`
`
`
`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 IPR2019-00688
`Patent 9,468,747
`__________________
`
`PRELIMINARY RESPONSE OF PATENT OWNER
`OPIANT PHARMACEUTICALS, INC.
`
`
`
`
`
`
`
`
`Case IPR2019-00688
`Patent 9,468,747
`
`
`TABLE OF CONTENTS
`
`
`I.
`
`II.
`
`BACKGROUND ............................................................................................. 3
`
`THE BOARD SHOULD DENY INSTITUTION IN LIGHT OF THE
`PARALLEL DISTRICT COURT ACTIONS. ................................................ 5
`
`A.
`
`B.
`
`C.
`
`The Teva Case Involves a Generic Manufacturer with Final
`Approval for an Intranasal Naloxone Product. ..................................... 6
`
`The Teva Case is Nearing Its Final Stages............................................ 9
`
`The Factual Record Developed in the Teva Case Will Be
`Onerous, if even Possible, to Re-create in this Proceeding ................ 12
`
`III.
`
`PETITIONER HAS NOT DEMONSTRATED A REASONABLE
`LIKELIHOOD OF SUCCESS WITH RESPECT TO ANY CLAIMS
`CHALLENGED IN THE PETITION. .......................................................... 15
`
`A.
`
`The POSA Would Not Have Been Motivated to Use a Single
`Intranasal Naloxone Dose of 4 mg. ..................................................... 16
`
`1.
`
`2.
`
`3.
`
`Petitioner Ignores Clinical Evidence and Provides No
`Testimony from a Clinician. .....................................................19
`
`The Prior Art Taught That an Initial Intranasal Dose of 2 mg or
`Less Was Therapeutically Effective. ........................................20
`
`The Prior Art Disclosed That Too Much Liquid Was a Problem
`for Nasal Delivery, Not Lack of Efficacy. ................................24
`
`4. Wyse Taught, and the POSA Would Have Understood, That
`Higher Doses of Naloxone Risked Withdrawal Symptoms and
`Other Significant Negative Effects. ..........................................26
`
`5.
`
`6.
`
`Contrary to Petitioner’s Misreading, Wyse Does Not Teach 4
`mg Doses of Naloxone. .............................................................37
`
`The Pharmacokinetic Data in Wyse Would Not Lead the POSA
`to a Single 4 mg Dose of Intranasal Naloxone. ........................43
`
`i
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`
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`Case IPR2019-00688
`Patent 9,468,747
`
`
`B.
`
`The POSA Would Not Have Been Motivated to Use BZK,
`Much Less With EDTA. ...................................................................... 49
`
`1. Wyse Teaches Away from BZK and BZK with EDTA. ..........50
`
`2.
`
`HPE Also Teaches Away From BZK and EDTA and Would
`Not Override Wyse’s Teach Away Anyway. ...........................57
`
`IV. CONCLUSION .............................................................................................. 59
`
`
`
`ii
`
`
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`Case IPR2019-00688
`Patent 9,468,747
`
`
`TABLE OF AUTHORITIES
`
`CASES
`
`SAS Inst. Inc. v. Iancu,
`138 S. Ct. 1348 (2018) .................................................................................. 16, 50
`
`Harmonic Inc. v. Avid Tech., Inc.,
`815 F.3d 1356 (Fed. Cir. 2016) ............................................................................ 5
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig., 676 F.3d 1063 (Fed. Cir. 2012) .................................................... 12
`
`In re Gurley,
`27 F.3d 551 (Fed. Cir. 1994) .............................................................................. 54
`
`Neptune Generics, LLC v. Eli Lilly & Co.,
`921 F.3d 1372 (Fed. Cir. 2019) ...................................................................... 7, 12
`
`St. Regis Mohawk Tribe v. Mylan Pharms., Inc.,
`896 F.3d 1322 (Fed. Cir. 2018) ...................................................................... 5, 14
`
`Tec Air, Inc. v. Denso Mfg. Mich. Inc.,
`192 F.3d 1353 (Fed. Cir. 1999) .......................................................................... 57
`
`W.L. Gore & Assoc., Inc. v. Garlock, Inc.,
`721 F.2d 1540 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984) .................. 59
`
`Mylan Pharmaceuticals, Inc. v. Bayer Intellectual Property GMBH,
`Case IPR2018-01143, Paper 13 (P.T.A.B. Dec. 3, 2018) .................................. 10
`
`Chevron Oronite Co. LLC v. Infineum USA L.P.,
`Case IPR2018-00923, Paper 9 (P.T.A.B. Nov. 7, 2018) .................................... 50
`
`Deeper, UAB v. Vexilar, Inc.,
`Case IPR2018-01310, Paper 7 (P.T.A.B. Jan. 24, 2019) ................................... 50
`
`E-One, Inc. v. Oshkosh Corp.,
`Case IPR2019-00161, Paper 16 (P.T.A.B. May 15, 2019) ...................... 5, 10, 11
`
`Garmin Int’l, Inc. v. Cuozzo Speed Techs. LLC,
`Case IPR2012-00001, Paper 26 (P.T.A.B. Mar. 5, 2013) .................................. 14
`
`iii
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`
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`Case IPR2019-00688
`Patent 9,468,747
`
`
`Gen. Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha,
`Case IPR2016-01357, Paper 19 (P.T.A.B. Sept. 6, 2017) .................................... 6
`
`Neptune Generics, LLC v. Aventis Generics S.A.,
`Case IPR2019-00136, Paper 15 (P.T.A.B. May 6, 2019) .................................... 7
`
`NHK Spring Co. v. Intri-Plex Techs. Inc.,
`Case IPR2018-00752, Paper 8 (P.T.A.B. Sept. 12, 2018) .............................. 9, 11
`
`Valve Corp. v. Elec. Scripting Prods., Inc.,
`Case IPR2019-00062, Paper 11 (P.T.A.B. Apr. 2, 2019) ................................... 12
`
`STATUTES
`
`35 U.S.C. §§ 314(a), (b) ..................................................................................... 15, 50
`
`35 U.S.C. § 316(b) ................................................................................................... 15
`
`35 U.S.C. § 325(d) ................................................................................................... 11
`
`REGULATIONS
`
`37 C.F.R. § 42.108 ................................................................................................... 20
`
`
`
`
`
`iv
`
`
`
`Ex. No
`
`Short Name
`
`2001 Williams Decl.
`
`2002 Amphastar Press
`Release
`
`Aquina
`
`Baca
`
`Case IPR2019-00688
`
`Patent 9,468,747
`
`EXHIBIT LIST
`
`Expert Declaration of Kenneth A. Williams,
`MD.
`
`Amphastar Announces the Receipt ofa CRL for
`Intranasal Naloxonefor the Emergency
`Treatment of Opioid Overdose (Feb. 21, 2017),
`available at http://ir.amphastar.com/static-
`files/l9b13150-7ff8-4d3b-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—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 IPR2019-00688
`
`Patent 9,468,747
`
`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/2014/205787Orig150001bl.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 IPR2019-00688
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`Patent 9,468,747
`
`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 IPR2019-00688
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`Patent 9,468,747
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`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): 1 25—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
`
`
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`Case IPR2019-00688
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`Patent 9,468,747
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`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.
`
`US. Patent 9,211,253
`
`2030 Wermeling ’354
`
`US. Patent Application No. 2010/0331354
`
`2031 Williams
`
`Kenneth Williams et al., Evidence-Based
`
`Guidelines for EMS Administration of Naloxone,
`
`Prehospital Emergency Care (2019)
`
`2032 Yealy
`
`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,
`Prehospital Emergency Care (2015) 19: 138—39
`
`2034
`
`’253 patent
`
`ix
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`Case IPR2019-00688
`Patent 9,468,747
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`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 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.
`
`This Petition 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.
`
`1
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`Case IPR2019-00688
`Patent 9,468,747
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`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 U.S. Patent 9,468,747 (“the ’747 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. 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 their
`
`own principal prior art 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”), even though the Petition’s same principal reference squarely
`
`teaches against it.
`
`2
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`Case IPR2019-00688
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`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,
`
`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 ’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
`
`3
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`Case IPR2019-00688
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`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
`
`render it unstable. They also decided to administer that dose, contrary to standard
`
`practice, in only one nostril.
`
`As a result of these features, 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
`
`4
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`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 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 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). 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.”).
`
`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
`
`5
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`
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`Case IPR2019-00688
`Patent 9,468,747
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`Pharma”) against Teva and Perrigo. Adapt Pharma Operations Ltd., et al. v. Teva
`
`Pharms. USA, Inc., et al., No. 2:16-cv-07721 (D.N.J.) (consolidated) (the “Teva
`
`Case”); Adapt Pharma Operations Ltd., et al. v. Perrigo UK FINCO Limited
`
`Partnership, No. 2:18-cv-15287 (D.N.J.).1 Institution of an IPR would be an
`
`inefficient use of Board resources, where the Teva Case, involving the same
`
`invention and the same prior art references, is nearing its final stages. The
`
`inefficiency concern is especially pronounced in this case, 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 approval from the FDA for an intranasal naloxone
`
`
`1 A complete list of all related matters is provided at the Mandatory Notices of Patent
`
`Owner Opiant Pharmaceuticals, Inc., Paper 5 (Mar. 12, 2019).
`
`6
`
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`Case IPR2019-00688
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`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
`
`IPRs. Petitioner is financially backed by, and appears to be the agent of, Burford
`
`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
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`through recourse to litigation and regulatory processes.” Burford Press Release, Ex.
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`2007. Notably, Burford Capital also backed Neptune Generics LLC, another non-
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`practicing entity that has a history of challenging pharmaceutical patents as an
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`investment tool.2
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`2 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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`7
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`Case IPR2019-00688
`Patent 9,468,747
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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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`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 IPR procedure is that a new group of non-practicing
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`entities (traditionally called “patent trolls”)—mainly investment companies and
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`hedge funds—are able to use the new system for their enrichment, while burdening
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`the owners of valuable patents. See Letter from Ten Congressmen to Michelle K.
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`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 FDA approval for a generic version of NARCAN® Nasal Spray, the
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`branded product. FDA Teva Press Release, Ex. 2009. Teva challenged the ’747
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`patent—and four other patents that Petitioner is challenging before the Board—
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`through the Hatch-Waxman process in the U.S. District Court for the District of New
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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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`8
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`Case IPR2019-00688
`Patent 9,468,747
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`Jersey. So has Perrigo. In Hatch-Waxman pharmaceutical cases like these,
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`experienced generic pharmaceutical companies (like Teva and Perrigo) have every
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`incentive to assert before the district court the strongest invalidity arguments
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`possible. The district court cases against Teva and Perrigo amply fulfill the general
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`public interest in making sure that economically significant patents receive scrutiny.
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`There is no equitable reason why Nalox-1 is entitled to its own trial before the Board.
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`This case is an ideal candidate for discretionary denial of review.
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`B.
`
`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). In NHK Spring, recently designated as precedential, the Board
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`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
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`the same asserted prior art will not conclude until” a year after institution. Id. The
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`Board reached the same conclusion in Mylan Pharmaceuticals, Inc. v. Bayer
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`9
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`
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`Case IPR2019-00688
`Patent 9,468,747
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`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
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`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
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`post-grant review procedures.’” Id. (quoting General Plastic, Paper 19 at 16–17).
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`And most recently, in E-One, the Board declined to institute review where, as here,
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`“trial in the Parallel District Court Case is scheduled to conclude before a final
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`decision would be due” in the IPR, “if [the Board] were to institute.” E-One, Paper
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`16 at 6. The Board noted that “[t]o date, the district court ha[d] already invested
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`substantial resources in the Parallel District Court Case.” Id. at 7.
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`Here, Teva, a motivated pharmaceutical company who has recently obtained
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`FDA approval for its generic intranasal naloxone product, filed a Paragraph IV
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`certification challenging the same patents and is currently litigating the Teva Case
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`in the District of New Jersey, as Petitioner acknowledges, Pet. at 7. The Teva Case,
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`moreover, involves the same prior art references as those asserted by Petitioner in
`
`this proceeding. Teva is relying on prior art references including Wyse (Ex. 1007),
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`Djupesland (Ex. 1010), HPE (Ex. 1012), and Wermeling ’354 (Ex. 2030)—a
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`continuation of the same application as, and sharing a common specification with,
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`10
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`
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`Case IPR2019-00688
`Patent 9,468,747
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`Wermeling ’291 (Ex. 1015)—in challenging the validity of the invention. Much of
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`that art, moreover, was also raised during prosecution. See 35 U.S.C. § 325(d).
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`These factors weigh heavily against instituting trial here. The district court will
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`imminently consider substantially the same prior art as applied to the same invention
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`as are at issue here.
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`Moreover, the Teva Case is “nearing its final stages.” NHK Spring, Paper 8
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`at 20. The parties have already served their opening and responsive expert reports,
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`and expert discovery is scheduled to close on July 5, 2019. See Teva Case Schedule
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`Stipulation, Ex. 2026. The Final Pretrial Conference is set to occur on July 25, 2019,
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`see Minute Order, No. 2:16-cv-07721, D.I. 197 (Apr. 18, 2019), and while a trial
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`date has not been set, one is expected soon, as Teva has Final Approval and the 30-
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`month stay date has passed. As in E-One, the district court has “invested substantial
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`resources” in the case, including hearing argument and issuing a claim construction
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`ruling. See Teva Case Claim Construction Opinion, Ex. 2025.
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`In contrast, a trial before the Board is likely to conclude much later. Under
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`the AIA, the Board has three months after receiving the preliminary response to
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`determine whether to institute review, 35 U.S.C. § 314(b), and another year after
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`institution to issue a Final Written Decision, id. § 316(a)(11). In other words,
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`assuming institution on the customary schedule, the statutory deadline for issuing a
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`Final Written Decision will be in August 2020, more than a year after the Final
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`11
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`
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`Case IPR2019-00688
`Patent 9,468,747
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`Pretrial Conference in the Teva Case. The fact that Petitioner is not a party to the
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`Teva Case is of no moment. The Board has expressly held that its discretionary
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`denial of institution based on its limited resources “is not limited solely to instances
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`when multiple [proceedings] are filed by the same petitioner.” Valve Corp. v. Elec.
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`Scripting Prods., Inc., Case IPR2019-00062, Paper 11 at 2 (P.T.A.B. Apr. 2, 2019)
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`(precedential). Indeed, under similar circumstances to this Petition, where a parallel
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`district court action was pending against a generic pharmaceutical company
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`unrelated to the petitioner, the Board recently declined to institute a petition filed
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`by Neptune Generics, LLC, another non-practicing entity backed by the same
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`investment company as Petitioner. Neptune Generics, Paper 15 at 35–37. In that
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`case, like this one, the parallel court proceedings involved the same invention and
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`the same prior art, but did not involve the IPR petitioner. The Board correctly stated
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`that “[w]e do not see how [AIA’s goal of efficiency] is served by ignoring or
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`declaring irrelevant the related and ongoing litigation history of the [challenged]
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`patent.” Id. at 35.
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`C. The Factual Record Developed in the Teva Case Will Be Onerous,
`if even Possible, to Re-create in this Proceeding
`
`There is yet another reason for the Board to exercise its discretion not to
`
`institute trial here. Objective indicia of non-obviousness must be considered as part
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`of the obviousness inquiry, In re Cyclobenzaprine Hydrochloride Extended-Release
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`12
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`
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`Case IPR2019-00688
`Patent 9,468,747
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`Capsule Patent Litig., 676 F.3d 1063, 1076 (Fed. Cir. 2012), and the record is
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`unusually extensive and relevant here, not only as to commercial success,
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`unexpected properties, skepticism of others, and copying by third parties, but also as
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`to failure of others.
`
`The national opioid crisis has given rise to a long-felt and urgent need for a
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`community-use needleless naloxone product, and many different companies and
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`research groups have tried—and failed—to develop one. As mentioned above, both
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`Indivior and Amphastar received Complete Response Letters from the FDA not
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`approving either of their intranasal naloxone products. See Amphastar Press
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`Release, Ex. 2002; Indivior Press Release, Ex. 2012. Neither has received approval
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`since then. Patent Owner’s successful NARCAN® Nasal Spray embodying the
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`claimed invention and Teva’s generic copy of it are to this day the only two FDA-
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`approved intranasal naloxone formulations.
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`It is essential that Patent Owner be in a position to present evidence on the
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`failures of others, including evidence that was obtained by third-party subpoena in
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`the Teva Case. It is also essential that Patent Owner be in a position to pr
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