UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Filed: May 8, 2019
`
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`MYLAN PHARMACEUTICALS INC. and
`DR. REDDY’S LABORATORIES, INC.
`Petitioners
`
`v.
`
`HORIZON PHARMA USA, INC. and NUVO PHARMACEUTICALS
`(IRELAND) DESIGNATED ACTIVITY COMPANY,
`Patent Owners
`
`____________________________
`
`Case No. IPR208-002721
`U.S. Patent No. 9,393,208 B2
`____________________________
`
`PETITIONERS’ REPLY TO PATENT OWNERS’ RESPONSE
`
`
`1 Petitioner Dr. Reddy’s Laboratories, Inc. from IPR2018-01341, has been joined as
`
`a Petitioner to this proceeding.
`
`

`

`TABLE OF CONTENTS
`
`
`Page
`
`D.
`
`V.
`
`
`INTRODUCTION .......................................................................................... 1
`I.
`PTAB ALREADY DECLINED TO TERMINATE THE PETITION .......... 2
`II.
`III. PETITIONERS’ EXPERTS ARE QUALIFIED ............................................ 2
`IV. THE ’285 PATENT ANTICIPATED THE ’208 PATENT ........................... 3
`A.
`The ’285 Patent Is Prior Art ................................................................. 3
`B.
`The ’285 Patent Disclosed the Claimed Formulation .......................... 6
`C. A POSA Would Have Understood the Formulation Was Given
`Twice Daily .......................................................................................... 9
`The Claimed PK/PD Limitations Are Inherent in the Dosage
`Form ................................................................................................... 10
`THE ’208 PATENT WOULD HAVE BEEN OBVIOUS OVER THE
`’285 PATENT ............................................................................................... 11
`A.
`Section 103(c) Does Not Exclude the ’285 Patent ............................. 11
`B.
`The Claimed PK/PD Limitations Were Obvious ............................... 14
`C.
`The Prior Art Did Not Teach Away ................................................... 16
`VI. THE ’208 PATENT WOULD HAVE BEEN OBVIOUS OVER THE
`’285 PATENT, THE EC-NAPROSYN LABEL, AND HOWDEN ............ 17
`A.
`The ’208 Patent Is Not Entitled to a Priority Date Before
`September 9, 2008 .............................................................................. 17
`The EC-Naprosyn Label Reflected Long-Known Naproxen
`Characteristics .................................................................................... 19
`C. Horizon Misrepresents Petitioners’ Ground 3 Argument .................. 20
`VII. HORIZON’S SECONDARY CONSIDERATIONS FAIL ......................... 22
`A. Horizon’s Secondary Considerations Lack Nexus ............................. 22
`B. Horizon’s Secondary Considerations Fail on the Merits ................... 23
`
`B.
`
`
`
`
`
`-i-
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`

`

`
`
`
`
`TABLE OF AUTHORITIES
`
`
`CASES
`AbbVie Inc. v. Mathilda & Terrence Kennedy Instit. of Rheumatology
`Trust,
`764 F.3d 1366 (Fed. Cir. 2014) ............................................................................ 8
`Actavis LLC v. Abraxis BioScience LLC,
`IPR2017-01103, 2017 WL 4546784 (PTAB Oct. 10, 2017) .............................. 16
`Atlas Powder Co. v. IRECO, Inc.,
`190 F.3d 1342 (Fed. Cir. 1999) ............................................................................ 7
`Aventis Pharma Deutschland GmbH v. Lupin, Ltd.,
`499 F.3d 1293 (Fed. Cir. 2007) .......................................................................... 25
`Breckenridge Pharm., Inc. v. Novartis Pharm. Corp.,
`IPR2017-01592, Paper 12 (PTAB Jan. 3, 2018) .................................................. 8
`Coherus Biosciences, Inc. v. AbbVie Biotechnology Ltd.,
`IPR2017-00822, Paper 14 (PTAB Sept. 7, 2017) ................................................. 9
`Dow Jones & Co., Inc. v. Ablaise Ltd.,
`606 F.3d 1338 (Fed. Cir. 2010) .......................................................................... 25
`EmeraChem Holdings, LLC v. Volkswagen Grp. of Am., Inc.,
`859 F.3d 1341 (Fed. Cir. 2017) ............................................................................ 5
`Estee Lauder, Inc. v. L’Oreal S.A.,
`129 F.3d 588 (Fed. Cir. 1997) ............................................................................ 18
`Ex Parte Desormeaux,
`25 U.S.P.Q.2d 2040, 1992 WL457519 (B.P.A.I. 1992) ....................................... 4
`Freebit AS v. Bose Corp.,
`IPR2017-01308, 2017 WL 5202106 (PTAB Nov. 8, 2017) ............................... 18
`Honeywell Int’l Inc. v. Mexichem Amanco Holdings S.A.,
`865 F.3d 1348 (Fed. Cir. 2017) .......................................................................... 15
`
`ii
`
`

`

`
`
`Horizon Pharma, Inc. v. Dr. Reddy’s Labs., Inc.,
`No. 11-cv-02317-MLC, 2017 WL 2979683 (D.N.J. July 12, 2017) .................. 23
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .................................................................... 14, 22
`In re Klopfenstein,
`380 F.3d 1345 (Fed. Cir. 2004) .......................................................................... 19
`In re Wyer,
`655 F.2d 221 (C.C.P.A. 1981) ............................................................................ 19
`Indus. Tech. Research Inst. v. Pac. Biosciences,
`640 F. App’x 871 (Fed. Cir. 2016) ..................................................................... 13
`Ineos USA LLC v. Berry Plastics Corp.,
`783 F.3d 865 (Fed. Cir. 2015) .............................................................................. 7
`Jazz Pharm., Inc. v. Amneal Pharm., LLC,
`895 F.3d 1347 (Fed. Cir. 2018) .......................................................................... 19
`King Pharm., Inc. v. Eon Labs, Inc.,
`616 F.3d 1267 (Fed. Cir. 2010) .......................................................................... 14
`Leggett & Platt, Inc. v. VUTEk, Inc.,
`537 F.3d 1349 (Fed. Cir. 2008) ............................................................................ 6
`Maxlinear, Inc. v. Cresta Tech. Corp.,
`IPR2015-00594, Paper 90 (PTAB Aug. 15, 2016) ............................................. 12
`Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co.,
`878 F.3d 1336 (Fed. Cir. 2018) .......................................................................... 15
`MRC Innovations, Inc. v. Hunter Mfg., LLP,
`747 F. 3d 1326 (Fed. Cir. 2014) ......................................................................... 22
`Netgear, Inc. v. Ruckus Wireless, Inc.,
`5 F. Supp. 3d 592 (D. Del. 2013) ........................................................................ 13
`Nuevolution A/S v. Chemgene Holdings APS,
`IPR2017-01599, Paper 46 (PTAB Jan. 9, 2019) .................................................. 8
`
`iii
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`

`

`
`
`Par Pharm., Inc. v. TWI Pharm., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) .......................................................................... 15
`Pernix Ir. Pain DAC v. Alvogen Malta Operations Ltd.,
`323 F. Supp. 3d 566 (D. Del. 2018).................................................................... 14
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) ...................................................................... 6, 10
`Riverwood International Corp. v. R.A. Jones & Co.,
`324 F.3d 1346 (Fed. Cir. 2003) ............................................................................ 5
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) .................................................................... 10, 14
`Schering Corp. v. Geneva Pharm., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003) ............................................................................ 9
`Sjolund v. Musland,
`847 F.2d 1573 (Fed. Cir. 1988) .......................................................................... 24
`The Medicines Co. v. Mylan Inc.,
`No. 11-CV-1285, 2014 WL 1227214 (N.D. Ill. Mar. 25, 2014) ........................ 23
`Therasense, Inc. v. Becton, Dickinson & Co.,
`593 F.3d 1289 (Fed. Cir. 2010), vacated for en banc rehearing on
`inequitable conduct, 374 F. App’x 35 (Fed. Cir. 2010) ..................................... 23
`STATUTES
`21 U.S.C. §§ 352-53................................................................................................. 19
`35 U.S.C. §102(e) .............................................................................................passim
`35 U.S.C. §103(c)(2)(A) (pre-AIA) ......................................................................... 13
`35 U.S.C. §103(c)(2)(C) (pre-AIA) ................................................................... 11, 12
`OTHER AUTHORITIES
`37 C.F.R. 1.71(g)(1) ................................................................................................. 12
`37 CFR 1.71(g) ........................................................................................................ 12
`
`iv
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`

`

`
`
`H.Rep. No. 108-425 (2004) ..................................................................................... 13
`
`H.Rep. No. 108-425 (2004) ..................................................................................... 13H.Rep. No. 108-425 (2004) ..................................................................................... 13
`MPEP 2156 .............................................................................................................. 12
`
`
`
`
`MPEP 2156 .............................................................................................................. 12MPEP 2156 .............................................................................................................. 12
`
`v
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`

`

`
`
`TABLE OF ABBREVIATIONS
`Area under the curve ........................................................................................... AUC
`
`Horizon Pharma USA, Inc. and Nuvo
`Pharmaceuticals (Ireland) Designated
`Activity Company (collectively) .....................................................................Horizon
`Mylan Pharmaceuticals Inc. and Dr. Reddy’s Laboratories, Inc. .............. Petitioners
`
`Non-steroidal anti-inflammatory drug ............................................................ NSAID
`
`Patent Owners’ Response (Paper 32) .................................................................. Resp.
`
`Person of ordinary skill in the art ...................................................................... POSA
`
`Pharmacodynamic ................................................................................................... PD
`
`Pharmacokinetic ...................................................................................................... PK
`
`Proton pump inhibitor ............................................................................................ PPI
`
`U.S. Patent No. 6,926,907 .................................................................... the ’907 patent
`
`U.S. Patent No. 8,557,285 .................................................................... the ’285 patent
`
`U.S. Patent No. 9,220,698 .................................................................... the ’698 patent
`
`U.S. Patent No. 9,393,208 .................................................................... the ’208 patent
`
`
`
`vi
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`

`

`
`
`I.
`
`INTRODUCTION
`The ’208 patent uses a known combination of naproxen and esomeprazole to
`
`target inherent therapeutic drug levels. Horizon applied for the ’208 patent more than
`
`seven years after the filing of the first patent application on that combination
`
`(resulting in the ’907 and ’285 patents). The ’208 patent adds only that formulation’s
`
`inherent PK/PD properties. This epitomizes unpatentability, as established in the
`
`Petition.
`
`Horizon’s response does not dispute either that the naproxen-esomeprazole
`
`formulation recited in the claims of the ’208 patent was known or that the claimed
`
`PK/PD values are the natural result of ingesting that formulation. Instead, Horizon
`
`lodges a series of collateral attacks on the prior art status of the ’285 patent and the
`
`priority date of the ’208 patent. These attacks fall short of removing the ’285 patent’s
`
`disclosure from the prior art.
`
`Horizon’s appeal to secondary considerations of nonobviousness also fails.
`
`Faced with nearly ten earlier patents on Vimovo, Horizon cannot establish nexus
`
`between these secondary considerations and the ’208 patent’s inherent PK/PD
`
`values. Other flaws abound.
`
`Petitioners respectfully request that PTAB find the ’208 patent’s claims
`
`unpatentable.
`
`- 1 -
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`

`

`
`
`II.
`
`PTAB ALREADY DECLINED TO TERMINATE THE PETITION.
`Horizon first re-argues (at 19-20) the Petition should be terminated in light of
`
`the district court’s finding that the challenged claims are indefinite. PTAB has
`
`already rejected this argument (Paper 35). Horizon offers nothing new here.
`
`Horizon argues (at 19) termination is proper because the claims are indefinite.
`
`Horizon has nonetheless appealed the district court’s decision. Exs. 1056-1058.
`
`Horizon also suggests (at 19-20) that Petitioners cannot show invalidity when faced
`
`with indefiniteness, and it therefore would be “inappropriate” for PTAB to continue.
`
`PTAB has already rejected this argument and should do so again for the same
`
`reasons. Paper 35, 6. The district court found the term “target” indefinite in the
`
`context of infringement. PTAB must apply the broadest reasonable interpretation for
`
`patentability, which does not compel identical results. Id.
`
`III. PETITIONERS’ EXPERTS ARE QUALIFIED.
`Horizon next argues (at 20-21) that Petitioner’s experts are “unreliable”
`
`because the definition of a POSA requires “collaboration” between the two
`
`specialties. Collaboration does not require direct communication. It means that
`
`certain aspects of the disclosure would be within a medical doctor’s purview, while
`
`others would be within a pharmacologist/pharmacokineticist’s purview. Here, Dr.
`
`Mayersohn
`
`offered
`
`his
`
`analysis
`
`from
`
`the
`
`perspective
`
`of
`
`a
`
`pharmacologist/pharmacokineticist. Ex. 1074 ¶9. Dr. Metz offered his opinion on
`
`- 2 -
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`

`

`
`
`the aspects of the claims that related to a medical doctor’s expertise. Ex. 1059 ¶8.
`
`Dr. Metz collaborated with a pharmacologist/pharmacokineticist by providing
`
`opinions that, when combined with those of Dr. Mayersohn, show the claims to be
`
`unpatentable. Id.; Ex. 1085, 8:3-12.
`
`IV. THE ’285 PATENT ANTICIPATED THE ’208 PATENT.
`Horizon raises a series of challenges to Ground 1—that the ’208 patent is
`
`anticipated by the ’285 patent. Horizon questions the ’285 patent’s prior art status.
`
`But the ’285 patent on its face has a different inventive entity than the ’208 patent,
`
`rendering it 35 U.S.C. § 102(e) prior art. Horizon next presses that the ’285 patent
`
`does not anticipate because it has examples other than, e.g., a naproxen-
`
`esomeprazole combination. This argument is wrong on the law and facts, at least
`
`because the ’285 patent only claims this combination. Finally, Horizon claims the
`
`’285 patent does not disclose twice-daily dosing, but this is misplaced, ignoring a
`
`POSA’s understanding of the ’285 patent and naproxen’s decades-old dosing.
`
`A. The ’285 Patent Is Prior Art.
`A patent is prior art to a later patent if the “patent granted on an application
`
`for patent by another filed in the United States before the invention by the applicant
`
`for patent.” 35 U.S.C. § 102(e). Horizon disputes (at 21-23) that the ’285 patent
`
`was “by another.” The ’208 patent includes three inventors in addition to Dr.
`
`Plachetka, the named inventor on the ’285 patent. The inventive entities on the two
`
`- 3 -
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`

`

`
`
`patents are different; the prior art ’285 patent is “by another.” See Ex Parte
`
`Desormeaux, 25 U.S.P.Q.2d 2040, 1992 WL457519 (B.P.A.I. 1992).
`
`Horizon admitted that “[s]ubsequent to the invention claimed” in the ’285
`
`patent, “Dr. Plachetka collaborated with” the listed co-inventors of the ’208 patent
`
`on the purported “claimed inventions.” Paper 7, 3. To avoid § 102(e), Horizon now
`
`reverses course (at 23-25), trying to discount the contributions of three other named
`
`inventors on the ’208 patent. But Horizon admits (at 24-25) that Drs. Orlemans, Ault,
`
`and Sostek—named inventors of the ’208 patent—designed and implemented the
`
`trials that led to recognizing the PK properties of the formulation claimed in the ’208
`
`patent. Dr. Orlemans testified that he “helped with the design of the study,” which
`
`was “one of the first studies that was done actually to find out what the effect is of
`
`the tablet on intragastric pH….” Ex. 2018, 21:6-14, 22:7-8. Dr. Sostek testified that
`
`several people, including he and Dr. Orlemans, “contributed…as a team in designing
`
`the study.” Ex. 2019, 130:14-24. Dr. Sostek further testified that Drs. Orlemans and
`
`Ault contributed to “the clinical trials and the data generated from their end….” Id.
`
`at 132:19-133:6. Drs. Orlemans, Ault, and Sostek identified the ’208 patent’s PK/PD
`
`limitations. See Resp. 10-13. Horizon—which possesses
`
`the
`
`relevant
`
`documentation—provided no contrary evidence.
`
`Conversely, Dr. Plachetka is the sole named ’285 patent inventor but had little
`
`to do with the study. Drs. Ault and Orlemans had “regular meetings” regarding the
`
`- 4 -
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`

`

`
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`“PN400 project”; Dr. Ault only met “Plachetka a few times.” Ex. 2020, 39:9-21. In
`
`fact, it’s not clear that Dr. Plachetka participated at all in the study or even saw the
`
`results until he signed the study’s summary report. Ex. 2018, 88:22-90:13.
`
`According to Dr. Sostek, Dr. Plachetka reviewed the study “but wasn’t quite as
`
`involved in the…details.” Ex. 2019, 134:13-18.
`
`Horizon’s cases (at 22-23) support Petitioners’ position. To illustrate, in
`
`Riverwood International Corp. v. R.A. Jones & Co., 324 F.3d 1346, 1356 (Fed. Cir.
`
`2003), the patentee argued that a reference was not from a different inventive entity
`
`because the contributions of two “extra” named inventors were deleted during
`
`prosecution; thus, only a single inventor (and the same inventor) should have been
`
`named on both patents. The patentee requested inventorship correction, and the
`
`Federal Circuit remanded for further proceedings, instructing that “if [the patentee]
`
`sustains its burden of proof that Ziegler is the sole inventor of the [asserted patent],
`
`then the ’806 patent would not be prior art to the [asserted] patent, and the district
`
`court should order correction of the inventorship of that patent.” Id. at 1357. Horizon
`
`here made no such effort.
`
`On this record, Horizon has not demonstrated Dr. Plachetka is the lone
`
`inventor of the ’208 patent. The ’285 patent lists a different inventive entity than the
`
`’208 patent and is prior art under § 102(e) as an invention “by another.” EmeraChem
`
`Holdings, LLC v. Volkswagen Grp. of Am., Inc., 859 F.3d 1341, 1345-48 (Fed. Cir.
`
`- 5 -
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`

`

`
`
`2017) (affirming that a patent listing four inventors was § 102(e) prior art to the
`
`challenged patent listing only two of those inventors, despite a conclusory and
`
`uncorroborated declaration from one of the named inventors).
`
`The ’285 Patent Disclosed the Claimed Formulation.
`B.
`Horizon next argues (at 31-33) that the ’285 patent does not inherently
`
`anticipate because, even though it “disclose[s] a solid oral dosage form that exhibits
`
`coordinated release and contains an immediate-release [PPI] and an enteric coated
`
`NSAID,” it discloses other formulations. According to Horizon, a POSA therefore
`
`would not necessarily select the correct formulation. Id.; Ex. 2025 ¶51-53; Ex. 2026
`
`¶¶63-65.
`
`Inherency does not require that every previously-disclosed embodiment result
`
`in the invention. Leggett & Platt, Inc. v. VUTEk, Inc., 537 F.3d 1349, 1356 (Fed.
`
`Cir. 2008) (rejecting “the erroneous assumption that the disclosure of multiple
`
`examples renders one example less anticipatory”). A single embodiment that would,
`
`when practiced, necessarily anticipate is all that is required. Id.; Perricone v. Medicis
`
`Pharm. Corp., 432 F.3d 1368, 1376 (Fed. Cir. 2005) (rejecting “the notion that [a
`
`compound] cannot anticipate because it appears without special emphasis in a longer
`
`list”).
`
`Figure 2 from the ’285 patent and its associated description disclose enteric-
`
`coated naproxen covered in a PPI that is “released...immediately.” Ex. 1005, 10:49-
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`- 6 -
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`

`

`
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`11:2; Ex. 1074 ¶14. The ’285 patent identified naproxen as “[t]he most preferred
`
`NSAID,” and esomeprazole as a “preferred” PPI. Ex. 1005, 44-46, 4:11-12; Ex. 1074
`
`¶13. This naproxen-esomeprazole formulation is the only formulation claimed in the
`
`’285 patent. Ex. 1005, claim 1. Claims 2-4 of the ’285 patent disclosed dosage ranges
`
`for naproxen (200-600mg) and esomeprazole (5-100mg) that encompass those
`
`claimed in the ’208 patent. “When a patent claims a range, as in this case, that range
`
`is anticipated by a prior art reference if the reference discloses a point within the
`
`range.” Ineos USA LLC v. Berry Plastics Corp., 783 F.3d 865, 869 (Fed. Cir. 2015)
`
`(citation omitted); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1346, 1349-50
`
`(Fed. Cir. 1999).
`
`Even if not so, a POSA reading the ’285 patent, knowing the commercially-
`
`available dosage forms of naproxen (500mg), and esomeprazole (20mg and 40mg),
`
`would have understood and envisioned that a combined esomeprazole-naproxen
`
`tablet would contain 20mg esomeprazole and 500mg naproxen. Ex. 1002 ¶68; Ex.
`
`1003 ¶¶128, 158; Ex. 1079, 16:4-17:7 (conceding that a POSA would read claim 4
`
`as encompassing a unit dosage form of naproxen 500 milligrams, and esomeprazole
`
`- 7 -
`
`

`

`
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`20 milligrams); Ex. 1059 ¶31; AbbVie Inc. v. Mathilda & Terrence Kennedy Instit.
`
`of Rheumatology Trust, 764 F.3d 1366, 1379 (Fed. Cir. 2014).2
`
`Horizon also asserts (at 33), without expert support, that an enteric coating on
`
`the naproxen may impact certain AUC values, and that “the ’285 patent teaches two
`
`broad classes of enteric coatings, those that release based on the pH of the medium
`
`and those that release over a period of time” and “[t]he type of enteric coating…will
`
`affect the pharmacokinetics…within that coating.” Horizon ignores that the two
`
`“broad classes” accomplish the same thing, releasing the NSAID at a pH above 3.5.
`
`Ex. 1005, 4:59-63 (describing the enteric coating based on time “with the rate
`
`adjusted so that the NSAID is not released until after the pH…has risen to at least
`
`3.5”); Ex. 1074 ¶27. Likewise, Horizon offers no support for its theory that
`
`esomeprazole’s AUC varies based on coating variables, citing only testimony
`
`regarding the values for “omeprazole administered with buffer.” Resp. 33 (citing Ex.
`
`2029, 90:22-91:11). In fact, Figure 2 disclosed an “immediate release” (i.e.,
`
`uncoated) esomeprazole (Ex. 1005, 10:66-11:1), which would also be encompassed
`
`by the ’285 patent’s claims. Regardless, contrary to Horizon’s attorney argument,
`
`
`2 Breckenridge Pharm., Inc. v. Novartis Pharm. Corp., IPR2017-01592, Paper 12 at
`
`6 (PTAB Jan. 3, 2018); Nuevolution A/S v. Chemgene Holdings APS, IPR2017-
`
`01599, Paper 46 at 25 (PTAB Jan. 9, 2019).
`
`- 8 -
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`

`

`
`
`whether esomeprazole is only partially uncoated or uncoated does not impact AUC.
`
`Ex. 1074 ¶27.
`
`C. A POSA Would Have Understood the Formulation Was Given
`Twice Daily.
`Horizon argues (at 31-32) that ’285 patent Examples 9 and 10, though
`
`disclosing
`
`twice-daily dosing, did not disclose a naproxen-esomeprazole
`
`formulation. This is contrary to both the ’285 patent’s disclosure and the POSA’s
`
`knowledge. Yes, Example 9 described doses of standalone naproxen and omeprazole
`
`(a PPI) rather than a combined naproxen-esomeprazole formulation. But a POSA
`
`nonetheless knew to administer naproxen twice daily and Examples 9 and 10 reflect
`
`that knowledge. Ex. 1059 ¶34; Ex. 1074 ¶25. Thus, a POSA would understand that
`
`a combination naproxen-esomeprazole product would also be administered twice a
`
`day. Ex. 1059 ¶34; Ex. 1074 ¶25; Coherus Biosciences, Inc. v. AbbVie Biotechnology
`
`Ltd., IPR2017-00822, Paper 14 at 8 (PTAB Sept. 7, 2017); Schering Corp. v. Geneva
`
`Pharm., Inc., 339 F.3d 1373, 1377-78 (Fed. Cir. 2003).3
`
`
`3 Horizon does not dispute this would have been obvious in light of the ’285 patent
`
`and the POSA’s knowing to administer the claimed formulation twice-daily. Resp.
`
`39-40.
`
`- 9 -
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`

`

`
`
`D. The Claimed PK/PD Limitations Are Inherent in the Dosage
`Form.
`Horizon does not dispute that the PK/PD limitations are the natural result of
`
`ingesting the formulation twice daily. Ex. 1059 ¶33; Ex. 1074 ¶¶17-18, 20; Ex. 1079,
`
`23:22-24:21; Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir.
`
`2012). In fact, Dr. Plachetka admitted that “there is no question if you take the drug,
`
`you are going to get blood levels of both Naproxen and Esomeprazole provided you
`
`absorb them.” Ex. 2016, 196:4-7; Ex. 1074 ¶19.
`
`Instead, Horizon presses (at 31, 33-34) that a POSA could not “target” the
`
`’208 patent’s claimed PK/PD values because the ’285 patent did not expressly
`
`disclose them. Inherency does not depend upon whether the prior art reference or a
`
`POSA expressly recognized the inherent, unstated characteristic. Perricone, 432
`
`F.3d at 1376. Regardless, an identical prior formulation—such as claimed in the ’285
`
`patent—would not merely target—i.e., set the goal of obtaining—the relevant
`
`PK/PD values, it would actually obtain those values. Ex. 1074 ¶20.4
`
`
`4 Notably, Horizon’s PK/PD expert admitted that he did not even consider the
`
`construction of “target.” Ex. 1079, 27:5-28:3.
`
`- 10 -
`
`

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`
`
`V. THE ’208 PATENT WOULD HAVE BEEN OBVIOUS OVER THE
`’285 PATENT.
`Horizon’s challenges to obviousness over the ’285 patent mirror many of its
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`anticipation positions and fail for similar reasons. Horizon again challenges the prior
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`art status of the ’285 patent, this time under § 103(c)(2). But Horizon fails to meet
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`§ 103(c)(2)’s requirements because Horizon has not shown both that the ’208 patent
`
`was amended to disclose the names of the parties to the joint research agreement and
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`that the parties are, in fact, the same. Horizon next argues that the ’208 patent is not
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`obvious in light of the “unpredictable” nature of the PK/PD parameters. This is
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`belied by a slew of Federal Circuit cases and unsupported by the record. Finally,
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`Horizon’s argument that the ’285 patent “teaches away” from, e.g., the 20mg
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`esomeprazole dose is contrary to both the ’285 patent—which acknowledges this
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`exact dose—and the POSA’s understanding that a 20mg-dose was commercially
`
`available.
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`Section 103(c) Does Not Exclude the ’285 Patent.
`A.
`Horizon’s attempt (at 35-37) to avoid the ’285 patent through the safe harbor
`
`of § 103(c)(2) fails at least because the ’208 patent was not amended to disclose the
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`names of parties to a joint research agreement as required by § 103(c)(2)(C). Section
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`103(c) is an exception to the definition of prior art for subject matter that would
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`qualify as prior art under § 102(e) if “at the time the claimed invention was made,
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`[the prior art and invention were] owned by the same person or subject to an
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`obligation of assignment to the same person.” This includes joint research
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`agreements if, among other things, “the application for patent for the claimed
`
`invention discloses or is amended to disclose the names of the parties to the joint
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`research agreement.” 35 U.S.C. § 103(c)(2)(C) (pre-AIA). Horizon bears the burden
`
`of production “that the safe haven of § 103(c) applies.” Maxlinear, Inc. v. Cresta
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`Tech. Corp., IPR2015-00594, Paper 90 at 24 (PTAB Aug. 15, 2016).
`
`The ’208 patent does not refer to a joint research agreement, as required for
`
`Horizon to rely on § 103(c). MPEP 2156 (“If the names of the parties to the joint
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`research agreement are not already stated in the application, it is necessary to amend
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`the application to include the names of the parties to the joint research agreement in
`
`accordance with 37 CFR 1.71(g).”); 37 C.F.R. 1.71(g)(1) (“The specification may
`
`disclose or be amended to disclose the names of the parties to a joint research
`
`agreement as defined in § 1.9(e).”). Horizon does not identify anywhere that the ’208
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`patent application “discloses or is amended to disclose the names of the parties to
`
`the joint research agreement” as required by § 103(c)(2)(C). The Collaboration and
`
`License Agreement (“CLA”)—purportedly a joint research agreement—is between
`
`Pozen and AstraZeneca. Ex. 2067, 8. In contrast, the ’208 patent lists Pozen and
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`Horizon, not AstraZeneca, as assignees. Ex. 1001. This alone precludes Horizon
`
`from relying on § 103(c).
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`Moreover, Horizon has not shown the ’208 and ’285 patents are both owned
`
`by the “parties to a joint research agreement” under § 103(c)(2)(A). See H.Rep. No.
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`108-425, at 9 (2004) (“the invention and the subject matter (i.e., the prior art…) that
`
`is being excluded [is] owned by, or otherwise subject to the control of, one or more
`
`parties to the joint research agreement”). The “parties” to the CLA were Pozen Inc.
`
`and AstraZeneca AB. Horizon asserts (at 37), without support, that the provisional
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`application from which the ’208 patent claims priority was filed “with Pozen and
`
`AstraZeneca as co-owners.” But “AstraZeneca” is not a single entity, and
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`“AstraZeneca” is not a party to the CLA. And the provisional application has a
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`correspondence address for Astra Zeneca Pharmaceuticals LP—AstraZeneca AB is
`
`not listed in the application or file history. Ex. 1080, 1. Without showing that, at the
`
`time of the purported invention, the invention was owned by Pozen Inc. and/or
`
`AstraZeneca AB, the CLA cannot be used to exclude the ’285 patent as prior art.5
`
`
`5 Netgear, Inc. v. Ruckus Wireless, Inc., 5 F. Supp. 3d 592 (D. Del. 2013), does not
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`say otherwise. Unlike here, in Netgear, the defendant did not dispute that the
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`references at issue were invented by and assigned to the same company. Id. at 617.
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`Neither can the later actions of an AstraZeneca entity or Horizon correct this
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`deficiency, as seemingly suggested by Horizon. Resp. 37 n.8; Indus. Tech. Research
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`Inst. v. Pac. Biosciences, 640 F. App’x 871, 883 (Fed. Cir. 2016) (“evidence of
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`The Claimed PK/PD Limitations Were Obvious.
`B.
`Horizon’s contention (at 37-39) that, although obviousness can be proven
`
`through inherency, the PK/PD properties here were “unexpected,” is contrary to
`
`Federal Circuit precedent and unsupported by the record. Horizon ignores the
`
`Federal Circuit’s many decisions holding that the natural results—including PK/PD
`
`results—of an obvious formulation are inherent in that formulation. Santarus, 694
`
`F.3d at 1354 (“The initial blood serum concentration resulting from administering a
`
`PPI dosage is an inherent property of the formulation, and an obvious formulation
`
`cannot become nonobvious simply by administering it to a patient and claiming the
`
`resulting serum concentrations.”); In re Huai-Hung Kao, 639 F.3d 1057 (Fed. Cir.
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`2011) (“food-effect” related serum concentration level “inherent property of [drug]
`
`itself”); King Pharm., Inc. v. Eon Labs, Inc., 616 F.3d 1267 (Fed. Cir. 2010)
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`(bioavailability “the natural result”); Pernix Ir. Pain DAC v. Alvogen Malta
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`Operations Ltd., 323 F. Supp. 3d 566, 605-7 (D. Del. 2018) (“necessarily present
`
`properties, such as the pharmacokinetic parameters of previously known
`
`
`common ownership by assignment after the application filing date does not establish
`
`common ownership or an obligation to assign ownership at the time of invention”).
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`compositions, do not add patentable weight when they are claimed as limitations”)
`
`(collecting cases).6
`
`Horizon offers a file history snippet from the prosecution of the related ’698
`
`patent (Ex. 1089), in which it self-servingly argued that the PD profile was
`
`“unexpected.” Resp. 39 (citing Ex. 2024, 7).7 Horizon cites no evidence that this
`
`argument was credited. Actually, the ’698 patent prosecution continued for more
`
`than two years with multiple obviousness rejections. Ex. 1081, 7 (rejecting as
`
`
`6 Horizon’s cases (at 37-39) do not support non-obviousness. Honeywell Int’l Inc. v.
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`Mexichem Amanco Holdings S.A., 865 F.3d 1348, 1354-56 (Fed. Cir. 2017) (where
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`Board credited evidence of unexpected results, proceeding was remanded for Board
`
`to c