`
`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 IPR2019-00687
`Patent 9,211,253
`__________________
`
`PRELIMINARY RESPONSE OF PATENT OWNER
`OPIANT PHARMACEUTICALS, INC.
`
`
`
`
`
`
`
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`
`
`I.
`
`II.
`
`TABLE OF CONTENTS
`
`BACKGROUND ............................................................................................. 4
`
`THE BOARD SHOULD DENY INSTITUTION BECAUSE THE
`PETITION IS REDUNDANT. ........................................................................ 6
`
`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. .....................................................21
`
`The Prior Art Taught That an Initial Intranasal Dose of 2 mg or
`Less Was Therapeutically Effective. ........................................22
`
`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. ..........................................26
`
`Davies Does Not Teach 4 mg Doses of Naloxone. ..................34
`
`Contrary to Petitioner’s Misreading, Wyse Does Not Teach 4
`mg Doses of Naloxone. .............................................................37
`
`i
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`
`7.
`
`The Pharmacokinetic Data in Wyse Would Not Lead the POSA
`to a Single 4 mg Dose of Intranasal Naloxone. ........................39
`
`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. ......................................45
`
`The POSA Would Have Been Taught Away from the Use of
`BZK and EDTA In Light of the Studies in Wyse. ....................47
`
`HPE Also Teaches Away From BZK and EDTA and Would
`Not Override Wyse’s Teach Away Anyway. ...........................53
`
`Bahal and Kushwaha Would Not Lead the POSA to Use BZK
`and EDTA. ................................................................................56
`
`V.
`
`CONCLUSION .............................................................................................. 57
`
`
`
`ii
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`
`TABLE OF AUTHORITIES
`
`CASES
`
`DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`567 F.3d 1314 (Fed. Cir. 2009) .......................................................................... 57
`
`E.I. DuPont de Nemours & Co. v. Synvina C.V.,
`904 F.3d 996 (Fed. Cir. 2018) ............................................................................ 36
`
`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) .............................................................................. 50
`
`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) .......................................................................... 54
`
`W.L. Gore & Assoc., Inc. v. Garlock, Inc.,
`721 F.2d 1540 (Fed. Cir. 1983) .......................................................................... 56
`
`Mylan Pharmas., Inc. v. Bayer Intellectual Property GMBH,
`Case IPR2018-01143, Paper 13 (P.T.A.B. Dec. 3, 2018) ............................ 12, 13
`
`Comcast Cable Commc’ns, LLC v. Rovi Guides, Inc.,
`Case IPR2019-00232, Paper 14 (P.T.A.B. May 20, 2019) .............................. 6, 7
`
`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
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`Gen. Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha,
`Case IPR2016-01357, Paper 19 (P.T.A.B. Sept. 6, 2017) .................................... 9
`
`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) ................................... 15
`
`STATUTES
`
`35 U.S.C. § 314 .................................................................................................. 14, 18
`
`35 U.S.C. § 316 ........................................................................................................ 18
`
`35 U.S.C. § 325 ........................................................................................................ 13
`
`REGULATIONS
`
`37 C.F.R. § 42.4 ......................................................................................................... 6
`
`37 C.F.R. § 42.108 ................................................................................................... 22
`
`
`
`
`
`
`
`iv
`
`

`

`Ex. No
`
`Short Name
`
`2001 Williams Decl.
`
`2002 Amphastar Press
`Release
`
`Case IPR2019-00687
`
`Patent 9,211,253
`
`EXHIBIT LIST
`
`Expert Declaration of Kenneth A. Williams,
`MD.
`
`AmphastarAnnounces the Receipt ofa CRL for
`Intranasal Naloxonefor the Emergency
`Treatment of Opioid Overdose (Feb. 21, 2017),
`available at http://ir.amphastar.com/static-
`files/19b13150-7ff8-4d3b-8e3f-452578083dbb
`
`
`
`Aquina
`
`Baca
`
`Christopher T. Aquina et al., Oxytocin 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—3 1
`
`Belz
`
`Daniel Belz et al., Naloxone Use in a Tiered-
`
`Buajordet
`
`Burford Press
`Release
`
`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
`
`

`

`Ex. No.
`
`2008
`
`EVZIO®
`Prescribing
`Information
`
`2009
`
`FDA Teva Press
`Release
`
`Case IPR2019-00687
`
`Patent 9,211,253
`
`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/2014/2057870rig1$0001b1.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
`
`
`
`2010 Gaddis
`
`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 US.
`PTO
`
`Indivior Receives Complete Response Letterfrom
`FDA Not Approving Naloxone Nasal Spray New
`Drug Application for Opioid Overdose (Nov. 24,
`2015), available at http://www.indivior.com/wp—
`content/uploads/20 1 5/ 1 1/Nasal-Naloxone-Final-
`Release_1 12415 .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, US. Patent and
`Trademark Office (Dec. 5, 2016), available at
`http://sls.gmu.edu/cpip/wp-
`content/uploads/sites/3 1/2016/12/Letter-to-
`Director—Lee-Regarding-IPR—Petitions.pdf
`
`vi
`
`

`

`Ex. No.
`
`2015
`
`Loimer 1992
`
`Norbert Loimer et al., Nasal Administration of
`
`Case IPR2019-00687
`
`Patent 9,211,253
`
`2016 NARCAN® Nasal
`Spray Prescribing
`Information
`
`2017 Osterwalder
`
`Naloxone for Detection of Opiate Dependence,
`Journal ofPsychiatric Research (1992)
`26(1 ):3 9—43
`
`NARCAN® (naloxone hydrochloride) nasal
`spray, Prescribing Information (Revised Jan.
`2017), available at
`https://www-accessdata.fda- gov/drugsatfda_docs/
`label/2017/20841 150011bl-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
`
`
`
`2018
`
`Pallasch
`
`Thomas J. Pallasch et al., Naloxone-Associated
`
`2019
`
`Popper
`
`2020
`
`Schwartz
`
`2021
`
`Sporer 1996
`
`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 ofEmergency
`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.
`
`Short Name
`
`2022
`
`Sporer 2007
`
`Case IPR2019-00687
`
`Patent 9,211,253
`
`Karl A. Sporer et al., Prescription Naloxone: A
`Novel Approach to Heroin Overdose Prevention,
`Annals ofEmergency 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
`
`
`
`Terman Slides
`
`G. Terman PowerPoint Presentation “Naloxone:
`
`Effects and Side Effects” at FDA 2012
`
`Workshop
`
`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)
`
`Teva Case
`
`Schedule
`
`Stipulation
`
`Stipulation and Order Regarding Expert
`Discovery Schedule, Adapt Pharma Operations
`Ltd. v. Teva Pharms. USA, Inc., No. 2: l6-cv—
`
`07721, D1. 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
`
`

`

`Case IPR2019-00687
`
`Patent 9,211,253
`
`2029 Wermeling 2015
`
`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
`
`US. Patent Application No. 2010/0331354
`
`2031 Williams
`
`Kenneth Williams et al., Evidence-Based
`
`Prehospital Emergency Care (2015) 19: 138—39
`
`2032 Yealy
`
`Guidelines for EMS Administration of Naloxone,
`
`Prehospital Emergency Care (2019)
`
`Donald M. Yealy et al., The Safety of Prehospital
`Naloxone Administration by Paramedics, Annals
`ofEmergency Medicine (1990) 19(8):902—05
`
`2033
`
`Zuckerman
`
`Matthew Zuckerman et al., Pitfalls of Intranasal
`
`Narcan — Response to a Letter to the Editor,
`
`ix
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`
`Nalox-1 Pharmaceuticals, LLC (“Nalox-1”) has filed a series of fifteen
`
`separate inter partes review (“IPR”) petitions, challenging five patents protecting
`
`NARCAN® Nasal Spray 4 mg. NARCAN® Nasal Spray 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, to which this Preliminary Response responds, largely
`
`duplicates the first, Case IPR2019-00685, merely adding grounds that make the
`
`same arguments with more-complicated combinations of more references.
`
`Accordingly, this Preliminary Response differs from the Preliminary Response in
`
`Case IPR2019-00685 at pages 6 through 8, 34 through 37, 45 through 47, and 56
`
`through 57. The fact that this Petition is redundant with the Petition in Case
`
`IPR2019-00685 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
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`
`As even a cursory review of the two Petitions reveals, not only are large
`
`swaths of text word-for-word identical, but in this Petition, Nalox-1 relies
`
`extensively on the Wyse reference that is the principal reference in Case IPR2019-
`
`00685. This Petition is little more than an effort to conjure up additional grounds,
`
`and it adds nothing substantive to Case IPR2019-00685. The simplest ground
`
`advanced 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.
`
`And in any event, this Petition (like Case IPR2019-00685) 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
`
`2
`
`

`

`
`Petitioner could prevail as to at least one claim of U.S. Patent 9,211,253 (“the ’253
`
`Case IPR2019-00687
`Patent 9,211,253
`
`patent”), Ex. 1001.
`
`And this Petition does no such thing. In multiple respects, the Petition
`
`misreads or ignores inconvenient aspects of the prior art references on which it relies,
`
`and fails to establish the obviousness of required claim elements. Every claim of the
`
`’253 patent requires a 4 mg dose of intranasal naloxone—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. Yet remarkably, and despite arguing that the
`
`person of ordinary skill in the art (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 the Wyse reference 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”)—elements of
`
`nearly all the claims—even though the Wyse reference squarely teaches against it.
`
`For each of these reasons, institution should be denied.
`
`3
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`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,
`
`as well as non-medically trained first responders such as police officers, to
`
`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 ’253 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
`
`at all once to a single nostril. This approach was contrary to the approved standard
`
`clinical practice and the longstanding literature on administration of naloxone to
`
`4
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`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 prior art taught would
`
`render it unstable. They also decided to administer that dose, contrary to standard
`
`practice, in only one nostril.
`
`As a result of this combination of 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 ’253 patent.
`
`Other companies worked to develop their own products at the same time, and
`
`failed where the inventors had succeeded. Amphastar Pharmaceuticals developed a
`
`2mg / 0.5 mL Nasal Spray and was issued a Complete Response Letter by the FDA
`
`5
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`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 product (0.4 mg naloxone by intramuscular injection).” Indivior Press
`
`Release, Ex. 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.”); 37
`
`C.F.R. § 42.4(a) (delegating discretionary decision to Board). 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). For example, where the same petitioner files more than one petition
`
`directed toward the same patent, the Board has denied institution because “the
`
`6
`
`

`

`Case IPR2019-00687
`Patent 9,211,253
`
`
`differences between the asserted art and arguments [are not] sufficiently material to
`
`outweigh the inefficiencies and costs of instituting an additional proceeding.” Id.
`
`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 IPR2019-00685 (the “Wyse Petition”). Petitioner copies
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`verbatim from the Wyse Petition’s critical arguments, including arguments that the
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`POSA would have limited the nasal spray to about 100 μL per spray, that the POSA
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`would have been motivated to use a 4–6 mg naloxone dose, and that the POSA would
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`have selected excipients including BZK and EDTA. Compare Pet. at 16–22 with
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`Wyse Petition at 16–22. Critically, Petitioner’s principal attempt to avoid the
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`overwhelming body of literature demonstrating why the POSA would not have used
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`a 4 mg dose is to misread Wyse. And it makes the same erroneous argument based
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`on Wyse here that it does in the Wyse Petition. Pet. at 60–61. In particular,
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`Petitioner repeats an argument about the supposed motivation to use a 4–6 mg
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`naloxone dose, based on the pharmacokinetic data reported in Wyse, in which
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`Petitioner does not even cite Davies—this Petition’s purported lead reference. See
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`Pet. at 18. Petitioner also extensively discusses the pharmacokinetic studies and
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`excipient screening studies disclosed by Wyse in the secondary considerations
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`section. See Pet. at 58–61. Petitioner also submits the same pharmacological expert
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`Case IPR2019-00687
`Patent 9,211,253
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`declaration for the Wyse Petition as for this Petition; and the formulator expert
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`declarations are identical for the first 277 pages and only offer different claim charts.
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`The Petition’s substantial reliance on Wyse is no accident. Wyse is the closest
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`prior art by far. No other reference discloses pilot and pivotal pharmacokinetic
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`testing or excipient stability screening studies for an intranasal naloxone
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`formulation. Davies, the reference from 2000 that Petitioner tries to contend is its
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`lead reference in this Petition was fifteen years old by 2015 and does not even come
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`close, lacking any disclosure of data whatsoever. Instituting this Petition, which so
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`extensively relies on Wyse and is substantially similar to the Wyse Petition, is an
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`inefficient use of the Board’s resources, and the Board should deny institution.
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`III. THE BOARD SHOULD DENY INSTITUTION IN LIGHT OF THE
`PARALLEL DISTRICT COURT ACTIONS.
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`As a “threshold issue,” the Board must decide whether to exercise its
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`discretion even to consider instituting this inter partes review proceeding “in view
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`of the overlap between the Petition and [a] Parallel District Court Case.” E-One,
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`Inc. v. Oshkosh Corp., Case IPR2019-00161, Paper 16 at 4 (P.T.A.B. May 15, 2019).
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`Here, the Board should deny institution, without even reaching the merits, in
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`light of the pending Hatch-Waxman district court litigation brought by Patent Owner
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`Opiant and limited exclusive licensee Adapt Pharma Operations Limited (“Adapt
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`Pharma”) against Teva (the “Teva Case”) and Perrigo. Adapt Pharma Operations
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`Case IPR2019-00687
`Patent 9,211,253
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`Ltd., et al. v. Teva Pharms. USA, Inc., et al., No. 2:16-cv-07721 (D.N.J.)
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`(consolidated); Adapt Pharma Operations Ltd., et al. v. Perrigo UK FINCO Limited
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`Partnership, No. 2:18-cv-15287 (D.N.J.). Institution of an IPR would be an
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`inefficient use of Board resources, where the Teva Case, involving the same
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`invention and many of the same prior art references, is nearing its final stages. The
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`inefficiency concern is especially pronounced in this case, because the extensive
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`secondary considerations and third-party discovery record will be onerous, if even
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`possible, to re-create in this proceeding.
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`A. The Teva Case Involves a Generic Manufacturer with Final
`Approval for an Intranasal Naloxone Product.
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`Instituting trial in this case would run counter to the goals of the America
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`Invents Act to curb the extractive activities of non-practicing entities and also to
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`“make the patent system more efficient by the use of post-grant review procedures.”
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`Gen. Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha, Case IPR2016-01357,
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`Paper 19 at 16 (P.T.A.B. Sept. 6, 2017) (precedential as to § II.B.4.i). A motivated
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`generic manufacturer with final approval from the FDA for an intranasal naloxone
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`product is challenging the same invention before a district court. Under these
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`circumstances, it makes no sense to institute a trial that will not be over until long
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`after the district court’s, particularly given that the district court will have a much
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`more fulsome record to consider.
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`Case IPR2019-00687
`Patent 9,211,253
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`The specific Petitioner entity, Nalox-1 Pharmaceuticals, LLC, is a Delaware
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`limited liability company formed on December 12, 2018 that appears to have been
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`created for the sole purpose of challenging the validity of the ’253 Patent and related
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`patents through inter partes reviews. Petitioner is financially backed by, and appears
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`to be the agent of, Burford Capital Limited—a litigation investment firm—and its
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`affiliate, Burford Capital Investment Management LLC, which recently closed a new
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`$500 million fund “to invest in assets that Burford believes are mispriced and where
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`value can be realized through recourse to litigation and regulatory processes.”
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`Burford Press Release, Ex. 2007. Notably, Burford Capital also backed Neptune
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`Generics LLC, another non-practicing entity that has a history of challenging
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`pharmaceutical patents as an investment tool.1
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`Despite Petitioner’s professed concern with the “critical and urgent need in
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`America for intranasal naloxone products intended for community use,” Pet. at 2—
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`a need that the Patent Owner and Adapt Pharma are currently meeting, and are
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`1 See Neptune Generics, LLC v. Eli Lilly & Co., 921 F.3d 1372 (Fed. Cir. 2019)
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`(affirming denial of Neptune Generics’ series of 12 IPR petitions); Neptune
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`Generics, LLC v. Aventis Generics S.A., Case IPR2019-00136, Paper 15 at 37
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`(P.T.A.B. May 6, 2019) (denying institution based on, inter alia, “the stage and
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`significant subject-matter overlap of the court proceedings”).
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`Case IPR2019-00687
`Patent 9,211,253
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`committed to meeting—Petitioner has not applied to the FDA to make a generic
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`version of NARCAN® Nasal Spray or any other pharmaceutical product. Indeed, an
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`unintended consequence of the inter partes review procedure is that a new group of
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`non-practicing entities (traditionally called “patent trolls”)—mainly investment
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`companies and hedge funds—are able to use the new system for their enrichment,
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`while burdening the owners of valuable patents. See Letter from Ten Congressmen
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`to Michelle K. Lee, Director of U.S. PTO, Ex. 2014. This is such a case.
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`Nalox-1—which has not sought regulatory approval for a competing
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`product—has only a pecuniary interest in using the IPR process as part of an
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`investment strategy. By contrast, Teva is a major generic pharmaceutical company
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`with final approval from the FDA for an Abbreviated New Drug Application for
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`generic intranasal naloxone based on NARCAN® Nasal Spray, the branded product.
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`FDA Teva Press Release, Ex. 2009. Teva challenged the ’253 patent—and four
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`other patents that Petitioner is challenging before the Board—through the Hatch-
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`Waxman process in the U.S. District Court for the District of New Jersey. So has
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`Perrigo. In Hatch-Waxman pharmaceutical cases like this one, where experienced
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`generic pharmaceutical companies—Teva and Perrigo—are seeking FDA approval
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`to market a copy of a patented product, they have every incentive to identify and
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`raise before the district court the strongest invalidity arguments possible. The
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`district court cases against Teva and Perrigo amply fulfill the general public interest
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`in making sure that economically significant patents receive scrutiny. There is no
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`equitable reason why Nalox-1 is entitled to its own trial before the Board. This case
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`Case IPR2019-00687
`Patent 9,211,253
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`is an ideal candidate for discretionary denial of review.
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`B.
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`The Teva Case is Nearing Its Final Stages.
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`Consistent with the recognition that an objective of the AIA “is to provide an
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`effective and efficient alternative to district court litigation,” General Plastic, Paper
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`19 at 16 (emphasis added), the Board routinely exercises discretion not to institute
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`trial when a parallel district court challenge “is nearing its final stages.” NHK Spring
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`Co. v. Intri-Plex Techs. Inc., Case IPR2018-00752, Paper 8 at 20 (P.T.A.B. Sept. 12,
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`2018) (precedential). For example, in NHK Spring, a case recently designated as
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`precedential, the Board declined to institute trial where the district court proceeding
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`involving the same prior art and arguments was “nearing its final stages, with expert
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`discovery ending” about seven weeks after the institution decision, “and a 5-day jury
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`trial set to begin” just over six months later. Id. By contrast, the Board observed,
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`“[a] trial before us on the same asserted prior art will not conclude until” a year after
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`institution. Id. The Board reached the same conclusion in Mylan Pharmaceuticals,
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`Inc. v. Bayer Intellectual Property GMBH, where “the district court trial is set to
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`occur on April 1, 2019, which is more than eight months before our Final Written
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`Decision would be due in December 2019, if we were to institute trial.” Case
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`IPR2018-01143, Paper 13 at 14 (P.T.A.B. Dec. 3, 2018). The Board commented
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`Case IPR2019-00687
`Patent 9,211,253
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`that instituting an inter partes review where there is a parallel and advanced district
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`court proceeding “would be contrary to the overall goal of the AIA to ‘make the
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`patent system more efficient by the use of post-grant review procedures.’” Id.
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`(quoting General Plastic, Paper 19 at 16–17). And most recently, in E-One, the
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`Board declined to institute review where, as here, “trial in the Parallel District Court
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`Case is scheduled to conclude before a final decision would