`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`NALOX-1 PHARMACEUTICALS, LLC,
`Petitioner,
`
`v.
`
`OPIANT PHARMACEUTICALS, INC.,
`Patent Owner.
`__________________
`
`Case IPR2019-00690
`Patent 9,468,747
`__________________
`
`PRELIMINARY RESPONSE OF PATENT OWNER
`OPIANT PHARMACEUTICALS, INC.
`
`
`
`
`
`
`
`
`

`

`Case IPR2019-00690
`Patent 9,468,747
`
`TABLE OF CONTENTS
`
`BACKGROUND ............................................................................................. 3
`
`THE BOARD SHOULD DENY INSTITUTION BECAUSE THE
`PETITION IS REDUNDANT. ........................................................................ 6
`
`
`
`
`I.
`
`II.
`
`III. THE BOARD SHOULD DENY INSTITUTION IN LIGHT OF THE
`PARALLEL DISTRICT COURT ACTIONS. ................................................ 8
`
`A.
`
`B.
`
`C.
`
`The Teva Case Involves a Generic Manufacturer with Final
`Approval for an Intranasal Naloxone Product. ..................................... 9
`
`The Teva Case is Nearing Its Final Stages.......................................... 12
`
`The Factual Record Developed in the Teva Case Will Be
`Onerous, if even Possible, to Re-create in this Proceeding ................ 15
`
`IV. PETITIONER HAS NOT DEMONSTRATED A REASONABLE
`LIKELIHOOD OF SUCCESS WITH RESPECT TO ANY CLAIMS
`CHALLENGED IN THE PETITION. .......................................................... 18
`
`A.
`
`The POSA Would Not Have Been Motivated to Use a Single
`Intranasal Naloxone Dose of 4 mg. ..................................................... 19
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`Petitioner Ignores Clinical Evidence and Provides No
`Testimony from a Clinician. .....................................................22
`
`The Prior Art Taught That an Initial Intranasal Dose of 2 mg or
`Less Was Therapeutically Effective. ........................................23
`
`The Prior Art Disclosed That Too Much Liquid Was a Problem
`for Nasal Delivery, Not Lack of Efficacy. ................................24
`
`The Art Taught, and the POSA Would Have Understood, That
`Higher Doses of Naloxone Risked Withdrawal Symptoms and
`Other Significant Negative Effects. ..........................................27
`
`Davies Does Not Teach 4 mg Doses of Naloxone. ..................34
`
`Contrary to Petitioner’s Misreading, Wyse Does Not Teach 4
`mg Doses of Naloxone. .............................................................38
`
`i
`
`

`

`
`
`Case IPR2019-00690
`Patent 9,468,747
`
`7.
`
`The Pharmacokinetic Data in Wyse Would Not Lead the POSA
`to a Single 4 mg Dose of Intranasal Naloxone. ........................40
`
`B.
`
`The POSA Would Not Have Been Motivated to Use the
`Required Stabilizing Agent, Much Less the Combination of
`BZK with EDTA. ................................................................................ 45
`
`1.
`
`2.
`
`3.
`
`4.
`
`Davies Does Not Teach the Use of BZK and a Stabilizing
`Agent at the Claimed Concentrations. ......................................46
`
`The POSA Would Have Been Taught Away from the Use of
`BZK and EDTA In Light of the Studies in Wyse. ....................48
`
`HPE Also Teaches Away From BZK and EDTA and Would
`Not Override Wyse’s Teach Away Anyway. ...........................54
`
`Bahal and Kushwaha Would Not Lead the POSA to Use BZK
`and EDTA. ................................................................................57
`
`V.
`
`CONCLUSION .............................................................................................. 58
`
`
`
`ii
`
`

`

`Case IPR2019-00690
`Patent 9,468,747
`
`
`
`TABLE OF AUTHORITIES
`
`CASES
`DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`567 F.3d 1314 (Fed. Cir. 2009) .......................................................................... 58
`
`E.I. DuPont de Nemours & Co. v. Synvina C.V.,
`904 F.3d 996 (Fed. Cir. 2018) ............................................................................ 37
`
`Harmonic Inc. v. Avid Tech., Inc.,
`815 F.3d 1356 (Fed. Cir. 2016) ............................................................................ 6
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) .................................................... 15
`
`In re Gurley,
`27 F.3d 551 (Fed. Cir. 1994) .............................................................................. 51
`
`Neptune Generics, LLC v. Eli Lilly & Co.,
`921 F.3d 1372 (Fed. Cir. 2019) .................................................................... 10, 15
`
`St. Regis Mohawk Tribe v. Mylan Pharms., Inc.,
`896 F.3d 1322 (Fed. Cir. 2018) ...................................................................... 6, 17
`
`Tec Air, Inc. v. Denso Mfg. Mich. Inc.,
`192 F.3d 1353 (Fed. Cir. 1999) .......................................................................... 55
`
`W.L. Gore & Assoc., Inc. v. Garlock, Inc.,
`721 F.2d 1540 (Fed. Cir. 1983) .......................................................................... 56
`
`Comcast Cable Commc’ns, LLC v. Rovi Guides, Inc.,
`Case IPR2019-00225, Paper 14 (P.T.A.B. June 3, 2019) .................................... 6
`
`Comcast Cable Commc’ns, LLC v. Rovi Guides, Inc.,
`Case IPR2019-00232, Paper 14 (P.T.A.B. May 20, 2019) .................................. 6
`
`E-One, Inc. v. Oshkosh Corp.,
`Case IPR2019-00161, Paper 16 (P.T.A.B. May 15, 2019) ...................... 8, 13, 14
`
`Garmin Int’l, Inc. v. Cuozzo Speed Techs. LLC,
`Case IPR2012-00001, Paper 26 (P.T.A.B. Mar. 5, 2013) .................................. 17
`
`iii
`
`

`

`
`Gen. Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha,
`Case IPR2016-01357, Paper 19 (P.T.A.B. Sept. 6, 2017) .................................... 9
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Mylan Pharms., Inc. v. Bayer Intellectual Property GMBH,
`Case IPR2018-01143, Paper 13 (P.T.A.B. Dec. 3, 2018) .................................. 12
`
`Neptune Generics, LLC v. Aventis Generics S.A.,
`Case IPR2019-00136, Paper 15 (P.T.A.B. May 6, 2019) .................................. 10
`
`NHK Spring Co. v. Intri-Plex Techs. Inc.,
`Case IPR2018-00752, Paper 8 (P.T.A.B. Sept. 12, 2018) ............................ 12, 14
`
`Valve Corp. v. Elec. Scripting Prods., Inc.,
`Case IPR2019-00062, Paper 11 (P.T.A.B. Apr. 2, 2019) ............................. 14, 15
`
`STATUTES
`
`35 U.S.C. § 314 .................................................................................................. 14, 18
`
`35 U.S.C. § 316 ........................................................................................................ 18
`
`35 U.S.C. § 325 ........................................................................................................ 13
`
`37 C.F.R. § 42.108 ................................................................................................... 23
`
`REGULATIONS
`
`
`
`
`
`
`
`
`
`iv
`
`

`

`
`
`Short Name
`Ex. No.
`2001 Williams Decl.
`
`2002 Amphastar Press
`Release
`
`2003 Aquina
`
`2004 Baca
`
`2005 Belz
`
`2006 Buajordet
`
`2007 Burford Press
`Release
`
`Case IPR2019-00690
`Patent 9,468,747
`
`EXHIBIT LIST
`
`
`Title
`Expert Declaration of Kenneth A. Williams,
`M.D.
`
`Amphastar Announces the Receipt of a CRL for
`Intranasal Naloxone for the Emergency
`Treatment of Opioid Overdose (Feb. 21, 2017),
`available at http://ir.amphastar.com/static-
`files/19b13150-7ff8-4d3b-8e3f-452578083dbb
`
`Christopher T. Aquina et al., OxyContin® Abuse
`and Overdose, Postgraduate Medicine (2009)
`121(2):163–67
`
`Catherine T. Baca et al., Take-home Naloxone to
`Reduce Heroin Death, Addiction (2005)
`100:1823–31
`
`Daniel Belz et al., Naloxone Use in a Tiered-
`Response Emergency Medical Services System,
`Prehospital Emergency Care (2006) 10(4):468–
`71
`
`Ingebjorg Buajordet, Adverse Events After
`Naloxone Treatment of Episodes of Suspected
`Acute Opioid Overdose, European Journal of
`Emergency Medicine (2004) 11:19–23
`
`Burford Capital Closes $500 Million Complex
`Strategies Investment Fund (July 3, 2017),
`available at https://www.burfordcapital.com/wp-
`content/uploads/2017/06/2017.07.03-Burford-
`Complex-Strategies-fund-close-FINAL.pdf
`
`v
`
`

`

`
`
`Short Name
`Ex. No.
`2008 EVZIO®
`Prescribing
`Information
`
`2009
`
`FDA Teva Press
`Release
`
`2010 Gaddis
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Title
`EVZIO® (naloxone hydrochloride injection)
`Auto-Injector for intramuscular or subcutaneous
`use, Prescribing Information (Revised Apr.
`2014), available at
`https://www.accessdata.fda.gov/drugsatfda_docs/
`label/2014/205787Orig1s000lbl.pdf
`
`FDA Approves First Generic Naloxone Nasal
`Spray to Treat Opioid Overdose (Apr. 19, 2019),
`available at https://www.fda.gov/news-
`events/press-announcements/fda-approves-first-
`generic-naloxone-nasal-spray-treat-opioid-
`overdose
`
`Gary M. Gaddis et al., Naloxone-Induced Patient
`Violence: An Overlooked Toxicity?, Annals of
`Pharmacotherapy (1992) 26:196–97
`
`2011 Goldfrank’s
`
`Goldfrank’s Toxicologic Emergencies (9th ed.)
`579–85
`
`2012
`
`Indivior Press
`Release
`
`2013 Kelly 2002
`
`2014 Letter from Ten
`Congressmen to
`Michelle K. Lee,
`Director of U.S.
`PTO
`
`Indivior Receives Complete Response Letter from
`FDA Not Approving Naloxone Nasal Spray New
`Drug Application for Opioid Overdose (Nov. 24,
`2015), available at http://www.indivior.com/wp-
`content/uploads/2015/11/Nasal-Naloxone-Final-
`Release_112415.pdf
`
`A-M. Kelly et al., Intranasal Naloxone for Life
`Threatening Opioid Toxicity, Emergency
`Medicine Journal (2002) 19:375
`
`Letter from Nydia M. Velasquez et al. to
`Michelle K. Lee, Director, U.S. Patent and
`Trademark Office (Dec. 5, 2016), available at
`http://sls.gmu.edu/cpip/wp-
`content/uploads/sites/31/2016/12/Letter-to-
`Director-Lee-Regarding-IPR-Petitions.pdf
`
`vi
`
`

`

`
`
`Short Name
`Ex. No.
`2015 Loimer 1992
`
`2016 NARCAN® Nasal
`Spray Prescribing
`Information
`
`2017 Osterwalder
`
`2018
`
`Pallasch
`
`2019
`
`Popper
`
`2020
`
`Schwartz
`
`2021
`
`Sporer 1996
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Title
`Norbert Loimer et al., Nasal Administration of
`Naloxone for Detection of Opiate Dependence,
`Journal of Psychiatric Research (1992)
`26(1):39–43
`
`NARCAN® (naloxone hydrochloride) nasal
`spray, Prescribing Information (Revised Jan.
`2017), available at
`https://www.accessdata.fda.gov/drugsatfda_docs/
`label/2017/208411s001lbl.pdf
`
`Joseph J. Osterwalder, Naloxone—For
`Intoxications with Intravenous Heroin and
`Heroin Mixtures—Harmless or Hazardous? A
`Prospective Clinical Study, Journal of
`Toxicology: Clinical Toxicology (1996)
`34(4):409–16
`
`Thomas J. Pallasch et al., Naloxone-Associated
`Morbidity and Mortality, Oral Surgery, Oral
`Medicine, Oral Pathology and Oral Radiology
`(1981) 52:602–03
`
`Caroline Popper et al., Naloxone Hazard In Drug
`Abuser, Lancet (1989)
`
`Jeffrey A. Schwartz et al., Naloxone-Induced
`Pulmonary Edema, Annals of Emergency
`Medicine (1987) 16:1294–96
`
`Karl A. Sporer et al., Out-of-hospital Treatment
`of Opioid Overdoses in an Urban Setting,
`Academic Emergency Medicine (1996) 3(7):660–
`67
`
`vii
`
`

`

`
`
`Ex. No.
`2022
`
`Short Name
`Sporer 2007
`
`2023
`
`Stoove
`
`2024 Terman Slides
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Title
`Karl A. Sporer et al., Prescription Naloxone: A
`Novel Approach to Heroin Overdose Prevention,
`Annals of Emergency Medicine (2007)
`49(2):172–17
`
`Mark A. Stoove et al., Overdose Deaths
`Following Previous Non-Fatal Heroin Overdose:
`Record Linkage of Ambulance Attendance and
`Death Registry Data, Drug and Alcohol Review
`(2009) 28: 347–52
`
`G. Terman PowerPoint Presentation “Naloxone:
`Effects and Side Effects” at FDA 2012
`Workshop
`
`2025 Teva Case Claim
`Construction
`Opinion
`
`Opinion, Adapt Pharma Operations Ltd. v. Teva
`Pharms. USA, Inc., No. 2:16-cv-07721, D.I. 200
`(Apr. 24, 2019)
`
`2026 Teva Case
`Schedule
`Stipulation
`
`2027
`
`van Dorp
`
`2028 Walley
`
`Stipulation and Order Regarding Expert
`Discovery Schedule, Adapt Pharma Operations
`Ltd. v. Teva Pharms. USA, Inc., No. 2:16-cv-
`07721, D.I. 210 (May 13, 2019)
`
`Eveline L.A. van Dorp et al., Naloxone
`Treatment in Opioid Addiction: the Risks and
`Benefits, Expert Opinion Drug Safety (2007)
`6(2):125–32
`
`A.Y. Walley et al., Opioid Overdose Rates and
`Implementation of Overdose Education and
`Nasal Naloxone Distribution in Massachusetts:
`Interrupted Time Series Analysis, BMJ (2013)
`346:174.
`
`viii
`
`

`

`
`
`
`
`
`Short Name
`Ex. No.
`2029 Wermeling 2015
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Title
`Daniel P. Wermeling, Review of Naloxone
`Safety for Opioid Overdose: Practical
`Considerations for New Technology and
`Expanded Public Access, Therapeutic Advance
`Drug Safety (2015) 6(1):20-31.
`
`2030 Wermeling ’354
`
`U.S. Patent Application No. 2010/0331354
`
`2031 Williams
`
`2032 Yealy
`
`2033 Zuckerman
`
`Kenneth Williams et al., Evidence-Based
`Guidelines for EMS Administration of Naloxone,
`Prehospital Emergency Care (2019)
`
`Donald M. Yealy et al., The Safety of Prehospital
`Naloxone Administration by Paramedics, Annals
`of Emergency Medicine (1990) 19(8):902–05
`
`Matthew Zuckerman et al., Pitfalls of Intranasal
`Narcan – Response to a Letter to the Editor,
`Prehospital Emergency Care (2015) 19:138–39
`
`2034
`
`’253 patent
`
`U.S. Patent 9,211,253
`
`
`
`ix
`
`

`

`Nalox-1 Pharmaceuticals, LLC (“Nalox-1”) has filed a series of fifteen
`
`Case IPR2019-00690
`Patent 9,468,747
`
`
`
`separate inter partes review (“IPR”) petitions, challenging five patents protecting
`
`NARCAN® Nasal Spray 4 mg. NARCAN® Nasal Spray 4 mg is the first ever FDA-
`
`approved nasal spray containing naloxone, an opioid inhibitor that reverses the
`
`dangerous effects of a wide variety of prescription and illegal drugs that are at the
`
`center of the country’s opioid epidemic. Reading Nalox-1’s strident rhetoric, one
`
`might be left with the impression that Nalox-1 is a generic pharmaceutical
`
`manufacturer that seeks to make intranasal naloxone more widely available. That
`
`impression would be false. Nalox-1, and the real parties in interest it has named, are
`
`non-practicing and non-pharmaceutical companies with a history of challenging
`
`pharmaceutical patents to realize profits for their stakeholders.
`
`Nalox-1’s third Petition regarding U.S. Patent 9,468,747 (“the 747 patent”),
`
`Ex. 1001, to which this Preliminary Response responds, largely duplicates the first,
`
`Case IPR2019-00688, merely adding grounds that make the same arguments with
`
`more complicated combinations of more references.
`
` Accordingly, this
`
`Preliminary Response contains substantive material not in the Preliminary
`
`Response in Case IPR2019-00688 at pages 6–8, 34–37, 45–47, and 56–57. The
`
`fact that this Petition is redundant with the Petition in Case IPR2019-00688 is an
`
`independent reason for the Board to decline to institute it even if the Board institutes
`
`in that case (which it should not).
`
`1
`
`

`

`As even a cursory review of the two Petitions reveals, not only are large
`
`Case IPR2019-00690
`Patent 9,468,747
`
`
`
`swaths of text word-for-word identical, but in this Petition, Nalox-1 relies
`
`extensively on the Wyse reference that is the principal reference Case IPR2019-
`
`00688. This Petition is little more than an effort to conjure additional grounds, and
`
`adds nothing meaningful to Case IPR2019-00688. The simplest ground in this
`
`Petition comprises four references, and for some claims Nalox-1 advances as many
`
`as six, one of which is Wyse itself. The Board frequently declines to institute
`
`secondary, redundant petitions, and it should do the same here.
`
`In any event, this Petition (like Case IPR2019-00688) is of a type the Board
`
`frequently, and appropriately, denies. Through the system established by the Hatch-
`
`Waxman Act, two generic pharmaceutical manufacturers, which unlike Nalox-1
`
`have filed Abbreviated New Drug Applications for intranasal naloxone, challenged
`
`the same patents at issue in these IPRs, and their patent infringement lawsuits are
`
`pending in the U.S. District Court for the District of New Jersey. In one of these,
`
`trial is likely to occur as soon as this summer—long before this proceeding will be
`
`completed if instituted. That case has involved extensive discovery into other failed
`
`attempts to formulate intranasal naloxone, which would be difficult to replicate in
`
`this forum. Accordingly, the Board should exercise its discretion not to institute trial
`
`here even if the Petition established a reasonable likelihood that Petitioner could
`
`prevail as to at least one claim of the ’747 patent.
`
`2
`
`

`

`And this Petition does no such thing. In multiple respects, the Petition
`
`Case IPR2019-00690
`Patent 9,468,747
`
`
`
`misreads or ignores inconvenient aspects of the prior art references on which it relies,
`
`and fails to establish the obviousness of required claim elements. The Petition
`
`contends that the person of ordinary skill in the art (“POSA”) would have found a 4
`
`mg dose of intranasal naloxone obvious—a dose that was completely unprecedented
`
`over decades of prior-art clinical experience. The prior art taught that 2 mg or less
`
`was therapeutically effective and that serious withdrawal effects could result from a
`
`higher naloxone dose. Remarkably, and despite arguing that the POSA would have
`
`clinical expertise, the Petition all but ignores the clinical literature teaching away
`
`from 4 mg and presents testimony from two expert witnesses who lack medical
`
`training or clinical experience with naloxone. They, and the Petition, misread Wyse
`
`to argue that it overcomes the rest of the prior art by teaching a 4 mg dose. In fact,
`
`it teaches no such thing. This fatal defect in the Petition warrants denial of
`
`institution. So too does the Petition’s baffling assertion that the prior art teaches the
`
`use of benzalkonium chloride (“BZK”) and disodium edetate (“EDTA”), even
`
`though the Wyse reference squarely teaches against it.
`
`For each of these reasons, institution should be denied.
`
`I.
`
`BACKGROUND
`
`NARCAN® Nasal Spray is the first FDA-approved intranasal naloxone spray.
`
`It saves lives by making it possible for untrained friends and family of opioid users,
`
`3
`
`

`

`
`as well as non-medically trained first responders such as police officers, to
`
`Case IPR2019-00690
`Patent 9,468,747
`
`administer naloxone and thus rescue overdose victims from respiratory arrest and
`
`death. These lifesaving benefits are directly attributable to the innovative
`
`formulations, devices, and methods of use that Opiant Pharmaceuticals, Inc.
`
`(“Opiant”) developed and claimed in the ’747 patent.
`
`Both the dose of naloxone and the remainder of NARCAN® Nasal Spray are
`
`novel and run contrary to the teachings of the art. Having set out to make a
`
`community-use naloxone product, the inventors recognized, ahead of everyone else,
`
`the importance of getting high amounts of naloxone into the subject’s system
`
`quickly. Thus, instead of matching the pharmacokinetic profile of the standard
`
`initial intramuscular naloxone dose of 0.4 mg—like everyone else in the field taught
`
`and did—the inventors intentionally chose to develop a product that achieved
`
`superior pharmacokinetic parameters. They therefore rejected the conventional
`
`wisdom to administer naloxone at a dose of no higher than 2 mg initially and re-dose
`
`only if needed. Instead, they decided to administer a single, 4 mg dose of naloxone
`
`all at once to a single nostril. This approach was contrary to the approved standard
`
`clinical practice and the longstanding literature on administration of naloxone to
`
`overdose patients, which taught that there were significant risks, including a risk of
`
`inducing serious withdrawal symptoms in patients, from so high a dose. In addition,
`
`the inventors selected a formulation with excipients that the prior art taught would
`
`4
`
`

`

`
`render it unstable. They also decided to administer that dose, contrary to standard
`
`Case IPR2019-00690
`Patent 9,468,747
`
`practice, in only one nostril.
`
`As a result of these features, the product of the invention exhibits properties
`
`that would have been entirely unexpected to the POSA. Furthermore, as a result of
`
`the inventors’ unconventional choices, the product of the invention, NARCAN®
`
`Nasal Spray, became the first and only community-use intranasal naloxone product
`
`ever to be approved and sold in the United States. It has saved countless lives, and
`
`has also become a commercial success. NARCAN® Nasal Spray launched in early
`
`2016 and achieved a market-leading share of the naloxone prescriptions retail market
`
`by the end of that year. By the end of 2018, its market share was in excess of 90
`
`percent. In the public interest market, NARCAN® Nasal Spray 4 mg is estimated to
`
`account for 70–80% of the entire market, and 100% for states including California,
`
`New York, Texas, and Florida. The commercial success is directly attributable to
`
`the patented invention claimed by the ’747 patent.
`
`Other companies worked to develop their own products at the same time, and
`
`failed where the inventors had succeeded. Amphastar developed a 2 mg / 0.5 mL
`
`Nasal Spray and was issued a Complete Response Letter by the FDA in February
`
`2017. Amphastar Press Release, Ex. 2002. Another manufacturer, Indivior, also
`
`received a Complete Response Letter in November 2015 from the FDA because its
`
`product did not “fully meet the FDA’s threshold as determined by the reference
`
`5
`
`

`

`
`product (0.4 mg naloxone by intramuscular injection).” Indivior Press Release, Ex.
`
`Case IPR2019-00690
`Patent 9,468,747
`
`2012, at 1. Despite working towards generally the same goal of a community-use
`
`nasal naloxone product, third parties repeatedly failed to arrive at the claimed
`
`invention.
`
`II. THE BOARD SHOULD DENY INSTITUTION BECAUSE THE
`PETITION IS REDUNDANT.
`
`The Board “has complete discretion to decide not to institute review.” St.
`
`Regis Mohawk Tribe v. Mylan Pharms., Inc., 896 F.3d 1322, 1327 (Fed. Cir. 2018);
`
`see also Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1367 (Fed. Cir. 2016)
`
`(“[T]he PTO is permitted, but never compelled, to institute an IPR proceeding.”). In
`
`deciding whether to exercise its discretion, the Board considers, among other things,
`
`whether “institution of multiple, concurrent proceedings would promote the efficient
`
`administration of the Office or the integrity of the system.” Comcast Cable
`
`Commc’ns, LLC v. Rovi Guides, Inc., Case IPR2019-00232, Paper 14 at 9 (P.T.A.B.
`
`May 20, 2019). The Board has denied institution of redundant petitions filed “by
`
`the same petitioner and includ[ing] challenges to the same claims . . . of the same
`
`patent . . . [where] the differences between the asserted art and arguments [were not]
`
`sufficiently material to outweigh the inefficiencies and costs of instituting an
`
`additional proceeding.” Id.; see also Comcast Cable Commc’ns, LLC v. Rovi
`
`6
`
`

`

`
`Guides, Inc., Case IPR2019-00225, Paper 14 at 6–7 (P.T.A.B. June 3, 2019)
`
`Case IPR2019-00690
`Patent 9,468,747
`
`(denying institution of five of six redundant petitions).
`
`Here, the Board should exercise its discretion to deny institution because this
`
`Petition is substantially similar to Nalox-1’s petition toward the same patent based
`
`on Wyse. See Case IPR2019-00688 (the “Wyse Petition”). Petitioner copies
`
`verbatim from the Wyse Petition’s critical arguments, including arguments that the
`
`POSA would have limited the nasal spray to about 100 μL per spray, would have
`
`been motivated to use a 4–6 mg naloxone dose, and would have selected excipients
`
`including BZK and EDTA. Compare Pet. at 15–20 with Wyse Petition at 18–23.
`
`Both here and in the Wyse Petition, Petitioner’s principal attempt to avoid the
`
`overwhelming body of literature demonstrating why the POSA would not have used
`
`a 4 mg dose is to misread Wyse. See Pet. at 62–64. In particular, Petitioner repeats
`
`an argument about the supposed motivation to use a 4–6 mg naloxone dose, based
`
`on the pharmacokinetic data reported in Wyse, in which Petitioner does not even cite
`
`Davies—this Petition’s purported lead reference. See Pet. at 17. Petitioner also
`
`extensively discusses the pharmacokinetic studies and excipient screening studies
`
`disclosed by Wyse in the secondary considerations section. See Pet. at 60–62.
`
`Petitioner also submits the same pharmacological expert declaration for the Wyse
`
`Petition as for this Petition; and the formulator expert declarations are identical for
`
`the first 321 pages and only offer different claim charts.
`
`7
`
`

`

`The Petition’s substantial reliance on Wyse is no accident. Wyse is the closest
`
`Case IPR2019-00690
`Patent 9,468,747
`
`
`
`prior art by far. No other reference discloses pilot and pivotal pharmacokinetic
`
`testing or excipient stability screening studies for an intranasal naloxone
`
`formulation. Davies, a 2000 reference that Petitioner tries to contend is its lead
`
`reference in this Petition, was fifteen years old by 2015 and does not even come
`
`close, lacking any disclosure of data whatsoever. Instituting this Petition, which so
`
`extensively relies on Wyse and is substantially similar to the Wyse Petition, is an
`
`inefficient use of the Board’s resources, and the Board should deny institution.
`
`III. THE BOARD SHOULD DENY INSTITUTION IN LIGHT OF THE
`PARALLEL DISTRICT COURT ACTIONS.
`
`As a “threshold issue,” the Board must decide whether to exercise its
`
`discretion even to consider instituting this IPR proceeding “in view of the overlap
`
`between the Petition and [a] Parallel District Court Case.” E-One, Inc. v. Oshkosh
`
`Corp., Case IPR2019-00161, Paper 16 at 4 (P.T.A.B. May 15, 2019).
`
`Here, the Board should deny institution, without even reaching the merits, in
`
`light of the pending Hatch-Waxman district court litigation brought by Patent Owner
`
`Opiant and limited exclusive licensee Adapt Pharma Operations Limited (“Adapt
`
`Pharma”) against Teva (the “Teva Case”) and Perrigo. Adapt Pharma Operations
`
`Ltd., et al. v. Teva Pharms. USA, Inc., et al., No. 2:16-cv-07721 (D.N.J.)
`
`(consolidated); Adapt Pharma Operations Ltd., et al. v. Perrigo UK FINCO Limited
`
`8
`
`

`

`
`Partnership, No. 2:18-cv-15287 (D.N.J.). Institution would be an inefficient use of
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Board resources, where the Teva Case, involving the same invention and many of
`
`the same prior art references, is nearing its final stages. This concern is especially
`
`pronounced here, because the extensive secondary considerations and third-party
`
`discovery record will be onerous, if even possible, to re-create in this proceeding.
`
`A. The Teva Case Involves a Generic Manufacturer with Final
`Approval for an Intranasal Naloxone Product.
`
`Instituting trial in this case would run counter to the goals of the America
`
`Invents Act to curb the extractive activities of non-practicing entities and also to
`
`“make the patent system more efficient by the use of post-grant review procedures.”
`
`Gen. Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha, Case IPR2016-01357,
`
`Paper 19 at 16 (P.T.A.B. Sept. 6, 2017) (precedential as to § II.B.4.i). A motivated
`
`generic manufacturer with final FDA approval for an intranasal naloxone product is
`
`challenging the same invention before a district court. Under these circumstances,
`
`it makes no sense to institute a trial that will not be over until long after the district
`
`court’s, particularly given that the district court will have a much more fulsome
`
`record to consider.
`
`The specific Petitioner entity, Nalox-1, is a Delaware limited liability
`
`company formed on December 12, 2018, that appears to have been created for the
`
`sole purpose of challenging the validity of the ’747 patent and related patents through
`
`9
`
`

`

`
`IPRs. Petitioner is financially backed by, and appears to be the agent of, Burford
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Capital Limited—a litigation investment firm—and its affiliate, Burford Capital
`
`Investment Management LLC, which recently closed a new $500 million fund “to
`
`invest in assets that Burford believes are mispriced and where value can be realized
`
`through recourse to litigation and regulatory processes.” Burford Press Release, Ex.
`
`2007. Notably, Burford Capital also backed Neptune Generics LLC, another non-
`
`practicing entity that has a history of challenging pharmaceutical patents as an
`
`investment tool.1
`
`Despite Petitioner’s professed concern with “this critically needed naloxone
`
`medication,” Pet. at 2—a need that the Patent Owner and Adapt Pharma are currently
`
`meeting, and are committed to meeting—Petitioner has not applied to the FDA to
`
`make a generic version of NARCAN® Nasal Spray or any other pharmaceutical
`
`product. Indeed, an unintended consequence of the IPR procedure is that a new
`
`group of non-practicing entities (traditionally called “patent trolls”)—mainly
`
`
`1 See Neptune Generics, LLC v. Eli Lilly & Co., 921 F.3d 1372 (Fed. Cir. 2019)
`
`(affirming denial of Neptune Generics’ series of 12 IPR petitions); Neptune
`
`Generics, LLC v. Aventis Generics S.A., Case IPR2019-00136, Paper 15 at 37
`
`(P.T.A.B. May 6, 2019) (denying institution based on, inter alia, “the stage and
`
`significant subject-matter overlap of the court proceedings”).
`
`10
`
`

`

`
`investment companies and hedge funds—are able to use the new system for their
`
`Case IPR2019-00690
`Patent 9,468,747
`
`enrichment, while burdening the owners of valuable patents. See Letter from Ten
`
`Congressmen to Michelle K. Lee, Director of U.S. PTO, Ex. 2014. This is such a
`
`case.
`
`Nalox-1—which has not sought regulatory approval for a competing
`
`product—has only a pecuniary interest in using the IPR process as part of an
`
`investment strategy. By contrast, Teva is a major generic pharmaceutical company
`
`with final FDA approval for a generic version of NARCAN® Nasal Spray, the
`
`branded product. FDA Teva Press Release, Ex. 2009. Teva challenged the ’747
`
`patent—and four other patents that Petitioner is challenging before the Board—
`
`through the Hatch-Waxman process in the U.S. District Court for the District of New
`
`Jersey. So has Perrigo. In Hatch-Waxman pharmaceutical cases like these,
`
`experienced generic pharmaceutical companies (like Teva and Perrigo) have every
`
`incentive to assert before the district court the strongest invalidity arguments
`
`possible. The district court cases against Teva and Perrigo amply fulfill the general
`
`public interest in making sure that economically significant patents receive scrutiny.
`
`There is no equitable reason why Nalox-1 is entitled to its own trial before the Board.
`
`This case is an ideal candidate for discretionary denial of review.
`
`11
`
`

`

`
`
`B.
`
`The Teva Case is Nearing Its Final Stages.
`
`Case IPR2019-00690
`Patent 9,468,747
`
`Consistent with the recognition that an objective of the AIA “is to provide an
`
`effective and efficient alternative to district court litigation,” General Plastic, Paper
`
`19 at 16 (emphasis added), the Board routinely exercises discretion not to institute
`
`trial when a parallel district court challenge “is nearing its final stages.” NHK Spring
`
`Co. v. Intri-Plex Techs. Inc., Case IPR2018-00752, Paper 8 at 20 (P.T.A.B. Sept. 12,
`
`2018) (precedential). In NHK Spring, recently designated as precedential, the Board
`
`declined to institute trial where the district court proceeding involving the same prior
`
`art and arguments was “nearing its final stages, with expert discovery ending” about
`
`seven weeks after the institution decision, “and a 5-day jury trial set to begin” just
`
`over six months later. Id. By contrast, the Board observed, “[a] trial before us on
`
`the same asserted prior art will not conclude until” a year after institution. Id. The
`
`Board reached the same conclusion in Mylan Pharmaceuticals, Inc. v. Bayer
`
`Intellectual Property GMBH, where “the district court trial is set to occur on April
`
`1, 2019, which is more than eight months before our Final Written Decision would
`
`be due in December 2019, if we were to institute trial.” Case IPR2018-01143, Paper
`
`13 at 14 (P.T.A.B. Dec. 3, 2018). The Board commented that instituting an IPR
`
`alongside a parallel and advanced district court proceeding “would be contrary to
`
`the overall goal of the AIA to ‘make the patent system more efficient by the use of
`
`post-grant review procedures.’” Id. (quoting General Plastic, Paper 19 at 16–17).
`
`12
`
`

`

`
`And most recently, in E-One, the Board declined to institute review where, as here,
`
`Case IPR2019-00690
`Patent 9,468,747
`
`“trial in the Parallel District Court Case is scheduled to conclude