
`2007, available at
`http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid
`=7676
`Purdue Pharma, L.P., “RYZOLT™ (tramadol hydrochloride extended-
`release tablets),” 2008, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021745s000lbl.
`AB Generics L.P., “Morphine Sulfate Extended Release Tablets 100mg
`and 200mg,” 1998, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/anda/98/74769ap_appltr_
`prntlbl_chemr.pdf
`Mylan Pharmaceuticals Inc., “FENTANYL- fentanyl patch,” 2014,
`available at
`http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2A2238E9-
`4B5D-C56D-8663-DD354FF9AE0C
`Mallinckrodt, Inc., “METHADONE HYDROCHLORIDE- methadone
`hydrochloride tablet,” 2015, available at
`https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eddf7077-
`02fb-4771-9823-31984f4ff2bb
`Aurobindo Pharma USA, Inc., “Tramadol Hydrochloride Extended-
`Release Tablets USP CIV,” 2015, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204421Orig1s
`000lbl.pdf
`Actavis Elizabeth LLC, “OXYMORPHONE hydrochloride extended-
`release tablets, for oral use, CII,” 2014, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/079046Orig1s
`013lbl.pdf
`Teva Pharmaceuticals USA, “Oxycodone Hydrochloride Extended
`Release Tablets,” 2004, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/76168lbl.pdf
`Watson Pharma, Inc., “Hydromorphone HCl Extended-Release Tablets,
`for oral use, CII,” 2014, available at
`http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/202144Orig1s
`000lbl&MG.pdf
`
`- xi -
`
`
`2074.
`
`2075.
`
`2076.
`
`2077.
`
`2078.
`
`2079.
`
`2080.
`
`2081.
`
`2082.
`
`
`
`KASHIV1005
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`
`
`Case IPR2016-01027 for
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`Nelson E. Sessler, Jerod M. Downing, Hrishikesh Kale, Howard D.
`Chilcoat, Todd F. Baumgartner, and Paul M. Coplan, “Reductions in
`reported deaths following the introduction of extended-release oxycodone
`(OxyContin) with an abuse-deterrent formulation,”
`Pharmacoepidemiology and Drug Safety 23 (2014), 1238–1246.
`OxyContin® Marketing Material 0PO571 (C8559)
`OxyContin® Marketing Material C8275 Oxy Field Card
`May 5, 2008 FDA Advisory Committee Minutes, available at
`http://www.fda.gov/ohrms/dockets/ac/08/minutes/2008-4356m1-final.pdf
`(last accessed Aug. 10, 2016)
`Excerpt of trial transcript from In re OxyContin Antitrust Litigation, 04-
`md-1603 (SHS) (Sept. 24, 2013) (Weingarten)
`Purdue Pharma L.P. slides, FDA Advisory Committee on Reformulated
`OxyContin—Public Session (Sept. 24, 2009), available at
`http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeeting
`Materials/Drugs/AnestheticAndLifeSupportDrugsAdvisoryCommittee/
`UCM248777.pdf (last accessed Aug. 10, 2016)
`Purdue Pharma L.P., FDA Advisory Committee Briefing Document on
`NDA 22-272 (reformulated OxyContin® tablets) (Sept. 24, 2009),
`available at http://www.fda.gov/downloads/AdvisoryCommittees/
`CommitteesMeetingMaterials/Drugs/AnestheticAndLifeSupportDrugs
`AdvisoryCommittee/UCM183205.pdf (last accessed Aug. 10, 2016)
`Sept. 24, 2009 FDA Advisory Committee Minutes, available at
`http://www.fda.gov/downloads/AdvisoryCommittees/Committees
`MeetingMaterials/Drugs/AnestheticAndAnalgesicDrugProducts
`AdvisoryCommittee/UCM187629.pdf (last accessed Aug. 10, 2016)
`Physician’s Desk Reference (51st ed.) (1997)
`Excerpt of trial transcript from Purdue Pharma L.P. et al. v. Amneal
`Pharmaceuticals, LLC, 13-cv-03372-SHS (July 14, 2014) (Oshlack)
`Trial Testimony (Breder, Wright)
`Proposed Protective Order
`HPE-3rd table of contents and index
`Supplemental expert declaration of Steven Byrn, Ph.D.
`
`- xii -
`
`
`2083.
`
`2084.
`2085.
`2086.
`
`2087.
`
`2088.
`
`2089.
`
`2090.
`
`2091.
`2092.
`
`2093.
`2094.
`2095.
`2096.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`Declaration of Benjamin Oshlack
`Declaration of Curtis Wright IV, M.D., M.P.H.
`Deposition of Dr. Palmieri (January 13, 2017)
`U.S. Patent No. 5,508,042
`U.S. Patent No. 5,549,912
`U.S. Patent No. 5,266,331
`U.S. Patent No. 5,656,295
`Opioid-X Summit slides (April 24, 2001)
`Excerpts from Purdue Pharma L.P. Notebook No. 394
`Excerpts from Purdue Pharma L.P. Notebook No. 503
`Excerpts from Purdue Pharma L.P. Notebook No. 491
`Excerpts from Purdue Pharma L.P. Notebook No. 495
`Severtson et al., Sustained Reduction of Diversion and Abuse After
`Introduction of an Abuse Deterrent Formulation of Extended Release
`Oxycodone, DRUG & ALCOHOL DEPENDENCE 168 (2016), 219-229
`Coplan et al., The Effect of an Abuse-Deterrent Opioid Formulation
`(OxyContin) on Opioid Abuse-Related Outcomes in the Postmarketing
`Setting, CLIN. PHARMACOLOGY & THERAPEUTICS 100:3 (Sept. 2016), 275-
`286
`Frederichs, Opioids, in ANALGESICS, FROM CHEMISTRY AND
`PHARMACOLOGY TO CLINICAL APPLICATION (2003), 127-150
`U.S. Food and Drug Administration, “Guidance for Industry Extended
`Release Oral Dosage Forms: Development, Evaluation, and Application of
`In Vitro/In Vivo Correlations,” Sept. 1997
`Zhang et al., Properties of Sustained-Release Tablets Prepared by Hot-
`Melt Extrusion, PHARM. DEV. & TECH. 4:2 (1999), 241–250
`Zhang et al., Properties of Hot-Melt Extruded Theophylline Tablets
`Containing Poly(Vinyl Acetate), DRUG DEV. & INDUS. PHARMACY 26:9
`(2000), 931–942
`McGinity et al., Hot-Melt Extrusion as a Pharmaceutical Process, AM.
`PHARM. REV. 4:2 (Summer 2001), 25-36
`
`- xiii -
`
`
`2097.
`2098.
`2099.
`2100.
`2101.
`2102.
`2103.
`2104.
`2105.
`2106.
`2107.
`2108.
`2109.
`
`2110.
`
`2111.
`
`2112.
`
`2113.
`
`2114.
`
`2115.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`Follonier et al., Evaluation Of Hot-Melt Extrusion as a New Technique for
`the Production Of Polymer-Based Pellets for Sustained Release Capsules
`Containing High Loadings of Freely Soluble Drugs,” DRUG DEV. &
`INDUS. PHARMACY, 20:8 (1994), 1323-1339
`(intentionally omitted)
`Crowley et al., Stability of Polyethylene Oxide in Matrix Tablets Prepared
`by Hot-Melt Extrusion, BIOMATERIALS 23 (2002), 4241-4248
`(intentionally omitted)
`(intentionally omitted)
`(intentionally omitted)
`Kim, Drug Release from Compressed Hydrophilic POLYOX-WSR
`Tablets, J. PHARM. SCI. 84:3 (Mar. 1995), 303-306
`Madorsky et al., Thermal Degradation of Polyethylene Oxide and
`Polypropylene Oxide, J. POLYMER SCI. 36 (1959), 183-194
`McGary, Degradation of Poly(ethylene Oxide), J. POLYMER SCI. 46 (1960),
`51-57
`Alderman, A Review of Cellulose Ethers in Hydrophilic Matrices for Oral
`Controlled-Release Dosage Forms, IN’L J. PHARM. TECH. & PROD. MFR.
`5:3 (Nov. 1984), 1-9
`(intentionally omitted)
`Pöyhiä et al., A Review of Oxycodone’s Clinical Pharmacokinetics and
`Pharmacodynamics, J. PAIN & SYMPTOM MGMT. 8:2 (Feb. 1993), 63-67
`Salomies et al., Determination of Oxycodone Hydrochloride in Oral
`Solutions by High-Performance Thin-Layer Chromatography/
`Densitometry, J. AOAC INT’L, 83:6 (2000), 1497-1501
`U.S. Patent No. 6,177,567
`Brogle et al., Peak Fronting in Reversed-Phase High-Performance Liquid
`Chromatography: A Study of the Chromatographic Behavior of
`Oxycodone Hydrochloride, J. PHARM. & BIOMEDICAL ANALYSIS 19 (1999),
`669-678
`
`- xiv -
`
`
`2116.
`
`2117.
`2118.
`
`2119.
`2120.
`2121.
`2122.
`
`2123.
`
`2124.
`
`2125.
`
`2126.
`2127.
`
`2128.
`
`2129.
`2130.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`Craig et al., The Relevance of the Amorphous State to Pharmaceutical
`Dosage Forms: Glassy Drugs and Freeze Dried Systems, INT’L J. PHARM.
`179 (1999), 179–207
`HPE-3rd, Magnesium Stearate, 305-308
`Ragnarsson et al., The Influence of Mixing Time and Colloidal Silica on the
`Lubricating Properties of Magnesium Stearate, INT’L J. PHARM. 3 (1979),
`127-131
`Murthy et al., Effect of Shear Mixing on In Vitro Drug Release of Capsule
`Formulations Containing Lubricants, J. PHARM. SCI. 66:9 (Sept. 1977),
`1215-1219
`Bossert et al., Effect of Mixing on the Lubrication of Crystalline Lactose by
`Magnesium Stearate, DRUG DEV. & INDUS. PHARMACY 6:6 (1980), 573-
`589
`Downie et al., The Abuse and Misuse of Prescribed and Over-the-Counter
`Medicines, HOSPITAL PHARMACIST 7:9 (Oct. 2000), 242-250
`Brookoff, Abuse Potential of Various Opioid Medications, J. GEN.
`INTERNAL MED. 8 (Dec. 1993), 688-690
`Chernin, Painkillers and Pill Popping, DRUG TOPICS 15:31 (Aug. 6, 2001),
`31-41
`Thompson, Prescription Drug Misuse Highlighted as National Problem,
`AM. J. HEALTH-SYST. PHARM. 58 (June 1, 2001), 956, 960
`Letter from T. Van Buskirk to P. Hendler (Feb. 6, 2017)
`U.S. Patent No. 6,067,749
`Byrn, Solid-Solid Reactions, in SOLID-STATE CHEMISTRY OF DRUGS
`(1982), 317-321
`Baker, CONTROLLED RELEASE OF BIOLOGICALLY ACTIVE AGENTS, 1-21
`(1987)
`
`- xv -
`
`
`2131.
`
`2132.
`2133.
`
`2134.
`
`2135.
`
`2136.
`
`2137.
`
`2138.
`
`2139.
`
`2140.
`2141.
`2142.
`
`2143.
`
`
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`TABLE OF ABBREVIATIONS
`
`Abbreviation
`
`Explanation
`
`’324 [application]
`
`U.S. Patent Application No. 13/726,324 (Ex. 1022)
`
`’412 [application]
`
`U.S. Patent Application No. 10/214,412 (Ex. 1025)
`
`’534 [application]
`
`U.S. Provisional Application No. 60/310,534 (Ex. 1026)
`
`’888 [patent]
`
`U.S. Patent No. 8,337,888 (Ex. 1002)
`
`’976 [patent]
`
`U.S. Patent No. 9,060,976 (Ex. 1001)
`
`Amneal
`
`API
`
`Bastin
`
`CPDD
`
`CPDD Paper
`
`CPM
`
`FDA
`
`HPE-3rd
`
`
`
`Amneal Pharmaceuticals, LLC (petitioner)
`
`active pharmaceutical ingredient
`
`International Publication No. WO 95/20947 (Ex. 1015)
`
`Committee/College on Problems of Drug Dependence
`
`Zacny et al., College on Problems of Drug Dependence
`taskforce on prescription opioid non-medical use and abuse:
`position statement, DRUG AND ALCOHOL DEPENDENCE 69
`(2003) 215-232 (Ex. 2012)
`chlorpheniramine maleate
`
`U.S. Food and Drug Administration
`
`Kibbe, Handbook of Pharmaceutical Excipients (3rd ed.)
`(2000)
`
`- xvi -
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`
`HME
`
`IDS
`
`Joshi
`
`McGinity
`
`NDA
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`hot-melt extrusion
`
`Information Disclosure Statement
`
`U.S. Patent Publication No. US 2002/0187192 (Ex. 1014)
`
`WO 97/49384 (Ex. 1013)
`
`New Drug Application
`
`original OxyContin®
`
`OxyContin®
`
`Palermo
`
`the first FDA-approved formulation of Purdue’s OxyContin®,
`approved in 1995 and lacking abuse-deterrent features
`abuse-deterrent formulation of Purdue’s OxyContin®
`approved by the FDA in 2010
`International Publication No. WO 99/32120 (Ex. 1011)
`
`PEG
`
`Pet.
`
`PEO
`
`POSA
`
`PTO
`
`Purdue
`
`SDNY
`
`
`
`polyethylene glycol
`
`Amneal’s present Petition for Inter Partes Review
`
`polyethylene oxide
`
`person of ordinary skill in the art
`
`U.S. Patent and Trademark Office
`
`Purdue Pharma L.P., The P.F. Laboratories, Inc., and Purdue
`Pharmaceuticals L.P. (owner of the ’976 patent)
`U.S. District Court for the Southern District of New York
`
`- xvii -
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`
`SDNY decision
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`Findings of Fact and Conclusions of Law, Purdue Pharma
`L.P. v. Amneal Pharms., LLC, No. 13-3372 (SHS), slip op.
`(S.D.N.Y. April 8, 2015) regarding the ’888 patent (Ex. 1003)
`
`
`
`- xviii -
`
`KASHIV1005
`IPR of Patent No. 9,492,392
`
`
`
`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`I.
`
`INTRODUCTION
`
`Patent Owners Purdue L.P., The P.F. Laboratories, Inc. and Purdue
`
`Pharmaceuticals L.P. (“Purdue”) hereby submit this Response to Amneal
`
`Pharmaceuticals, LLC’s (“Amneal”) petition for inter partes review of the sole
`
`claim of the ’976 patent, Case No. IPR2016-01027, and the Board’s institution of
`
`trial based on evidence submitted in the Petition.
`
` In its Institution Decision, the Board rejected the first ground initially
`
`asserted by Amneal based on anticipation. As the Board found, no single prior art
`
`reference contains each and every limitation of the challenged claim. Currently,
`
`one obviousness ground remains in this petition based on the combination of three
`
`references—McGinity in view of Joshi and Palermo.
`
`Amneal relies heavily on the prior adjudication of the ’888 parent patent for
`
`its obviousness determination. The Examiner considered this decision, however,
`
`before allowing the ’976 patent claim. Amneal and its expert failed to consider a
`
`critical difference between the ’976 patent and ’888 patent