Paper No.
`
`
`
`Filed: March 15, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_______________
`
`TEVA PHARMACEUTICALS USA, INC.,
`Petitioner
`
`v.
`
`MONOSOL RX, LLC,
`Patent Owner
`_______________
`
`Case IPR2016-00281
`
`Patent 8,603,514 B2
`_______________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`PURSUANT TO 35 U.S.C. § 313 & 37 C.F.R. § 42.107
`
`
`
`
`
`
`
`
`Filed: March 15, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_______________
`
`TEVA PHARMACEUTICALS USA, INC.,
`Petitioner
`
`v.
`
`MONOSOL RX, LLC,
`Patent Owner
`_______________
`
`Case IPR2016-00281
`
`Patent 8,603,514 B2
`_______________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`PURSUANT TO 35 U.S.C. § 313 & 37 C.F.R. § 42.107
`
`
`
`
`
`
`
`
`
`
`
`
`TABLE OF CONTENTS
`
`V.
`
`INTRODUCTION ........................................................................................... 1
`I.
`STATEMENT OF FACTS .............................................................................. 3
`II.
`III. THE PETITION IS TIME-BARRED UNDER § 315(b) ................................ 5
`IV. CLAIM CONSTRUCTION ............................................................................ 9
`A.
`“dried without loss of substantial uniformity” (Claims 1 and 62) ...... 10
`PETITIONER HAS NOT SHOWN A REASONABLE LIKELIHOOD
`THAT THE CHALLENGED CLAIMS OF THE ’514 PATENT ARE
`UNPATENTABLE ........................................................................................ 11
`A.
`Petitioner has not proffered any prior art reference disclosing the 10%
`DCU limitation of claims 1 and 62, from which all other challenged
`claims depend. ..................................................................................... 13
`Petitioner’s conclusory reliance on “routine experimentation” does not
`render the 10% uniformity limitation obvious. ................................... 22
`Petitioner has not proffered any evidence that the 5% DCU limitation
`of claims 9 and 65 is obvious over the prior art. ................................. 31
`VI. CONCLUSION .............................................................................................. 33
`
`
`B.
`
`C.
`
`i
`
`
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`
`CASES
`Abbott Labs. v. Sandoz, Inc.,
`544 F.3d 1341 (Fed. Cir. 2008) .......................................................................... 20
`ACTV, Inc. v. Walt Disney Co.,
`346 F.3d 1082 (Fed. Cir. 2003) ...................................................................... 9, 10
`Apple Inc. v. ContentGuard Holdings, Inc.,
`IPR2015-00441, Paper 11 (PTAB July 13, 2015) ........................................ 23, 24
`Cardiac Pacemakers, Inc. v. St. Jude Med., Inc.,
`381 F.3d 1371 (Fed. Cir. 2004) .......................................................................... 20
`In re Cuozzo Speed Techs., LLC,
`793 F.3d 1268 (Fed. Cir. 2015), reh’g en banc denied, 793 F.3d 1297
`(Fed. Cir. 2015), cert. granted, 2016 WL 205946 (U.S. Jan. 15, 2016) .............. 8
`In re Suitco Surface, Inc.,
`603 F.3d 1255 (Fed. Cir. 2010) ............................................................................ 8
`Insite Vision Inc. v. Sandoz, Inc.,
`783 F.3d 853 (Fed. Cir. 2015) ............................................................................ 20
`Institut Pasteur v. Focarino,
`738 F.3d 1337 (Fed. Cir. 2013) .................................................................... 20, 21
`InTouch Techs., Inc. v. VGO Commc’ns, Inc.,
`751 F.3d 1327 (Fed. Cir. 2014) .......................................................................... 22
`K/S HIMPP v. Hear-Wear Techs., LLC,
`751 F.3d 1362 (Fed. Cir. 2014) .......................................................................... 20
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 20-22
`Lannett Holdings, Inc. v. Astrazeneca AB,
` IPR 2015-01629, Paper 14 (PTAB Jan. 27, 2016) .............................................. 6
`
`ii
`
`
`
`
`
`
`
`
`Microsoft Corp. v. Proxyconn, Inc.,
`IPR2012-00026, Paper 17 (PTAB Dec. 21, 2012) ............................................... 8
`Perfect Web Techs., Inc. v. InfoUSA, Inc.,
`587 F.3d 1324 (Fed. Cir. 2009) .......................................................................... 21
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ..................................................................... 19,20
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc) ............................................................ 9
`Plantronics, Inc. v. Aliph, Inc.,
`724 F.3d 1343 (Fed. Cir. 2013) .......................................................................... 24
`Teva Pharms. USA, Inc., v. Indivior UK Ltd.,
`IPR2016-00280, Paper 8 (PTAB Feb. 18, 2016) ................................................. 7
`Terremark N. Am. LLC v. Joao Control & Monitoring Sys., LLC,
`IPR2015-01482, Paper 10 (PTAB Dec. 28, 2015) ................................................ 6
`TriMed, Inc. v. Stryker Corp.,
`608 F.3d 1333 (Fed. Cir. 2010) .......................................................................... 20
`United States v. Locke,
`471 U.S. 84 (1985) ............................................................................................ 6, 7
`STATUTES
`35 U.S.C. § 315(b) ............................................................................................passim
`CODE OF FEDERAL REGULATIONS
`37 C.F.R. § 42.65(a) ........................................................................................... 21, 28
`37 C.F.R. § 42.100(b) ................................................................................................ 8
`37 C.F.R. § 42.101 ..................................................................................................... 6
`OTHER AUTHORITIES
`77 Fed. Reg. 48756, 48766 (Aug. 14, 2012) ............................................................. 8
`
`iii
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`
`
`EXHBIT
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`
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`
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`*2001
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`*2002
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`*2003
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`*2004
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`*2005
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`*2006
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`*2007
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`*2008
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`2009
`
`2010
`
`2011
`
`
`
`EXHIBIT LIST
`
`DESCRIPTION
`FedEx shipping labels for tracking numbers 7751 1902
`8582; 7751 1902 8983; and 7751 1902 9203 and FedEx
`on-line tracking histories for tracking numbers 7751
`1902 8582; 77511902 8983; and 7751 1902 9203.
`January 8, 2016 emails with PTAB at Trials@uspto.gov.
`
`Email chain regarding Petitioner’s problems.
`
`Summons in Reckitt Benckiser Pharmaceuticals Inc., RB
`Pharmaceuticals Limited, et al v. Teva Pharmaceuticals
`USA, Inc., Civil Action 14-1451 (D. Del.).
`Complaint (without exhibits) in Reckitt Benckiser
`Pharmaceuticals Inc., RB Pharmaceuticals Limited, et al
`v. Teva Pharmaceuticals USA, Inc., Civil Action 14-
`1451 (D. Del.).
`Declaration of Daniel Doran
`
`Declaration of Michael I. Chakansky
`
`USPTO Patent Review Processing System (PRPS) web
`page at http://www.uspto.gov/patents-application-
`process/appealing-patent-decisions/trials/patent-review-
`processing-system-prps-0 (downloaded on March 7,
`2016).
`A. F. Borges et al., Oral Films: Current Status and Future
`Perspectives II – Intellectual Property, Technologies and
`Market Needs, Journal of Controlled Release 206, pp.
`108-21 (2015).
`H. Kathpalia and A. Gupte, An Introduction to Fast
`Dissolving Oral Thin Film Drug Delivery Systems: A
`Review, Drug Delivery & Formulation 10, pp. 667-84
`(2013).
`J. O. Morales and J. T. McConville, Manufacture and
`Characterization of Mucoadhesive Buccal Films,
`European Journal of Pharmaceutics and
`iv
`
`
`
`
`
`
`
`2012
`
`
`
`Biopharmaceutics 77, pp. 187-99 (2011).
`V.A. Perumal et al., Investigating a New Approach to
`Film Casting for Enhanced Drug Content Uniformity in
`Polymeric Films, Drug Dev. & Indust. Pharm. 34, pp.
`1036-47 (2008).
`
`
`*Patent owner’s exhibits 2001-2008 were previously filed and are listed here again
`pursuant to 37 C.F.R. § 42.63.
`
`
`v
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`U.S. Patent No. 8,603,514 B2
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`1
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`IPR2016-00281
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`Patent Owner MonoSol Rx, LLC (“Patent Owner”), pursuant to 35 U.S.C.
`
`§ 313 and 37 C.F.R. § 42.170, respectfully requests that the Patent Trial and
`
`Appeal Board (“PTAB” or “Board”) deny institution of IPR2016-00281 (281 IPR).
`
`This filing is timely made within three months of the date of the Notice according
`
`the Petition in the 281 IPR the filing date of December 4, 2015. Notice, Paper 3.
`
`I.
`
`INTRODUCTION
`
`Patent Owner respectfully submits that inter partes review of U.S. Patent
`
`No. 8,603,514 (“the ’514 Patent”) should not be instituted in this matter because
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`Petitioner has failed to timely file the Petition. Petitioner was served with a
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`complaint on December 3, 2014 alleging infringement of the ’514 Patent. Because
`
`the Petition was filed more than one year after the date on which Petitioner was
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`served with a complaint alleging infringement of the patent, no inter partes review
`
`may be instituted. See 35 U.S.C. § 315(b).1
`
`
`1 Petitioner filed a motion on February 29, 2016 to change the date of filing in the
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`281 IPR (Paper 10) to December 3, 2015. Patent Owner opposed that motion on
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`March 10, 2016, explaining its lack of merit. (Paper 12). Should Petitioner’s
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`U.S. Patent No. 8,603,514 B2
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`IPR2016-00281
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`The Petition is also defective for other reasons. First, because Petitioner
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`provides an unreasonable or incorrect claim construction for a key claim term,
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`there cannot be a reasonable likelihood of prevailing. Second, because each
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`challenged independent claim contains a 10% drug content uniformity limitation
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`that Petitioner fails to demonstrate is disclosed or suggested by the Petitioner’s
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`references, Petitioner does not show a reasonable likelihood that any challenged
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`claim would have been obvious over the Petitioner’s references. Indeed, Petitioner
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`fails to meet its burden in demonstrating that the challenged claims are rendered
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`obvious by the Petitioner’s references—almost all of which were cited in original
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`prosecution. The Petitioner’s citation to decisions in reexaminations relating to
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`other patents owned by Patent Owner is inapposite both because the claim
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`language addressed therein was different than in the ’514 Patent and because the
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`evidence of record here is substantially different than those cases. Unlike those
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`reexaminations, the record here includes a great deal of additional evidence from a
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`co-pending litigation involving the ’514 Patent and encompasses numerous
`
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`motion be denied, there is no dispute that the 281 IPR Petition is time-barred under
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`35 U.S.C. § 315(b). See discussion herein.
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`U.S. Patent No. 8,603,514 B2
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`publications and extensive expert testimony that further confirm that Petitioner
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`cannot meet its burden of showing a reasonable likelihood that any challenged
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`claim, each of which require at least 10% drug content uniformity, is rendered
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`obvious by Petitioner’s references.
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`Finally, the Petition should be denied as to dependent claims 9 and 65 on the
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`distinct basis that Petitioner has failed to show a reasonable likelihood that the 5%
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`uniformity limitation of those claims is disclosed or suggested by the Petitioner’s
`
`references.
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`II.
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`STATEMENT OF FACTS
`
`The challenged claims in the ’514 Patent are directed to cast films
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`containing, among other things, a particulate active having a specific level of
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`uniformity. Claims 1 and 62 each claim in relevant part:
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`A drug delivery composition comprising: (i) a cast film
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`comprising a flowable water-soluble or water swellable
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`film-forming matrix
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`comprising
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`one
`
`or more
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`substantially water soluble or water swellable polymers;
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`and a desired amount of at least one active;
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`U.S. Patent No. 8,603,514 B2
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`wherein said matrix has a viscosity sufficient to aid in
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`substantially
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`maintaining
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`non-self-aggregating
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`uniformity of the active in the matrix;
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`(ii) a particulate active substantially uniformly stationed in the
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`matrix; and
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`(iii) a taste-masking agent . . . to provide taste-masking of the
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`active;
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`wherein the particulate active [or combined particulate and
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`taste-masking agent] has a particle size of 200 microns or
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`less and said flowable water-soluble or water swellable
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`film-forming matrix is capable of being dried without
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`loss of substantial uniformity in the stationing of said
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`particulate active therein; and
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`wherein the uniformity subsequent to casting and drying of the
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`matrix
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`is measured by substantially equally sized
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`individual unit doses which do not vary by more than
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`10% of said desired amount of said at least one active.
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`U.S. Patent No. 8,603,514 B2
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`Ex. 1001, ’514 Patent at Claims 1, 62.
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`Challenged claims 1 and 62 thus both contain a 10% drug content uniformity
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`(“DCU”) limitation. See id. Those two claims, moreover, are independent claims
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`from which all other challenged claims depend. See Paper 1, Pet., p. 1; Ex. 1001,
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`’514 Patent at Claims 1–3, 9, 15, 62–65, 69–73, 75.
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`Dependent claims 9 and 65 require an even higher degree of drug content
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`uniformity. They are directed to the drug delivery composition of the respective
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`independent claims, “wherein said variation of drug content is less than 5% by
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`weight per film dosage unit.” Ex. 1001, ’514 Patent at Claims 9, 65 (emphasis
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`added).
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`III. THE PETITION IS TIME-BARRED UNDER § 315(b)
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`Petitioner certified in the 281 IPR petition that it had standing and was not
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`barred, inter alia, by the 1-year bar of 35 U.S.C. § 315(b). Paper 1, Pet., p. 8. That
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`certification depended on Petitioner receiving a December 3, 2015 filing date (id.),
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`which it did not receive. Rather, the PTAB properly accorded the 281 IPR Petition
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`a filing date of December 4, 2015.2 Because Petitioner was served with a
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`complaint claiming infringement of the ’514 Patent (among others) on December
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`3, 2014, Petitioner’s filing of the Petition on December 4, 2015 is outside the
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`statutory bar date.3
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`The statute and the associated regulation clearly provide that no inter partes
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`review may be instituted on a patent more than one year after Petitioner was served
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`with a complaint alleging infringement of that patent. 35 U.S.C. § 315(b); 37
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`C.F.R. § 42.101. If Petitioner filed its Petition outside that one-year-period, no inter
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`partes review may be instituted. See, e.g., Terremark N. Am. LLC v. Joao Control
`
`& Monitoring Sys., LLC, IPR2015-01482, Paper 10 at p. 5 (PTAB Dec. 28, 2015)
`
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`2 Indeed, it was unknown to the PTAB at the time that Petitioner also had only
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`attempted service on December 4, 2015 by tendering incomplete sets of documents
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`to FedEx on that day (Ex 2007, Chakansky Dec. ¶¶ 2–8; Ex 1041, Yost Dec. ¶ 35).
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`3 “Petitioner was served with a complaint asserting the ’514 patent on December 3,
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`2014 in Reckitt Benckiser Pharmaceuticals Inc., RB Pharmaceuticals Limited, et al
`
`v. Teva Pharmaceuticals USA, Inc., Civil Action 14-1451 (D. Del.).” Paper 1, Pet.,
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`p. 8.
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`U.S. Patent No. 8,603,514 B2
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`IPR2016-00281
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`(“Because at least one of the petitioning parties was served with a complaint on
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`June 23, 2014 (Exs. 2002–2005), the statutory bar date for IPR2015-01485 is June
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`23, 2015. 35 U.S.C. § 315(b); 37 C.F.R. § 42.101(b). Petitioner, however, was
`
`accorded a filing date of June 24, 2015. Paper 3.” (“[T]he Petition falls outside the
`
`one-year time bar set forth in 35 U.S.C. § 315(b). We, thus, deny inter partes
`
`review of the ’363 patent.”); Paper 10 at p. 16 see also Lannett Holdings, Inc. v.
`
`Astrazeneca AB, IPR 2015-01629, Paper 14 (PTAB Jan. 27, 2016) (denying
`
`institution where Petition was filed one day after one year statutory bar date). As
`
`the Supreme Court has explained:
`
`Filing deadlines, like statutes of limitations, necessarily
`operate harshly and arbitrarily with respect to individuals
`who fall just on the other side of them, but if the concept
`of a filing deadline is to have any content, the deadline
`must be enforced. Any less rigid standard would risk
`encouraging a lax attitude toward filing dates … A filing
`deadline cannot be complied with, substantially or
`otherwise, by filing late—even by one day.
`United States v. Locke, 471 U.S. 84, 100–01 (1985) (emphasis added) (citations
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`omitted).
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`U.S. Patent No. 8,603,514 B2
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`Here, it is not disputed that Petitioner was served with a complaint on
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`December 3, 2014 alleging infringement of the ’514 Patent.4 It is also not disputed
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`that the petition has been accorded a filing date of December 4, 2015 and that if
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`Petitioner’s Motion to Change the Filing Date from December 4 to December 3,
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`2015 is denied, the Petition is time-barred under § 315(b).5 For reasons stated in
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`Patent Owner’s opposition to that motion (Paper 12), Patent Owner respectfully
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`submits that Petitioner’s motion is without merit and should be denied.
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`Accordingly, Patent Owner requests that the Board deny institution of inter partes
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`review in the 281 IPR under 35 U.S.C. § 315(b).
`
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`4 Petitioner admits “Petitioner was served with a complaint asserting the ’514 patent
`
`on December 3, 2014
`
`in Reckitt Benckiser Pharmaceuticals
`
`Inc., RB
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`Pharmaceuticals Limited, et al. v. Teva Pharmaceuticals USA, Inc., Civil Action
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`14-1451 (D. Del.).” Paper 1, Pet., p. 8.
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`5 See Teva Pharms. USA, Inc. v. Indivior UK Ltd., IPR 2016-00280, Paper 8 at p. 2
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`(PTAB Feb. 18, 2016) (“Both parties agreed that an effective filing date of
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`December 4, 2015, for the Petition in this case would implicate a time bar under 35
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`U.S.C. § 315(b).”).
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`IV. CLAIM CONSTRUCTION
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`In an inter partes review, claim terms are interpreted according to their
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`"broadest reasonable construction in light of the specification of the patent in
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`which it appears.” In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1275–79 (Fed.
`
`Cir. 2015)6; 37 C.F.R. § 42.100(b); Office Patent Trial Practice Guide, 77 Fed.
`
`Reg. 48756, 48766 (Aug. 14, 2012). The broadest reasonable interpretation must
`
`be consistent with the specification. In re Suitco Surface, Inc., 603 F.3d 1255,
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`1259–60 (Fed. Cir. 2010) (“[C]laims should always be read in light of the
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`specification and teachings in the underlying patent” when determining their
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`broadest reasonable construction).
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`In the absence of a reasonable claim construction, a petitioner cannot show a
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`reasonable likelihood of success on its grounds for unpatentability. See Microsoft
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`Corp. v. Proxyconn, Inc., IPR2012-00026, Paper 17 at p. 24 (PTAB Dec. 21, 2012)
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`6 reh’g en banc denied, 793 F.3d 1297 (Fed. Cir. 2015), cert. granted, 136 S.Ct.
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`890, 2016 WL 205946 (U.S. Jan. 15, 2016) (No. 15-446). Should the Supreme
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`Court change this standard, Patent Owner may at that time request leave to address
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`the impact of such a ruling.
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`(explaining that “[a]s this argument is premised on Petitioner’s erroneous claim
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`construction we are not persuaded of a reasonable likelihood of prevailing.”)
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`Because Petitioner has not offered a reasonable claim construction of the limitation
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`“dried without loss of substantial uniformity,” Petitioner has not demonstrated that
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`it has a reasonable likelihood of prevailing to show the claims are unpatentable.
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`A.
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`“dried without loss of substantial uniformity” (Claims 1 and 62)
`Petitioner asserts that it is construing the claim limitation “dried without loss
`
`
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`of substantial uniformity,” but it only addresses the word “drying” in isolation,
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`ignoring the rest of the phrase which expressly provides that the drying must not
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`result in the loss of substantial uniformity. Paper 1, Pet., p. 15. As such, Petitioner
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`has failed to propose a reasonable construction for the claim limitation.
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`
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`By addressing only the term “drying,” Petitioner effectively reads out the
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`explicit requirement of the claims that the drying occur without the loss of
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`substantial uniformity. This cannot be the broadest reasonable construction, as
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`Petitioner disregards the language of the claim and the disclosure of the
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`specification. See Phillips v. AWH Corp., 415 F.3d 1303, 1314 (Fed. Cir. 2005) (en
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`banc) (“[T]he context in which a term is used in the asserted claim can be highly
`
`instructive.”); ACTV, Inc. v. Walt Disney Co., 346 F.3d 1082, 1088 (Fed. Cir.
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`U.S. Patent No. 8,603,514 B2
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`2003) (“While certain terms may be at the center of the claim construction debate,
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`the context of the surrounding words of the claim also must be considered in
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`determining the ordinary and customary meaning of those terms.”)
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`For the foregoing reasons, the Petitioner’s proposed incorrect construction
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`should not be adopted, and the broadest reasonable construction of the claim term
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`as a whole—i.e., “dried without loss of substantial uniformity”—should be its
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`plain meaning.
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`V.
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`
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`PETITIONER HAS NOT SHOWN A REASONABLE LIKELIHOOD
`THAT THE CHALLENGED CLAIMS OF THE ’514 PATENT ARE
`UNPATENTABLE
`Even if the Petition were not untimely and were not based on an incorrect
`
`claim construction, Petitioner has failed to establish a reasonable likelihood that
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`the challenged claims are unpatentable. Claims 1 and 62 are independent claims
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`from which all other challenged claims depend, and each contains a 10% DCU
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`limitation that Petitioner fails to demonstrate is disclosed or suggested by the prior
`
`art. Because Petitioner has not shown a reasonable likelihood that claims 1 and 62
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`would have been obvious over the prior art, Patent Owner requests that the PTAB
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`deny inter partes review as to all claims.
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`U.S. Patent No. 8,603,514 B2
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`The PTAB should also deny the Petition as to claims 9 and 65 on the
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`separate basis that Petitioner has failed to show a reasonable likelihood that the 5%
`
`uniformity limitation of those claims is disclosed or suggested by the prior art.
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`U.S. Patent No. 8,603,514 B2
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`A.
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`Petitioner has not proffered any prior art reference disclosing the
`10% DCU limitation of claims 1 and 62, from which all other
`challenged claims depend.
`
`The Petition fails to identify any prior art reference disclosing the 10% DCU
`
`limitation present in all challenged claims.
`
`
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`At the outset, the evidence cited by the Petition makes no mention
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`whatsoever of 10% variation, or of any measure of final film DCU. The Petition
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`begins by noting that Chen (Ex. 1005) “describes a casting process,” that “employs
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`adequate viscosity, and degassing . . . to ensure uniformity during casting and
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`drying,” and that Chen’s matrix has a viscosity range" overlapping the ’514
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`Patent’s most preferred range. Paper 1, Pet., p. 32. These parameters of Chen,
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`however, say nothing about whether Chen disclosed final film uniformity within
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`10%. Similarly, although the Petition points to Bess’s (Ex. 1004) mention of a
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`“uniform gel,” Paper 1, Pet., pp. 39, 42, the fact that the liquid matrix was
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`“uniform” at a point in its processing prior to drying says nothing about uniformity
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`of the final cast film.
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`U.S. Patent No. 8,603,514 B2
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`As Dr. Langer testified in extensive detail in the co-pending litigation, there
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`are a host of forces that come into play after mixing and during casting and drying
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`that can cause drug migration and aggregation and thus result in a lack of the
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`desired DCU. Ex. 1010, Tr. 486:1-490:15. In Chen, the only discussion of
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`homogeneity relates to mixing before the active ingredient is added, and does not
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`address at all the uniformity of the active in the matrix after it is added or during
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`the casting and drying steps. (Id. at Tr. 504:8-508:15 (Langer).)
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`The Petition then asks the PTAB to draw a groundless inference from the
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`fact that Chen’s films “are made by cutting shapes out of the coated and dried
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`sheet.” Paper 1, Pet., p. 32. But the cutting of films from a sheet says nothing itself
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`about DCU. According to Petitioner, a person of ordinary skill would believe that
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`“individual doses of pharmaceutical films can only be manufactured in this way if
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`the film is at least as uniform as the claimed 10% limit.” Paper 1, Pet., pp. 32-33
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`(emphasis added). Moreover, Petitioner’s assertion is based on an assumption that
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`the manufacturing is of a film approved by FDA for marketing and sale, and there
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`is absolutely nothing to suggest Chen had accomplished that. Petitioner’s expert
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`relies on regulations governing pharmaceutical products requiring that drug content
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`variation fall within 10%, Ex. 1003, Panyam Decl. at ¶ 84, yet there is no evidence
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`of record that the Chen formulators sought, let alone obtained, regulatory approval
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`for their cast film. Petitioner undoubtedly would feature such evidence if it existed.
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`Petitioner next makes an unsupported attempt to correlate DCU with
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`variation in other final film attributes, which is similarly lacking in factual basis
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`and should be rejected. The Petition asserts that variation within 10% of the total
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`“weight and thickness of individual dosage units” in Chen and Bess somehow
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`corresponds to final film drug content, Paper 1, Pet., p. 33 (emphasis added); see
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`also id. at 34–36, and that Cremer’s (Ex. 1006) description of a “homogeneous
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`thickness, density, and width” of the gel must be read in view of a “direct relation .
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`. . between a unit of length of the [film] and the dose of active substance.” Paper 1,
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`Pet., p. 47 (quoting Cremer at 1); see also id. at 50. But nowhere do the Petitioner’s
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`references describe or suggest any purported “direct relation” between the final
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`film’s variation in length, weight, or thickness and variation in drug content, let
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`alone support a conclusion that active content would have varied by less than 10%
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`from the desired amount of active ingredient (the label claim). For example, it is
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`entirely possible that one 70 mg film could contain 20 mg of active, while another
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`70 mg film could contain just 1 mg of active; the evidence does not bear out any
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`correlation between total weight and DCU.7 Indeed, this was a problem being
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`solved by the inventors in the ’514 Patent.
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`To the extent Petitioner relies upon the weight data in Example 1 of Bess,
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`Bess’s weight data do not provide evidence of uniformity. Because the weight
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`data do not measure the amount of active in the film, they cannot be used to
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`quantify whether the active content would have varied by less than 10% from the
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`7 Dr. Panyam’s declaration is tellingly noncommittal and fails to support the
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`Petition’s assertions. In describing example 1 of Chen, Dr. Panyam posits that low
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`variance in weight and thickness of individual dosage units “demonstrates that
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`Chen’s manufacturing process produced the example 1 film in a very uniform
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`manner, and it would have bolstered the person of ordinary skill’s reasonable
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`expectation that the methods in Chen, combined with general knowledge in the
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`film formulation art” could attain “the claimed—or better—uniformity.” Ex. 1003,
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`Panyam Decl. at ¶ 85 (emphasis added).
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`desired amount of active ingredient, as required by the ’514 Patent claims.8 As Dr.
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`Langer testified in the litigation, the only rigorous way of testing DCU, as a POSA
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`would understand, is to use “chemical methods,” i.e., a chemical assay. Ex. 1010,
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`Tr. 561:9-563:18 (Langer).
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`Moreover, Bess’s weight data are reported as a mean and standard deviation,
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`and Petitioner ignores that the full range of sample values is 70 mg ± 9 mg, as
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`evident from Petitioner’s Exhibit 1010. Exhibit 1010 is a trial transcript from the
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`co-pending litigation, dated November 3–4, 2015, which contains the testimony of
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`Patent Owner’s expert Dr. Robert Langer and the defendants’ expert Dr. Craig
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`Dyar. See generally Ex. 1010.9 The opposing experts were in agreement that under
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`8 Indeed, as noted below, to the extent film weight data could be used as a
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`measurement of active content uniformity, the data in Bess shows that its films had
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`greater than 10% variation in weight. (Ex. 1010, Tr. 608, 622-23 (Langer).)
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`9 Petitioner filed as Exhibit 1010 an uncorrected transcript from the co-pending
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`litigation, the consolidated case of Reckitt Benckiser Pharms. Inc. v. Watson Labs,
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`Inc., No. 13-cv-1674 (D. Del.) and Reckitt Benckiser Pharms. Inc. v. Par Pharms.,
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`Inc., No. 14-cv-422 (D. Del.). The transcript caption incorrectly references a
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`the three-sigma rule, a standard deviation must be tripled to approximate the full
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`range of sample measurements.10 Applying this rule, as Patent Owner’s expert Dr.
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`Langer explained, the range of values in the weight data of Bess clearly fall outside
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`the 10% content uniformity variation limit of the challenged claims. Ex. 1010, Tr.
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`604:9–608:9 (Langer). In contrast, the film weight sample range reported in the
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`’514 Patent is within a 10% variation limit even when the standard deviation is
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`tripled. Ex. 1001, ’514 Patent at 47:56–57. Thus, Bess’s weight data could not be
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`taken to indicate the claimed DCU; if anything, they show Bess did not achieve
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`content uniformity within 10%.
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`different case in which Petitioner is the defendant, Reckitt Benckiser Pharms. Inc.
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`v. Teva Pharms USA, Inc., No. 14-cv-1451 (D. Del.). This caption, and the trial
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`transcript, were later corrected after the instant Petition was filed. The corrections
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`to the transcript are immaterial to Patent Owner’s analysis herein.
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`10 It is understood in the field that only 68% of sample measurements would be
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`expected to fall within a single standard deviation. To show the full range of
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`sample measurements, the standard deviation must be tripled; hence the “3-sigma
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`rule.” Ex. 1010, Tr. 378:7–15 (Dyar), 517:5–519:21, 622:9–24 (Langer).
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`In the end, Petitioner’s contention that the prior art disclosed less than 10%
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`variation rests principally on Figure 5 of Chen, which shows the results of
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`dissolution testing on certain cast films produced by Chen et al. Paper 1, Pet., pp.
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`39, 42, 47, 50; Ex. 1005. As a preliminary matter, the Petition itself undermines the
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`reliability of Figure 5, recognizing that “[a] person of ordinary skill would not
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`usually choose to use a dissolution test like the one reported in Figure 5 to
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`measure [DCU]” and that dissolution testing’s measurement of the amount of
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`active content released over time “is at best an indirect measure of uniformity that
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`is subject to various sources of error.” Paper 1, Pet., p. 34 (emphases added).11
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`Moreover, Petitioner’s own evidence confirms that Figure 5 contained no
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`disclosure of 10% uniformity. As Petitioner’s Exhibit 1010 shows, in the co-
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`pending litigation, the defendants’ expert Dr. Dyar admitted that he could not
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`11 As Petitioner’s expert explains, the error bars in Figure 5 of Chen “include all
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`error associated with the dissolution test including human error, instrument error,
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`and any other possible errors,” and “[s]ome indeterminate amount of the variation
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`of drug content uniformity may be buried within those error bars.” Ex. 1003,
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`Panyam Decl. at ¶ 86 n.11.
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`determine whether Figure 5 of Chen showed 10% variation. Ex. 1010, Tr. 369:17–
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`371:3 (Dyar). This admission was consistent with the opinion of Patent Owner’s
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`expert in the same litigation that Chen did not disclose 10% variation. Ex. 1010,
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`Tr. 504:8–519:21 (Langer). Like both sides’ experts, a person of ordinary skill in
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`the art would not understand Figure 5 of Chen as indicating whether the 10%
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`variation requirement is met.
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`The opposing experts in the co-pending litigation both recognized that the
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`error bars in Figure 5 of Chen represent one standard deviation from the mean
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`percentage of drug released, which means that only 68% of sample measurements
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