Case: 18-1285
`
`Document; 47
`
`Page:1
`
`Filed: 07/02/2018
`
`Nos. 18-1285, 18-1286
`
`
`0111:1211 étates QEuurt of Qppeals
`
`fur the jfeheral Qtircuit
`
`
`
`PURDUE PHARMA L.P.,
`P.F. LABORATORIES, INC.,
`PURDUE PHARMACEUTICALS L.P.,
`
`‘
`
`Appellants,
`
`v.
`
`ANDREI IANCL’, Director, U.S. Patent and Trademark Office,
`
`Interven or.
`
`Appeals from the United States Patent and Trademark Office, Patent Trial and
`Appeal Board in Nos. IPR 2016-01027 and IPR 2016-01028
`
`APPELLANTS" OPENING BRIEF
`
`JOHN J. NORMJLE
`
`GASPER J. LAROSA
`
`JONES DAY
`
`250 Vesey Street
`New York, NY 10281
`(212) 326-3939
`jjnormile@jonesday.com
`
`GREGORY A. CASTANIAS
`
`JENNIFER L. SWIZE
`
`ROBERT STANDER
`
`JONES DAY
`51 Louisiana Avenue, NW.
`Washington, DC. 20001
`(202) 879-3939
`gcastanias@jonesday.eom
`
`Counsel fbrA . ellants
`
`
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 1
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 1
`
`

`

`Casez18—1285
`
`Document: 47
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`Page:2
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`Filed: 07/02/2018
`
`US. Patent No. 9,060,976 Claim 1
`
`1. An extended release abuse deterrent dosage fonn comprising:
`
`a. a core matrix comprising a blended mixture of:
`
`(a) PEO having a molecular weight of from about 300,000 daltons to
`about 5,000,000 daltons:
`
`(b) magnesium stearate; and
`
`(2c) oxycodone or a pharmaceutically acceptable Salt thereof;
`
`wherein the core matrix is heated to melt at least a portion of the PEO
`included in the core matrix during preparation of the dosage form; and
`
`b. PEG applied onto the core matrix;
`
`wherein the dosage form provides extended release of the drug.
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 2
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 2
`
`

`

`Casez18-1285
`
`Document: 47
`
`Page:3
`
`Filed: 07/02/2018
`
`UNITED STATES COURT OF APPEALS FOR THE FEDERAL
`
`CIRCUIT
`
`Purdue Pharma L.P. et al. v. Iancu
`
`Case Nos. 18-1285‘ -1286
`
`CERTIFICATE OF INTEREST
`
`Counsel for the:
`(appellants) [:I (respondent) E] (appellee) E]
`El (petitioner)
`(amicus) El (name of party)
`
`Purdue. Pharma L.P.' The P.F. Laboratories Inc: and Purdue
`
`Pharmaceuticals L.P.
`
`certifies the followin v:
`
`1. Full Name of Party
`Rep-resented by me
`
`2. Name of party in
`interest represented by
`me is:
`
`3. Parent corporations and
`publicly held companies
`that own 10% or more of
`
`stock in the party
`
`Purdue Pharma L. P.
`
`Purdue Pharma L.P
`
`The P.F Laboratories,
`Inc.
`
`The P. F. Laboratories,
`Inc.
`
`None
`
`Purdue Pharmaceuticals
`
`Purdue Pharmaceuticals
`
`L. P
`
`
`
`4 The names of all law firms and the partners or associates that appeared
`for the party or amicus now represented by me in the trial court or agency or are
`expected to appear in this court (and who have not or will not enter an appearance
`in this case) are:
`
`JONES DAY: Pablo D. Hendler; Kelsey I. Nix; Jason G. Winchester;
`Kenneth S. Canfield; Sarah A. Geers; Lisarnarie LoGiudice
`
`5. The title and number of any case known to counsel to be pending in this
`or any other court or agency that will directly affect or be directly affected by this
`court’s decision in the pending appeal. See Fed. Cir. R. 47 .4(a)(5) and 47.5(b).
`
`The patent at
`defendants in:
`
`issue in this appeal
`
`is asserted against
`
`the respective
`
`Purdue Pharma L. P. et al. v. Amneal Pharmaceuticals LLC, N0. 15-cv-1 152
`
`(D. Del);
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 3
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 3
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 4
`
`Filed: 07/02/2018
`
`Purdue Pharma L.P. et a]. v. Intellzpharmaceutim Int ’1, Inc. 2161]., No. 17-
`cv-392 (D. Del.);
`
`Purdue Pharma LP. 61‘ a]. v. Intel/iplzarmacel(tics Int’l, Inc. et (11., No. 18-
`cv-404 (D. Del.);
`
`Purdue. Pharmu L. P. el al. v. Ascent Pharmaceuticals, Inc, No. IS-CV-O83
`(D. Del.):
`
`(D. Del.)
`
`cc: Counsel of record via CM/ECF
`
`[5/ Gregory A. Castanias
`Signature of counsel
`
`Greuog A. Castanias
`Printed name of counsel
`
`
`
`ii
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 4
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 4
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 5
`
`Filed: 07/02/2018
`
`TABLE OF CONTENTS
`
`Page
`
`TABLE OF AUTHORITIES ...................................................................................vi
`
`TABLE OF ABBREVIATIONS .............................................................................ix
`
`STATEMENT OF RELATED CASES .................................................................... x
`
`STATEMENT OF JURISDICTION ......................................................................... 1
`
`STATEMENT OF THE ISSUES .............................................................................. 2
`
`STATEMENT OF THE CASE ................................................................................. 2
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`Preliminary Statement ..........................................................................2
`
`Purdue Develops A Family Of Patented Abuse-Deterrent Forms
`Of Oxycodone ...................................................................................... 4
`
`The ’976 Patent Combines Magnesium Stearate And PEO In
`An Abuse-Deterrent, Extended-Release Dosage Form Of
`Oxycodone?
`
`Amneal Petitions For Inter Partes Review .......................................... 8
`
`The Asseited Prior Art ......................................................................... 9
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`McGinity (1997): Extended—Release Drug Formulation
`Using Hot-Melt Extrusion And PEO ......................................... 9
`
`Joshi (2001): Drug Composition Containing A Stimulant
`And PEO As An Abuse—Deterrent Gel .................................... 11
`
`Palermo (1999): Method Of Reducing Abuse Potential
`By Combining An Opioid Agonist With An Antagonist ........ 12
`
`Bastin (1994): Immediate-Release, Abuse-Deterrent
`Formulations That Sandwich An Active Ingredient
`Between Layers Of PEO .......................................................... 13
`
`Handbook (1999): General Pharmaceutical Reference ........... 13
`
`PDR (1999): General Pharmaceutical Reference .................... l 5
`
`F.
`
`Amneal Changes Its Experts And Positions During The Inter
`Partes Review Proceedings ................................................................ 15
`
`G.
`
`The Board’s Decisions ....................................................................... 16
`
`SUMMARY OF THE ARGUMENT ..................................................................... 24
`
`iii
`
`~PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 5
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 5
`
`

`

`Casez18-1285
`
`Document: 47
`
`Page26
`
`Filed: 07/02/2018
`
`TABLE OF CONTENTS
`
`(continued)
`
`Page
`
`STANDARD OF REVIEW .................................................................................... 24
`
`ARGUMENT .......................................................................................................... 25
`
`I.
`
`THE BOARD ERRONEOUSLY CONSTRUED THE CLAIM ................. 25
`
`A. Magnesium Stearate Is Part Of The Core Matrix That “Is
`Heated” ............................................................................................... 26
`
`1.
`
`2.
`
`3.
`
`4.
`
`The Claim Language Requires Magnesium Stearate In
`The “Core Matrix“ When Heat Is Applied .............................. 26
`
`The Experts Agreed That “The Core Matrix Is Heated”
`Means That Magnesium Stearate Must Be In The “Core
`Matrix” ..................................................................................... 27
`
`The Specification Does Not Support The Board’s
`Construction ............................................................................. 29
`
`The Prosecution History Does Not Support The Board’s
`Construction ............................................................................. 30
`
`B.
`
`The Preamble Term “Abuse Deterrent” Is Limiting .......................... 32
`
`1.
`
`2.
`
`The Claim Language Demonstrates That “Abuse
`Deterrent” Is Limiting .............................................................. 33
`
`The SpeCification Confirms That “Abuse Deterrent” Is
`Limiting .................................................................................... 34
`
`II.
`
`PROPERLY CON STRUED. THE CLAIM WOULD NOT HAVE.
`
`BEEN OBVIOUS ......................................................................................... 36
`
`A.
`
`B.
`
`An Artisan Would Have Avoided Combining Magnesium
`Stearate And Oxycodone In A Hot—Melt—Extrusion Process ............. 37
`
`An Artisan Would Have Avoided Using PEO For An Extended-
`Release Oxycodone Product ............................................................... 39
`
`III.
`
`THE BOARD’S REASONS FOR FINDING THE CLAIM
`
`OBVIOUS LACK SUBSTANTIAL EVIDENCE ....................................... 42
`
`A.
`
`The Board Primarily Relied On Its Incorrect Claim
`Construction ....................................................................................... 42
`
`iv
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 6
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 6
`
`

`

`Case: 18-1285
`
`Document: 47
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`Page: 7
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`Filed: 07/02/2018
`
`TABLE OF CONTENTS
`
`(continued)
`
`B.
`
`The Board’s Reliance On McGinity In Its Alternative Analysis
`Lacks Substantial Evidence ................................................................ 43
`
`Page
`
`I.
`
`2.
`
`3.
`
`4.
`
`The Board’s Reliance On McGinity For Magnesium
`Stearate In The Heated Core Matrix Contradicts The
`
`Unanimous Agreement Of Both Sides’ Experts ......................44
`
`The Board Failed To Articulate Any Motivation To
`Combine Magnesium Stearate, PEO, And Oxycodone In
`A Hot-Melt Formulation .......................................................... 47
`
`The Board Had No Basis To Conclude That McGinity
`Resolved The Serious Problems With Unpredictability .......... 51
`
`The Board Erroneously Shifted The Burden Of’ Proof To
`Purdue ...................................................................................... 55
`
`C.
`
`The Board’s Assessment Of The Remaining Prior Art Lacks
`Substantial Evidence .......................................................................... 56
`
`1.
`
`An Artisan Would Not Have Been Motivated To
`
`Combine Joshi With McGinity (Grounds l & 2) .................... 57
`
`2.
`
`An Artisan Would Not Have Been Motivated To
`
`Combine Palermo With McGinity (Grounds 1 & 3) ............... 58
`
`3.
`
`Bastin Teaches Away From Using PEO In An Extended-
`Release Oxycodone Formulation (Ground 2) .......................... 60
`
`IV.
`
`THE COMMERCIAL SUCCESS OF OXYCONTIN® CONFIRMS
`
`THE NON-OBVIOUSNESS OF THE CLAIM ........................................... 62
`
`CONCLUSION ....................................................................................................... 66
`
`ADDENDUM .............................................................................................................
`
`v
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 7
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 7
`
`

`

`Casez18-1285
`
`Document: 47
`
`Page:8
`
`Filed: 07/02/2018
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`
`Allergan, Inc. v. Sandoz, Inc,
`796 F.3d 1293 (Fed. Cir. 2015) ..........................................................................43
`
`Boehringer Inge/hem: Vettnedt‘ca. Inc. v. Schering—Plough Corp.
`320 F.3d 1339 (Fed. Cir. 2003) .................................................................... 33, 35
`
`Catalina Marketing Int ’1, Inc. v. Coosavingscom. Inc. .
`289 F.3d 801 (Fed. Cir. 2002') ................................................................ 33, 34, 35
`
`(:7rmtc'1rk ("ommsn Inc. v. Harris ("or/7.,
`156 F.3d 1182 (Fed. Cir. 1998) .......................................................................... 30
`
`Cordis Corp. v. Medtronic Ave, Inc,
`511 F.3d 1157 (Fed. Cir. 2008) .......................................................................... 32
`
`Cuozzo Speed Techs., LLC‘ v. Lee,
`136 S. Ct. 2131 (2016) ........................................................................................ 22
`
`Deckers Corp. v. United States,
`532 F.3d 1312 (Fed. Cir. 2008) .................................................................... 31, 32
`
`Deere & (‘0. v. Bush Hog, LLC,
`703 F.3d 1349 (Fed. Cir. 2012) .............................................................. 33, 34, 35
`
`Eaton Corp. v. Roe/arc}! Int '1. Com,
`323 F.3d 1332 (Fed. Cir. 2003) .................................................................... 33, 34
`
`"
`Ecolochem, Inc. v. S. Cal. Ed. Co,
`227 F.3d 1361 (Fed. Cir. 2000) .................. . ....................................................... 63
`
`Grain Processing Corp. v. Am. Maize-Prods. (70.,
`840 F.2d 902 (Fed. Cir. 1988) ............................................................................ 49
`
`Icon Health & Fitness, Inc. v. Strava, Inc,
`849 F.3d 1034 (Fed. Cir. 2017.) ..................................... . ................................... 46
`
`In re Magnum Oil Tools Int ’1', Ltd,
`829 F.3d 1364 (Fed. Cir. 2016) .......................................................................... 55
`
`In re: ().\'_1A=(.‘ontin Antitrust Litigation,
`N0. 13-cv-3372, 2015 WI 11217239 (S.D.N.Y. Apr. 4, 2015) ................... 20, 21
`
`In re Power Integrations, Inc.,
`884 F.3d 1370 (Fed. Cir. 2018) .......................................................................... 44
`
`Vi
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 8
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 8
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page29
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`Filed: 07/02/2018
`
`TABLE OF AUTHORITIES
`
`(continued)
`
`Page(s)
`
`In re Yamamoto,
`740 F.2d 1569 (Fed. Cir. 1984) .......................................................................... 3O
`
`Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd.,
`821 F.3d 1359 (Fed. Cir. 2016) .......................................................................... 37
`
`KSR Int ’1 Co. v. Teleflex, Inc.,
`550 US. 398 (2007) ............................................................................................ 60
`
`Leo Pharm. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013) .................................................................... 50, 63
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1372 (Fed. Cir. 2012) .......................................................................... 63
`
`Pers. Web Techs., LLC v. Apple, Inc.,
`848 F.3d 987 (Fed. Cir. 2017) ................................................................ 36, 48, 49
`
`Polaris Indus., Inc v. Arctic Cat, Inc,
`882 F.3d 1056 (Fed. Cir. 2018) ........................................................22, 49, 63, 64
`
`Poly-America, L.P. v. GSE Lining Tech, Inc.,
`383 F.3d 1303 (Fed. Cir. 2004) .......................................................................... 33
`
`PPC Broadband, Inc. v. Corning Optical Commc ’ns RF, LLC,
`815 F.3d 747 (Fed. Cir. 2016) ............................................................................ 22
`
`Purdue Pharma L.P. v. Amneal Pharmaceuticals LLC,
`15-cv-1152 (D. Del.) ............................................................................................. 8
`
`Shinn Fu Co. 0fAm., Inc. v. Tire Hanger Corp,
`701 F. App’x 942 (Fed. Cir. 2017) ..................................................................... 37
`
`SightSound Techs., LLC v. Apple, Inc.,
`809 F.3d 1307 (Fed. Cir. 2015) .................................................................... 65, 66
`
`Straight Path IP Group, Inc. v. Sipnet EU SR. 0.,
`806 F.3d 1356 (Fed. Cir. 2015) .......................................................................... 22
`
`Warner—Lambert Co. v. Apotex Corp,
`316 F.3d 1348 (Fed. Cir. 2003) .......................................................................... 27
`
`Wi-Lan, Inc. v. Apple, Inc.,
`811 F.3d 455 (Fed. Cir. 2016) ............................................................................ 34
`
`Vii
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 9
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 9
`
`

`

`Casez18-1285
`
`Document: 47
`
`Page: 10
`
`Filed: 07/02/2018
`
`TABLE OF AUTHORITIES
`
`(continued)
`
`Page(s)
`
`STATUTES
`
`5 U.S.C. § 557 .......................................................................................................... 36
`
`5 U.S.C. § 706 .................................................................................................... 36, 48
`
`28 U.S.C. § 1295 ........................................................................................................ 1
`
`35 U.S.C. § 141 .......................................................................................................... 1
`
`35 U.S.C. § 142 .......................................................................................................... 1
`
`35 1.7.3.0 § 311 .......................................................................................................... 1
`
`35 L7.S.C. § 316 ........................................................................................................ 55
`
`35 L'.S.C. § 319 .......................................................................................................... 1
`
`OTHER AUTHORITIES
`
`37 C.F.R. § 90.3 ......................................................................................................... 1
`
`83 Fed. Reg. 21221 (May 9. 2018) .................................................................... 22, 26
`
`viii
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 10
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 10
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 11
`
`Filed: 07/02/2018
`
`TABLE OF ABBREVIATIONS
`
`Pharmaceutical Terms
`
`PEO
`
`PEG
`
`HME
`
`Purdue Patents
`
`’976 patent
`
`’8 88 patent
`
`Asserted Prior Art
`
`McGinity
`
`Joshi
`
`Palermo
`
`Polyethylene oxide
`
`Polyethylene glycol
`
`Hot-melt extrusion
`
`US. Patent No. 9,060,976 (Pharmaceutical
`Formulation Containing Gelling Agent)
`
`US. Patent No. 8,337,888 (Pharmaceutical
`Formulation Containing Gelling Agent)
`
`W0 97/493 84 (Hot-Melt Extrudable Pharmaceutical
`Dosage Form)
`
`US 2002/0187192 (Pharmaceutical Composition
`Which Reduces 0r Eliminates Drug Abuse Potential)
`
`WO 99/32120 (Method of Preventing Abuse of Opioid
`Dosage Forms)
`
`Bastin
`
`WO 95/20947 (Abuse Resistant Tablets)
`
`Handbook
`
`Handbook of Pharmaceutical Excipients (3d ed. 1999)
`
`PDR
`
`Physicians’ Desk Reference (53d ed. 1999)
`
`ix
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 11
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 11
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 12
`
`Filed: 07/02/2018
`
`STATEMENT OF RELATED CASES
`
`a. There has been no previous appeal from the same proceedings before the
`
`Patent Trial and Appeal Board.
`
`b. The patent at issue in this appeal (US. Patent No. 9,060,976) is asserted
`
`against the respective defendants in the following pending district court actions:
`
`0 Purdue Pharmu LP. er a]. r. Amneal Pharmaceuticals LLC,
`No. lS-cv—1152 (D. Del.) (consolidated with 15-cv-83l);
`
`0 Purdue Pharma L. P. et a]. v. Intellipharmaceulics In! ’1 Inc. et al.,
`No. 17-cv-392 (D. Del.);
`
`0 Purdue Pharma LP. et a]. v. Intellipharmaceutics Int ’1, Inc. et al.,
`No. l8-cv-404 (D. Del);
`
`0 Purdue Pharma LP. et al. v. Ascent Pharmaceuticals, Inc, No. 18-
`cv-083 (D. Del);
`
`0 Purdue Pharma L.P. et a]. v. Ascent Pharmaceuticals, Inc. No. 18-
`cv-855 (D. Del.)
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 12
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 12
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 13
`
`Filed: 07/02/2018
`
`STATEMENT OF JURISDICTION
`
`This is a consolidated appeal from two interpartes reviews before the Patent
`
`Trial and Appeal Board. The Board had jurisdiction under 35 U.S.C. § 311. This
`
`Court has jurisdiction under 35 U.S.C. §§ 141(0) & 319, and 28 U.S.C.
`
`§ 1295(a)(4)(A). The Board entered a final written decision in both cases on
`
`November 8, 2017. (Appxl, Appx45.) Appellants filed notices of appeal in both
`
`cases on December 4, 2017, within the time prescribed by 35 U.S.C. § 142 and 37
`
`CPR. § 90.3(a).
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 13
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 13
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 14
`
`Filed: 07/02/2018
`
`STATEMENT OF THE ISSUES
`
`The single claim of US. Patent No. 9,060,976 (“the ’976 patent”) covers a
`
`pharmaceutical formulation of abuse-deterrent, extended-release oxycodone. The
`
`formulation contains magnesium stearate and oxycodone, plus a gelling agent that
`
`swells when the tablet is tampered with, creating a gunky mass that is difficult to
`
`snort or inject. The issues presented are:
`
`l .
`
`Did the Board err by construing the term “the core matrix is heated"
`
`not to require heating of the core matrix, contrary to the plain language of the
`
`claim and all expert opinion in the proceedings?
`
`2.
`
`Did the Board err by construing the language “abuse deterrent” in
`
`the ’976 claim’s preamble as not limiting the claim, where “abuse deterrent”
`
`provides antecedent basis for a subsequent claim term and recites a fundamental
`
`characteristic of the claim?
`
`3.
`
`Did the Board err by concluding that the ’976 claim is unpatentable as
`
`obvious, notwithstanding that experts for both sides agreed that the prior art taught
`
`away from blending and heating magnesium stearate and oxycodone as claimed?
`
`STATEMENT OF THE CASE
`
`A.
`
`Preliminary Statement
`
`OxyContin® is a powerful, extended-release, pain medication sold by
`
`Appellants (collectively, “Purdue”). Oxycodone, the active ingredient in
`
`OxyContin®, is a potent and addictive opioid. Purdue researched, developed, and
`
`2
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 14
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 14
`
`

`

`Case: 18-1285
`
`Document: 47
`
`Page: 15
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`ultimately patented several innovative formulations so that OxyContin® would be
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`less prone to abuse.
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`This appeal is about one of those abuse-deterrent, extended—release
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`formulations, disclosed in the ’976 patent. Its sole claim centers on what the claim
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`calls a “core matrix,” which comprises “a blended mixture of” three components—
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`PEO, or polyethylene oxide; magnesium stearate; and oxycodone. That three-
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`component (or more) “core matrix is heated to melt at least a portion of the PEO
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`included in the core matrix.”- The resulting “abuse deterrent dosage form,”
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`principally because of the melted PEO, swells and creates a gunky mass that is
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`difficult for an abuser to snort or inject.
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`The Board, however, viewed this advancement as obvious and unpatentable.
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`It used proceedings from a different case in. a district court, involving a different
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`patent with different claim language, and different prior art asserted against it, as at
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`least informative, if not conclusive, on the question of obviousness.
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`Then, despite the claim’s definition of “a core matrix” as including all three
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`recited components, the Board held that the requirement that “the core matrix is
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`heated” can be satisfied where “the heating step ... occur[s] before the magnesium
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`stearate is included,” thereby allowing the Board to disregard a critical aspect of
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`the claim distinguishing it from the prior art—a conclusion reached on the basis of
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`PGR2018-00048
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`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 15
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 15
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`Case: 18-1285
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`Document: 47
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`Page: 16
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`Filed: 07/02/2018
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`bare attorney argument, in the face of unanimous expert testimony, and contrary to
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`basic tenets of claim interpretation.
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`The Board also concluded that “extended release abuse deterrent dosage
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`form” was only a preamble term, and so the claim does not require actual abuse
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`deterrence. This conclusion was also contrary to both sides’ experts, and ignored
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`that the body of the claim, which referred to “the dosage form,” required the
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`preamble to give antecedent basis for these references, such that the preamble gave
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`life and vitality to the claim as a whole.
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`Finally, in an alternative holding, the Board concluded that McGinity, the
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`principal prior-art reference used by the Board (and common to all three asserted
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`grounds of obviousness) suggests blending magnesium stearate with oxycodone in
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`its hot-melt-extrusion, or “HME,” process. This conclusion was also contrary to
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`the testimony of both sides’ experts, yet the Board adopted it based solely on the
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`musings of Petitioner’s lawyer during oral argument.
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`The Board did not follow the law. Reversal, or at minimum remand, is
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`required.
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`B.
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`Purdue Develops A Family Of Patented Abuse—Deterrent Forms
`Of Oxycodone
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`Opioids like oxycodone provide life-changing pain relief to millions of
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`people. (Appx4030, Appx2329.) Despite this important therapeutic effect,
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`PGR2018-00048
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`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 16
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 16
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`Case: 18-1285
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`Document: 47
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`Page: 17
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`Filed: 07/02/2018
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`oxycodone is prone to abuse, and particularly, as the industry came to learn, in
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`extended—release formulations.
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`OxyContin® is an extended-release dosage form of oxycodone sold by
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`Purdue. Designed to treat severe pain requiring around-the-clock treatment,
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`OxyContin® delivers a large dose of oxycodone slowly over time. (Appx4078-
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`4079.) Though the extended-release feature is remarkably good at treating pain, it
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`must be carefully controlled. (Appx4038-4040.) Releasing drug too fast could
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`lead to overdose; too slow could lead to debilitating breakthrough pain. Designing
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`an extended-release oxycodone formulation requires precision and predictability.
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`(Appx4038-4040.)
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`Aside from the capacity to treat pain, OxyContin®’s extended-release
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`properties initially appeared less susceptible to abuse. That is what Purdue and the
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`FDA both believed in 1996, when Purdue originally introduced OxyContin®.
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`(Appx4097.) By 2000, however, it became apparent that people had discovered
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`ways to abuse OxyContin®. (Appx4097.) Seeking an instant euphoria, abusers
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`would crush the extended-release tablet, reducing it to an immediate-release
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`powder, and then either snort the powder or inject it after adding water and
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`drawing it into a syringe. (Appx4097.) The consequences ofthat abuse—-
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`addiction, overdose, and deathwwere devastating.
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`PGR2018-00048
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`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 17
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 17
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`Case: 18-1285
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`Document: 47
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`Page: 18
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`Filed: 07/02/2018
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`Purdue searched hard for a solution to the abuse problem. Over the next
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`several years, through a costly and time-consuming project called Opioid X,
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`Purdue spent untold hours and invested millions of dollars attempting to design a
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`tamper~resistant, extended—release dosage of oxycodone. (Appx4097.) This wide-
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`ranging and comprehensive program placed Purdue at the forefront of a nascent
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`field. (Appx4082.) Purdue’s goal was to create an abuse-deterrent product with
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`the identical extended-release properties of the original OxyContin®. (Appx4100.)
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`One early idea Purdue scientists explored was to combine oxycodone with
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`an opioid antagonistwthe “chemical approach." (Appx4098.) The goal was for
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`the antagonist to have no effect under normal use, but to release and counteract the
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`oxycodone if an abuser tampers with the product. (Appx4098.) The chemical
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`approach did not lead to a reformulated OxyContin® product.
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`Purdue scientists also brainstormed through a range of additives that would
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`physically modify the dosage form-the “physical approach.” (Appx4099.) These
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`additives included bittering agents, irritants, dyes, and gelling agents. All of these
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`additives would deter either intravenous or nasal abuse, such as by irritating or
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`discolon'ng the nasal passages, or physically interfering with the ability to snort or
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`inject the drug. Purdue evaluated many other options as well. (Appx4099.) The
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`Opioid X project ultimately led to families of patents claiming abuse-deterrent
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`formulations of oxycodone, including the '976 patent.
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`PGR2018-00048
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`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 18
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 18
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`Case: 18-1285
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`Document: 47
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`Page: 19
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`Filed: 07/02/2018
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`The Opioid X project also led to reformulated OxyContin®. The new
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`OxyContin® uses a gelling agent—PEO—that gels when moistened, making it
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`difficult for abusers to snort or inject the dosage form. Released in 2010, new
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`OxyContin® has been highly successful—both in overall commercial success and
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`in deterring abuse. (Appx2336.) OxyContin® sales exceeded $2 billion annually
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`from 2010 to 2016. (Appx2336.) Abuse of 0xyContin® significantly declined
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`after Purdue introduced the reformulated, abused-deterrent product. (Appx4105.)
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`C.
`
`The ’976 Patent Combines Magnesium Stearate And PEO In An
`Abuse-Deterrent, Extended-Release Dosage Form Of Oxycodone
`
`The ’976 patent covers abuse-deterrent, extended-release oxycodone
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`formulations made by melting a blended mixture of PEO, magnesium stearate, and
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`oxycodone. This blended mixture is called a “core matrix.” (Appx‘204.) The
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`single claim of the ’976 patent (Appx204) recites as follows:
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`1. An extended release abuse deterrent dosage form comprising:
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`a. a core matrix comprising a blended mixture of:
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`(a) PEO having a molecular weight of from about 300,000 daltons
`to about 5,000,000 daltons;
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`(b) magnesium stearate; and
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`(c) oxycodone or a pharmaceutically acceptable salt thereof;
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`wherein the core matrix is heated to melt at least a portion of the
`PEO included in the core matrix during preparation of the dosage
`form; and
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`b. PEG applied onto the core matrix;
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`wherein the dosage form provides extended release of the drug.
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`PGR2018-00048
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`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 19
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 19
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`Casez18-1285
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`Document: 47
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`Page: 20
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`Filed: 07/02/2018
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`The specification defines PEO as a “gelling agent,” which is one of several
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`types of “aversive agents” suitable for abuse deterrence. (Appx186, 4: 12-14;
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`Appx187, 6:45-63.) It defines “gelling agent” as “a compound or composition
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`used to impart gel-like or thickening quality to a tampered dosage form upon the
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`addition of moisture or liquid.” (Appx187, 5:18-21.) Purdue applied for the patent
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`on December 24, 20} 2, the patent issued on June 23, 2015, and its effective filing
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`date is August 6, 2001 . (Appx18].)
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`D.
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`Amneal Petitions For Inter Partes Review
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`Amneal Pharmaceuticals sought to market a generic copy of reformulated
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`OxyContin®. To obtain regulatory approval before expiration of the ’976 patent,
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`Amneal certified to the F DA an allegation that the ’976 patent is invalid,
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`unenforceable, or would not be infringed by Amneal’s generic drug. Based on
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`Amneal’s application and certifications, Purdue filed Hatch-Waxman litigation
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`against Amneal asserting several patents, including the ’976 patent. See Purdue
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`Pharma L.P. v. Amneal Pharmaceuticals LLC, lS-cv-1152 (D. Del.) (consolidated
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`cases). Thereafier, Amneal filed two petitions for inrerpartes review of the ’976
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`claim. (Appx109, Appx9002.) Amneal’s petitions raised a total of four grounds of
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`unpatentability, including one ground of anticipation (based on Amneal’s
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`insistence that the ‘976 patent should have a priority date of 2012, rather than
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`2001) and three obviousness grounds. (Appx121, Appx9013—9014.) The Board
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`PGR2018-00048
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`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 20
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 20
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`Case: 18-1285
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`Document: 47
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`Page: 21
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`Filed: 07/02/2018
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`declined to institute review on the anticipation ground, but instituted review on the
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`three obviousness grounds.
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`E.
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`The Asserted Prior Art
`
`Amneal asserted the following combinations of prior art:
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`1. McGinity (WO 97/49384) (Appx498),
`Joshi (US 2002/0187192) (Appx527),
`Palermo ONO 99/32120) (Appx446)=
`(IPR2016-01027);
`
`2. McGinity (Appx498),
`Joshi (Appx527),
`Bastin (W0 95/20947) (Appx533),
`PDR (Appx572),
`(IPR2016-0 1028);
`
`3. McGinity (Appx498),
`Palermo (Appx446),
`Handbook (Appx493),
`(IPR2016-01028).
`
`McGinity is common to all three grounds, and is the reference on which the
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`Board largely relied. A short description of each reference follows.
`
`1. McGinity (1997): Extended-Release Drug Formulation
`Using Hot-Melt Extrusion And PEO
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`McGinity does not address drug abuse. (Appxl468.) Rather, McGinity is
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`directed to preparing extended-release formulations by a particular means: “hot-
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`melt extrusion of mixtures containing high molecular weight PEG and a
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`therapeutic compound.” (AppxSOO, 1:10-11.) Hot-melt extrusion is conducted in
`
`PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 21
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 21
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`Case: 18-1285
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`Document: 4