Case 3:11-cv-02317-MLC-DEA Document 498 Filed 07/12/17 Page 1 of 65 PageID: 17741
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`UNITED STATES DISTRICT COURT
`DISTRICT OF NEW JERSEY
`
`HORIZON PHARMA, INC. and POZEN :
` Case No. 11-2317 (MLC) (DEA)
`INC.,
`:
`: REDACTED
`: AMENDED MEMORANDUM OPINION :
`
`Plaintiffs,
`
`
`
`v.
`
`DR. REDDY’S LABORATORIES,
`INC., et al.,
`
`:
`:
`:
`:
`:
`:
`Defendants.
`__________________________________ :
`
`COOPER, District Judge
`I. Background.............................................................................................................................. 2
`
`II. Legal Standards ....................................................................................................................... 6
`A. Infringement ......................................................................................................................... 6
`B. Written Description .............................................................................................................. 7
`C. Enablement / Utility ............................................................................................................. 8
`D. Obviousness ......................................................................................................................... 9
`
`Infringement and Related § 112 Challenges to the ’285 Patent ...................................... 10
`III.
`A. Written Description (Uncoated Naproxen) ...................................................................... 11
`B. Written Description (Sustained Release Formulations) ................................................... 23
`C. Infringement ....................................................................................................................... 27
`
`IV. Obviousness and Related § 112 Challenges ..................................................................... 31
`A. Obviousness ....................................................................................................................... 31
`B. Enablement ......................................................................................................................... 59
`C. Written Description (Uncoated PPI) ................................................................................. 62
`
`V. Conclusion ............................................................................................................................. 65
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`I.
`
`Background
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`This is a patent dispute between Plaintiffs Horizon Pharma, Inc. and Pozen Inc.
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`(together, “Horizon”) and two groups of generic drug manufacturers: (1) Dr. Reddy’s
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`Laboratories, Inc. and Dr. Reddy’s Laboratories, Ltd. (“DRL”); and (2) Mylan, Inc.; Mylan
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`Pharmaceuticals Inc.; and Mylan Laboratories Ltd. (“Mylan,” and together with DRL,
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`“Defendants”). Horizon holds New Drug Application (“NDA”) No. 022511 for Vimovo, a
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`branded drug product whose active pharmaceutical ingredients are naproxen and
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`esomeprazole magnesium. (Dkt. 421 at 6.)1
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`This case arises out of Defendants’ submission of Abbreviated New Drug
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`Applications (“ANDAs”) to the FDA pursuant to the Hatch-Waxman Act, 21 U.S.C.
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`§ 355(j), for the purpose of obtaining FDA approval for the commercial manufacture, use,
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`import, offer for sale, and sale of a generic version of Vimovo. Specifically, DRL filed
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`ANDA No. 202461 (“DRL ANDA I”) and ANDA No. 204206 (DRL ANDA II”). Mylan
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`filed ANDA No. 204920 (“Mylan ANDA”). Based on submissions by the parties in the pre-
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`trial order, all three ANDAs relate to tablets containing 375 mg or 500 mg of naproxen and 20
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`mg esomeprazole magnesium. (Dkt. 421 at 7–8.)2 All three ANDAs included so-called
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`“Paragraph IV” certifications that the products would not infringe Horizon’s patents and/or
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`that those patents are invalid or unenforceable. (Id.) The Paragraph IV certifications covered
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`U.S. Patent No. 6,926,907 (“the ’907 patent”) and No. 8,557,285 (“the ’285 patent”)
`
`1 The Court will cite documents filed on the Electronic Case Filing System (“ECF”) by referring to
`the docket entry numbers as “dkt.” Pincites reference ECF pagination.
`2 Lupin Pharmaceuticals, Inc. and Lupin Ltd. (“Lupin”) submitted an ANDA filing (No. 202654).
`Horizon’s case against Lupin (Case No. 11-4275) has been stayed pending the outcome of this case.
`(Dkt. 455.)
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`Case 3:11-cv-02317-MLC-DEA Document 498 Filed 07/12/17 Page 3 of 65 PageID: 17743
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`(together, the “Asserted Patents”). In response to those Paragraph IV certifications,
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`Horizon asserted infringement of claims 5, 15, 52, and 53 of the ’907 patent.3 Horizon
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`has also asserted claims 1 through 4 of the ’285 patent.4
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`Mylan has stipulated that its ANDA product would infringe the Asserted Patents.
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`(Dkt. 421 at 8.) DRL has admitted that its DRL ANDA I Product would infringe the Asserted
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`Patents. (Id.) We previously granted summary judgment in DRL’s favor that its ANDA II
`
`i)
`
`3 The asserted claims of the ’907 patent (together with claim 1 for context) are:
`1. A pharmaceutical composition in unit dose form suitable for oral administration to a
`patient, comprising:
`(a) an acid inhibitor present in an amount effective to raise the gastric pH of said patient
`to at least 3.5 upon the administration of one or more of said unit dosage forms;
`(b) a non-steroidal anti-inflammatory drug (NSAID) in an amount effective to reduce or
`eliminate pain or inflammation in said patient upon administration of one or more of
`said unit dosage forms; and wherein said unit dosage form provides for coordinated
`release such that:
`said NSAID is surrounded by a coating that, upon ingestion of said unit dosage form
`by said patient, prevents the release of essentially any NSAID from said dosage form
`unless the pH of the surrounding medium is 3.5 or higher;
`ii) at least a portion of said acid inhibitor is not surrounded by an enteric coating and, upon
`ingestion of said unit dosage form by said patient, is released regardless of whether the
`pH of the surrounding medium is below 3.5 or above 3.5.
`5. The pharmaceutical composition of claim 1, wherein said acid inhibitor is a proton pump
`inhibitor selected from the group consisting of: omeprazole, esomeprazole, lansoprazole,
`pantoprazole and rabeprazole.
`15. The pharmaceutical composition of . . . claim[] 1 . . . wherein said acid inhibitor is a
`proton pump inhibitor.
`51. A method of treating a patient for pain or inflammation, comprising administering to
`said patient the pharmaceutical composition of claim 15.
`52. The method of claim 51, wherein said pain or inflammation is due to either
`osteoarthritis or rheumatoid arthritis.
`53. The pharmaceutical composition of any one of claims 5-11 wherein said unit dosage form
`is a multilayer tablet comprising a single core and one or more layers outside of said single core,
`wherein:
`i)
`said NSAID is present in said core;
`ii) said coating that does not release said NSAID unless the pH of the surrounding medium is
`3.5 or higher surrounds said core; and
`iii) said acid inhibitor is in said one [or] more layers outside said core.
` (’907 patent at col. 20, line 9 to col. 24, line 6.)
`3
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`Product does not infringe the ’907 patent. (Dkt. 380). Accordingly, the only infringement
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`dispute at trial was whether DRL’s ANDA II Product infringes the ’285 patent. Most of the
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`trial was focused on Defendants’ contentions that claims in the Asserted Patents are invalid
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`under 35 U.S.C. § 103 and/or § 112.
`
`We held a six day bench trial on those issues from January 12–20, 2017 and heard
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`closing arguments on May 17, 2017.5 We heard live testimony from seven witnesses. Dr.
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`John Plachetka, called by Horizon, was the named inventor on the Asserted Patents. (Tr. 15–
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`192.) Dr. David Metz, called by Defendants, was qualified as an expert in gastroenterology,
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`including the treatment of acid peptic disorder. (Tr. 260–396.) Dr. Arthur Kibbe, called by
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`Defendants, was qualified as an expert in pharmaceutical formulation and development. (Tr.
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`4 The asserted claims of the ’285 patent are as follows:
`1. A pharmaceutical composition in unit dosage form comprising therapeutically effective
`amounts of:
`(a) esomeprazole, wherein at least a portion of said esomeprazole is not surrounded by an
`enteric coating; and
`(b) 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;
`wherein said 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.
`2. The pharmaceutical composition of claim 1, wherein naproxen is present in said unit dosage
`form in an amount of 200-600 mg.
`3. The pharmaceutical composition of claim 1, wherein esomeprazole is present in said unit
`dosage form in an amount of from 5 to 100 mg.
`4. The pharmaceutical composition of claim 1, wherein naproxen is present in said unit dosage
`form in an amount of between 200-600 mg and esomeprazole in an amount of from 5 to 100
`mg per unit dosage form.
`(’285 patent at col. 22, lines 8–28.)
`5 The trial transcript is separated into seven volumes, but the pages are numbered consecutively. (See
`dkt. 458 (Vol. 1), dkt. 461 (Vol. 2), dkt. 463 (Vol. 3), dkt. 466 (Vol. 4), dkt. 468 (Vol. 5), dkt. 471
`(Vol. 6), and dkt. 491 (Vol. 7).) We will cite to the trial transcript using the designation “Tr.” without
`indicating the specific volume.
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`408–565.) Dr. Michael Mayersohn, called by Defendants, was qualified as an expert on
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`pharmacokinetics and pharmacodynamics. (Tr. 569–603; Tr. 610–707.) Dr. Robert
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`Williams, III, called by Horizon, was qualified as an expert in pharmaceutical formulation.
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`(Tr. 716–842; Tr. 849–1017.) Dr. David Taft, called by Horizon, was qualified as an expert
`
`in pharmacokinetics. (Tr. 1018–1102.) Dr. David Johnson, called by Horizon, was qualified
`
`as an expert in gastroenterology. (Tr. 1108–1266.) The parties also submitted designated
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`deposition testimony from Brian Ault (DTX-1393); Mark Sostek (DTX-1396); Jeff Sherman
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`(DTX-1397); Dennis McNamara (DTX-1398); Abhijit Desmukh (PTX-581); John Horn
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`(PTX-582); T. Sudhakar Koudinya (PTX-583); Snehalatha Movva (PTX-584); and Badri
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`Viswanathan (PTX-585).6
`
`This opinion follows the parties’ division of the relevant legal issues raised at trial and
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`addresses the interrelated infringement and § 112 issues in Section III, infra, and the
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`interrelated obviousness and § 112 issues in Section IV, infra. In support of their arguments,
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`Horizon and Defendants submitted separate post-trial briefs on the issues addressed in Section
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`III (dkt. 489-2; dkt. 489-3) and Section IV (dkt. 489; dkt. 489-1).
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`For the reasons below, we conclude that DRL’s ANDA II Product infringes the ’285
`
`patent and that the asserted claims are not invalid under 35 U.S.C. § 103 and/or § 112.
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`Accordingly, we will grant judgment in Horizon’s favor and issue an appropriate order.
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`6 Defendants object to Dr. Horn’s deposition testimony as inadmissible hearsay. (Dkt. 472.) We
`conclude that Dr. Horn’s testimony is admissible because it satisfies the requirements of the hearsay
`exception in Federal Rule of Civil Procedure 32(a) for deposition testimony of an unavailable witness.
`See Novozymes A/S v. Genencor Int'l, Inc., No. 05-160, 2006 WL 318936, at *1 (D. Del. Feb. 10,
`2006). We note, however, that the exclusion of Dr. Horn’s testimony would not have changed any of
`our conclusions in this opinion.
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`II.
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`Legal Standards
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`A.
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`Infringement
`
`The standard for patent infringement is set forth in 35 U.S.C. § 271, which states that
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`“whoever without authority makes, uses, offers to sell, or sells any patented invention, within
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`the United States or imports into the United States any patented invention during the term of
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`the patent therefor, infringes the patent.” 35 U.S.C. § 271(a). The burden to prove
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`infringement rests with the patentee who must prove infringement by a preponderance of the
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`evidence. Medtronic, Inc. v. Mirowski Family Ventures, LLC, 134 S. Ct. 843, 846 (2014).
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`To prove infringement, the patentee must show that an accused product is within the claim
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`limitations of the patent-in-suit either literally or under the doctrine of equivalents. See
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`Warner Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520 U.S. 17, 21 (1997); Amgen Inc.
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`v. F. Hoffman La Roche Ltd., 580 F. 3d 1340, 1374 (Fed. Cir. 2009). In a Hatch-Waxman
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`case, the actual act of infringement is the filing of an ANDA to obtain approval to engage
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`in the commercial manufacture, use, or sale of a patented drug or method of use. 35
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`U.S.C. § 271(e)(2). Specifically, § 271(e)(2)(A) provides that it shall be an act of
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`infringement to submit an ANDA “if the purpose of such submission is to obtain
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`approval . . . to engage in the commercial manufacture, use, or sale of a drug . . . claimed
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`in a patent or the use of which is claimed in a patent before the expiration of such patent.”
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`The infringement analysis is a two-step process in which we must: (1) determine the
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`scope and meaning of the disputed patent claim terms; and (2) compare the properly
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`construed claims to the allegedly infringing product or device. Advanced Steel Recovery,
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`LLC v. X-Body Equip., Inc., 808 F.3d 1313, 1316 (Fed. Cir. 2015).
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`B. Written Description
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`A patent specification must contain “a written description of the invention.”
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`35 U.S.C. § 112(a). To satisfy that requirement, “the specification must describe an
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`invention understandable to [a] skilled artisan and show that the inventor actually
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`invented the invention claimed.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
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`1351 (Fed. Cir. 2010). “The purpose of the written description requirement is to prevent
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`an applicant from later asserting that he invented that which he did not.” Amgen Inc. v.
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`Hoechst Marion Roussel, 314 F.3d 1313, 1330 (Fed. Cir. 2003). The requirement thus
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`mandates that the applicant “recount his invention in such detail that his future claims can
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`be determined to be encompassed within his original creation.” Vas-Cath Inc. v.
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`Mahurkar, 935 F.2d 1555, 1561 (Fed. Cir. 1991).
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`The “hallmark of written description is disclosure,” and the test for its sufficiency
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`is “whether the disclosure . . . reasonably conveys to those skilled in the art that the
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`inventor had possession of the claimed subject matter as of the filing date.” Ariad, 598
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`F.3d at 1351. “It is the specification itself that must demonstrate possession” and
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`analysis of the adequacy of the written description “requires an objective inquiry into the
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`four corners of the specification from the perspective of a person of ordinary skill in the
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`art.” Id. at 1351–52. The disclosure must “allow one skilled in the art to visualize or
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`recognize the identity of the subject matter purportedly described.” Enzo Biochem, Inc.
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`v. Gen-Probe Inc., 323 F.3d 956, 968 (Fed. Cir. 2002).
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`“There is no rigid requirement that the disclosure contain ‘either examples or an
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`actual reduction to practice.’” Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1308 (Fed.
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`Cir. 2015) (quoting Ariad, 598 F.3d at 1352). Rather, “the proper inquiry is whether the
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`patentee has provided an adequate description that ‘in a definite way identifies the
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`claimed invention’ in sufficient detail such that a person of ordinary skill would
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`understand that the inventor had made the invention at the time of filing.” Id. at 1308.
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`Moreover, “an applicant is not required to describe in the specification every conceivable
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`and possible future embodiment of his invention.” See Cordis Corp. v. Medtronic AVE,
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`Inc., 339 F.3d 1352, 1365 (Fed. Cir. 2003). The challenging party must show lack of
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`adequate written description by clear and convincing evidence to rebut the patent’s
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`presumption of validity. Alcon Research Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1188–
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`91 (Fed. Cir. 2014).
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`C.
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`Enablement / Utility
`
`35 U.S.C. § 112 requires applicants to describe the manner of making and using
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`the invention “in such full, clear, concise, and exact terms as to enable any person skilled
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`in the art . . . to make and use the same . . . .” The Federal Circuit has explained that “the
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`how to use prong of section 112 incorporates as a matter of law the requirement of 35
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`U.S.C. § 101 that the specification disclose as a matter of fact a practical utility for the
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`invention.” Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1323 (Fed. Cir.
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`2005) (citing In re Cortright, 165 F.3d 1353, 1356 (Fed. Cir. 1999)). As a result, “an
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`applicant’s failure to disclose how to use an invention may support a rejection under . . .
`
`section 112 . . . when there is a complete absence of data supporting the statements which set
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`forth the desired results of the claimed invention.” Id. (internal quotations omitted).
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`Conversely, “a specification disclosure which contains a teaching of the manner and
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`process of making and using the invention . . . must be taken as in compliance with the
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`enabling requirement of the first paragraph of [section] 112 unless there is reason to
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`doubt the objective truth of the statements contained therein which must be relied on for
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`enabling support.” Id. The challenging party bears the burden of showing by clear and
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`convincing evidence that the specification lacks adequate enablement. ALZA Corp. v.
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`Andrx Pharms., 603 F.3d 935, 940 (Fed. Cir. 2010).
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`D.
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`Obviousness
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`Under 35 U.S.C. § 103, a “patent may not be obtained . . . if the differences between
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`the subject matter sought to be patented and the prior art are such that the subject matter as a
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`whole would have been obvious at the time the invention was made to a person having
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`ordinary skill in the art to which said subject matter pertains.” “Obviousness is a question of
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`law, which depends on several underlying factual inquiries.” See Senju Pharm. Co. v. Apotex
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`Inc., 717 F. Supp.2d 404, 418 (D. Del. 2010), aff’d, 485 Fed. App’x 433 (Fed. Cir. 2012).
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`Those inquiries include the scope and content of the prior art, differences between the prior art
`
`and the claims at issue, and the level of ordinary skill in the pertinent art. KSR Int’l Co. v.
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`Teleflex Inc., 550 U.S. 398, 406 (2007) (quoting Graham v. John Deere Co., 383 U.S. 1, 17-
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`18 (1966)). We also consider as part of the obviousness analysis “secondary considerations,”
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`including commercial success, long felt but unsolved needs, and failure of others. Id. “A
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`nonmovant may rebut a prima facie showing of obviousness with objective indicia of
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`nonobviousness.” Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299, 1311 (Fed. Cir.
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`2006). “Although secondary considerations must be taken into account, they do not
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`necessarily control the obviousness conclusion.” In re Huai–Hung Kao, 639 F.3d 1057,
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`1068 (Fed. Cir. 2011).
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`“[A] patent composed of several elements is not proved obvious merely by
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`demonstrating that each of its elements was, independently, known in the prior art.” Id. at
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`418; see also Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011).
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`Instead, proof of obviousness requires proof that a person of ordinary skill in the art
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`(“POSA”) “would have been motivated to combine the teachings of the prior art references to
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`achieve the claimed invention, and . . . would have had a reasonable expectation of success in
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`doing so.” Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989, 994 (Fed. Cir.
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`2009). A POSA would interpret prior art references “using common sense and appropriate
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`perspective.” Unigene Labs., 655 F.3d at 1361. The party challenging the validity of the
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`patent must prove obviousness by clear and convincing evidence. See Novo Nordisk A/S v.
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`Caraco Pharm. Labs., Ltd., 719 F.3d 1346, 1352 (Fed. Cir. 2013)
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`III.
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`Infringement and Related § 112 Challenges to the ’285 Patent
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`The only infringement question at trial was whether DRL’s ANDA II Product
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`infringes claims 1, 2, 3, and 4 of the ’285 patent. See Section I, supra. Horizon submitted
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`evidence that DRL’s ANDA II Product satisfies each limitation of the asserted claims. In
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`response, Defendants offer a pair of arguments in the alternative. One argument (and, per
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`Defendants, the “better decision” for us to reach) is that the asserted ’285 patent claims are
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`invalid for lack of written description on two distinct grounds. The other is that DRL’s
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`ANDA II Product cannot infringe the ’285 patent if we construe the claims such that they
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`survive the written description challenges. In this section, we reject both written description
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`challenges and conclude that DRL’s ANDA II Product infringes the ’285 patent.
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`A. Written Description (Uncoated Naproxen)
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`Defendants’ first written description challenge involves two primary contentions.
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`First, Defendants contend that claim 1 of the ’285 patent encompasses formulations that
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`include naproxen that is released immediately. Second, they contend that the ’285 patent
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`specification discloses a coordinated release product that does not permit the immediate
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`release of naproxen. This purported disconnect between the scope of the claims and the
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`specification forms the basis of the written description challenge. This section consequently
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`proceeds in two parts. First, we review the parties’ evidence and arguments related to the
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`scope of the ’285 patent claims and the written description of the invention in the ’285 patent
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`specification. Second, we assess whether the ’285 patent claims are adequately described by
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`the patent specification under the applicable legal standards.
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`1.
`
`Parties’ Evidence and Arguments
`
`(i)
`
`Scope of the ’285 patent claims
`
`Claim 1 of the ’285 patent reads:
`
`A pharmaceutical composition in unit dosage form comprising
`therapeutically effective amounts of:
`
`(a) esomeprazole, wherein at least a portion of said esomeprazole
`is not surrounded by an enteric coating; and
`
`(b) 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;
`
`wherein said unit dosage form provides for release of said
`esomeprazole such that upon introduction of said unit dosage form
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`into a medium, at least a portion of said esomeprazole is released
`regardless of the pH of the medium.
`
`(’285 patent at col. 22, lines 8–14.)
`
`Any product alleged to infringe claim 1 must, of course, satisfy the enteric coated
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`naproxen claim limitation set forth in subsection (b). The question before us is the scope of
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`claim 1 as it pertains to uncoated naproxen that may be released into the body immediately
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`regardless of pH level.7 The plain language of claim 1 does not explicitly restrict the amount
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`of uncoated naproxen that may be present in the claimed formulation and indeed the parties
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`agree that the claim encompasses formulations that have at least some uncoated naproxen.
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`The real dispute between the parties is whether claim 1 limits how much uncoated naproxen
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`may be present in the claimed formulation. Broadly, Defendants urge us to adopt the “plain
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`meaning” of the claim, which “imposes no limitation on the amount of naproxen that may be
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`outside the enteric coating.” (Dkt. 489-2 at 12.) Horizon argues that the claim covers
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`formulations that contain uncoated naproxen so long as it is less than a “therapeutically
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`effective amount.”8 (Dkt. 489-3 at 16–17.)
`
`Defendants’ proposed reading of claim 1 is straightforward: the plain language of the
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`claim imposes no limitation on the amount of uncoated naproxen that may be present in
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`claimed formulations, and it would be improper to read in such a limitation. (Dkt. 489-2 at
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`7 We follow the parties in using the phrase “enteric coating” as shorthand to describe the pH-sensitive
`coating used to satisfy the limitation in claim 1, subsection (b). We use the term “uncoated naproxen”
`to mean naproxen without an enteric coating that may be released immediately regardless of pH.
`Because the enteric coating in Vimovo is applied around a naproxen “core” of the tablet, the term
`“uncoated naproxen” can also refer to the naproxen outside the (enteric coated) core.
`8 The parties appear to use the term “therapeutic amount” and “therapeutically effective amount”
`interchangeably.
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`12–14.) Defendants argue that a POSA “would recognize that any amount of naproxen
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`outside the enteric coating (and that could fit in a “unit dosage form”) would be covered
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`by the ’285 patent claims.” (Id. at 12.) They note that Horizon expert Dr. Williams
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`testified that a POSA would understand the term “comprising” to permit the inclusion of
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`additional elements. (Id.; Tr. 821:6-25.) Dr. Williams also explained, in his infringement
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`analysis, that he could “ignore” uncoated naproxen given the “comprising” language. (Tr.
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`855:12-24.)
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`Defendants submit that their interpretation is consistent with the history of the ’285
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`patent because Horizon deliberately removed the claim limitation related to uncoated
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`naproxen. (Dkt. 489-2 at 8–9.) As Defendants explain, the ’285 patent differs somewhat
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`from the earlier-issued ’907 patent. Claim 1 of the ’907 patent restricts the amount of
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`uncoated naproxen that may be present by requiring NSAID surrounded by a coating that
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`prevents the release of “essentially any NSAID . . . unless the pH of the surrounding medium
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`is 3.5 or higher.” (’907 patent at col. 20, lines 8–32.) Allegedly to avoid infringement of the
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`’907 patent, DRL formulated its ANDA II Product with some naproxen outside of the enteric
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`coated core of the tablet. (Dkt. 489-2 at 7.) As part of this litigation, we previously construed
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`the term “essentially any NSAID” to mean “the minimum amount of NSAID released by an
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`enteric coated dosage form, or tablet.” (Dkt. 380 at 18–22.) Because DRL’s ANDA II
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`product
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`, we
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`concluded that DRL’s ANDA II Product does not infringe the ’907 patent. (Id. at 22–23.)
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`Horizon was later granted the ’285 patent, which does not contain the “essentially any
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`NSAID” language that formed the basis of our non-infringement finding for the ’907 patent.
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`Horizon disagrees with Defendants’ proposed reading of claim 1 of the ’285 patent,
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`and urges us to interpret the claim to limit the amount of permissible uncoated naproxen to
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`less than a “therapeutic amount.”9 Dr. Williams testified that a POSA would understand
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`the claim to allow only “less than a therapeutic amount” of uncoated naproxen. (Tr.
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`821:15–822:7.) Horizon also points to a decision from the Patent Trial and Appeal Board
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`(“PTAB”) denying Inter Partes review of the ’285 patent and purportedly supporting
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`Horizon’s “therapeutic amount” limitation.10 The PTAB concluded that claim 1 of the
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`’285 patent “does not exclude the presence of additional naproxen outside of the coating”
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`and “does not exclude a unit dosage form that has an amount of naproxen outside the
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`coating that is not therapeutically effective.” (PTX-351 at 13.) Consequently, the PTAB
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`rejected the argument that claim 1 “encompass[ed] a composition where the vast majority
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`of the naproxen, i.e., a therapeutically effective amount, would be outside the coating.”
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`(PTX-351 at 12.)
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`Defendants argue that Horizon’s proposed therapeutic amount limitation is
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`inconsistent with an FDA Citizen’s Petition filed by Horizon. (Dkt. 489-2 at 26–27;
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`DTX-1248.) In that petition, Horizon argued to the FDA that “locating any naproxen
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`9 The ’285 patent states that the “most preferred NSAID is naproxen in an amount of between 50 mg
`and 1500 mg, and more preferably, in an amount between 200 mg and 600 mg.” (’285 patent at col.
`4, lines 11–14.) The parties accordingly appear to agree that the smallest “therapeutic amount” of
`Naproxen would be 50 mg. The distinction is irrelevant for infringement purposes in this case
`because DRL’s ANDA II Product
`10 See Dr. Reddy’s Laboratories, Inc. v. Pozen Inc., IPR2015-00802, Paper No. 28 (P.T.A.B. Oct. 9,
`2015). For ease of reference, we will cite this PTAB decision by its trial exhibit number, PTX-351.
`We acknowledge Defendant Mylan’s concern that it was not a party to the PTAB proceeding. (Tr.
`547:23–459:19.) None of our conclusions depend on the PTAB’s decision but, as discussed below,
`we are mindful of instances where the PTAB rejected arguments comparable to those made at trial.
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`outside the enteric coated core will result in the immediate release of at least some
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`portion of the naproxen at the same time as esomeprazole is released. Any portion of the
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`generic product’s naproxen that is released prematurely in the stomach will act both
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`topically and systemically without the benefit of the raised gastric pH produced by the
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`esomeprazole component.” (DTX-1248 at 7 (emphasis added).) In the same petition,
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`Horizon argued that esomeprazole/naproxen combination tablets with uncoated naproxen
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`“could subject patients to significantly increased risk of potentially fatal side effects.”
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`(DTX-1248 at 7; Tr. 436:19–437:5.) Because Horizon has separately argued to the FDA
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`that any amount of uncoated naproxen might pose a safety risk, Defendants claim that
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`Horizon’s therapeutic amount limitation is not credible. Defendants further argue that a
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`therapeutic amount limitation does not make sense because the FDA rejected the notion
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`that the sequential release of esomeprazole and naproxen in Vimovo is clinically
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`significant. (DTX-1250 at 7; Tr. 358:11-23; Tr. 462:10-23.)
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`Defendants also ask us to reject Horizon’s proposed therapeutic amount limitation
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`because it was not raised during discovery. (Dkt. 489-2 at 18.) Dr. Williams did not
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`explicitly propose a therapeutic amount limitation in his deposition. Instead, Dr.
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`Williams testified at his deposition that some amount of naproxen outside of an enteric
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`coating might pose a safety issue but did not quantify how much. (Tr. 855:19–858:11.)
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`Moreover, Defendants claim that Horizon “admitted” that the “plain meaning of the ’285
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`patent claims applied and they had no limitation on the amount