Filed: April 6, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`DR. REDDY’S LABORATORIES INC.,
`
`Petitioner
`
`v.
`
`POZEN INC. and HORIZON PHARMA USA, INC.,
`
`Patent Owners
`
`U.S. Patent No. 9,220,698 to Ault et al.
`
`Inter Partes Review IPR2018-00894
`
`Petition for Inter Partes Review of U.S. Patent No. 9,220,698
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`1167899
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`TABLE OF CONTENTS
`
`Page
`INTRODUCTION .......................................................................................... 1
`
`
`
`I.
`
`II. MANDATORY NOTICES ............................................................................ 1
`
`A. Real Parties-In-Interest Under 37 C.F.R. § 42.8(b)(1) ......................... 1
`
`B.
`
`C.
`
`D.
`
`Related Matters Under 37 C.F.R. § 42.8(b)(2)..................................... 1
`
`Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3).................. 2
`
`Service Information Under 37 C.F.R. § 42.8(b)(4) .............................. 2
`
`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 AND 42.104) ............. 3
`
`IV.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED (37 C.F.R. § 42.22(A) AND 37
`C.F.R. § 42.104(b)) ......................................................................................... 3
`
`V.
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW .............. 4
`
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED ............... 4
`
`A.
`
`B.
`
`C.
`
`Summary of the Argument ................................................................... 4
`
`Level of Ordinary Skill in the Art ........................................................ 8
`
`The ’698 Patent and Its Prosecution ..................................................... 8
`
`1.
`
`2.
`
`3.
`
`NSAID Gastropathy ................................................................... 8
`
`Specification of the ’698 Patent ................................................. 9
`
`The ’698 Patent Prosecution .................................................... 14
`
`D.
`
`Claim Construction (37 C.F.R. §§ 42.100(b), 42.104(b)(3)) ............. 16
`
`1.
`
`“Target” Means “With The Goal of Obtaining” ...................... 16
`
`E.
`
`Scope and Content of the Prior Art .................................................... 19
`
`
`
`i
`
`

`

`1.
`
`2.
`
`PK/PD Overview ...................................................................... 19
`
`References Disclosing Combined Naproxen-
`Esomeprazole Formulations ..................................................... 21
`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`’285 Patent ..................................................................... 21
`
`’907 Patent ..................................................................... 24
`
`Hochberg 2008 ............................................................... 25
`
`Goldstein 2008 ............................................................... 26
`
`Hassan-Alin 2005 .......................................................... 27
`
`3.
`
`References Disclosing the PK/PD of Immediate-Release
`PPIs .......................................................................................... 28
`
`a.
`
`b.
`
`Howden 2005 ................................................................. 28
`
`Zegerid® Label ............................................................... 28
`
`4.
`
`References Disclosing the Pharmacokinetics of Naproxen ..... 30
`
`a.
`
`b.
`
`c.
`
`d.
`
`EC-Naprosyn® Label ...................................................... 31
`
`Khosravan 2006 ............................................................. 32
`
`Jung 1994 ....................................................................... 33
`
`Davies 1997 ................................................................... 34
`
`F.
`
`Ground 1: All Claims of the ’698 Patent Are Anticipated by the
`’285 Patent .......................................................................................... 34
`
`1.
`
`The Method of Claim 1 Is Anticipated by the ’285 Patent ...... 34
`
`a.
`
`b.
`
`The ’285 patent disclosed the drug formulation in
`claim 1 ............................................................................ 34
`
`The PK/PD elements in claim 1 are inherent in the
`formulation .................................................................... 36
`
`2.
`
`The dependent claims are anticipated by the ’285 patent ........ 40
`
`
`
`ii
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`a.
`
`b.
`
`c.
`
`Dependent claim 2 is anticipated ................................... 40
`
`Dependent claims 3 and 4 are anticipated ..................... 41
`
`Dependent claims 5-7 are anticipated ............................ 41
`
`G. Ground 2: All Claims of the ’698 Patent Are Obvious Over the
`’285 Patent .......................................................................................... 43
`
`H. Ground 3: All Claims of the ’698 Patent Are Obvious Over the
`’285 patent in View of the EC-Naprosyn® Label and Howden
`2005 ....................................................................................................48
`
`1.
`
`The Method of Claim 1 Is Obvious Over the ’285 patent
`in View of the EC-Naprosyn® Label and Howden 2005 .......... 48
`
`a.
`
`b.
`
`c.
`
`The EC-Naprosyn® label disclosed the PK
`elements for naproxen .................................................... 50
`
`Howden 2005 disclosed the PK elements for
`esomeprazole ................................................................. 53
`
`Howden 2005 disclosed the PD element ....................... 58
`
`2.
`
`The dependent claims are obvious over the ’285 patent in
`view of the EC-Naprosyn® label and Howden 2005 ................ 59
`
`a.
`
`b.
`
`c.
`
`Dependent claim 2 is obvious ........................................ 59
`
`Dependent claims 3 and 4 are obvious .......................... 60
`
`Dependent claims 5-7 are obvious ................................. 60
`
`I.
`
`No Secondary Considerations Support Nonobviousness ................... 60
`
`1.
`
`There Are No Unexpected Results ........................................... 61
`
`
`
`
`
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`
`ii
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`

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`2.
`
`3.
`
`4.
`
`The ’698 Patent Satisfied No Long-Felt But Unmet Need ...... 63
`
`There Was No Industry Skepticism ......................................... 63
`
`Copying by Generic Drug Makers Is Irrelevant ...................... 64
`
`VII. CONCLUSION ............................................................................................. 64
`
`
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`iii
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`

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`TABLE OF AUTHORITIES
`
`
`
`Page
`
`CASES
`
`Atlas Powder Co. v. Ireco, Inc.,
`190 F.3d 1342 (Fed. Cir. 1999) .......................................................................... 38
`
`Bayer Healthcare Pharms., Inc. v. Watson Pharms., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) .......................................................................... 64
`
`Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) ......................................................................5, 37
`
`Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) ............................................................................ 63
`
`Cuozzo Speed Techs., LLC v. Lee,
`No. 15-446, 136 S. Ct. 2131 (2016) .................................................................... 16
`
`Eli Lilly & Co. v. Barr Labs., Inc.,
`251 F.3d 955 (Fed. Cir. 2001) ............................................................................ 37
`
`Ex parte DesOrmeaux,
`25 U.S.P.Q. 2d 2040 (Bd. Pat. App. & Inter. 1992) ........................................... 22
`
`In re Am. Acad. of Sci. Tech. Ctr.,
`367 F.3d 1359 (Fed. Cir. 2004) .......................................................................... 16
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Litigation,
`676 F.3d 1063 (Fed. Cir. 2012) ..........................................................................15
`
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................................... 45
`
`King Pharmaceuticals, Inc. v. Eon Labs, Inc.,
`616 F.3d 1267 (Fed. Cir. 2010) .....................................................................45, 46
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................................ 48
`
`Millennium Pharm., Inc. v. Sandoz Inc.,
`862 F.3d 1356 (Fed. Cir. 2017)…………………………………………….46, 47
`
`
`
`iv
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`

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`Par Pharm., Inc. v. TWi Pharms., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ...............................................................44, 45, 46
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 60
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .......................................................................... 17
`
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) ...................................................................passim
`
`Schering Corp. v. Geneva Pharms., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003)……………………………………………...... 37
`
`SmithKline Beecham Corp. v. Apotex Corp.,
`403 F.3d 1331 (Fed. Cir. 2005) .....................................................................7, 37
`
`Sun Studs, Inc. v. ATA Equip. Leasing, Inc.,
`872 F.2d 978 (Fed. Cir. 1989) ............................................................................ 22
`
`Taurus IP, LLC v. DaimlerChrysler Corp.,.
`726 F.3d 1306 (Fed. Cir. 2013) .......................................................................... 23
`
`STATUTES
`
`35 U.S.C. § 102 ....................................................................................................4 47
`
`35 U.S.C. § 102(e)(2)...............................................................................................22
`
`35 U.S.C. § 103 .............................................................................................4, 45, 47
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`35 U.S.C. §§ 311-319 ................................................................................................. 1
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`35 U.S.C. § 314(a) ..................................................................................................... 4
`
`REGULATIONS
`
`37 C.F.R. § 42 ............................................................................................................ 1
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 1
`
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 1
`
`
`
`v
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`

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`37 C.F.R. § 42.8(b)(3) ................................................................................................ 2
`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 2
`
`37 C.F.R. § 42.10(b) .................................................................................................. 1
`
`37 C.F.R. § 42.15(a) ................................................................................................... 1
`
`37 C.F.R. § 42.22(a) ................................................................................................... 3
`
`37 C.F.R. § 42.63(e) ................................................................................................... 1
`
`37 C.F.R. § 42.100(b) .............................................................................................. 16
`
`37 C.F.R. § 42.103 ..................................................................................................... 1
`
`37 C.F.R. § 42.104(a) ................................................................................................. 3
`
`37 C.F.R. § 42.104(b) ................................................................................................ 3
`
`37 C.F.R. § 42.104(b)(3) .......................................................................................... 16
`
`37 C.F.R. § 42.106(a) ................................................................................................. 1
`
`OTHER AUTHORITIES
`MPEP § 2136.03 ...................................................................................................... 22
`
`
`
`vi
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`

`

`Exhibit
`1001
`
`1002
`1003
`1004
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`1005
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`1006
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`1007
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`1008
`
`1009
`1010
`1011
`
`LISTING OF EXHIBITS
`
`Description
`U.S. Patent No. 9,220,698, Method for Delivering a
`Pharmaceutical Composition to Patient in need thereof (filed
`Sept. 3, 2009) (issued Dec. 29, 2015) (“the ’698 patent”)
`Declaration of Meyer N. Solny, M.D. (“Solny Decl.”)
`Declaration of Richard Bergstrom, Ph.D. (“Bergstrom Decl.”)
`U.S. Patent No. 6,926,907, Pharmaceutical Compositions for
`the Coordinated Delivery of NSAIDS (filed May 31, 2002)
`(issued Aug. 9, 2005)
`U.S. Patent No. 8,557,285, Pharmaceutical Compositions for
`the Coordinated Delivery of NSAIDS (filed Aug. 23, 2011)
`(issued Oct. 15, 2013)
`Howden, Review Article: Immediate-Release Proton-Pump
`Inhibitor Therapy – Potential Advantages, 22 (Suppl. 3)
`ALIMENT. PHARMACOL. THER. 25 (2005)
`U.S. Patent No. 5,877,192, Method for the Treatment of
`Gastric Acid-Related Diseases and Production of Medication
`using (-) Enantiomer of Omeprazole (filed Apr. 11, 1997)
`(issued Mar. 2, 1999)
`Products on NDA 020067 (EC-Naprosyn), FDA.GOV,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?
`event= overview.process&ApplNo=020067 (last visited
`Aug. 23, 2017)
`EC-Naprosyn prescribing information (Jan. 2007)
`Zegerid approval letter and prescribing information (2004)
`Goldstein et al., 116 A Single Tablet Multilayer Formulation
`of Enteric-Coated Naproxen Coupled with Non-Enteric
`Coated OMEPRAZOLE is Associated with a Significantly
`Reduced Incidence of Gastric Ulcers vs. Enteric-Coated
`Naproxen: A Prospective, Randomized, Double-Blind Study,
`134(4) GASTROENTEROLOGY A19 (2008)
`
`vii
`
`
`
`
`
`

`

`Exhibit
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`Description
`Hochberg et al., A Novel, Single-Tablet Formulation that
`Delivers Immediate-Release Omeprazole Followed by Enteric-
`Coated (EC) Naproxen Significantly Reduces the Incidence of
`Gastric Ulcers Compared with EC Naproxen Alone: Results of
`a Prospective, Randomised, Double-Blind, 6-Month Study
`including Patients with OA and RA, EULAR (2008)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Amendment C and Response to Final Office Action (Jan. 30,
`2013)
`Wolfe et al., Acid Suppression: Optimizing Therapy for
`Gastroduodenal Ulcer Healing, Gastroesophageal Reflux
`Disease, and Stress-Related Erosive Syndrome, 118
`GASTROENTEROLOGY S9 (2000)
`Bell et al., Appropriate Acid Suppression for the Management
`of Gastro-Oesophageal Reflux Disease, 51 (suppl. 1)
`DIGESTION 59 (1992)
`Hassan-Alin et al., Lack of Pharmacokinetic Interaction
`between Esomeprazole and the Nonsteroidal Anti-
`Inflammatory Drugs Naproxen and Rofecoxib in Healthy
`Subjects, 25(11) CLIN. DRUG INVEST. 731 (2006)
`Khosravan et al., Pharmacokinetic Interactions of
`Concomitant Administration of Febuxostat and NSAIDs, 46 J.
`CLIN. PHARMA. 855 (2006)
`Jung et al., Steady-State Pharmacokinetics of Enteric-Coated
`Naproxen Tablets Compared with Standard Naproxen Tablets,
`16(6) CLIN. THER. 923 (1994)
`Davies et al., Clinical Pharmacokinetics of Naproxen, 32(4)
`CLIN. PHARMACOKINET. 268 (1997)
`Naprosyn/EC-Naprosyn/Anaprox DS Prescribing Information
`(Mar. 2017)
`
`
`
`viii
`
`

`

`Exhibit
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`1031
`
`1032
`
`1033
`
`Description
`Dan M. Roden, Principles of Clinical Pharmacology, in
`HARRISON’S PRINCIPLES OF INTERNAL MEDICINE 13 (Dennis L.
`Kasper et al. eds., 16th ed. 2005)
`Malcolm Rowland & Thomas N. Tozer, CLINICAL
`PHARMACOKINETICS (3d ed. 1995)
`Clissold et al., Omeprazole A Preliminary Review of its
`Pharmacodynamic and Pharmacokinetic Properties, and
`Therapeutic Potential in Peptic Ulcer Disease and Zollinger-
`Ellison Syndrome, 32 DRUGS 15 (1986)
`U.S. Patent No. 7,411,070, Form of S-Omeprazole (filed Sept.
`25, 2003) (issued Aug. 12, 2008)
`U.S. Patent No. 5,714,504, Compositions (filed Jan. 23, 1995)
`(issued Feb. 3, 1998)
`Michael Mayersohn, Principles of Drug Absorption, in
`MODERN PHARMACEUTICS 21 (3d ed. 1996)
`Howden, Clinical Pharmacology of Omeprazole, 20(1) CLIN.
`PHARMACOKINET. 38 (1991)
`Lind et al., Esomeprazole Provides Improved Acid Control vs.
`Omeprazole in Patients with Symptoms of Gastro-Oesophageal
`Reflux Disease, 14 ALIMENT. PHARMACOL. THER. 861 (2000)
`Regårdh et al., Pharmacokinetics and Metabolism of
`Omeprazole in Animals and Man – An Overview, 20(suppl.
`108) SCAND. J. GASTROENTEROL 79 (1985)
`Vimovo prescribing information (Dec. 2014)
`Target, WEBSTER’S NEW WORLD COLLEGE DICTIONARY (4th
`ed. 2005)
`Target, THE AMERICAN HERITAGE DICTIONARY OF THE ENGLISH
`LANGUAGE (4th ed. 2006)
`Target, MERRIAM-WEBSTER’S CONCISE DICTIONARY (Large
`print ed. 2006)
`
`
`
`ix
`
`

`

`Exhibit
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`1044
`
`Description
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Office Action Summary (Jan. 5, 2012)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Office Action Summary (July 30, 2012)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Office Action Summary (June 16, 2014)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Office Action Summary (Mar. 26, 2015)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Amendment B in Response to January 5, 2012 Office
`Action (May 8, 2012)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Response to Non-Final Office Action Mailed June 16, 2014
`(Dec. 12, 2014)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Response to Final Office Action Mailed March 26, 2015 (Sept.
`25, 2015)
`U.S. Patent No. 9,220,698 Prosecution History Excerpt:
`Advisory Action (Oct. 9, 2015)
`Goldlust et al., Nighttime Dosing of Omeprazole Immediate-
`Release Oral Suspension Rapidly Decreases Nocturnal Gastric
`Acidity, 99(10) AM. J. GASTROENTEROLOGY S39 (2004)
`Declaration of David C. Metz, M.D. (“Metz Decl.”)
`Declaration of Michael Mayersohn, Ph.D. (“Mayersohn
`Decl.”)
`
`
`
`x
`
`

`

`I.
`
`INTRODUCTION
`
`Dr. Reddy’s Laboratories Inc. (“Petitioner”) petitions for Inter Partes Review
`
`of claims 1-7 of U.S. Patent No. 9,220,698 (“the ’698 patent”) (Ex. 1001), which is
`
`assigned to Pozen Inc. (“Pozen”) and Horizon Pharma USA, Inc. (“Horizon”)
`
`(collectively, “Patent Owners”), under 35 U.S.C. §§ 311-319 and 37 C.F.R. Part 42
`
`and seeks a determination that all claims (1-7) of the ’698 patent be canceled as
`
`unpatentable.
`
`This Petition is filed in accordance with 37 C.F.R. § 42.106(a). Filed
`
`herewith is a power of attorney and exhibit list per § 42.10(b) and § 42.63(e).
`
`Pursuant to 37 C.F.R. § 42.103, the fee set forth in § 42.15(a) accompanies this
`
`Petition.
`
`II. MANDATORY NOTICES
`
`Petitioner provides the following mandatory notices.
`
`A. Real Parties-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`
`The real parties-in-interest for Petitioner are Dr. Reddy’s Laboratories Inc.
`
`and Dr. Reddy’s Laboratories Ltd.
`
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2)
`
`The following litigations or instituted inter partes reviews related to the ’698
`
`patent are pending:
`
` Inter Partes Review IPR2017-01995 of Mylan Pharmaceuticals Inc.;
`
`
`
`1
`
`

`

` Horizon Pharma, Inc. v. Dr. Reddy’s Labs., Inc., No. 15-3324 (D.N.J.);
`
` Horizon Pharma, Inc. v. Dr. Reddy’s Labs., Inc., No. 16-4918 (D.N.J.);
`
` Horizon Pharma, Inc. v. Dr. Reddy’s Labs., Inc., No. 16-9035 (D.N.J.);
`
` Horizon Pharma, Inc. v. Mylan Pharms. Inc., No. 15-3327 (D.N.J.);
`
` Horizon Pharma, Inc. v. Mylan Pharms. Inc., No. 16-4921 (D.N.J.);
`
`and
`
` Horizon Pharma, Inc. v. Lupin Ltd., No. 16-4920 (D.N.J.).
`
`C.
`
`Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`
`
`
`
`
`Lead Counsel
`Alan H. Pollack (Reg. No. 39,802)
`BUDD LARNER, P.C.
`150 John F. Kennedy Parkway
`Short Hills, New Jersey 07078
`Tel: (973) 379-4800
`apollack@buddlarner.com
`
`Back Up Counsel
`Dmitry V. Shelhoff (motion for Pro
`Hac Vice admission to be filed)
`Stuart D. Sender (Reg. No. 34,248)
`Louis H. Weinstein (Reg. No. 45,205)
`BUDD LARNER, P.C.
`150 John F. Kennedy Parkway
`Short Hills, New Jersey 07078
`Tel: (973) 379-4800
`dshelhoff@buddlarner.com
`ssender@buddlarner.com
`lweinstein@buddlarner.com
`
`D.
`
`Service Information Under 37 C.F.R. § 42.8(b)(4)
`
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`contact information above. Petitioner consents to electronic service by e-mail at the
`
`following email addresses: apollack@buddlarner.com; dshelhoff@buddlarner.com;
`
`ssender@buddlarner.com; lweinstein@buddlarner.com
`
`
`
`2
`
`

`

`III. GROUNDS FOR STANDING (37 C.F.R. §§ 42.101 and 42.104)
`
`Pursuant to 37 C.F.R. § 42.104(a), Petitioner certifies that the ’698 patent is
`
`available for inter partes review and that Petitioner is not barred or estopped from
`
`requesting inter partes review on the grounds identified herein.
`
`Pursuant to 37 C.F.R. § 42.104(a), Petitioner certifies that the ’698 patent is
`
`available for inter partes review and that Petitioner is not barred or estopped from
`
`requesting inter partes review on the grounds identified herein. Though Petitioner
`
`filed the Petition more than one year after the date on which Petitioner was served
`
`with a complaint alleging infringement of the ’698 patent, the Petition is timely
`
`because Petitioner has filed it no later than one month after the institution date of
`
`an inter partes review for which joinder is requested. The time period set forth in §
`
`42.101(b) does not apply because the Petition is accompanied by a request for
`
`joinder to Mylan Pharmaceuticals Inc. v. Pozen Inc. and Horizon Pharma USA,
`
`Inc., Case No. IPR2017-00323 (“the Mylan IPR”), which was instituted on March
`
`8, 2018 (Paper 18)
`
`IV.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED (37 C.F.R. § 42.22(a) and 37 C.F.R. §
`42.104(b))
`
`Petitioner respectfully requests inter partes review and cancellation of claims
`
`1-7 on the grounds set forth below.
`
`
`
`3
`
`

`

`Ground 1: Claims 1-7 are unpatentable as anticipated under 35 U.S.C. §
`
`102 by U.S. Patent No. 8,557,285 (“the ’285 patent”).
`
`Ground 2: Claims 1-7 are unpatentable as obvious under 35 U.S.C. § 103
`
`over the ’285 patent.
`
`Ground 3: Claims 1-7 are unpatentable as obvious under 35 U.S.C. § 103
`
`over the ’285 patent in view of the EC-Naprosyn® label and Howden 2005.
`
`Petitioner’s full statement of the reasons for the relief requested is set forth
`
`below. In support of these grounds for unpatentability, Petitioner submits the expert
`
`declarations of Dr. Meyer N. Solny, M.D. (Ex. 1002 (“Solny Decl.”)) and Dr.
`
`Richard Bergstrom, Ph.D. (Ex. 1003 (“Bergstrom Decl.”)) and relies on the other
`
`Exhibits set forth in the concurrently filed Listing of Exhibits.
`
`V. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`A petition for inter partes review must demonstrate “a reasonable likelihood
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`that the petitioner would prevail with respect to at least 1 of the claims challenged
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`in the petition.” 35 U.S.C. § 314(a). This Petition clears that threshold. As explained
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`below, there is a reasonable likelihood that Petitioner will prevail with respect to at
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`least one of the challenged claims.
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`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
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`A.
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`Summary of the Argument
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`The claims of the ’698 patent are directed to a method of administering a drug
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`formulation with certain pharmacokinetic (PK) and pharmacodynamic (PD)
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`parameters. But, the drug formulation and method of administration were both
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`known—Patent Owners had previously disclosed them in two prior art patents: U.S.
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`Patent Nos. 6,926,907 (Ex. 1004) and 8,557,285 (Ex. 1005). And there is nothing
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`novel about the PK/PD elements either—they are the natural result of administering
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`the known formulation according to the known method. To extend patent protection
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`eight years beyond the ’907 patent’s expiration, the inventors of the ’698 patent
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`simply ran a routine clinical trial using a known drug and known method to
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`document an inherent property of the drug. They then claimed the expected and
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`unsurprising results. “Newly discovered results of known processes directed to the
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`same purpose are not patentable because such results are inherent.” Bristol-Myers
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`Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1376 (Fed. Cir. 2001). The
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`’698 patent’s claims are unpatentable as anticipated by, or obvious over, the ’285
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`patent.
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`Specifically, the ’698 patent claims a method of treating arthritis by
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`administering a combination tablet of naproxen 500mg (EC-Naprosyn®) and
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`esomeprazole 20mg (Nexium®) twice daily. Naproxen relieves arthritis pain and
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`inflammation, but long-term administration was known to cause gastric injury. To
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`solve this problem, proton pump inhibitors (PPIs)—esomeprazole for example—
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`were prescribed to raise gastric pH, preventing naproxen-induced injury.
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`As a result, skilled artisans designed tablets combining naproxen and PPIs.
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`In 2001, the ’285 and ’907 patents disclosed and claimed the “PN formulation,” a
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`specific tablet structure combining naproxen and esomeprazole. The PN
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`formulation purportedly features “coordinated release,” whereby esomeprazole is
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`immediately released and the naproxen releases only once the esomeprazole has
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`raised gastric pH. Dr. John Plachetka, one of the four inventors of the ’698 patent,
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`is the named inventor of the ’285 and ’907 patents.
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`The ’698 patent claims the precise formulation and method of administration
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`disclosed in Dr. Plachetka’s ’285 and ’907 patents seven years prior. The only other
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`elements it recites are certain PK/PD values for naproxen and esomeprazole. But
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`these PK/PD values result from administering the prior art PN formulation per the
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`prior art method. The ’698 patent concedes this point, referring to the ’907 patent
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`as a formulation that “can be effective in improving NSAID tolerability through
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`dosages of esomeprazole and naproxen that produce the desired pharmacodynamic
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`response and pharmacokinetic values.” Ex. 1001, 1:30-37.
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`The law does not permit Patent Owners to extend their monopoly nearly a
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`decade by simply claiming an inherent characteristic of their previously disclosed
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`formulation and method of administration. Indeed, the ’698 patent is exactly why
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`the inherency doctrine exists: “one of the principles underlying the doctrine of
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`inherent anticipation is to ensure that the public remains free to make, use or sell
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`prior art compositions or processes, regardless of whether or not they understand
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`their complete makeup or the underlying scientific principles which allow them to
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`operate.” SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1345-46 (Fed.
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`Cir. 2005) (quotation and alteration omitted).
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`The Federal Circuit has previously held that “an obvious formulation cannot
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`become nonobvious simply by administering it to a patient and claiming the
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`resulting serum concentrations.” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344,
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`1354 (Fed. Cir. 2012). Yet, that is exactly what Patent Owners did here—they gave
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`a known formulation to patients and claimed the resulting serum concentrations.
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`“The initial blood serum concentration resulting from administering a PPI dosage
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`is an inherent property of the formulation.” Id. All claims of the ’698 patent are
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`anticipated by or obvious over at least the ’285 patent.
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`Alternatively, all claims of the ’698 patent are obvious over the ’285 patent
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`in view of the EC-Naprosyn® label (Ex. 1009) and Howden 2005 (Ex. 1006). Even
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`if not inherent, a skilled artisan would have known to target the claimed PK/PD
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`values because they were known to be produced by effective drugs already on the
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`market: EC-Naprosyn® for naproxen and Zegerid® for esomeprazole. Skilled
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`artisans would understand from the EC-Naprosyn® label and Howden 2005 that EC-
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`Naprosyn® and Zegerid® produced PK/PD values at which delayed-release
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`naproxen and immediate-release esomeprazole were effective. When developing
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`the claimed PN formulation, skilled artisans would target PK/PD values known to
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`provide efficacy. As the ’698 patent’s claims require only that the prior art teach a
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`skilled artisan to “target” the claimed PK/PD values, all claims are obvious over the
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`’285 patent in view of the EC-Naprosyn® label and Howden 2005.
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`B.
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`Level of Ordinary Skill in the Art
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`A person of ordinary skill in the art (“POSA”) is presumed to be aware of all
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`pertinent art, thinks along conventional wisdom in the art, and is a person of
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`ordinary creativity. The field of art involves the knowledge of a medical doctor and
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`that of a pharmacologist or pharmacokineticist with experience in dosage form
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`design and evaluation. Thus, the hypothetical POSA is a collaboration between a
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`pharmacologist or pharmacokineticist having a Ph.D. degree or equivalent training,
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`or a M.S. degree with at least 2 years of some experience in dosage form design and
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`in in vitro and in vivo evaluation of dosage form performance, and a medical doctor
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`having at least 2 years of practical experience treating patients in the
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`gastroenterology field. Ex. 1002 ¶¶23-24; Ex. 1003 ¶¶19-20.
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`C.
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`The ’698 Patent and Its Prosecution
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`1.
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`NSAID Gastropathy
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`The ’698 patent relates to formulations and methods of treatment to prevent
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`injury caused by chronic use of non-steroidal anti-inflammatory drugs (“NSAIDs”).
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`NSAIDs are a class of drugs used to treat pain and inflammation, including pain
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`and inflammation associated with arthritis. Ex. 1002 ¶25. The class includes, e.g.,
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`aspirin, naproxen, ibuprofen, and diclofenac. Id. NSAIDs are among the most
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`commonly prescribed medications in the world and have been in use for decades.
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`Id. The NSAID naproxen was first approved by the FDA in 1976 under the trade
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`name Naprosyn. Ex 1020, 1.
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`NSAIDs can cause a variety of side effects over chronic administration. Ex.
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`1002 ¶26. These NSAID-induced side effects are commonly called “NSAID-
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`related injury” or “gastropathy.” Id. This injury, however, can be reduced by
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`controlling acid in the stomach through concomitant administration of an acid
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`inhibitor with the NSAID. Id.
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`2.
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`Specification of the ’698 Patent
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`The ’698 patent claims priority to a provisional application filed on
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`September 9, 2008. It relates to methods of administering to a patient delayed-
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`release naproxen 500mg and immediate-release esomeprazole 20mg in a single
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`tablet. Ex. 1001, 24:45-49; Ex. 1002 ¶¶29, 37-38; Ex. 1003 ¶¶40-44, 58-66. The
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`specification calls this formulation as “PN400/E20.” Ex. 1001, 26:44-45; Ex. 1002
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`¶¶34-36; Ex. 1003 ¶44. The ’698 patent recites in its claims certain PK/PD results
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`for patients administered PN400/E20. See, e.g., Ex. 1001, col. 35, Tbls. 6, 11; Ex.
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`1003 ¶45. As explained in more detail infra, Section VI.E.1, when a patient intakes
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`a drug, it has a particular effect, i.e., it reduces pain and/or increases stomach pH.
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`Ex. 1003 ¶¶26-27. Scientists measure these effects by determining PK/PD values.
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`Ex. 1003 ¶27. PK measures the body’s absorption of the drug; PD describes the
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`drug’s effect on the body. Ex. 1003 ¶¶25-28.
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`The ’698 patent describes certain PK parameters: “Cmax,” “Tmax,” and “area
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`under the curve” or “AUC.” Id. ¶45. To a skilled artisan, Cmax is the maximum
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`concentration the drug achieves in the patient’s blood plasma. Id. ¶31. Tmax refers
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`to the time after administration at which the patient’s Cmax is reached. Id. Finally,
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`“area under the curve” or AUC measures the total amount of drug delivered over a
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`certain period after administration, for example after ten hours (AUC0-10) or after
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`twenty-four hours (AUC0-24). Ex. 1003 ¶¶31, 38. Because there is natural intra- and
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`inter-patient variation, pharmacokinetic parameters are generally recited as average
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`(mean) values plus or minus a variation. Ex. 1003 ¶32.
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`The background of the ’698 patent notes that NSAIDs were understood to
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`induce gastrointestinal injury, such as ulcers, when used frequently. Ex. 1001, 1:19-
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`24; Ex. 1002 ¶30; Ex. 1003 ¶46. Skilled artisans knew that stomach acid was “[a]
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`major factor contributing to the development of gastrointestinal lesions.” Ex. 1001,
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`1:24-25; Ex. 1003 ¶46. The specification next refers to several strategies previously
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`taken “to reduce the gastrointestinal risk associated with taking NSAIDs by
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`administering agents that inhibit stomach acid secretion, such as, for example,
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`proton pump inhibitors with the NSAID.” Ex. 1001, 1:27-30; Ex. 1002 ¶¶31-3