Case: 18-1285
`
`Document:47
`
`Page:1
`
`Filed: 07/02/2018
`
`Nos. 18-1285, 18-1286
`
`
`Gnited States Court of Appeals
`for the Federal Circuit
`
`
`
`PURDUE PHARMA L.P.,
`PF, LABORATORIES,INC.,
`PURDUE PHARMACEUTICALSL.P.,
`
`_
`
`Appellants,
`
`V.
`
`ANDREI IANCU, Director, U.S. Patent and Trademark Office,
`
`Intervenor.
`
`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. NORMILE
`GASPER J. LAROSA
`JONES DAY
`250 Vesey Street
`New York, NY 10281
`(212) 326-3939
`jynormile@jonesday.com
`
`GREGORYA. CASTANIAS
`JENNIFER L.. SWIZE
`ROBERT STANDER
`JONES DAY
`51 Louisiana Avenue, N.W.
`Washington, D.C. 20001
`(202) 879-3939
`gcastanias@jonesday.com
`
`Counsel for Appellants
`
` PGR2018-00048
`
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 1
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 1
`
`

`

`Case: 18-1285
`
`Document:47
`
`Page:2
`
`Filed: 07/02/2018
`
`U.S. Patent No. 9,060,976 Claim 1
`
`1. An extended release abuse deterrent dosage form comprising:
`a. a core matrix comprising a blended mixtureof:
`(a) PEO having a molecular weight of from about 300,000 daltons to
`about 5,000,000 daltons:
`
`(b) magnesium stearate: and
`(c) oxycodoneor 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 extendedrelease of the drug.
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 2
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 2
`
`

`

`Case: 18-1285
`
`Document:47
`
`Page:3
`
`Filed: 07/02/2018
`
`UNITED STATES COURT OF APPEALS FOR THE FEDERAL
`CIRCUIT
`
`Purdue Pharma L.P. et al. v. lancu
`
`Case Nos. 18-1285: -1286
`
`CERTIFICATE OF INTEREST
`
`Counsel for the:
`[_] (petitioner)Ex](appellants) [_] (respondent) [_] (appellee) ([]
`(amicus) [_] (nameof party)
`Purdue Pharma L.P.: The P.F. Laboratories, Inc.; and Purdue
`Pharmaceuticals L.P.
`
`certifies the following:
`3. Parent corporations and
`1. Full Nameof Party
`2. Nameof party in
`
`Represented by me interest represented by|publicly held companies
`meis:
`that own 10% or more of
`stock in the party
`
`Purdue PharmaL.P.
`
`Purdue Pharma L.P
`
`The P.F. Laboratories
`Inc.
`
`The P.F. Laboratories,
`Inc.
`
`None
`
`Purdue Pharmaceuticals|Purdue Pharmaceuticals
`L.P.
`L.P.
`
`
`
`4. The namesofall law firms and the partners or associates that appeared
`for the party or amicus now represented by mein thetrial court or agency or are
`expected to appear in this court (and whohavenotor 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; Lisamarie LoGiudice
`
`5. The title and numberof any case known to counsel to be pendingin 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
`issue in this appeal
`is asserted against
`the respective
`defendantsin:
`
`Purdue Pharma L.P. et al. v. Amneal Pharmaceuticals LLC, No. 15-cv-1152
`(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 al. v. Intellipharmaceutics Int’l, Inc. et al., No. 17-
`cv-392 (D. Del.);
`Purdue Pharma L.P. et al. v. Intellipharmaceutics Int'l, Inc. et al., No. 18-
`cv-404 (D. Del.);
`
`Purdue Pharma L.P. et al. v. Ascent Pharmaceuticals, Inc., No. 18-cv-083
`(D. Del.):
`
`ec: Counsel of record via CM/ECF
`
`(D. Del.).
`
`July 2, 2018
`Date
`
`/s/ Gregory A. Castanias
`Signature of counsel
`
`Gregory 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.........ceeccececceccescesecoteeeencnseecsececesesvaceseeceneseeveeneaseneeseesvi
`
`TABLE OF ABBREVIATIONS....00.....:.ccesceseseeeseseeeeseeeeeeeceeseescenesesesneneeaeenseasenseseix
`
`STATEMENT OF RELATED CASES0000... ccseeeeeeesssecssetsesneaceaseaccnsesaeeesesenaesereres X
`
`STATEMENTOF JURISDICTION.....0.....ccccecesceseecesceseseeeasseceeenceceeesneeeenateneeeeeeees 1
`
`STATEMENTOF THE ISSUES. ..000...0..cccccececcceceeeceecteceeeeeeececesneeeeeececsneseeeseseeeaseees 2
`
`STATEMENTOF THE CASE. ..........ccccccccescecceeceeceeceececeeeeeseeeeceeneceanereesaeteaesaeeeteees 2
`
`A.
`B.
`
`C.
`
`D.
`
`E.
`
`Preliminary Statement .0......0...eccceeceececeeeeseeeeeeeneeseeecececeeeeeeseeeeeeeeaees2
`Purdue Develops A Family Of Patented Abuse-Deterrent Forms
`©) @>45/0101s(0)1 4
`The ’976 Patent Combines Magnesium Stearate And PEO In
`An Abuse-Deterrent, Extended-Release Dosage Form Of
`OXYCODONE... cece eccnceeteecceccetaeecenndune nate cece Sbeeceedadaceaeddecdeeddenescesdeersonaall
` Amneal Petitions For Inter Partes Review .........0....cccccccecccceesseseeseceeees 8
`
`The Asserted Prior Art ..........ccccccccceessecssceecesececeesseesecseaeesecueeeseseeeneess 9
`
`1.|McGinity (1997): Extended-Release Drug Formulation
`Using Hot-Melt Extrusion And PEO ........0........c:cececseseeseeseeees9
`Joshi (2001): Drug Composition Containing A Stimulant
`And PEO As An Abuse-Deterrent Gel.......0..0000.0.ccceeeceeeeeeeee 11
`
`2.
`
`3.
`
`4.
`
`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...cccssssecseeseetsesncesesssessseesensensens 13
`5.|Handbook (1999): General Pharmaceutical Reference........... 13
`6.
`|PDR(1999): General Pharmaceutical Reference.................... 15
`Amneal ChangesIts Experts And Positions During The /nter
`Partes Review Proceedings...............-.ceccsceccecesseceececeeeeceeeeeeeseseeeseeeees 15
`G.—_The Board’s Decisions 00.0.0...eee cceeceeeeeeseeseeceesesceeeeenseseceesesaeeceuees 16
`
`F.
`
`SUMMARYOF THE ARGUMENT 02... .-ccccceceecec cece eceeceeecceesceaceaeeneeseesenenees24
`
`iil
`
`-PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 5
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 5
`
`

`

`Case: 18-1285
`
`Document:47
`
`Page:6
`
`Filed: 07/02/2018
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`STANDARD OF REVIEW.........c:cccccceccsceescosessesceseeecaceeceeecnecaeeneesesenaesnaeesesneerenes 24
`
`ARGUMENT nooo cc cecccsccc ces cecccsceecceeeceecseeseeeeuaesecaceneaaeseeeerascaeeseeaesncncecassseeeeneseees 25
`
`I.
`
`THE BOARD ERRONEOUSLY CONSTRUED THE CLAIM................. 25
`
`A.
`
`MagnesiumStearate Is Part Of The Core Matrix That “Is
`Heated” oo. ccecccesceessecececececeeeseseneceesenessceceecanecseneceneceeceeaeeeeceneeaneenes 26
`
`1.
`
`2.
`
`3.
`
`4.
`
`The Claim Language Requires MagnesiumStearate In
`The “Core Matrix” WhenHeat Is Applied .........0.0000000. 26
`The Experts Agreed That “The Core Matrix Is Heated”
`Means That Magnesium Stearate Must Be In The “Core
`Matra?a. gc ege ca cnn heise catelvdee adgellecseeeagh seeded ence dt esl peesaeGtevetenteeas 27
`
`The Specification Does Not Support The Board’s
`COMSEIUCTION 20... eeccecccteescenececeeseecseeseceecessneesseecaeeesssenceeseeeeees 29
`
`The Prosecution History Does Not Support The Board’s
`COmSHUCTION ooo. cece cee ceceneenecceeeneeeansesueecsaeessesenseeneeceeesees 30
`
`B.
`
`The Preamble Term “Abuse Deterrent” Is Limiting.......0.00000.000.0.. 32
`1.
`The Claim Language Demonstrates That “Abuse
`Deterrent” Is Limiting... eee ccceecceesceecceeeseeneeseseceeeeneeeness 33
`The Specification Confirms That “Abuse Deterrent’ Is
`113916!aee re 34
`
`2.
`
`Il.
`
`PROPERLY CONSTRUED, THE CLAIM WOULD NOT HAVE
`BEEN OBVIOUS 0.oooooco cece cecceccceecenceceececceeeeeeceeceeecaeesseucescecsecessnensceeesesaces 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..............cccccccccccescesecseceeeeeecseeseseeseeseentene 39
`
`lil.
`
`THE BOARD’S REASONSFOR FINDING THE CLAIM
`OBVIOUS LACK SUBSTANTIAL EVIDENCE....00..ecccceeecceteeceeeeseeeeees 42
`
`A.—The Board Primarily Relied On Its Incorrect Claim
`COMSHIUCTION ooo... eee ee ceceececeececceeeseeesseeceeeaeeeecaceeecaceseeeeeeaecaeseeaeentaes42
`
`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
`
`Page:7
`
`Filed: 07/02/2018
`
`TABLE OF CONTENTS
`(continued)
`
`B.
`
`The Board’s Reliance On McGinity In Its Alternative Analysis
`Lacks Substantial Evidence. ................c::ccceccesccceeeeeeeeeeeeeeeeneesecesseeseens43
`
`Page
`
`1.
`
`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 OxycodoneIn
`A Hot-Melt Formulation ...........0.....2.ccceccesceseecceeeeeeeceeeeeseeeeees 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
`PUIG on one apap ends en cnn dhe stb Se ss Giants Dane net anne dha cafe edad enensenae 55
`
`C.
`
`The Board’s Assessment Of The Remaining Prior Art Lacks
`Substantial EVIdence 0.0.0... ccceccsccecenseecscecesnseeeceneeecsseeeessneneceenes 56
`
`1.
`
`2.
`
`An Artisan Would Not Have Been Motivated To
`Combine Joshi With McGinity (Grounds 1 & 2) .0..00.00.022.... 57
`
`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)...ese 60
`THE COMMERCIAL SUCCESS OF OXYCONTIN® CONFIRMS
`THE NON-OBVIOUSNESSOF THE CLAIM. ...0....cccccccccsceeseteeeseseeesneees 62
`
`IV.
`
`CONCLUSION...... cc cccccsecssecsessecsresnecsrccnecsessessersnesacencesnsacsstecsesenceceseusenssseesseeneesnseas 66
`
`ADDENDUM........ccccccssccsscssceseessesseesersessseccasenseaseneseaesaceaesatsaecaaesaaeseeaaseneeeasenssaeeses
`
`Vv
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 7
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 7
`
`

`

`Case: 18-1285
`
`Document:47
`
`Page:8
`
`Filed: 07/02/2018
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`
`Allergan, Ine. v. Sandoz, Inc.,
`796 F.3d 1293 (Fed. Cir. 2015) occ eccccescssescceseeeseceeeseeseseeseseneneeeseesseatseeees43
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp.,
`320 F.3d 1339 (Fed. Cir, 2003) oo... ccc ceccecseecseeeeceseeeeeeeceaeeneecnaeeseseneeseenes 33,35
`
`Catalina Marketing Int'l, Inc. v. Coosavings.com, Inc.,
`289 F.3d 801 (Fed. Cir, 2002) 0.0... cccccsseessssesteseseeseecsessaeeneesreneseaeens33, 34, 35
`
`Comark Comms., Inc. v. Harris Corp.,
`156 F.3d 1182 (Fed. Cir, 1998) oo... ccccecec cece cecceeenececeeeeeneeeeeeeeeaeseeeeeeees30
`
`Cordis Corp. v. MedtronicAve, Inc.,
`511 F.3d 1157 (Fed. Cir. 2008) 22... .ccccccecccceecccceeccecceceeeceeneceseeesceseeseeesttetenenteees 32
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016)oc ccceecccsessesesseseesevseceesseceesseeeesaesessasersaseesseesesess22
`Deckers Corp. v. United States,
`$32 F.3d 1312 (Fed. Cir. 2008) ooo... cccccccececeececcnceceeeeceneceeecnecseeenseeseeees31, 32
`Deere & Co. v. Bush Hog, LLC,
`703 F.3d 1349 (Fed. Cir. 2012) ooo... ccecceeccesececeeceesceceseseeeseeseenseess33, 34, 35
`
`Eaton Corp. v. Rockwell Int'l. Corp.,
`323 F.3d 1332 (Fed. Cir. 2003) ooo... eecceccceccceseeeeeecececeeceeeseeeesnaeceeeseetenteees 33, 34
`Ecolochem, Inc. v. §. Cal. Ed. Co.,
`.
`227 F.3d 1361 (Fed. Cir. 2000) ow. Bi cevscedicotaed bicdn acco eecdeednionet eres diaeie ses deni 63
`Grain Processing Corp. v. Am. Maize-Prods. Co.,
`840 F.2d 902 (Fed. Cir, 1988) ooo... ccceecsceseccceeeeseeseeeeeeeaceceeeseeeaeeeeatsnesenseenaee49
`
`Icon Health & Fitness, Inc. v. Strava, Inc.,
`849 F.3d 1034 (Fed. Cir. 2017.) oo... cece eeeeeeetees ve sseesuceceecaeeaeseevaeeeceeeeeees46
`
`In re Magnum Oil ToolsInt'l, Ltd.,
`829 F.3d 1364 (Fed. Cir. 2016) o.oo. cece ceeecene cence eesceeneeeecaaeeeseeseeseeeseens 55
`
`In re: OxyContin Antitrust Litigation,
`No. 13-cv-3372, 2015 WL 11217239 (S.D.N.Y. Apr. 4, 2015)... 20, 21
`In re Power Integrations, Inc.,
`884 F.3d 1370 (Fed. Cir, 2018) ooo ce ccecsecsceeseeeeceeeeneeseesseeaeeeseeesaseeesaeeeneaees44
`
`vl
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 8
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 8
`
`

`

`
`
`Case: 18-1285 Page:9_Filed: 07/02/2018Document:47
`
`
`
`TABLE OF AUTHORITIES
`(continued)
`
`Page(s)
`
`In re Yamamoto,
`740 F.2d 1569 (Fed. Cir, 1984) occ cccsececesesseseeeenseseesenseessenecsensetetseseeseeenes 30
`Intelligent Bio-Sys., Inc. v. Hlumina Cambridge Lid.,
`821 F.3d 1359 (Fed. Cir. 2016) .2.....c.cccceecccccceceeccecceeeesececeeeeeeceeceseceeeeaeeeeeeeaneaees37
`KSR Int'l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007)...eeeeccee cece scesceeeeeceeeeeceaceececeeesseseeuseasseeeeeeneesearaceesenseeeseees 60
`Leo Pharm. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013) ooo. ccc ceeecccceeecereesccececeeceeeeneeeeceuseeseaeeenees 50, 63
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1372 (Fed. Cir, 2012) o.....cccececceecceecssesecsceseeseeeeeececeseceeeeeeateaesaeeaeeeeesees 63
`Pers. Web Techs., LLC v. Apple, Inc.,
`848 F.3d 987 (Fed. Cir. 2017) oo... cceececcecceeeceeeeeeeeceecenececsceeeseeneeeeees36, 48, 49
`
`Polaris Indus., Inc v. Arctic Cat, Inc.,
`882 F.3d 1056 (Fed. Cir. 2018) o.oo... cee cecceeceeceteeeceeeeeseeeeceeeeeeeeeeeees22, 49, 63, 64
`
`Poly-America, L.P. v. GSE Lining Tech., Inc.,
`383 F.3d 1303 (Fed. Cir. 2004) o.oo... cececececeececeeseeeeeceseseeaneseeeeeeseaecaeeseneeseeeees 33
`PPC Broadband, Inc. v. Corning Optical Commc’nsRF, LLC,
`S15 F.3d 747 (Fed. Cir, 2016) ccsssicoscuss sssceiessctentsscssthacesceett eessteatecast setvedtisevededs 22
`Purdue Pharma L.P. v. Amneal Pharmaceuticals LLC,
`15-cV-1152 (D,. Del.) ccc ccceeccsseceseceeaaecneeseseeeeeeeenencueeeneesereseaseenseetennereuaes 8
`Shinn Fu Co. ofAm., Inc. v. Tire Hanger Corp.,
`701 F. App’x 942 (Fed. Cir. 2017) oo. cccccccceeeeseseseseeseeseeceaeseeeeseteteecesesneenenees 37
`SightSound Techs., LLC v. Apple, Inc.,
`809 F.3d 1307 (Fed. Cir. 2015) 202... ..ccceeccecceecceceecceeeeeeeeceeeeeceecneeceaeeesneneeanees 65, 66
`Straight Path IP Group, Inc. v. Sipnet EU S.R.O.,
`806 F.3d 1356 (Fed. Cir. 2015) ooo... cece cece ee ceeeceeceeeeeeeececececenecnseeeceeeeseeneeeaees 22
`Warner—Lambert Co. v. Apotex Corp.,
`316 F.3d 1348 (Fed. Cir, 2003) on. eee eeescccseeccenceseesenereeesesaeseeeneeesseeseseaeenees 27
`Wi-Lan, Inc. v. Apple, Inc.,
`811 F.3d 455 (Fed. Cir, 2016) one ceeeseseceeeeeceeesseneseeseeesacsessesesseseetenaeas 34
`
`vii
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 9
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 9
`
`

`

`Case: 18-1285
`
`Document:47
`
`Page: 10
`
`Filed: 07/02/2018
`
`TABLE OF AUTHORITIES
`(continued)
`
`Page(s)
`
`STATUTES
`
`S US... § S57 ooo ccccccccsccccsccnscceseeeesccencscesenssessecessssecesesceueceessecesesecatecseeeaeeeeenesecssees 36
`
`5 U.S.C. § 706 ooo ce ccccc cece cesecasessennscossssscenseenseseecrsessaeeeesecnseerenaeessenesseeseenees 36, 48
`
`28 U.S.C. § 1295 occ cccccsscsscesseessessseescesecsseeceseuscusneceecsenseseersaeeseneeseaesesesateneeeaeees 1
`
`BS U.S.C. § VAD cece cece ccc cnecenseseeeseecaeeceecesseeseensececenstensesisesssceeeeseenseeseeeas 1
`
`BY WSC § WAZ. sce cesta csecceseceeeeseceeshe me coediaes steeenesatadteeehbeseaceescesdesdzenaeterensneaésthasiSBerees 1
`
`35 U.S.C. § Bdnec cecccecccensecesecenscneessessasscaeseeessaeeecenseceaeecssessecssessaseeesseeneecesenes 1
`
`35 U.S.C. § 316 ccc ccc cccccccececcesenescossassesessessessesesaceceaserseceasesseseseeaceseeseensenaee 55
`
`BS: WLG.G§: B19 s,s cciens sdessecasestcdescesadesedscseceenerensessacchhanesenssadencablesBectacarteacesneseasseazeasens I
`
`OTHER AUTHORITIES
`
`37 CER. § 90.3 ccc ccc cscs cecseecseeneecaecneccceesseesessseesaeecnsseaseeeeceesssseeaeenseneecneceeens 1
`
`83 Fed. Reg. 21221 (May9, 2018) ooo. ccccescesseeceeseaeeseeeeeenseseeseaseneeens22, 26
`
`viil
`
`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
`
`888 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)
`
`U.S. Patent No. 8,337,888 (Pharmaceutical
`Formulation Containing Gelling Agent)
`
`WO 97/49384 (Hot-Melt Extrudable Pharmaceutical
`Dosage Form)
`
`US 2002/0187192 (Pharmaceutical Composition
`Which Reduces Or Eliminates Drug Abuse Potential)
`
`WO99/32120 (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)
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 11
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 11
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`

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`Case: 18-1285
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`Document:47
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`Page:12
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`Filed: 07/02/2018
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`STATEMENT OF RELATED CASES
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`a. There has been no previous appeal from the same proceedings before the
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`Patent Trial and Appeal Board.
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`b. The patent at issue in this appeal (U.S. Patent No. 9,060,976) is asserted
`
`against the respective defendants in the following pendingdistrict court actions:
`
`e Purdue Pharma L.P. et al. vy. Amneal Pharmaceuticals LLC,
`No. 15-cv-1152 (D. Del.) (consolidated with 15-cv-831);
`
`e Purdue Pharma L.P. et al. v. Intellipharmaceutics Int'l Inc. et al.,
`No. 17-cv-392 (D. Del.);
`
`e Purdue Pharma L.P. et al. v. Intellipharmaceutics Int’l, Inc.et al.,
`No. 18-cv-404 (D. Del.);
`
`e Purdue Pharma L.P. et al. v. Ascent Pharmaceuticals, Inc., No. 18-
`cv-083 (D. Del.);
`
`e Purdue Pharma L.P. et al. v. Ascent Pharmaceuticals, Inc., No. 18-
`cv-855 (D. Del.).
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 12
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 12
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`

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`Case: 18-1285
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`Document:47
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`Page: 13
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`Filed: 07/02/2018
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`STATEMENT OF JURISDICTION
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`This is a consolidated appeal from twointerpartes reviews before the Patent
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`Trial and Appeal Board. The Board hadjurisdiction under 35 U.S.C. § 311. This
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`Court has jurisdiction under 35 U.S.C. §§ 141(c) & 319, and 28 U.S.C.
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`§ 1295(a)(4)(A). The Board entered a final written decision in both cases on
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`November8, 2017. (Appx1, Appx45.) Appellants filed notices of appeal in both
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`cases on December 4, 2017, within the time prescribed by 35 U.S.C. § 142 and 37
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`C.F.R. § 90.3(a).
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 13
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 13
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`

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`Case: 18-1285
`
`Document:47
`
`Page: 14
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`Filed: 07/02/2018
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`STATEMENTOF THE ISSUES
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`The single claim of U.S. Patent No. 9,060,976 (‘the "976 patent”) covers a
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`pharmaceutical formulation of abuse-deterrent, extended-release oxycodone. The
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`formulation contains magnesium stearate and oxycodone,plus a gelling agent that
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`swells when the tablet is tampered with, creating a gunkymassthatis difficult to
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`snort or inject. The issues presented are:
`
`1.
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`Did the Board err by construing the term “the core matrix is heated”
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`not to require heating of the core matrix, contrary to the plain language ofthe
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`claimandall expert opinion in the proceedings?
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`2.
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`Did the Board err by construing the language “abuse deterrent”in
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`the 976 claim’s preamble as not limiting the claim, where “abuse deterrent”
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`provides antecedent basis for a subsequent claim termandrecites a fundamental
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`characteristic of the claim?
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`3.
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`Did the Board err by concludingthat the *976 claimis unpatentable as
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`obvious, notwithstanding that experts for both sides agreed that the prior art taught
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`away from blending and heating magnesium stearate and oxycodoneas claimed?
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`STATEMENT OF THE CASE
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`A.
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`Preliminary Statement
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`OxyContin® is a powerful, extended-release, pain medication sold by
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`Appellants (collectively, “Purdue”). Oxycodone,the active ingredient in
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`OxyContin®,is a potent and addictive opioid. Purdue researched, developed, and
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`2
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 14
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 14
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`

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`Case: 18-1285
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`Document:47
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`Page: 15
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`Filed: 07/02/2018
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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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`includedin the core matrix.” The resulting “abuse deterrent dosage form,”
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`principally because ofthe melted PEO, swells and creates a gunky massthat 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 ina district court, involving a different
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`patent with different claim language, and different prior art asserted againstit, 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 includingall three
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`recited components, the Board held that the requirementthat “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 onthe basis of
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`PGR2018-00048
`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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`

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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 attomey argument, in the face of unanimous expert testimony, and contraryto
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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, whichreferred 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 commonto 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 wasalso contrary to
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`the testimony of both sides’ experts, yet the Board adoptedit based solely on the
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`musingsof 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.
`
`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
`
`people. (Appx4030, Appx2329.) Despite this important therapeutic effect,
`
`PGR2018-00048
`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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`

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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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`oxycodoneis prone to abuse, and particularly, as the industry cameto learn,in
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`extended-release formulations.
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`OxyContin® is an extended-release dosage form of oxycodonesold by
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`Purdue. Designedto 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 goodattreating 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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`FDAboth believed in 1996, when Purdueoriginally 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 powderorinject it after adding water and
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`drawingit into a syringe. (Appx4097.) The consequences ofthat abuse—
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`addiction, overdose, and death--were devastating.
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`PGR2018-00048
`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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`

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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 Purdueat the forefront of a nascent
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`field. (Appx4082.) Purdue’s goal wasto create an abuse-deterrent product with
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`the identical extended-release properties of the onginal OxyContin®. (Appx4100.)
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`Oneearly idea Purduescientists explored was to combine oxycodone with
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`an opioid antagonist—the “chemical approach.” (Appx4098.) The goal was for
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`the antagonist to have no effect under normaluse, 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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`Purduescientists 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 intravenousor nasal abuse, suchas byirritating or
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`discoloring 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
`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, makingit
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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 OxyContin® 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
`
`formulations made by melting a blended mixture of PEO, magnesium stearate, and
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`oxycodone. This blended mixtureis called a “core matrix.” (Appx204.) The
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`single claim of the ’976 patent (Appx204) recites as follows:
`
`1. An extended release abuse deterrent dosage form comprising:
`a. a core matrix comprising a blended mixtureof.
`(a) PEO having a molecular weight of from about 300,000 daltons
`to about 5,000,000 daltons;
`
`(b) magnesium stearate; and
`(c) oxycodoneor a pharmaceutically acceptable salt thereof;
`wherein the core matrix is heated to melt at least a portion of the
`PEOincludedin the core matrix during preparation of the dosage
`form; and
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`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 19
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`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 19
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`Case: 18-1285
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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. (Appx 186, 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.” (Appx 187, 5:18-21.) Purdue applied forthe patent
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`on December24, 2012, the patent issued on June 23, 2015, and its effective filing
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`date is August 6, 2001. (Appx181.)
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`D.
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`Amneal Petitions For Inter Partes Review
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`Ammneal 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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`Amnealcertified to the FDA 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-Waxmanlitigation
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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, 15-cv-1152 (D. Del.) (consolidated
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`cases). Thereafter, Amnealfiled two petitions for interpartes 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 ofanticipation (based on Amneal’s
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`insistence that the °976 patent should havea 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
`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,butinstituted review on the
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`three obviousness grounds.
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`E.
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`The Asserted Prior Art
`
`Amnealasserted the following combinationsofpriorart:
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`1. McGinity (WO 97/49384) (Appx498),
`Joshi (US 2002/0187192) (Appx527),
`Palermo (WO 99/32120) (Appx446),
`(IPR2016-01027);
`
`2. McGinity (Appx498),
`Joshi (Appx527),
`Bastin (WO 95/20947) (Appx533),
`PDR (Appx572),
`(IPR2016-01028);
`
`3. McGinity (Appx498),
`Palermo (Appx446),
`Handbook (Appx493),
`(IPR2016-01028).
`
`McGinity is commonto all three grounds, and is the reference on which the
`
`Board largely relied. A short description of each reference follows.
`
`1. McGinity (1997): Extended-Release Drug Formulation
`Using Hot-Melt Extrusion And PEO
`
`McGinity does not address drug abuse. (Appx1468.) Rather, McGinity is
`
`directed to preparing extended-release formulations by a particular means: “hot-
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`melt extrusion of mixtures containing high molecular weight PEO and a
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`therapeutic compound.” (Appx500, 1:10-11.) Hot-melt extrusion is conducted in
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 21
`
`PGR2018-00048
`Collegium v. Purdue
`Collegium Exhibit 1080 - Page 21
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`Case: 18-1285
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`Document:47
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`Page: 22
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`Filed: 07/02/2018
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`an extruder, shown below, composed ofa feeding hopper, barrel, screw,die, screw
`
`drive unit, and a heating device. (Appx4047.)
`
`
`
`Metering
`Zone
`
`it
`ckY Sy \\\
`ee:a Lye <
`“ a Rasy
`fi
`Ne
`=
`eetlapeSutal
`Convesing
`Zone
`
`=
`=
`Melting Zone
`
`Schematic ofan extruder illustrating various functional
`|
`zones including the hopper, solid conveying zone, melting
`zone, metering zone anddie.
`|
`(Appx4527.)
`
`Extrusion subjects ingredients to intense agitation at high temperatures.
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`(Appx4048, Appx4505, Appx4518.) This subjects drug particles and other
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`ingredients to “both thermal and shearing stresses” (Appx4505) that intimately mix
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`drug particles within the melted PEO. (Appx4048-4049, Appx4527.)
`
`McGinity does not disclose using magnesium stearate in the composition
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`during hot-melt extrusion. (Appx4054.) McGinity briefly discloses magnesium
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`stearate, but only for use as a lubricant added to the extrudate after the extrusion
`
`process is perf