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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________
`
`COLLEGIUM PHARMACEUTICAL, INC.,
`Petitioner,
`
`v.
`
`PURDUE PHARMA L.P., PURDUE PHARMACEUTICALS L.P.,
`AND THE P.F. LABORATORIES INC.,
`Patent Owner.
`_____________________
`
`Case PGR2018-00048
`Patent 9,693,961 B2
`_____________________
`
`
`
`PETITIONER’S REPLY
`
`
`
`
`
`
`
`

`

`TABLE OF CONTENTS
`
`Page
`
`
`INTRODUCTION .......................................................................................... 1
`I.
`THE CHALLENGED CLAIMS ARE ELIGIBLE FOR PGR. ...................... 3
`II.
`III. NO WRITTEN DESCRIPTION: THE CHALLENGED CLAIMS
`ARE THE RESULT OF IMPERMISSIBLE “PICKING AND
`CHOOSING.” ................................................................................................. 4
`A.
`The description of optional binders is not a disclosure of PGGs. ........ 5
`B. A POSA would not consider PGGs to be an aversive agent, let
`alone a “preferred” aversive agent. ...................................................... 7
`1.
`PGGs are not gelling agents. ...................................................... 9
`2.
`Purdue did not set forth the necessary “blazemarks”
`establishing that PGGs are a preferred gelling agent. .............. 11
`IV. NO WRITTEN DESCRIPTION: PURDUE IMPERMISSIBLY
`OBTAINED CLAIM LANGUAGE THAT IS BROADER THAN
`THE DISCLOSURE. .................................................................................... 15
`THE CHALLENGED CLAIMS ARE INVALID FOR LACK OF
`ENABLEMENT. .......................................................................................... 18
`A.
`Purdue’s “scope of the claims” analysis is premised on its
`mistaken application of law. ............................................................... 19
`Purdue’s argument that the art is “not so unpredictable” is
`without merit. ..................................................................................... 22
`1.
`Purdue’s construction of “homogenous mixture” is
`wrong, but even under its construction, the art is
`unpredictable. ........................................................................... 23
`Purdue’s unpredictability analysis is contradicted by its
`own statements. ........................................................................ 24
`VI. COLLEGIUM’S ANTICIPATION EVIDENCE IS UNREBUTTED. ....... 27
`VII. CONCLUSION ............................................................................................. 27
`
`V.
`
`B.
`
`2.
`
`
`
`
`
`-ii-
`
`
`
`

`

`
`
`PGR2018-00048
`U.S. Patent No. 9,693,961
`TABLE OF AUTHORITIES1
`
` Page(s)
`
`Cases
`ALZA Corp. v. Andrx Pharms., LLC,
`603 F.3d 935 (Fed. Cir. 2010) ............................................................................ 24
`Cooper Cameron Corp. v. Kvaerner Oilfield Prods.,
`291 F.3d 1317 (Fed. Cir. 2002) .......................................................................... 21
`Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co.,
`276 F. Supp. 3d 629 (E.D. Tex. 2017) ................................................................ 17
`Falkner v. Inglis,
`448 F.3d 1357 (Fed. Cir. 2006) .......................................................................... 22
`Gentry Gallery, Inc. v. Berkline Corp.,
`134 F.3d 1473 (Fed. Cir. 1998) .......................................................................... 22
`MorphoSys AG v. Janssen Biotech, Inc.,
`No. 16-221-LPS, 2019 U.S. Dist. LEXIS 12772 (D. Del. Jan. 25,
`2019) ................................................................................................................... 25
`Nat’l Recovery Techs. v. Magnetic Separation Sys.,
`166 F.3d 1190 (Fed. Cir. 1999) .......................................................................... 25
`Novozymes A/S v. Dupont Nutrition Biosciences APS,
`723 F.3d 1336 (Fed. Cir. 2013) .............................................................. 16, 17, 20
`PGG CAE Screenplates, Inc. v. Heinrich Fiedler GmbH & Co.,
`224 F.3d 1308 (Fed. Cir. 2000) .................................................................... 11, 13
`Sitrick v. Dreamworks, LLC,
`516 F.3d 993 (Fed. Cir. 2008) ............................................................................ 24
`
`
`1 Unless otherwise noted, all (i) citations and internal quotations are omitted and
`
`(ii) emphasis is added.
`
`iii
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`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`Snitzer v. Etzel,
`465 F.2d 899 (C.C.P.A. 1972) ............................................................................ 17
`Streck, Inc. v. Research & Diagnostic Sys.,
`665 F.3d 1269 (Fed. Cir. 2012) .......................................................................... 22
`Trustees of Boston Univ. v. Everlight Elecs. Co.,
`896 F.3d 1357 (Fed. Cir. 2018) .......................................................................... 25
`Wyeth & Cordis Corp. v. Abbott Labs.,
`720 F.3d 1380 (Fed. Cir. 2013) .......................................................................... 24
`Statutes
`35 U.S.C. § 100(i)(1) ........................................................................................... 8, 10
`35 U.S.C. § 321 note .................................................................................................. 8
`Public Law 112-29 §§3(a), (n)(1), 6(f)(2)(A) (Sept. 16, 2011) ................................. 8
`
`
`
`iv
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`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`TABLE OF EXHIBITS2
`
`
`Exhibit No. Document Name
`Ex. 1001 U.S. Patent 9,693,961 to Wright et al.
`Am. Ex. 1002 Declaration of Walter G. Chambliss, Ph.D.
`Ex. 1003 Curriculum Vitae of Walter G. Chambliss, Ph.D
`Ex. 1004 U.S. Application No. 15/015,722 to Wright et al.
`Ex. 1005
`Provisional Application No. 60/310,534 to Wright et al.
`Ex. 1006 U.S. Application No. 10/214,412, published as US
`2003/0068375 (Abandoned)
`Ex. 1007 U.S. Application No. 12/262,015, issued as U.S. 8,389,007
`Ex. 1008 U.S. Application No. 13/765,368, issued as U.S. 9,040,084
`Ex. 1009 U.S. Application No. 13/890,874, issued as U.S. 9,308,170
`Ex. 1010 U.S. Application No. 13/946,418, issued as U.S. 8,999,961
`Ex. 1011 U.S. Application No. 14/638,685, issued as U.S. 9,867,783
`Ex. 1012
`Preliminary Amendment filed June 2, 2015 in Application
`14/728,601 to Wright et al.
`Ex. 1013 Office Action in Application 14/728,601 to Wright et al., dated
`August 5, 2015
`F. R. Gusterson et al., Letter, “Analgesia in Terminal Malignant
`Disease”, British Medical Journal (July 7, 1979)
`Ex. 1015 NDA 7337/S24, Percodan Final Printed Labeling (January
`1989)
`Ex. 1016 U.S. Patent 5,468,744 to Raffa et al.
`Ex. 1017
`The United States Pharmacopeia, The National Formulary, USP
`23/NF 18 (1994)
`E. Bourret et al., “Rheological Behaviour of Saturated
`Polyglycolysed Glycerides”, 46 J. Pharm. Pharmacol. 538 (1994)
`
`Ex. 1014
`
`Ex. 1018
`
`
`2 Unless otherwise noted, all exhibits are cited by their original page, column, or
`
`paragraph numbers.
`
`v
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`Exhibit No. Document Name
`Ex. 1019 W. Sutananta et al., “An Investigation into the Effect of
`Preparation Conditions on the Structure and Mechanical
`Properties of Pharmaceutical Glyceride Bases”, 110 Int. J. of
`Pharmaceutics 75 (1994)
`Ex. 1020 U.S. Patent No. 6,248,363 to Patel et al.
`Ex. 1021
`International Publication Number WO 96/36330 to Lin
`Ex. 1022 U.S. Patent No. 6,225,444 to Shashoua
`Ex. 1023 U.S. Patent No. 4,882,167 to Jang
`Ex. 1024 U.S. Patent No. 6,120,751 to Unger
`Ex. 1025 K. Harvey et al., “Parenteral Lipid Emulsions in Guinea Pigs
`Differentially Influence Plasma and Tissue Levels of Fatty Acids,
`Squalene, Cholesterol, and Phytosterols”, 49(8) Lipids 777 (2014)
`Ex. 1026 C. Shacky et al., “A Comparative Study of Eicosapentainoic Acid
`Metabolism by Human Platelets in vivo and in vitro”, 26 J. of
`Lipid Research 457 (1985)
`Ex. 1027 A. Kibbe ed., Handbook of Pharmaceutical Excipients (3rd Ed.
`2000)
`International Publication No. WO 00/38649 to DuFour
`(Certified Translation)
`Ex. 1029 UK Patent Application GB 2 162 061 A to Bardhan
`Ex. 1030 U.S. Patent 4,175,119 to Porter
`Ex. 1031 OxyContin® Label 2001
`Ex. 1032 Declaration under 37 C.F.R. 1.132, submitted in Application No.
`14/946,275 to Rariy et al.
`J. Sprowls, Ph.D., Prescription Pharmacy (2nd Ed. 1970)
`Ex. 1033
`Ex. 1034 U.S. Patent 3,184,386 to Stephenson
`Ex. 1035
`L. Lachman et al., The Theory and Practice of Industrial
`Pharmacy (3rd ed. 1986)
`Ex. 1036 U.S. Patent 5,656,295 to Oshlack et al.
`Ex. 1037
`Left intentionally blank
`Ex. 1038 Master Batch Record, Oxycodone DETERx™, Batch
`Production Record #Oxy-10152008 (FILED UNDER
`SEAL)
`
`Ex. 1028
`
`vi
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`Exhibit No. Document Name
`Ex. 1039 U.S. Patent 3,980,766 to Shaw et al.
`Ex. 1040 U.S. Patent 6,309,668 to Bastin et al.
`Ex. 1041 US 2004/0010000 to Ayer et al.
`Ex. 1042
`Provisional Application 60/376470 to Ayer et al.
`Ex. 1043 U.S. Patent Application Publication No. 2015/0164835 to King
`et al.
`Ex. 1044 U.S. Patent Application Publication No. 2014/0271835 to
`Wengner
`Ex. 1045 U.S. Patent 8,569,228 to Jenkins et al.
`Ex. 1046 U.S. Patent Application Publication No. 2011/0142943 to
`Rariy et al.
`Ex. 1047 Declaration of Todd Scungio
`Ex. 1048 Collegium Pharmaceutical Study: Intravenous Abuse
`Comparison of Oxycodone DETERx™ Versus
`OxyContin™ (FILED UNDER SEAL)
`Ex. 1049 Complaint, Purdue Pharma L.P. et al., v. Collegium
`Pharmaceutical, Inc., 17-cv-11814 [Dkt 1]
`Ex. 1050 Order Granting Consolidation, Purdue Pharma, L.P. et al. v.
`Collegium Pharmaceutical, Inc., 15-cv-13099 [Dkt 152]
`Joint Claim Construction and Prehearing Statement, Purdue
`Pharma, L.P. et al. v. Collegium Pharmaceutical, Inc., 15- cv-
`13099 [Dkt 116]
`Ex. 1052 A. Gennaro ed., Remington: The Science and Practice of
`Pharmacy (20th ed. 2000)
`E. Cone et al., “An Iterative Model for in vitro Laboratory
`Assessment of Tamper Deterrent Formulations”, 131 Drug and
`Alcohol Dependence 100 (2013)
`FDA, Abuse-Deterrent Opioids - Evaluation and Labeling:
`Guidance for Industry (April 2015)
`Ex. 1055 U.S. Patent No. 6,228,863 to Palermo et al.
`Ex. 1056
`Left intentionally blank
`
`Ex. 1054
`
`Ex. 1051
`
`Ex. 1053
`
`vii
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`Exhibit No. Document Name
`Ex. 1057 Department of Justice, National Drug Intelligence Center,
`Information Bulletin, “OxyContin Diversion and Abuse” (January
`2001)
`Plaintiffs’ Opening Claim Construction Brief, Purdue Pharma
`L.P. et al. v. Collegium Pharmaceutical, Inc., 15- cv-13099 [Dkt
`99] (Redacted version filed in district court)
`Ex. 1059 U.S. Patent 8,652,497 to Sackler
`Ex. 1060
`S. Passik et al., “Psychiatric and Pain Characteristics of
`Prescription Drug Abusers Entering Drug Rehabilitation”, 20:2 J.
`of Pain & Palliative Care Pharmacotherapy 5 (2006)
`Ex. 1061 U.S. Patent 5,545,628 to Deboeck et al.
`Ex. 1062 U.S. Patent 6,468,559 to Chen et al.
`Ex. 1063 Bulletin Technique Gattefossé Report (1988)
`Ex. 1064
`S. Harris et al., “Abuse Potential, Pharmacokinetics,
`Pharmacodynamics, and Safety of Intranasally Administered
`Crushed Oxycodone HCl Abuse-Deterrent Controlled-Release
`Tablets in Recreational Opioid Users”, 54(4) J. of Clinical
`Pharmacology 468 (2013)
`Ex. 1065 B. Lara-Hernandez et al., “Effect of Stearic Acid on the
`Properties of Metronidazole/Methocel K4M Floating
`Matrices”, 45(3) Brazilian J. of Pharm. Scis. 497 (2009)
`Left Intentionally Blank
`Ex. 1066
`Ex. 1067 B. Alberts et al., Essential Cell Biology (2nd ed. 2004)
`Ex. 1068 C. Smith et al., “Oral and Oropharyngeal Perceptions of Fluid
`Viscosity Across the Age Span”, Dysphagia (2006)
`Ex. 1069 Rowe et al. eds., Handbook of Pharmaceutical Excipients (7th
`ed. 2012)
`Ex. 1070 Y. Zhang et al., “Effect of Processing Methods and Heat Treatment
`on the Formation of Wax Matrix Tablets for Sustained Drug
`Release”, 6(2) Pharm. Dev. and Tech. 131 (2001)
`I. Ghebre-Sellassie ed., Pharmaceutical Pelletization
`Technology (1989)
`Transcript of Conference Call - 08.03.2018
`
`Ex. 1072
`
`Ex. 1058
`
`Ex. 1071
`
`viii
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`Exhibit No. Document Name
`Ex. 1073 Non-Addressed PGGs – Exhibit from Deposition of Panayiotis P.
`Constantinides
`Ex. 1074 U.S. Patent No. 6,312,704 to Farah et al.
`Ex. 1075 Ratsimbazafy, “Effect of Formulation on the Rheology of
`Theophylline Compound Suspensions in Gelucires”
`Ex. 1076 Handbook of Pharmaceutical Excipients 3rd Ed. Index
`Ex. 1077 Handbook of Pharmaceutical Excipients 6th Ed. Index
`Ex. 1078 Handbook of Pharmaceutical Excipients 6th Ed.
`Polyoxylglycerides
`Ex. 1079 McGinity, “Hot-Melt Extrusion as a Pharmaceutical Process”
`Ex. 1080
`Purdue Appeal Brief
`Ex. 1081 Deposition Transcript of Panayiotis P. Constantinides taken on
`3/20/2019
`Ex. 1082 Gennaro, “Remington: The Science and Practice of Pharmacy”
`Ex. 1083
`The Pharmaceautical Codex (12th Ed.)
`Ex. 1084 Damian et al, “Physicochemical characterization of solid
`dispersions of the antiviral agent UC-781 with polyethylene glycol
`6000 and Gelucire 44/14”
`Ex. 1085 Hawleys Condensed Chemical Dictionary (13th Ed.)
`Ex. 1086 Krowczynski, “Extended-Release Dosage Forms”
`Ex. 1087
`Supplemental Declaration of Dr. Walter G. Chambliss
`Ex. 1088 Gelucire USPTO Trademark Registration Certificate
`Ex. 1089
`2/2/2017 Response to Office Action
`Ex. 1090 Handbook of Pharmaceutical Excipients 3rd Ed. Docusate Sodium,
`et al.
`
`ix
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`Exhibit No. Document Name
`Ex. 1091
`‘961 Litigation Deposition Transcript of Panayiotis P.
`Constantinides taken on September 21, 2018
`
`This Exhibit was marked and referred to as Ex-1072 during the
`March 20, 2019 deposition of Panayiotis P. Constantinides (see
`generally Ex-1081). The parties’ March August 3, 2018 conference
`call with the Board, however, was already marked as Ex-1072. For
`this reason, the September 21, 2018 deposition transcript of Dr.
`Constantinides is now found at Ex-1091.
`
`x
`
`

`

`
`
`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`I.
`
`INTRODUCTION
`
`The Challenged Claims are neither described nor enabled in the specification
`
`of the ʼ961 patent. That the Challenged Claims lack § 112 support is unsurprising:
`
`Purdue submitted the ʼ961 patent application some fifteen years after filing the
`
`original priority application and at the same time that Collegium was
`
`commercializing its independently developed and separately patented extended-
`
`release oxycodone product. Purdue’s gambit—seeking to obtain impermissibly
`
`broad claims that cover subject matter actually developed and patented by
`
`Collegium—led to the issuance of claims that are invalid on the asserted grounds.
`
`The Institution Decision correctly observed that the Priority Applications3 fail
`
`to demonstrate written description for the Claimed Pharmaceutical Ingredients—
`
`especially PGGs—that were seemingly cherry-picked and chosen at random from
`
`various categories of ingredients found in disparate parts of the Priority
`
`Applications. This lack of written description is dispositive of both PGR eligibility
`
`and the invalidity of the ʼ961 patent. Thus, the lack of the inventors’ possession of
`
`PGGs in the claimed combination is of central importance and is fully dispositive
`
`of this PGR.
`
`
`3 The applications in the ʼ961 priority chain are collectively referenced as the
`
`“Priority Applications.”
`
`1
`
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`Admissions of Purdue’s expert, Dr. Constantinides, confirm and strengthen
`
`the evidence of lack of § 112 support. For example, Dr. Constantinides admitted
`
`that the “single sentence” relied on by Purdue as a disclosure of the combination of
`
`Claimed Pharmaceutical Ingredients does not and, in fact, cannot describe the
`
`inclusion of PGGs because it references hydrophobic, and not the required
`
`hydrophilic, binder materials.
`
`Purdue’s alternative basis for finding written description support mandates a
`
`complex and illogical series of leaps across disparate parts of the specification that
`
`requires a POSA to wade through a series of optional categories and subcategories,
`
`after which—without the benefit of hindsight—s/he is supposed to land on the
`
`specific selection of PGGs. To do so, Purdue proposes that PGGs were such well-
`
`understood gelling agents that a POSA would immediately envisage them when the
`
`Priority Applications reference “aversive agents.” This notwithstanding that the
`
`specification never states, let alone even suggests, that PGGs are gelling agents.
`
`Purdue’s argument—based entirely on hindsight—has no support whatsoever in
`
`the record evidence. Critically, Dr. Constantinides admitted that he cannot point to
`
`a single literature reference supporting his central argument that PGGs are gelling
`
`agents.
`
`Separately, Dr. Constantinides further admitted that his declaration
`
`significantly misstated the number of PGGs, leading to an understatement of the
`
`2
`
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`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`enablement problem. This shortcoming is compounded by Purdue’s mistaken
`
`belief that it need only enable pharmaceutical excipients that were used in
`
`previously described, FDA-approved products. Purdue is incorrect; instead, it must
`
`enable the full scope of the claimed invention. Finally, Purdue advances an
`
`erroneous construction of “homogenous mixture” in an unsuccessful attempt to
`
`“knock-out” Collegium’s unpredictability evidence (Ex-1032) and to distract from
`
`its previous statements telling the Federal Circuit that the art is unpredictable.
`
`Collegium has established that the Challenged Claims are invalid. Therefore,
`
`the Board should cancel the Challenged Claims.
`
`II. THE CHALLENGED CLAIMS ARE ELIGIBLE FOR PGR.
`
`“It is well-established by prior Board decisions” that transitional patents must
`
`demonstrate adequate § 112 support “in the earlier-filed application in order to
`
`avoid PGR-eligibility.” (Paper 18 at 10-11.) Purdue, however, argues—purportedly
`
`based on the legislative record—that transitional applications are per se ineligible
`
`for PGR. (Paper 23 at 22-23.) But the Institution Decision was correctly decided.
`
`Purdue’s reliance on two out-of-context sentences from the AIA-legislative record
`
`is misplaced and does not address the clear mandate that the ʼ961 patent is PGR-
`
`eligible because it cannot claim priority to a pre-AIA application. See Public Law
`
`112-29 §§3(a), (n)(1), 6(f)(2)(A) (Sept. 16, 2011); 35 U.S.C. § 321 note
`
`(Applicability); 35 U.S.C. § 100(i)(1).
`
`
`
`3
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`III. NO WRITTEN DESCRIPTION: THE CHALLENGED CLAIMS ARE
`THE RESULT OF IMPERMISSIBLE “PICKING AND CHOOSING.”
`
`The Priority Applications include no teaching or Example demonstrating that
`
`the inventors possessed a combination of the Claimed Pharmaceutical Ingredients.
`
`(Am. Ex-1002 ¶ 106.) The Examples teach the use of over fifteen other
`
`pharmaceutical excipients, none of which are the Claimed Pharmaceutical
`
`Ingredients. (Id. ¶ 106.) In particular, PGGs are mentioned nowhere in the
`
`Examples, and only once in the entire disclosure, which characterizes PGGs, not as
`
`gelling agents, but as one of many optional surfactants. (Id. ¶ 108; Ex-1081, 31:25-
`
`32:3.) Further, the Priority Applications provide no teaching or Example where a
`
`dosage form of the Claimed Pharmaceutical Ingredients, or any dosage form for
`
`that matter, is exposed to the claimed tampering at a temperature greater than 45º
`
`C. (Am. Ex-1002 ¶ 113; Ex-1081, 184:7-12.)
`
`As explained by Dr. Chambliss, this lack of teaching is telling, as a POSA
`
`would look for these disclosures given that the claimed excipients have varied
`
`physical-chemical properties that play important and conflicting roles in regulating
`
`API release. (Am. Ex-1002 ¶ 112.) Stated another way, the identity and/or amount
`
`of the Claimed Pharmaceutical Ingredients will influence the release of the
`
`oxycodone API, thus affecting whether the dosage form satisfies the Functional
`
`Claim Limitations. (Id. ¶ 112.) As a result, to the extent the inventors were actually
`
`4
`
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`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`in possession of the claimed invention, a POSA would have expected discussion
`
`both of (i) how to combine the Claimed Pharmaceutical Ingredients and (ii) how
`
`this method of combination would influence the functional behavior of the dosage
`
`form. (Id.) As a result, the Board should re-affirm its Institution Decision: the
`
`Challenged Claims are invalid for lack of written description. (Paper 18 at 12-17.)
`
`
`
`Purdue does not dispute this description of the Priority Applications, but
`
`nevertheless argues that the inventors were in possession of the claimed invention,
`
`including with the recited PGGs, because according to Purdue (i) “[t]he ʼ961
`
`Priority Applications’ description of a combination of binders also includes the
`
`claimed combination of ingredients” (Paper 23 at 33), and (ii) “[a] POSA would
`
`recognize PGGs as a preferred aversive agent for the claimed sustained release
`
`materials.” (Id. at 31). Purdue is wrong.
`
`
`
`A.
`The description of optional binders is not a disclosure of PGGs.
`Purdue contends that the disclosure of optional binders in the Priority
`
`
`
`Applications provides written description support because it would cause a POSA
`
`to “immediately envisage PGGs.” (Paper 23 at 33-36.) Specifically, Purdue argues
`
`that the disclosure of “hydrophobic binder materials … including but not limited to
`
`fatty acid esters, [and] fatty acid glycerides” is a teaching of PGGs. (Id. (citing Ex-
`
`1001, 16:22-29).) As a threshold matter, the Board already considered and rejected
`
`this argument. (Paper 18 at 15.) Regardless, Dr. Constantinides’ deposition
`
`5
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`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`testimony removed all doubt; he admitted this section does not and cannot suggest
`
`PGGs. (Ex-1081, 145:7-12.)
`
`First, the discussion of binders in the Priority Applications does not list or
`
`reference PGGs. (Ex-1081, 143:2-5.) Instead, the sole reference to PGGs is in a
`
`different part of the Priority Applications, which include a laundry list of optional
`
`surfactants. (Id. at 31:25-32:13.) In other words, the inventors knew how to
`
`reference a PGG when desired, and the different language used in the binder
`
`section of the Priority Applications should be accorded a different meaning. PGG
`
`CAE Screenplates, Inc. v. Heinrich Fiedler GmbH & Co., 224 F.3d 1308, 1317
`
`(Fed. Cir. 2000) (“[D]ifferent terms … connote[] different meanings.”). If the
`
`inventors had in fact intended to describe PGGs as a proposed binder, they knew
`
`how to do it, but they did not.
`
`Second, the binder section does not disclose the constituent parts of a PGG.
`
`Both experts agree that a PGG is “a mixture of mono-, di- and triesters of glycerol
`
`with mono- and diesters of PEG.” (Ex-1081, 30:22-31:8.) The binder section,
`
`however, only discloses the genus of “fatty acid esters” and does not disclose or
`
`suggest the required PGG species: PEG fatty acid esters. (Ex-1087 ¶¶ 31-33.)
`
`Third, even if the disclosure of the genus—fatty acid esters—was somehow a
`
`disclosure of PEG fatty acid esters, Purdue’s argument still fails. The binder
`
`section exclusively describes hydrophobic excipients and therefore does not
`
`6
`
`

`

`PGR2018-00048
`U.S. Patent No. 9,693,961
`disclose the constituent parts that constitute a PGG, as is now admitted by Dr.
`
`Constantinides. As agreed by both experts, the “PEG fatty acid ester will always be
`
`the hydrophilic constituent of the PGG.” (Ex-1081, 31:13-16, 144:25-145:5.) But
`
`because the binder section describes only hydrophobic fatty acid esters, it cannot
`
`be a disclosure of the hydrophilic fatty acid ester that is required for a PGG. (Ex-
`
`1087 ¶ 34.) Dr. Constantinides agrees:
`
`Q: In the fatty acid ester, though, that’s described here in column 16 is not a
`
`hydrophilic fatty acid ester [but] a hydrophobic fatty acid ester, correct?
`
`A: Yes, it appears so, because it refers to hydrophobic binder materials.
`
`(Id. at 145:7-12, 144:11-15.)
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`In sum, the binders section does not disclose PGGs. Therefore, this section of
`
`the Priority Applications cannot provide written description support.
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`B. A POSA would not consider PGGs to be an aversive agent, let alone a
`“preferred” aversive agent.
`Purdue alternatively proposes, for the first time in its POR, that the “melt
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`extruded matrix” section of the Priority Applications—specifically, its disclosure
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`of “aversive agents”—provides written description support for the Challenged
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`Claims. (Paper 23 at 27 (citing Ex-1001, 17:64-18:2).) This section of the Priority
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`Applications never discloses or recites PGGs. (Ex-1087 ¶ 23.) As a result, to argue
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`that the broad disclosure of the genera aversive agent is actually a recitation of
`
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`PGR2018-00048
`U.S. Patent No. 9,693,961
`PGGs requires Purdue to use the specification like a hopscotch grid, impermissibly
`
`picking and choosing among the Priority Applications’ various teachings.
`
`First, Purdue must argue that aversive agents, according to the specification
`
`of the Priority Applications, include gelling agents. (Ex-1001, 4:27-29.) Second,
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`Purdue must sort through the laundry list of disclosed categories of gelling agents
`
`to select the category “surfactant.” (Id. at 6:64-7:13.) Third, Purdue must then
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`jump some twenty-two columns forward in the Priority Applications to a list of
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`over forty-five optional surfactants, only a subset of which might actually be
`
`gelling agents. (Id. at 28:35-58.) Fourth, from that list of optional surfactants, a
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`POSA must then select PGGs and must further conclude—contrary to fact—that
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`PGGs are not only surfactants, but gelling agents. (Id.) Indeed, just to connect
`
`these hopscotch squares, Purdue spends half a page of its POR describing the
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`necessary leaps in logic. (Paper 23 at 31.)
`
`Purdue’s argument seems to be that PGGs were so well-known as preferred
`
`gelling agents that a POSA would immediately think of them when encouraged by
`
`the specification to choose an “aversive agent.” Notwithstanding that the Priority
`
`Applications never describe PGGs as gelling agents, Purdue seems to argue—at
`
`the exclusion of the multitudes of other ingredients expressly disclosed as aversive
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`agents—that a POSA would select PGGs. Not only is Purdue’s argument
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`dependent on the benefit of hindsight, but it is scientifically and legally inaccurate.
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`8
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`PGR2018-00048
`U.S. Patent No. 9,693,961
`
`1. PGGs are not gelling agents.
`As a threshold matter, PGGs are not gelling agents. (Ex-1087 ¶ 22.) Neither
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`the Priority Applications nor any other record evidence supports Purdue’s
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`unsubstantiated assertion that PGGs are gelling agents.
`
`The Priority Applications do not disclose that a PGG can be used to make an
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`abuse-deterrent dosage form:
`
`Q: And there’s nowhere in the [Priority Applications] that states that
`PGGs are an ingredient that can be used to deter abuse[?]
`….
`A: Not by name again.
`
`(Ex-1081, 80:7-11.) There is a list of gelling agents in the Priority Applications,
`
`but it does not include PGGs. (Id. at 79:15-18.) In fact, this list of gelling agents
`
`merely states that some surfactants can act as a gelling agent. (Ex-1001, 6:64-7:13;
`
`Ex-1081, 135:9-12 (agreeing that not all surfactants are gelling agents).) Thus, as
`
`agreed by Dr. Constantinides, the disclosure of PGGs as surfactants is not
`
`sufficient to describe PGGs as gelling agents. (Ex-1087 ¶ 23.)
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`Further, as of the Purported Priority Date (and still today) the art does not
`
`describe PGGs as gelling agents, and thus a POSA would not recognize the
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`Priority Applications as disclosing PGGs as a preferred gelling agent. (Id. ¶ 24.)
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`Tellingly, Dr. Constantinides admits he did not “cite any literature in [his]
`
`supplemental declaration for the fact that a PGG can be a gelling agent.” (Ex-1081,
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`PGR2018-00048
`U.S. Patent No. 9,693,961
`75:7-15, 187:12-15.) Thus, even according to Dr. Constantinides, PGGs are not
`
`gelling agents. (Id. at 20:10-23 (testifying that excipients are not gelling agents—
`
`even if stated as having that property in the Priority Applications—unless there is
`
`literature supporting this abuse-deterrent function).) Moreover, Dr. Constantinides
`
`has never used a PGG as a gelling agent, nor has he heard of others doing so. (Ex-
`
`1091, 28:20-23, 37:7-9.)
`
`The operative version of the Handbook of Pharmaceutical Excipients (“HPE”)
`
`did not include PGGs as of the Purported Priority Date. (Ex-1081, 82:7-11.) This is
`
`because PGGs were a relatively new excipient in 2001. (Ex-1087 ¶¶ 24-25; Ex-
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`1081, 95:10-18, 97:5-14 (agreeing that the IIG4 does not include a PGG entry).)
`
`PGGs were subsequently added to the HPE, and upon inclusion, they were not
`
`listed as gelling agents. (Ex-1081, 105:25-106:9.) Instead, PGGs were listed with
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`the following non-abuse deterrent functions: dissolution enhancer, emulsifying
`
`agent, penetration enhancer, solubilizing agent, surfactant, sustained-release agent.
`
`(Id. at 109:19-112:2; Ex-1078 at 558.) The HPE discloses numerous representative
`
`
`4 The IIG (Ex-2007) is an FDA-maintained list of previously-approved
`
`pharmaceutical excipients. This is the same version of the IIG that Dr.
`
`Constantinides relies upon to argue—as of the Purported Priority Date—the
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`number of fatty acids used in FDA-approved products.
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`10
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`PGR2018-00048
`U.S. Patent No. 9,693,961
`excipients that may have abuse-deterrent properties—gelling agents, hydrogels,
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`stiffening agents, thickening agents, and viscosity-increasing agents—but PGGs
`
`are not listed in any of these functional categories. (Ex-1081, 106:20-109:1; Ex-
`
`1077 at 868, 870, 883, 885, 887.) There is no record evidence supporting Purdue’s
`
`unsubstantiated assertion that PGGs are gelling agents. (Ex-1087 ¶¶ 24-25).
`
`2.
`
`Purdue did not set forth the necessary “blazemarks” establishing
`that PGGs are a preferred gelling agent.
`Despite the HPE listing PGGs as a representative excipient for six
`
`pharmaceutical functions, none of which are as a gelling agent (Ex-1081, 112:8-
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`12), Purdue bases its case on the contention that a POSA would “recognize PGGs
`
`as a preferred aversive agent.” (Paper 23 at 31). Purdue’s conclusory assertions are
`
`riddled with hindsight and lack any supporting disclosure in the Priority
`
`Applications; accordingly, this post-hoc rationalization should be rejected.
`
`Novozymes A/S v. Dupont Nutrition Biosciences APS, 723 F.3d 1336, 1349 (Fed.
`
`Cir. 2013) (rejecting arguments because patentee—“[w]orking backward from a
`
`knowledge of [the claims], that is by hindsight”—sought to “derive written
`
`description support from an amalgam of disclosures plucked selectively from the
`
`[priority] application”). Indeed, among the slew of competing possibilities, there is
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`PGR2018-00048
`U.S. Patent No. 9,693,961
`no teaching in the Priority Applications setting forth blazemarks that would lead a
`
`POSA toward the combination of Claimed Pharmaceutical Ingredients.5 Id.
`
`
`5 Purdue argues that claim elements contained on a list can, in certain instances,
`
`satisfy the written-description requirement. (Paper 23 at 13-17, 37.) Purdue’s
`
`authority, though, does not save the Challenged Claims, as in each instance, the
`
`court was not presented with a “picking-and-choosing” argument, and instead was
`
`asked whether a list—that contained the single-structural element recited in the
`
`claims—satisfied the written description. See, e.g., Snitzer v. Etzel, 465 F.2d 899,
`
`900 (C.C.P.A. 1972) (claiming only “trivalent ytterbium ions”);
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`Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co., 276 F. Supp. 3d 629, 640-41
`
`(E.D. Tex. 2017) (claiming only “inhibitor of phosphodiesterase”). Here, however,
`
`the Challenged Claims recite a combination of Claimed Pharmaceutical Ingredients
`
`that must also satisfy the Functional Claim Limitations. (Am. Ex-1002 ¶ 104.) For
`
`this reason, Purdue’s cited authority is inapposite. Further, and in contradictory
`
`fashion, Purdue took the exact opposite position it now advocates in this PGR,
`
`when seeking issuance of the Challenged Claims. (Ex-1089 at 11 (arguing prior art
`
`was inapplicable because it “fail[ed] to provide any guidance to [a POSA] to select
`
`polyglycolyzed glycerides from the exhaustive list”).)
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`12
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`PGR2018-00048
`U.S. Patent No.