UNITED STATES PATENT AND TRADEMARK OFFICE
`
`______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`______________
`
`
`
`COALITION FOR AFFORDABLE DRUGS VII LLC
`Petitioner
`
`v.
`
`POZEN INC.
`Patent Owner
`
`______________
`
`
`
`Case No. IPR2015-01680
`Patent No. 8,852,636
`
`______________
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`37 C.F.R. § 42.107
`
`
`
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`

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`Case No. IPR2015-01680
`Patent No. 8,852,636
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`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ........................................................................................... 1
`
`BACKGROUND ............................................................................................. 2
`
`III. DENIAL OF INSTITUTION OF IPR2015-00802 ......................................... 5
`
`IV. LEVEL OF ORDINARY SKILL IN THE ART ............................................. 7
`
`V.
`
`CLAIM INTERPRETATION ......................................................................... 8
`
`A.
`
`The Petition Incorrectly Interprets “Unit Dosage Form” ...................... 8
`
`VI. PROSECUTION HISTORY ........................................................................... 9
`
`VII. THE BOARD SHOULD DENY CFAD’S PETITION BECAUSE IT
`FAILS TO DEMONSTRATE A REASONABLE LIKELIHOOD OF
`PREVAILING ............................................................................................... 11
`
`A. Ground 1: The Petition Has Not Established a Reasonable
`Likelihood That Claims 1-18 are Obvious over Goldman in
`View of Remington and Lindberg ....................................................... 11
`
`B. Ground 2: The Petition Has Not Established a Reasonable
`Likelihood That Claims 1-6 and 13-15 are Obvious Over Gimet
`in View of Goldman in Further View of Lindberg ............................. 17
`
`1.
`
`2.
`
`There Was No Motivation to Combine the Cited
`References ................................................................................. 18
`
`There Was No Reasonable Expectation of Success ................. 20
`
`C. Ground 3: The Petition Has Not Established a Reasonable
`Likelihood That Claims 7-12 and 16-18 are Obvious over Ouali
`in View of Lindberg ............................................................................ 25
`
`D.
`
`The Petition Fails to Offer Evidence Refuting Objective Indicia
`of Nonobviousness .............................................................................. 26
`
`1.
`
`2.
`
`Surprising and Unexpected Results .......................................... 31
`
`Long Felt but Unresolved Need ................................................ 33
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`3.
`
`4.
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`Licensing ................................................................................... 34
`
`Copying ..................................................................................... 35
`
`E.
`
`Each of the Grounds is Horizontally Redundant ................................ 35
`
`VIII. CONCLUSION .............................................................................................. 36
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`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Bumble Bee Foods, LLC v. Kowalski,
`IPR2014-00224, Paper No. 18 (P.T.A.B. June 5, 2014) ............................... 18
`
`Cisco Sys., Inc. v. C-Cation Techs., LLC,
`IPR2014-00454, Paper No. 12 (P.T.A.B. Aug. 29, 2014) ..................... 28, 29
`
`Crocs, Inc. v. Int’l Trade Comm’n,
`598 F.3d 1294 (Fed. Cir. 2010) ................................................................ 2, 27
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) ............................................... 28
`
`DeSilva v. DiLeonardi,
`181 F.3d 865 (7th Cir. 1999) ......................................................................... 29
`
`Dr. Reddy’s Labs., Inc. v. Pozen, Inc.,
`IPR2015-00802, Paper No. 2, Petition for Inter Partes Review
`of Patent No. 8,557,285 (Feb. 24, 2015) ......................................................... 6
`
`Dr. Reddy’s Labs., Inc. v. Pozen, Inc.,
`IPR2015-00802, Paper No. 28, Decision of the Patent Trial and
`Appeal Board (P.T.A.B. Oct. 9, 2015) ................................................. 7, 9, 22
`
`Fid. Nat’l Info. Servs., Inc. v. DataTreasury Corp.,
`IPR2014-00489, Paper No. 9 (P.T.A.B. Aug. 13, 2014) ........................ 28, 30
`
`In re Haruna,
`249 F.3d 1327 (Fed. Cir. 2001) ..................................................................... 24
`
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .......................................................... 2, 27, 28
`
`Liberty Mutual Insurance Co. v. Progressive Casualty Insurance Co.,
`CBM2012-00003, Paper No. 7 (P.T.A.B. Oct. 25, 2012) ............................. 36
`
`McGinley v. Franklin Sports, Inc.,
`262 F.3d 1339 (Fed. Cir. 2001) ..................................................................... 35
`
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`Micron Tech., Inc. v. Bd. of Trs. of the Univ. of Ill.,
`IPR2013-00005, Paper No. 54 (P.T.A.B. Mar. 10, 2014) ............................. 31
`
`Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc.,
`520 F.3d 1358 (Fed. Cir. 2008) ..................................................................... 26
`
`In re Portola Packaging, Inc.,
`110 F.3d 786 (Fed. Cir. 1997) ....................................................................... 10
`
`In re Rouffet,
`149 F.3d 1350 (Fed. Cir. 1998) ..................................................................... 34
`
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) ..................................................................... 23
`
`Stratoflex, Inc. v. Aeroquip Corp.,
`713 F.2d 1530 (Fed. Cir. 1983) .............................................................. 27, 28
`
`Tec Air, Inc. v. Denso Mfg. Mich. Inc.,
`192 F.3d 1353 (Fed. Cir. 1999) ..................................................................... 24
`
`United States v. Chemical Found., Inc.,
`272 U.S. 1 (1926) ........................................................................................... 10
`
`
`
`Statutes
`
`35 U.S.C. § 313 .......................................................................................................... 1
`
`35 U.S.C. § 325(d) ..................................................................................................... 7
`
`
`
`Rules
`
`37 C.F.R. § 42.107 ..................................................................................................... 1
`
`37 C.F.R. § 42.6(a)(3) ....................................................................................... 28, 30
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`
`
`Other Authorities
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`M.P.E.P. § 609.02(A)(2) .......................................................................................... 10
`
`Rules of Practice for Trials Before The Patent Trial and Appeal Board
`and Judicial Review of Patent Trial and Appeal Board
`Decisions; Final Rule, 77 Fed. Reg. 48,612 (Aug. 14, 2012) ....................... 29
`
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`TABLE OF EXHIBITS
`
`2001
`
`2002
`
`EX. NO. DESCRIPTION
`License Agreement between Patent Owner Pozen Inc. and Exclusive
`Licensee Horizon Pharma, Inc.
`Norman & Hawkey, What you need to know when you prescribe a
`proton pump inhibitor, Frontline Gastroenterology, 1-7 (2011)
`(“Norman 2011”)
`Comprehensive Pharmacy Review, Chapter 17: Drug Metabolism,
`Prodrugs, and Pharmacogenetics, 398-420 (Leon Shargel et al. eds.,
`2010) (“Shargel 2010”)
`Cederberg et al., Omeprazole: Pharmacokinetics and Metabolism in
`Man, Scand. J. of Gastroenterology 24:33-40 (1989) (“Cederberg
`1989”)
`Prosecution History of U.S. Patent No. 6,926,907 (“the ’907 patent”)
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`
`
`Reserved
`Wolfe et al., Gastrointestinal Toxicity of Nonsteroidal
`Antiinflammatory Drugs, New England Journal of Medicine,
`340(24):1888-99 (1999) (“Wolfe 1999”)
`Stedman & Barclay, Review article: comparison of the
`pharmacokinetics, acid suppression and efficacy of proton pump
`inhibitors, Aliment Pharmacol. Ther. 14:963-78 (2000) (“Stedman
`2000”)
`Bell & Hunt, Progress with Proton Pump Inhibition, Yale J. Biology &
`Med., 65:649-57 (1992) (“Bell 1992”)
`Sachs et al., Review article: the control of gastric acid and Helicobacter
`pylori eradication, Aliment Pharmacol. Ther. 14:1383-401 (2000)
`(“Sachs 2000”)
`Chiverton et al., Does misoprostol given as a single large dose improve
`its antisecretory effect?, Aliment Pharmacol Ther. 3(4):403-7 (1989)
`(“Chiverton 1989”)
`
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`Pursuant
`
`to 35 U.S.C. § 313 and 37 C.F.R. § 42.107, Horizon
`
`Pharmaceuticals, Inc. (“Horizon”) and Pozen Inc. (“Pozen”) (collectively, “Patent
`
`Owner”)1 submit this Patent Owner’s Preliminary Response to the Petition for
`
`Inter Partes Review (“Petition”) of claims 1-18 of U.S. Patent No. 8,852,636 (“the
`
`’636 patent”), filed by Coalition for Affordable Drugs VII LLC (“CFAD” or
`
`“Petitioner”). This Response is timely under 35 U.S.C. § 313 and 37 C.F.R.
`
`§ 42.107.
`
`INTRODUCTION
`
`I.
`The Petition seeking inter partes review of the ’636 patent should be denied
`
`because it fails to demonstrate a reasonable likelihood that any of the challenged
`
`claims are obvious. In particular, the Petition fails to provide any motivation to
`
`combine the cited references and provides no reasonable expectation of success in
`
`doing so. Further, the Petition asserts substantially the same prior art and
`
`arguments that were: (1) asserted by the Examiner during prosecution and
`
`successfully overcome by the Patent Owner; and (2) presented in a petition for
`
`inter partes review of a parent patent of the ’636 patent for which institution was
`
`
`
`1 As explained in Patent Owner’s Mandatory Notices, Paper No. 7, Pozen is the
`
`assignee of the ’636 patent and Horizon is its exclusive licensee.
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`denied.2 Furthermore, the Petition fails to address the objective indicia of
`
`nonobviousness, even though evidence must always be considered and is often the
`
`most probative. In re Huai-Hung Kao, 639 F.3d 1057, 1067 (Fed. Cir. 2011);
`
`Crocs, Inc. v. Int’l Trade Comm’n, 598 F.3d 1294, 1310 (Fed. Cir. 2010).
`
`II. BACKGROUND
`Non-steroidal anti-inflammatory drugs (“NSAIDs”) are valuable agents in the
`
`treatment of arthritis and other musculoskeletal disorders and are one of the most
`
`widely used classes of drugs in the United States. The use of NSAIDs, however,
`
`has been associated with mucosal injury to the upper gastrointestinal (GI) tract,
`
`including
`
`the development of peptic ulcer disease, upper gastrointestinal
`
`hemorrhage, and perforation. VIMOVO® is a unique drug product specifically
`
`designed to reduce the potential for gastric mucosal tissue damage due to NSAID
`
`use. VIMOVO® consists of a delayed-release, enteric-coated NSAID core
`
`(naproxen) surrounded by an immediate-release acid inhibitor (esomeprazole
`
`magnesium). The acid inhibitor is released before the NSAID, allowing its
`
`gastroprotective effects to take hold before naproxen is released, thus reducing the
`
`potential for gastric damage.
`
`
`
`2 IPR2015-00802.
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`The ’636 patent is one of twelve patents listed in the U.S. Food and Drug
`
`Administration’s (“FDA”) Approved Drug Products with Therapeutic Equivalence
`
`Evaluations (the “Orange Book”) that cover VIMOVO®.3 As described in more
`
`detail below, the ’636 patent claims pharmaceutical compositions that provide for
`
`the coordinated release of an immediate-release acid inhibitor and a delayed-
`
`release NSAID within a single oral dosage form that reduces the risk of GI injury
`
`arising from NSAID therapy. (Ex. 1001 at 1:21-27.) The ’636 patent also claims
`
`methods of treating a patient for pain or inflammation with said pharmaceutical
`
`compositions.
`
`
`
`3 VIMOVO® is also protected by U.S. Patent No. 8,557,285, at issue in IPR2015-
`
`00802 with institution denied; U.S. Patent No. 8,858,996, at issue in IPR2015-
`
`01344 (filed by Petitioner) and IPR2015-01773; U.S. Patent No. 6,926,907, at
`
`issue in IPR2015-01241 (filed by Petitioner); U.S. Patent No. 8,945,621, at issue in
`
`IPR2015-01718 (filed by Petitioner) and U.S. Patent Nos. 5,714,504, 5,900,424,
`
`6,369,085, 7,411,070, 7,745,466, and 9,161,920. U.S. Patent No. 8,865,190, at
`
`issue in IPR2015-01775, also covers VIMOVO® but is not listed in the Orange
`
`Book. The ’636 patent is also at issue in IPR2015-01774.
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`The immediate-release acid inhibitor in VIMOVO® is a proton pump
`
`inhibitor (“PPI”). In contrast to VIMOVO®’s immediate-release PPI, it was—and
`
`remains—widely accepted that PPIs must be administered with an enteric coating
`
`to protect the drug from gastric acid degradation. (Norman 2011, Ex. 2002 at 1.)
`
`For example, in 2010, Petitioner’s declarant, Dr. Leon Shargel, wrote that
`
`“[e]nteric coated formulations can protect acid-sensitive drugs as they pass through
`
`the acidic environment of the stomach. . . . [O]meprazole [a PPI] [is an] example[]
`
`of acid-sensitive agents that are available as enteric-coated preparations.” (Shargel
`
`2010, Ex. 2003 at 15.) While this enteric coating protects acid-labile PPIs from
`
`acid degradation, it also delays the PPI’s absorption into the systemic circulation.
`
`(Cederberg 1989, Ex. 2004 at 6-7.)
`
`No prior art disclosed, taught, or suggested pharmaceutical compositions
`
`providing coordinated release of a delayed-release NSAID and an immediate-
`
`release acid inhibitor, as claimed in the ’636 patent. Indeed, the ’636 patent issued
`
`over several references cited by the Petition, including Goldman. (Ex. 1004.)
`
`And, in the Notice of Allowance for U.S. Patent No. 6,926,907, a parent of the
`
`’636 patent, the Examiner correctly recognized that Goldman, was one of “the
`
`closest prior art [references] of record.” (3/29/05 Notice of Allowance, Ex. 2005 at
`
`45.) The claims of the ’907 patent, like the claims of the ’636 patent, are directed
`
`to coordinated release compositions with an immediate release acid inhibitor and a
`
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`delayed release NSAID, and the Petition does not address why Goldman or any of
`
`the other
`
`references
`
`thoroughly considered by
`
`the Examiner warrants
`
`reconsideration by the Board now. As discussed below, the ’636 patent’s claimed
`
`inventions are not taught or suggested by the prior art.
`
`Although co-administrations of NSAIDs with acid inhibitors were attempted
`
`in the prior art, none of those efforts utilized or suggested unit dosage forms with
`
`the specific structural features and functional properties that provide for
`
`coordinated delivery of an immediate-release acid inhibitor and a delayed-release
`
`NSAID. (Ex. 1001 at 2:27-37.)
`
`III. DENIAL OF INSTITUTION OF IPR2015-00802
`The ʼ636 patent is related in scope and priority to U.S. Patent No. 8,557,285,
`
`(“the ’285 patent”) at issue in IPR2015-00802. Specifically, the ’636 patent is a
`
`continuation of the ’285 patent and the claims of each patent have several common
`
`elements, as shown in the table below.
`
`Claim 1 of ’636 Patent
`
`Claim 1 of ’285 Patent
`
`A pharmaceutical composition in
`unit dose form
`
`A pharmaceutical composition in unit
`dosage form
`
`comprising: (a) esomeprazole [and]
`(b) naproxen
`
`comprising . . . (a) esomeprazole [and] (b)
`naproxen
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`coating surrounds [the naproxen] and
`does not release said naproxen until
`the pH of the surrounding medium is
`3.5 or higher
`
`naproxen surrounded by a coating that
`inhibits its release from said unit dosage
`form unless said dosage form is in a
`medium with a pH of 3.5 or higher
`
`esomeprazole [is] not surrounded by
`an enteric coating
`
`at least a portion of said esomeprazole is
`not surrounded by an enteric coating
`
`upon ingestion of said tablet by a
`patient, said esomeprazole is released
`into said patient's stomach.
`
`unit dosage form provides for release of
`said esomeprazole such that upon
`introduction of said unit dosage form into
`a medium, at least a portion of said
`esomeprazole is released regardless of the
`pH of the medium
`
`The grounds for unpatentability set forth in IPR2015-00802 and the instant
`
`Petition are similar in substance. For example, both petitions rely on prior art that
`
`discloses PPIs that have been enteric coated to protect them from gastric acid.
`
`Neither petition cites to art teaching that an immediate-release PPI could be
`
`combined with a delayed-release NSAID as in the claimed combination. While the
`
`Petition does not address this shortcoming, the Petitioner’s declarant, Dr. Shargel,
`
`like the petition in IPR2015-00802, cites to the Pilbrant reference to attempt to
`
`show that one of skill in the art would combine the teachings of the cited
`
`references to arrive at the claimed invention and, more particularly, that
`
`omeprazole need not be enteric coated to provide a therapeutic effect. (Compare
`
`Dr. Reddy’s Labs., Inc. v. Pozen, Inc., IPR2015-00802, Paper No. 2 at 47–53
`
`(P.T.A.B. Feb. 24, 2015) (Petition for Inter Partes Review of Patent No.
`
`
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`8,557,285) to Ex. 1003, ¶¶ 328-37.) But the Board, however, denied institution in
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`IPR2015-00802 and agreed with the Patent Owner that “Pilbrant teaches away
`
`from the claimed combination.” Dr. Reddy’s Labs., Inc. v. Pozen, Inc., IPR2015-
`
`00802, Paper No. 28 at 25 (P.T.A.B. Oct. 9, 2015) (Decision of the Patent Trial
`
`and Appeal Board, hereinafter “IPR2015-00802 Non-Institution Decision”).
`
`Not only are the instant Petition’s grounds substantively meritless, as
`
`discussed below, they are also duplicative of considerations already settled at the
`
`Patent Office and rejected by a prior panel of this Board. In determining whether
`
`to institute or order a proceeding, the Board “may take into account whether, and
`
`reject the petition or request because, the same or substantially the same prior art or
`
`arguments previously were presented to the Office.” 35 U.S.C. § 325(d). Thus,
`
`the Board should deny the Petition not only because it fails to demonstrate a
`
`reasonable likelihood of prevailing, but also because revisiting these contentions is
`
`unnecessary and would be both burdensome upon the Board and the Patent Owner
`
`and wasteful of time and resources.
`
`IV. LEVEL OF ORDINARY SKILL IN THE ART
`Patent Owner proposes the following definition of a person of ordinary skill
`
`in the art (“POSA”): “A person with at least a graduate degree in pharmacy,
`
`chemistry, chemical engineering, pharmaceutics, or a comparable field, and some
`
`relevant pharmaceutical formulation work experience in industry.” While that
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`definition is similar to the first definition provided by the Petition, i.e., “a
`
`pharmacist, medical doctor, or pharmaceutical scientist having a doctor of
`
`medicine degree, a doctor of pharmacy degree, or a Ph.D. degree, or equivalent
`
`training or degree, and at least two years of practical experience or clinical research
`
`in pharmaceutical formulations,” (Pet. at 10), the Petition’s definition of a POSA
`
`does not extend to a person having a graduate degree in chemistry or chemical
`
`engineering.
`
`The Petition’s alternative definition also misses the mark. The Petition
`
`describes the “alternative” POSA as “a pharmacologist or pharmacokineticist
`
`having a Ph.D. degree or equivalent training or degree and at least two years of
`
`practical experience or clinical research in pharmacology or pharmacokinetics.”
`
`(Id.) The study of pharmacokinetics is concerned with drug absorption,
`
`bioavailability, distribution, metabolism, and excretion. The disciplines of
`
`pharmaceutical formulation and pharmacokinetics are not co-extensive and the
`
`Petition fails to distinguish or explain how a POSA from either discipline would
`
`understand and interpret the prior art.
`
`V. CLAIM INTERPRETATION
`A. The Petition Incorrectly Interprets “Unit Dosage Form”
`The Petition’s proposed definition of the term “unit dose form” and “unit
`
`dosage form” found in claims 1, 3, 4, 7, 9, and 10 is “a single entity for drug
`
`
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`administration,” taken in isolation with no limitation on route of administration. It
`
`is clear from the specification and claims of the ’636 patent that “unit dosage
`
`form” should be interpreted as a “unit dosage form suitable for oral administration
`
`to a patient.” (Ex. 1001 at 3:27-29.) The specification states that “[a]ll of the
`
`dosage forms are designed for oral delivery and provide for the coordinated release
`
`of therapeutic agents, i.e., for the sequential release of acid inhibitor followed by
`
`analgesic.” (Ex. 1001 at 6:20-23.) Accordingly, the term is at the core of the
`
`“invention” and should be construed, consistent with the specification, as directed
`
`solely to oral delivery.
`
`The Board has construed “unit dosage form” previously in its institution
`
`decision in IPR2015-00802 for U.S. Patent No. 8,557,285,4 as meaning “a single
`
`entity for drug administration that is suitable for oral administration.” (IPR2015-
`
`00802 Non-Institution Decision at 17.) The Patent Owner maintains that the phrase
`
`should be construed consistent with the Board’s prior decision, i.e., as meaning “a
`
`single entity for drug administration that is suitable for oral administration.”
`
`VI. PROSECUTION HISTORY
`The Petition, without any support, states “The ’636 Patent was not
`
`substantively examined.” (Pet. at 8.) Although the examiner did not find that the
`
`
`4 The ’285 patent has the same specification as the ’636 patent.
`
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`claims of the ’636 patent required a rejection, there is no evidence to support the
`
`Petition’s conclusion that there was no substantive examination. As an initial
`
`matter, “government officials are presumed to have ‘properly discharged their
`
`official duties.’” United States v. Chemical Found., Inc., 272 U.S. 1, 15 (1926). If
`
`the references were in front of the examiner, it must be assumed that he or she
`
`reviewed them. In re Portola Packaging, Inc., 110 F.3d 786, 790 (Fed. Cir. 1997).
`
`Furthermore, the prosecution history of the ’636 patent evidences communication
`
`between the examiner and the applicant regarding the status of the claims and
`
`various patentability concerns raised by the Office during prosecution. (8/8/14
`
`Interview Summary, Ex. 1002 at 56.) In addition, the ’636 patent is part of a long
`
`lineage of issued patents directed to similar subject matter, each of which also was
`
`substantively examined. The M.P.E.P. admonishes examiners to “consider
`
`information which has been considered by the Office in a parent application” when
`
`examining a continuing application. M.P.E.P. § 609.02(A)(2).
`
`Accordingly,
`
`the Patent Owner submits
`
`that
`
`the ’636 patent was
`
`substantively examined during prosecution as evidenced in its own prosecution
`
`history and the prosecution histories of the other patents in its lineage to which it
`
`claims priority.
`
`The Patent Owner also disagrees with the Petition’s allegation that “the
`
`references included in this petition, or similar disclosures thereof . . . are buried
`
`
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`among hundreds of other cited references.” (Pet. at 8-9.) But it is plain from the
`
`prosecution history that the examiner was meticulous in her review of the cited
`
`documents. Not only did she initial that she had reviewed the references, the
`
`examiner also issued an interview summary reiterating the fact that “The IDS filed
`
`July 31, 2014 was considered by the Examiner.” (See 8/20/14 Communication to
`
`Applicant, Ex. 1002 at 18.) The prosecution history of this patent and its parent
`
`patents, evidences that the Office considered the teachings of the prior art and
`
`issued the ’636 patent over those teachings.
`
`VII. THE BOARD SHOULD DENY CFAD’S PETITION BECAUSE IT
`FAILS TO DEMONSTRATE A REASONABLE LIKELIHOOD OF
`PREVAILING
`
`Each of the proposed grounds in the Petition alleges that the challenged
`
`claims are unpatentable as obvious. As discussed below, each ground is legally
`
`deficient and should be denied.
`
`A. Ground 1: The Petition Has Not Established a Reasonable
`Likelihood That Claims 1-18 are Obvious Over Goldman in View
`of Remington and Lindberg
`
`The Petition does not establish a reasonable likelihood that it would prevail
`
`on Ground 1. Ground 1 is centered on Goldman, which discloses a combination of
`
`an NSAID or acetaminophen with an H1 or H2 blocker or a proton pump inhibitor
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`for the treatment of headaches and indigestion with “overindulgence.” (Ex. 1004,
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`3:3-16.) Goldman does not disclose that immediate-release esomeprazole could be
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`Patent No. 8,852,636
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`combined with delayed release naproxen to form the claimed invention. The
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`Petition attempts to overcome the shortcomings of Goldman by combining it with
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`Remington, a general purpose pharmaceutical textbook, and Lindberg, which
`
`relates to enteric-coated, delayed-release esomeprazole. But neither of those
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`references discloses that immediate-release esomeprazole could or should be
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`combined with naproxen.
`
`With respect to the Goldman reference, the Petition relies on substantially
`
`the same arguments that were considered by the examiner during prosecution of
`
`the application resulting in the ’907 patent, which is a parent of the ’636 patent.
`
`During prosecution of the ’907 patent, the Applicants cited the Goldman reference
`
`as reference AB2 in an Information Disclosure Statement filed on April 24, 2003.
`
`(4/24/03 ’907 Information Disclosure Statement, Ex. 2005 at 554.) The Examiner
`
`initially rejected the then-pending claims as anticipated over Goldman because:
`
`The [Goldman] reference clearly shows a pharmaceutical composition
`comprised of an acid inhibitor and a non-steroidal anti-inflammatory
`drug (NSAID). The particular H2 blockers and proton pump inhibitors
`are the same as applicants’. The effective dosage amounts are the
`same as applicants’. The composition of Goldman would therefore
`inherently impart the same effects on the gastric ph as applicants’.
`Particular dosage forms including capsules are shown . . . .
`
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`(4/22/04 ’907 Office Action Summary, Id. at 96.) In response, Applicants argued
`
`that Goldman failed to teach the coordinated release of the active ingredients as
`
`claimed in the pending application:
`
`All of Applicant’s claims have requirements not only with respect to
`the type of active ingredients present in compositions or methods, but
`also with respect to the way in which the active ingredients are
`delivered in relation to one another. . . . [T]hese characteristics are not
`disclosed or suggested [by] Goldman. . . . By preventing NSAID from
`being released until the surrounding environment becomes more
`basic, the pharmaceutical composition defined in claim 1 provides for
`safer delivery.
`
`(7/22/04 ’907 Response to Office Action, Id. at 86.) In the subsequent Office
`
`Action, the Examiner maintained the rejection because “[t]here is nothing in claim
`
`1 that enables the release that applicant is referring to. . . . Amending claim 1 to
`
`incorporate a polymer coating as set forth in claims 24 and 51-54 would be given
`
`favorable consideration in overcoming the prior art rejection.”5 (10/20/04 ’907
`
`Office Action Summary, Id. at 74.)
`
`
`
`5 Then-pending claim 51 recited:
`
`The pharmaceutical composition of any one of claims 1-11,
`wherein said NSAID is surrounded by an enteric coating that
`does not dissolve until the pH of the surrounding medium is 3.5
`
`
`
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`
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`Applicant filed a Request for Continued Examination, and amended claims
`
`1-3 and 12-20, among others “to comply with suggestions in the Office Action and
`
`to emphasize characteristics that Applicants believe are central to their invention.”
`
`Applicant stated:
`
`Amended claims require that NSAID be surrounded by a coating that
`prevents its release from the dosage form unless the pH of the
`surrounding medium is 3.5 or higher, and that at least a portion of the
`acid inhibitor in compositions is not surrounded by an enteric coating
`and is released regardless of whether the pH is above 3.5 or below 3.5.
`
`(11/22/04 ’907 Amendment and Response, Id. at 62.)
`
`The Examiner allowed the amended claims, noting that Goldman failed to disclose
`
`the coordinated release element, which resulted in a safer delivery of the active
`
`agents. (3/29/05 ’907 Notice of Allowance, Id. at 45.)
`
`In the Notice of Allowance for the ’636 patent, the Examiner again
`
`emphasized the coordinated release aspect of the claimed inventions that are not
`
`taught by the prior art, including Goldman:
`
`
`
`or higher, and said acid inhibitor is either not surrounded by an
`enteric coating or it surrounded by an enteric coating that
`dissolves when the surrounding medium is at a pH below 3.5.
`
`(10/17/03 ’907 Preliminary Amendment, Ex. 2005 at 123.)
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`[T]he general state of the art is that solid oral dosage forms
`comprising proton pump inhibitors (PPIs) such as esomeprazole are
`enterically coated to prevent the acid sensitive PPI from being
`degraded by the acidic environment of the stomach before it can be
`absorbed. While some art teaches that enteric coatings need not be
`applied to dosage forms containing PPIs for oral administration like
`those of the instant claims, those prior art documents do not disclose a
`combination dosage form as in the present claims of esomeprazole
`with naproxen. Prior art that discloses a combination of an NSAID
`such as naproxen enterically coat the naproxen and PPI portions of the
`dosage form. Compositions in which at least a portion of the
`esomeprazole is released regardless of the pH of the medium in
`combination with naproxen have been previously allowed (US
`8,557,285). The instant claims are narrower, specifying that at least
`one of the esomeprazole layers does not contain naproxen and releases
`the esomeprazole into the stomach when ingested.
`
`(8/8/14 Notice of Allowance, Ex. 1002 at 53.)
`
`As
`
`the Examiner correctly concluded, Goldman does not disclose
`
`formulations with an immediate release acid inhibitor and a delayed release
`
`NSAID that would provide coordinated release. Nor does Goldman teach that
`
`coordinated release of an acid inhibitor with an NSAID is in any way desirable.
`
`Even if Goldman could be combined with Remington and Lindberg, the
`
`combination does not cure this deficiency.
`
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`Both Lindberg and Remington teach away from the use of non-enteric
`
`coated esomeprazole. Lindberg teaches enteric coated esomeprazole to protect it
`
`from the acidic environment of the stomach.
`
`Granules and tablets [of esomeprazole] may be coated with an enteric
`coating which protects the active compound from acid catalyzed
`degradation as long as the dosage form remains in the stomach.
`. . .
`Soft gelatine capsules [of esomeprazole] may also be enteric-coated as
`described above.
`. . .
`[Hard gelatin] capsules [of esomeprazole] may be enteric-coated as
`described above.
`
`(Lindberg, Ex. 1007 at 5:36-39, 5:48-50, 5:56-57.) Further, Example 13 of
`
`Lindberg describes how to prepare enteric coated tablets. (Id. at 12:12-43.)
`
`Remington teaches that enteric coated tablet formulations are used with acid
`
`labile drug substances:
`
`Enteric-Coated Tablets (ECT)-These are compressed tablets coated
`with substances that resist solution in gastric fluid but disintegrate in
`the intestine. Enteric coatings can be used for tablets containing drug
`s