UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`COALITION FOR AFFORDABLE DRUGS VII LLC,
`Petitioner,
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`v.
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`POZEN INC.,
`Patent Owner.
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`IPR2015-01718
`Patent 8,945,621
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`PETITIONER’S REPLY TO PATENT OWNER’S RESPONSE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`COALITION FOR AFFORDABLE DRUGS VII LLC,
`Petitioner,
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`v.
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`POZEN INC.,
`Patent Owner.
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`IPR2015-01718
`Patent 8,945,621
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`PETITIONER’S REPLY TO PATENT OWNER’S RESPONSE
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`I.
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`II.
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`IPR2015-01718
`Patent 8,945,621
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`TABLE OF CONTENTS
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`INTRODUCTION ........................................................................................... 1
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`BACKGROUND OF THE ’621 PATENT ..................................................... 1
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`A.
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`B.
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`The ’621 Patent Is an Improper Attempt to Extend the Term of
`Patents for Vimovo® ............................................................................. 1
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`The Claimed “Inventions” of the ’621 Patent Reside in the
`Final “Wherein” Clause of the Independent Claims ............................. 4
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`III. ARGUMENT ................................................................................................... 5
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`A.
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`The Final “Wherein” Clause Is Not Entitled to Patentable
`Weight ................................................................................................... 5
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`1.
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`2.
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`3.
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`The Final “Wherein” Clause Merely States a Result .................. 5
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`Patent Owner Cites No Case Law to Support Giving the
`Final “Wherein” Clause Patentable Weight ................................ 7
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`The Final “Wherein” Clause Is Unpatentable Under 35
`U.S.C. § 101 .............................................................................. 11
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`B.
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`Ground 1: The Final “Wherein” Clause Is Obvious Over
`Plachetka in View of Graham and Goldstein ...................................... 12
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`1.
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`2.
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`3.
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`The Evidence Proves that the Claims are Obvious Over
`Plachetka in View of Graham and Goldstein ............................ 12
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`A POSA Would Have Considered Graham and Goldstein ...... 15
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`The Cited Prior Art References Do Not “Teach Away”
`from the Claimed Invention ...................................................... 18
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`C.
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`Ground 2: The Final “Wherein” Clause Is the Inherent Result of
`Plachetka. ............................................................................................ 20
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`IV. CONCLUSION .............................................................................................. 22
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`i
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`IPR2015-01718
`Patent 8,945,621
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`TABLE OF AUTHORITIES
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`Cases
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`Amgen Inc. v. Hoechst Marion Roussel, Inc.,
`314 F.3d 1313 (Fed. Cir. 2003) .......................................................................... 16
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`Ass’n for Molecular Pathology v. Myriad Genetics, Inc.,
`133 S. Ct. 2107 (2013) ........................................................................................ 11
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`Beckman Instruments, Inc. v. LKB Produkter AB,
`892 F.2d 1547 (Fed. Cir. 1989) .......................................................................... 16
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`Biosig Instruments, Inc. v. Nautilus, Inc.,
`783 F.3d 1374 (Fed. Cir. 2015) ............................................................................ 9
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`Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) ............................................................................ 7
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`DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`567 F.3d 1314 (Fed. Cir. 2009) .......................................................................... 19
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`Eltech Sys. Corp. v. PPG Indus., Inc.,
`710 F. Supp. 622 (W.D. La. 1988), aff’d in part, 903 F.2d 805 (Fed. Cir.
`1990) ................................................................................................................... 10
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`Gottschalk v. Benson,
`409 U.S. 63 (1972) .............................................................................................. 11
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`Hoffer v. Microsoft Corp.,
`405 F.3d 1326 (Fed. Cir. 2005) (per curiam) ....................................................... 8
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`In re Fulton,
`391 F.3d 1195 (Fed. Cir. 2004) .......................................................................... 19
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`In re Pearson,
`494 F.2d 1399 (CCPA 1974) .............................................................................. 21
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`In re Schreiber,
`128 F.3d 1473 (Fed. Cir. 1997) .......................................................................... 21
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`ii
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`In re Spada,
`911 F.2d 705 (Fed. Cir. 1990) ............................................................................ 21
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`IPR2015-01718
`Patent 8,945,621
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`In re Zierden,
`411 F.2d 1325 (CCPA 1969) .............................................................................. 21
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`Mayo Collaborative Servs. v. Prometheus Labs., Inc.,
`132 S. Ct. 1289 (2012) ................................................................................. 11, 12
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`Minton v. National Ass’n of Securities Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) ........................................................................6, 7
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`Par Pharm., Inc. v. TWI Pharm., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) .......................................................................... 22
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`Research Found. of State Univ. of New York v. Mylan Pharm. Inc.,
`723 F. Supp. 2d 638 (D. Del. 2010) ..................................................................7, 8
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`Symbol Tech., Inc. v. Opticon, Inc.,
`935 F.2d 1569 (Fed. Cir. 1991) .......................................................................... 16
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`Syntex (U.S.A.) LLC v. Apotex, Inc.,
`407 F.3d 1371 (Fed. Cir. 2005) ............................................................................ 7
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`Texas Instruments, Inc. v. U.S. Int’l Trade Comm’n.,
`988 F.2d 1165 (Fed. Cir. 1993) ............................................................................ 6
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`Thermalloy Inc. v. Aavid Eng’g, Inc.,
`935 F. Supp. 55 (D.N.H. 1996), amended by, 935 F. Supp. 63 (D.N.H.
`1996), aff’d, 121 F.3d 691 (Fed. Cir. 1997) ....................................................... 10
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`Statutes
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`35 U.S.C. § 101 ........................................................................................................ 11
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`35 U.S.C. § 103 ................................................................................................... 4, 16
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`iii
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`I.
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`INTRODUCTION
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`IPR2015-01718
`Patent 8,945,621
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`During the institution phase of this proceeding, the Board found that the
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`“Petition establishes a reasonable likelihood” that all claims 1–16 of the ’621
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`patent are unpatentable on both Grounds 1 and 2 of the Petition. Decision at 21.
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`The Board also raised the issue of whether the final “wherein” clause of the
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`independent claims should be entitled to patentable weight. Decision at 15, 20.
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`None of the arguments raised by Patent Owner in its Response are sufficient
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`to alter the prior decision of the Board. Patent Owner has no new answer for
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`overcoming the prior art asserted in Grounds 1 and 2 of the Petition. Nor does
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`Patent Owner plausibly explain why the final “wherein” clause—which recites the
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`natural result of using an existing pharmaceutical product—should be entitled to
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`any patentable weight.
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`The Board’s initial findings are supported by more than substantial evidence
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`and are correct as a matter of law. Petitioner, therefore, respectfully requests that
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`the Board issue a Final Written Decision finding the instituted claims to be
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`unpatentable.
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`II. BACKGROUND OF THE ’621 PATENT
`A. The ’621 Patent Is an Improper Attempt to Extend the Term of
`Patents for Vimovo®
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`It is undisputed that the ’621 Patent is directed to methods of treating
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`patients by administering an existing pharmaceutical product. In its Response,
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`1
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`Patent Owner explains that “[t]he ’621 patent is directed to methods of reducing
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`the incidence of gastric ulcers associated with the use of NSAIDs in patients who
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`are also taking LDA.” Response at 15 (citing Ex. 1001, ’621 Patent, at claim 1).
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`Patent Owner further explains that “[t]hese methods require the administration of a
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`unit dosage form that is comprised of 20 mg of the acid inhibitor esomeprazole
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`and 500 mg of the non-selective NSAID naproxen.” Id. (emphasis added).
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`Although Patent Owner refers to this “unit dosage form” pharmaceutical product
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`generically, there is no question that Patent Owner is referring to Vimovo®, which
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`existed years before the ’621 Patent’s earliest claimed priority date of June 25,
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`2009.1
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`The ’621 Patent is one of at least nine patents listed in the FDA’s Orange
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`Book as covering the pharmaceutical product Vimovo®. (Ex. 2021, Makuch
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`Decl., at ¶ 32; Ex. 2022, Johnson Decl., at ¶ 43; Ex. 1036, Orange Book Patent
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`Data for Vimovo®, at 2.) Patent Owner’s expert, David A. Johnson, M.D.,
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`confirmed at his deposition that “PN400,” the pharmaceutical product that is
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`described in the ’621 Patent, is another name for Vimovo®. (Ex. 1037, Johnson
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`Dep. Tr., at 33:16–18.)
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`1 It is undisputed that the’621 Patent’s earliest claimed priority date is June 25,
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`2009. See Response at 18 (citing Ex. 1001, ’621 Patent).
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`2
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`The earliest Vimovo® patent listed in the Orange Book that is directed to a
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`Patent 8,945,621
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`“unit dosage form” pharmaceutical product is U.S. Patent No. 6,926,907, which is
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`the prior art reference referred to as “Plachetka” in this IPR proceeding. (Ex. 1036,
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`Orange Book Patent Data for Vimovo®, at 2; Petition at 4; Ex. 1004, Plachetka.)
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`Patent Owner’s expert, Dr. Johnson, also confirmed that Plachetka is directed to
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`Vimovo®. (Ex. 1037, Johnson Dep. Tr., at 48:13–49:1.)
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`Plachetka issued as the ’907 Patent on August 9, 2005, approximately four
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`years before the earliest priority date of the ’621 Patent. (Ex. 1004, Plachetka.)
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`Despite the fact that both Plachetka and the ’621 Patent are directed to Vimovo®,
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`and they share one named inventor (John R. Plachetka), the two patents are not in
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`the same patent family. The ’621 Patent does not claim priority to Plachetka.
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`(Ex. 1004, Plachetka; Ex. 1001, ’621 Patent.) As such, ’621 Patent’s term is not
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`set to expire until October 17, 2031—over eight years after Plachetka will expire.2
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`(Ex. 1001, ’621 Patent.)
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`The ’621 Patent should be seen for what it is—an improper attempt to
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`extend the term of Plachetka and related patents directed to Vimovo®. The Board
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`2 Plachetka’s term is expected to expire on February 28, 2023. (Ex. 1004,
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`Plachetka.)
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`3
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`should see through Patent Owner’s evergreening scheme and find that all 16 claims
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`Patent 8,945,621
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`of the ’621 Patent are unpatentable.
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`B.
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`The Claimed “Inventions” of the ’621 Patent Reside in the Final
`“Wherein” Clause of the Independent Claims
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`It is undisputed that the patentability of all 16 claims of the ’621 Patent
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`depends on the viability of the final “wherein” clause of each of the independent
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`claims:
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`wherein administration of the unit dose form is more effective at
`reducing the incidence of the NSAID-associated ulcers in patients
`taking LDA than in patients not taking LDA who are administered the
`unit dose form.
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`(Ex. 1001, ’621 Patent, at claims 1, 8, 15, 16.) During prosecution, without the
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`final “wherein” clause, all of the claims stood rejected by the Examiner as obvious
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`under 35 U.S.C. § 103 over Plachetka. Response at 19–20. As explained by
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`Patent Owner, the Examiner added the final “wherein” clause by entering an
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`Examiner’s Amendment with the Notice of Allowance. Response at 21.
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`The Examiner adopted the final “wherein” clause based on the Applicants’
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`representation that administering the claimed unit dosage form to patients
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`produced “unexpected results.” Response at 20–21, 29–30. The Examiner stated
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`that adding the final “wherein” clause rendered the claims commensurate in scope
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`4
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`with the “demonstrated unexpected results” of administering the claimed unit
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`IPR2015-01718
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`dosage form to patients. Id.
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`The Examiner, however, failed to consider whether the so-called
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`“unexpected results” merely were the natural results of using the claimed unit
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`dosage form. The Examiner also failed to consider whether the results were
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`obvious over all of the relevant prior art, including the prior art references asserted
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`in this IPR proceeding. As discussed below, when all of these issues are
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`considered, it is clear that the final “wherein” clause is not viable and cannot save
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`the patentability of the claims of the ’621 Patent.
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`III. ARGUMENT
`A. The Final “Wherein” Clause Is Not Entitled to Patentable Weight
`1.
`The Final “Wherein” Clause Merely States a Result
`The final “wherein” clause at issue does nothing more than recite the results
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`of administering the claimed unit dosage form to a patient. Specifically, the final
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`“wherein” clause states that “administration of the unit dose form is more effective
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`at reducing the incidence of the NSAID-associated ulcers in patients taking LDA
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`than in patients not taking LDA.” (Ex. 1001, ’621 Patent, at claims 1, 8, 15, 16.)
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`This clause does not recite a further limitation of a composition or a process, and it
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`does not describe any function. In fact, none of the claim language explains how
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`5
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`or why the claimed unit dosage form functions to reduce the incidence of NSAID-
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`IPR2015-01718
`Patent 8,945,621
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`associated ulcers in patients taking LDA.
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`The claimed results simply were observed by the named inventors of the
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`’621 Patent. As explained by Patent Owner, “in 2009, the inventors of the ’621
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`patent unexpectedly and surprisingly found that the unit dose form claimed in the
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`’621 patent results in a greater reduction in incidence of gastric ulcer in patients
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`also taking LDA than in patients not taking LDA.” Response at 3 (emphasis
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`added).
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`As the Board noted in the Institution Decision, a “whereby” or “wherein”
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`clause “that merely states the result of the limitations in the claim adds nothing to
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`the patentability or substance of the claim.” Decision at 15–16 (citing Texas
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`Instruments, Inc. v. U.S. Int’l Trade Comm’n., 988 F.2d 1165, 1172 (Fed. Cir.
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`1993); Minton v. National Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381
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`(Fed. Cir. 2003)). Here, the final “wherein” clause plainly states the results of
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`administering the claimed unit dosage form to a patient and nothing more. This
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`language is not limiting and is not entitled to patentable weight.
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`The law is well settled on this issue. The Federal Circuit repeatedly has held
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`that claim language that “is only a statement of purpose and intended result” which
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`“does not result in a manipulative difference in the steps of the claim” is not
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`limiting. Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1376
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`6
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`(Fed. Cir. 2001); see also Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1378
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`IPR2015-01718
`Patent 8,945,621
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`(Fed. Cir. 2005) (finding clause that “simply describes the intended result” of
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`following the steps in claimed method was not limiting). Thus, in general “[a]
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`whereby [or wherein] clause in a method claim is not given weight when it simply
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`expresses the intended result of a process step positively recited.” Minton, 336
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`F.3d at 1381.
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`2.
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`Patent Owner Cites No Case Law to Support Giving the
`Final “Wherein” Clause Patentable Weight
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`Patent Owner argues that the final “wherein” clause is limiting and entitled
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`to patentable weight because it was “added during prosecution by the Examiner to
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`recite unexpected results.” Response at 31. But none of the cases cited by Patent
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`Owner support this argument.
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`First, Patent Owner misrepresents a District of Delaware decision—
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`Research Found. of State Univ. of New York v. Mylan Pharm. Inc.—as “holding
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`that a ‘wherein’ clause added by the examiner during prosecution to overcome
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`prior art was limiting and entitled to patentable weight.” Response at 31 (citing
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`Mylan, 723 F. Supp. 2d 638, 653–54 (D. Del. 2010)). This was not the holding of
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`the Delaware court. In this decision, the court did not even reach a final
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`determination as to the validity or patentability of any of the claims at issue
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`because it was a ruling on a motion for a preliminary injunction. See Mylan, 723
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`7
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`F. Supp. 2d at 644. Instead, the court made a preliminary determination that the
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`plaintiff was likely to prevail on the issue of validity at trial. Id. at 652. And, in
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`contrast to the present case, the court’s determination of likely validity was not
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`solely based on a final “wherein” clause added by an examiner. Id. at 652–54.
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`Importantly, the court found that the prior art failed to disclose multiple claim
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`limitations, including limitations directed to the specific compound and dosage of
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`the pharmaceutical product to be administered. Id. at 652–53.
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`The next case, Hoffer v. Microsoft Corp., on which Patent Owner relies, is
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`distinguishable from the claims at issue here. Response at 31 (citing Hoffer, 405
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`F.3d 1326, 1329–30 (Fed. Cir. 2005) (per curiam)). In Hoffer, the Federal Circuit
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`held that the disputed “whereby” clause did not merely state “the intended result of
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`a process step,” but rather was “part of the process itself.” Hoffer, 405 F.3d at
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`1330. The Federal Circuit further held that “when the ‘whereby’ clause states a
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`condition that is material to patentability, it cannot be ignored in order to change
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`the substance of the invention.” Id. at 1329. Here, although the ’621 Patent’s
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`specification indicates that reducing the incidence of NSAID-associated ulcers in
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`8
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`patients taking LDA is important,3 it is not part of the process itself—it is the
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`IPR2015-01718
`Patent 8,945,621
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`intended result of the process. And, unlike the “whereby” clause in Hoffer, the
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`final “wherein” clause of the ’621 Patent’s claims could be ignored without
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`changing the substance of the claimed invention. As Patent Owner admits, the
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`Applicants initially submitted the claims sans the final “wherein” clause and fought
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`through three rounds of Office Action rejections before agreeing to allow the
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`Examiner add it to the claims. Response at 19–21.
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`Another distinguishable case that Patent Owner cites is Biosig Instruments,
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`Inc. v. Nautilus, Inc., in which the Federal Circuit found a “whereby” clause that
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`described a “function” to be limiting. Response at 31 (citing Biosig, 783 F.3d
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`1374, 1383 (Fed. Cir. 2015)). Unlike the “whereby” clause at issue in Biosig, the
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`final “wherein” clause at issue here does not describe a function or explain how
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`the claimed unit dosage form reduces the incidence of NSAID-associated ulcers in
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`patients taking LDA—it merely recites the results of administering the claimed
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`unit dosage form.
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`3 See, e.g., Ex. 1001, ’621 Patent, col. 18 ll. 48–52 (“Minimization of gastric side
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`effects is of particular importance in chronic NSAID users who also take LDA for
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`cardiovascular prophylaxis.”).
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`9
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`Yet another distinguishable case on which Patent Owner relies is Thermalloy
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`Patent 8,945,621
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`
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`Inc. v. Aavid Eng’g, Inc., in which the court found a “wherein” clause to be
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`limiting. Response at 32 (citing Thermalloy, 935 F. Supp. 55, 60 (D.N.H. 1996),
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`amended by, 935 F. Supp. 63 (D.N.H. 1996), aff’d, 121 F.3d 691 (Fed. Cir. 1997)).
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`In Thermalloy, the claim at issue was directed to a method for manufacturing a
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`heat sink apparatus. Thermalloy, 935 F. Supp. at 57. The “wherein” clause at
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`issue there specifically limited the claimed process of forming parallel grooves and
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`fins to a “six to one fin height to groove width ratio.” Id. at 60. Here, the final
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`“wherein” clause does not specify any boundaries or parameters of administering
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`the claimed unit dosage form. Again, it merely recites the results of administering
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`the claimed unit dosage form.
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`The last case that Patent Owner cites, Eltech Sys. Corp. v. PPG Indus., Inc.,
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`is also distinguishable because the “whereby” clause at issue there added an
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`essential step to the claimed method. Response at 32 (citing Eltech, 710 F. Supp.
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`622, 633 (W.D. La. 1988), aff’d in part, 903 F.2d 805 (Fed. Cir. 1990)). In Eltech,
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`the claim at issue was directed to a method for preparing dimensionally stable
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`asbestos diaphragms that were resistant to swelling during cell operation. Eltech,
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`710 F. Supp. at 626–27. The “wherein” clause at issue there specifically
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`“require[d] that a diaphragm prepared by the claimed method must be
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`dimensionally stable during cell operating conditions.” Id. at 633. Here, the final
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`10
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`“wherein” clause does not require any specific conditions for administering the
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`Patent 8,945,621
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`claimed unit dosage form—it merely recites the results of administering the
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`claimed unit dosage form.
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`3.
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`The Final “Wherein” Clause Is Unpatentable Under 35
`U.S.C. § 101
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`An additional reason that the final “wherein” clause should not be given any
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`patentable weight is that it describes the results of a natural process that merely
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`were discovered, and it would not pass scrutiny under 35 U.S.C. § 101.
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`“Phenomena of nature, though just discovered, mental processes, and abstract
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`intellectual concepts are not patentable, as they are the basic tools of scientific and
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`technological work.” Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S.
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`Ct. 1289, 1293 (2012) (quoting Gottschalk v. Benson, 409 U.S. 63, 67 (1972)).
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`“Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy
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`the § 101 inquiry.” Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133
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`S. Ct. 2107, 2117 (2013).
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`As the Supreme Court has made clear, “to transform an unpatentable law of
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`nature into a patent-eligible application of such a law, one must do more than
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`simply state the law of nature while adding the words ‘apply it.’” Mayo, 132 S. Ct.
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`at 1294 (citing Benson, 409 U.S. 71–72). Yet, the claims of the ’621 Patent do
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`nothing more than instruct doctors to treat patients with an existing unit dosage
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`11
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`form pharmaceutical product. Upon ingestion of the unit dosage form, the
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`IPR2015-01718
`Patent 8,945,621
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`patients’ bodies will naturally process the active compounds to achieve the claimed
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`results. This natural process is not patentable subject matter under 35 U.S.C. 101.
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`See Mayo, 132 S. Ct. at 1297 (“The relation is a consequence of the ways in which
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`thiopurine compounds are metabolized by the body—entirely natural processes.
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`And so a patent that simply describes that relation sets forth a natural law.”).
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`B. Ground 1: The Final “Wherein” Clause Is Obvious Over
`Plachetka in View of Graham and Goldstein
`1.
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`The Evidence Proves that the Claims are Obvious Over
`Plachetka in View of Graham and Goldstein
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`Citing the expert declaration of Leon Shargel, Ph.D., R.Ph., the Petition
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`provides in Ground 1 that the final “wherein” clause of the independent claims is
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`disclosed by Plachetka in view of Graham and Goldstein:
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`Specifically, Graham and Goldstein disclose that 6.25% of patients
`taking a combination of 15 mg of lansoprazole and an NSAID with
`LDA have gastric ulcers, while 23% of patients taking a combination
`of 15 mg of lansoprazole and an NSAID without LDA have gastric
`ulcers. (Id. at ¶ 83.) Similarly, Graham and Goldstein disclose that
`0% of patients taking a combination of 30 mg of lansoprazole and an
`NSAID with LDA have gastric ulcers, while 17% of patients taking a
`combination of 30 mg of lansoprazole and an NSAID without LDA
`have gastric ulcers. (Id.)
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`Petition at 17–18 (citing Ex. 1003, Shargel Decl., at ¶ 83).
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`12
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`Although Petitioner did not quote Dr. Shargel’s full analysis of the Graham
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`IPR2015-01718
`Patent 8,945,621
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`and Goldstein results in the body of the Petition due to page-limit constraints, the
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`basis for Petitioner’s conclusion that Graham and Goldstein render the final
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`“wherein” clause obvious is included in the record. Dr. Shargel’s full analysis—
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`the basis for the conclusion that Graham and Goldstein render the final “wherein”
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`clause obvious—is located in Appendix B to the Shargel Declaration,4 which
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`discusses the Graham and Goldstein results in depth and provides in relevant part:
`
`Graham shows that, for the total study population of patients who
`were long-term users of NSAIDS, 49% of the patients in the placebo
`group had GUs (51% free), 21% of the patients in the lansoprazole 15
`mg group had GUs (79% free of GUs), and 17% of the patients in the
`lansoprazole 30 mg group had GUs (83% free of GUs). Goldstein
`shows that, for the total study population of patients who were long
`term users of NSAIDS and on LDA, 65% of the patients in the
`placebo group had GUs (35% free of GUs), 6.25% of the patients in
`the lansoprazole 15 mg group had GUs (93.75% free of GUs), and 0%
`of the patients in the lansoprazole 30 mg group had GUs (100% free
`of GUs).
`
`
`4 Ex. 1003, Shargel Decl., ¶ 55 (“I agree with and incorporate the claim chart for
`
`this ground, which is attached hereto as Appendix B . . . .”).
`
`13
`
`
`
`
`(Ex. 1003, Shargel Decl., Appendix B at 12.) Dr. Shargel also provides, in
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`IPR2015-01718
`Patent 8,945,621
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`Appendix B, that a POSA would have been able to use simple math to determine
`
`the number of patients in the study who were not on LDA:
`
`A POSA would have understood Graham and Goldstein to disclose
`the number of patients not on LDA to be 111 for those in the placebo
`group, 120 for those in the lansoprazole 15 mg group, and 125 for
`those in the lansoprazole 30 mg group. Thus, a POSA would have
`understood Graham and Goldstein to disclose the percentage of
`patients not on LDA with GUs to be 46% for the placebo group, 23%
`for the lansoprazole 15 mg group, and 18% for the lansoprazole 30
`mg group.
`
`(Id. at 13.) Dr. Shargel further provides that “a POSA would have arrived at the
`
`following table,” summarizing the simple math:
`
`
`
`14
`
`
`
`
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`IPR2015-01718
`Patent 8,945,621
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`(Id. at 13–14.) Finally, Dr. Shargel ties the numbers in the table to the arguments
`
`
`
`made in the Petition:
`
`Graham and Goldstein show that, in the lansoprazole 15 mg group,
`those taking LDA had a less chance (6.25% versus 23%) of gastric
`ulcers compared to those not on LDA. Similarly, in the lansoprazole
`30 mg group, those taking LDA had a less chance (0% versus 18%) of
`gastric ulcers compared to those not on LDA. Thus, a POSA would
`have understood Graham and Goldstein to disclose this limitation
`given the structural, functional, and other similarities between
`Graham’s and Goldstein’s lansoprazole and Plachetka’s
`esomeprazole.
`
`(Id. at 14.) Dr. Shargel’s analysis, therefore, establishes that Graham and
`
`Goldstein disclose that the administration of the combination of an acid inhibitor
`
`with an NSAID is more effective at reducing the incidence of NSAID-associated
`
`ulcers in patients taking LDA than in patients not taking LDA. (Ex. 1003, Shargel
`
`Decl., at ¶ 83, Appendix B at 12–14.)
`
`A POSA Would Have Considered Graham and Goldstein
`
`2.
`Patent Owner does not dispute the accuracy of Dr. Shargel’s math or deny
`
`that the results of the Graham and Goldstein studies actually show that the
`
`15
`
`
`
`
`administration of the combination of an acid inhibitor with an NSAID is more
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`IPR2015-01718
`Patent 8,945,621
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`effective at reducing the incidence of NSAID-associated ulcers in patients taking
`
`LDA. Instead, Patent Owner attempts to discredit the Graham and Goldstein
`
`papers by asserting that a POSA “would not rely on the data from Graham and
`
`Goldstein to draw any conclusions regarding LDA usage.” Response at 5. In
`
`particular, Patent Owner argues that a POSA would not rely on Graham and
`
`Goldstein “because the Graham study is not an appropriate study from which to
`
`select data to analyze the effect of such concomitant administration.” Response at
`
`37. But Patent Owner provides no legal or evidentiary basis for making this
`
`allegation—it is unsupported attorney argument.
`
`Under a 35 U.S.C. § 103 analysis, a reference qualifies as prior art “for
`
`whatever is disclosed therein.” Amgen Inc. v. Hoechst Marion Roussel, Inc., 314
`
`F.3d 1313, 1357 (Fed. Cir. 2003). The law does not require a § 103 prior art
`
`reference to perfectly teach a POSA how to make and use the invention to qualify
`
`as an invalidating reference for an obviousness analysis. Even “[a] non-enabling
`
`reference may qualify as prior art for the purpose of determining obviousness.”
`
`Symbol Tech., Inc. v. Opticon, Inc., 935 F.2d 1569, 1578 (Fed. Cir. 1991). Under
`
`§ 103, even “an inoperative device . . . is prior art for all that it teaches.” Beckman
`
`Instruments, Inc. v. LKB Produkter AB, 892 F.2d 1547, 1551 (Fed. Cir. 1989).
`
`16
`
`
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`In addition to having no legal basis, Patent Owner’s argument is not
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`IPR2015-01718
`Patent 8,945,621
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`
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`supported by the evidence. Patent Owner cites paragraph 46 of the declaration of
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`its expert in biostatistics, Robert W. Makuch, Ph.D., for the assertion that “a POSA
`
`would not look to the Graham data to draw any conclusions regarding patients’
`
`LDA usage.” Response at 38 (citing Ex. 2021, Makuch Decl., at ¶ 46). Paragraph
`
`46 of Dr. Makuch’s declaration, however, does not leap to that conclusion. (Ex.
`
`2021, Makuch Decl., at ¶ 46.) And when Dr. Makuch was asked at his deposition
`
`whether a POSA would have relied on Graham to draw any conclusions about
`
`LDA use and NSAID associated GI injury, he admitted that, in his opinion, a
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`POSA would have considered Graham:
`
`·9· · · · · · · So my question is, is it also
`10· ·your opinion that a POSA would not rely on
`11· ·Graham to draw any conclusions about LDA
`12· ·use and any difference in rates of NSAID
`13· ·associated GI injury?
`14· · · · A· · ·I can’t speak for what others
`15· ·would do, but in my opinion the Graham
`16· ·paper is a larger study and so it is
`17· ·something that I believe a POSA would at
`18· ·least consider.
`
`(Ex. 1038, Makuch Dep. Tr., at 31:9–18 (emphasis added).) Thus, both
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`Petitioner’s and Patent Owner’s experts agree that a POSA would have considered
`
`17
`
`
`
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`the Graham study. (Ex. 1003, Shargel Decl., at ¶¶ 57–59; Ex. 1038, Makuch Dep.
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`IPR2015-01718
`Patent 8,945,621
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`Tr., at 31:9–18.) And the results of the Graham study, which are further reported
`
`in Goldstein, indicate that the administration of the combination of an acid
`
`inhibitor with an NSAID is more effective at reducing the incidence of NSAID-
`
`associated ulcers in patients taking LDA than in patients not taking LDA.
`
`(Ex. 1003, Shargel Decl., at ¶ 83, Appendix B at 12–14.)
`
`3.
`
`The Cited Prior Art References Do Not “Teach Away” from
`the Claimed Invention
`
`Patent Owner further argues that a POSA would not have expected that
`
`administering LDA with the unit dosage form disclosed in Plachetka would result
`
`in a reduced incidence of gastric ulcer because the prior art “taught away” from the
`
`co-administration of LDA with non-aspirin NSAIDs. Response at 44–45. This
`
`argument is inapposite because it ignores the effect of adding an acid inhibitor to
`
`the mix, which is required by the ’621 Patent’s claims.
`
`The claims at issue require the co-administration of LDA with non-aspirin
`
`NSAIDs and an acid inhibitor. Similarly, all three prior art references—Plachetka,
`
`Graham, and Goldstein—contemplate the concomitant use of LDA with non-
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`aspirin NSAIDs and an acid inhibitor. (Ex. 1004, Plachetka, col. 2 ll. 35–40,
`
`col. 21 l. 46–col. 22 l. 17; Ex. 1005, Graham, at 169; Ex. 1005, Goldstein, at 171.)
`
`None of these references “teach away,” as Patent Owner argues, because none
`
`18
`
`
`
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`“‘criticize, discredit, or otherwise discourage’ investigation into the invention
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`IPR2015-01718
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`claimed.” DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314,
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`1327 (Fed. Cir. 2009) (quoting In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir.
`
`2004)).
`
`Indeed, Patent Owner’s expert, Dr. Makuch, admitted that neither Graham
`
`nor Goldstein “teach away” from administering a combination of an acid inhibitor
`
`and an NSAID to a patient who is also taking LDA:
`
`19· · · · Q· · ·Is it your opinion that either
`20· ·Graham or Goldstein teaches away from
`21· ·administering a combination of an acid
`22· ·inhibitor in an NSAID while a patient is
`23· ·also taking low dose aspirin?
`
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