`
`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
`
`
`
`E.
`
`F.
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`TABLE OF AUTHORITIES
`
`Page
`
`
`
`
`
`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
`
`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
`
`2001.
`
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`2003.
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`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),
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`File history of 14/728,601, PTO, Notice of Allowance and Examiner-
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`therein
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` 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
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`Joshi International Publication No. WO 02/087558
`Biographical information for authors of CPDD Paper
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`(Intentionally omitted)
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`- vi -
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`File History Of 14/733,659, PTO, Notice Of Allowance And Examiner-
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`HPE-3rd table of contents (highlighting plasticizers)
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`Case IPR2016-01027 for
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`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
`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
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`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/
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`AdvisoryCommittee/UCM183205.pdf (last accessed Aug. 10, 2016)
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`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
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`Release Oral Dosage Forms: Development, Evaluation, and Application of
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`Melt Extrusion, PHARM. DEV. & TECH. 4:2 (1999), 241–250
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`Containing Poly(Vinyl Acetate), DRUG DEV. & INDUS. PHARMACY 26:9
`(2000), 931–942
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`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.
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`
`
`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
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`by Hot-Melt Extrusion, BIOMATERIALS 23 (2002), 4241-4248
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`(intentionally omitted)
`(intentionally omitted)
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`51-57
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`Chromatography: A Study of the Chromatographic Behavior of
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`
`- xiv -
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`2119.
`2120.
`2121.
`2122.
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`2123.
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`2124.
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`2125.
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`2126.
`2127.
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`2128.
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`2130.
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`KASHIV1005
`IPR of Patent No. 9,492,392
`
`

`

`Case IPR2016-01027 for
`U.S. Patent No. 9,060,976
`
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`(1982), 317-321
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`2131.
`
`2132.
`2133.
`
`2134.
`
`2135.
`
`2136.
`
`2137.
`
`2138.
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`2141.
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`
`2143.
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`
`
`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 -
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`KASHIV1005
`IPR of Patent No. 9,492,392
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`

`

`
`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 -
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`

`

`
`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 -
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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
`
`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