`
`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 IPR2019-00695
`Patent 9,629,965
`__________________
`
`PRELIMINARY RESPONSE OF PATENT OWNER
`OPIANT PHARMACEUTICALS, INC.
`
`
`
`
`
`
`
`
`
`
`Case IPR2019-00695
`Patent 9,629,965
`
`
`TABLE OF CONTENTS
`
`BACKGROUND ............................................................................................. 4
`
`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.
`
`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. ..........................................26
`
`5. Wang Does Not Teach 4 mg Doses of Naloxone. ....................34
`
`6.
`
`Contrary to Petitioner’s Misreading, Wyse Does Not Teach 4
`mg Doses of Naloxone. .............................................................39
`
`i
`
`
`
`Case IPR2019-00695
`Patent 9,629,965
`
`The Pharmacokinetic Data in Wyse Would Not Lead the POSA
`to a Single 4 mg Dose of Intranasal Naloxone. ........................41
`
`7.
`
`B.
`
`The POSA Would Not Have Been Motivated To Use the
`Required Stabilizing Agent, Much Less the Combination of
`BZK with EDTA. ................................................................................ 46
`
`1. Wang Does Not Teach a Stabilizing Agent, or the Combination
`of BZK and EDTA. ...................................................................47
`
`2.
`
`3.
`
`4.
`
`The POSA Would Have Been Taught Away from the Use of
`BZK and EDTA In Light of the Studies in Wyse. ....................48
`
`The POSA Would Not Have Relied on HPE To Select BZK, or
`the Combination of BZK with EDTA. ......................................54
`
`Bahal and Kushwaha Would Not Lead the POSA To Use BZK
`and EDTA. ................................................................................57
`
`V.
`
`CONCLUSION .............................................................................................. 58
`
`
`
`ii
`
`
`
`TABLE OF AUTHORITIES
`
`Case IPR2019-00695
`Patent 9,629,965
`
`
`
`
`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) ............................................................................ 35
`
`Ex parte Benjamin Klein & Odette Eng,
`Appeal 2016-007173, 2017 WL 3947858 (P.T.A.B. Aug. 24, 2017) ................ 36
`
`Harmonic Inc. v. Avid Tech., Inc.,
`815 F.3d 1356 (Fed. Cir. 2016) ............................................................................ 6
`
`In re Benno,
`768 F.2d 1340 (Fed. Cir. 1985) .......................................................................... 36
`
`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 and Company,
`921 F.3d 1372 (Fed. Cir. 2019) .......................................................................... 10
`
`St. Regis Mohawk Tribe v. Mylan Pharms., Inc.,
`896 F.3d 1322 (Fed. Cir. 2018) ...................................................................... 6, 17
`
`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
`
`iii
`
`
`
`Garmin Int’l, Inc. v. Cuozzo Speed Techs. LLC,
`Case IPR2012-00001, Paper 26 (P.T.A.B. Mar. 5, 2013) .................................. 17
`
`Case IPR2019-00695
`Patent 9,629,965
`
`
`Gen. Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha,
`Case IPR2016-01357, Paper 19 (P.T.A.B. Sept. 6, 2017) .............................. 9, 12
`
`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
`
`STATUTES
`
`35 U.S.C. § 314 .................................................................................................. 14, 18
`
`35 U.S.C. § 316 .................................................................................................. 14, 18
`
`35 U.S.C. § 325 ........................................................................................................ 13
`
`37 C.F.R. § 42.108 ................................................................................................... 23
`
`REGULATIONS
`
`
`
`
`
`
`
`
`
`iv
`
`
`
`
`
`_hortName
`
`200Nlo -WlliamsDecl
`
`
`2002 Am-phastarPress
`
`Release
`
`2003
`
`2004
`
`Case IPR2019-00695
`
`Patent 9,629,965
`
`E—XHIBITLIST
`
`ExpertDeclarationofKennethAWilliams,
`AmphastarAnnouncestheReceiptofaCRLfor
`
`Intranasal Naloxonefor 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):]63—67
`
`Catherine T. Baca et al., Take-home Naloxone to
`Reduce Heroin Death, Addiction (2005)
`100:1823—31
`
`
`
`2005
`
`Daniel Belz et al., Naloxone Use in a Tiered-
`
`2006
`
`Buajordet
`
`2007
`
`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/20 l 7/06/20 l 7 .07 .03-Burford-
`Complex-Strategies-fund-close-FINAL.pdf
`
`
`
`Ex. No.
`
`2008
`
`EVZIO®
`Prescribing
`Information
`
`2009
`
`FDA Teva Press
`Release
`
`Case IPR2019-00695
`
`Patent 9,629,965
`
`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/201 5/ 1 l/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 1/201 6/ l 2/Letter-to-
`Director-Lee-Regarding—IPR—Petitions.pdf
`
`vi
`
`
`
`Ex. No.
`
`2015
`
`Loimer 1992
`
`Norbert Loimer et al., Nasal Administration of
`
`Case IPR2019-00695
`
`Patent 9,629,965
`
`2016 NARCAN® Nasal
`Spray Prescribing
`Information
`
`2017 Osterwalder
`
`2018
`
`Pallasch
`
`2019
`
`Popper
`
`2020
`
`Schwartz
`
`2021
`
`Sporer 1996
`
`
`
`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/2017/20841150011bl-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—1 6
`
`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 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 IPR2019-00695
`
`Patent 9,629,965
`
`Karl A. Sporer et al., Prescription Naloxone: A
`Novel Approach to Heroin Overdose Prevention,
`Annals ofEmergency Medicine (2007)
`49(2): 172—1 7
`
`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: 1 74.
`
`viii
`
`
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`Case IPR2019-00695
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`Patent 9,629,965
`
`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
`
`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,
`Prehospital Emergency Care (2015) 19: 138—39
`
`
`
`2034
`
`’253 patent
`
`US. Patent 9,211,253
`
`2035
`
`’747 patent
`
`US. Patent 9,468,747
`
`2036
`
`’177 patent
`
`US. Patent 9,561,177
`
`2037
`
`Minute Entry, Adapt Pharma Operations Ltd. v.
`Teva Case Status
`Conference Minute Teva Pharms. USA, Inc., No. 2: 16-cv-07721, D.I.
`Entry
`221 (June 26, 2019)
`
`
`ix
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`
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`Case IPR2019-00695
`Patent 9,629,965
`
`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 has not filed an application to market any drug,
`
`and the real parties in interest it has named are non-pharmaceutical companies with
`
`a history of challenging pharmaceutical patents to realize profits for their
`
`stakeholders.
`
`Nalox-1’s second Petition regarding U.S. Patent 9,629,965 (“the ’965
`
`patent”), Ex. 1001, to which this Preliminary Response responds, largely duplicates
`
`the first, Case IPR2019-00694, 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 IPR2019-00694 at pages 6–8, 34–39, 47–48 and 57–58. The
`
`fact that this Petition is redundant with the Petition in Case IPR2019-00694 is an
`
`1
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`Case IPR2019-00695
`Patent 9,629,965
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`independent reason for the Board to decline to institute it even if the Board institutes
`
`in that case (which it should not).
`
`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-
`
`00694. This Petition is little more than an effort to conjure additional grounds, and
`
`adds nothing meaningful to Case IPR2019-00694. The simplest ground in this
`
`Petition seeks to combine an astonishing five references, and another three grounds
`
`combine six. The Board frequently declines to institute secondary, redundant
`
`petitions, and it should do the same here.
`
`In any event, this Petition (like Case IPR2019-00694), 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 scheduled to begin on August 26, 2019—less than two months away, and
`
`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
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`2
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`Case IPR2019-00695
`Patent 9,629,965
`
`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 ’965
`
`patent.
`
`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 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 Wyse squarely teaches against it.
`
`For each of these reasons, institution should be denied.
`
`3
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`
`
`I.
`
`BACKGROUND
`
`Case IPR2019-00695
`Patent 9,629,965
`
`
`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 described and claimed in the ’965 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
`
`4
`
`
`
`Case IPR2019-00695
`Patent 9,629,965
`
`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 ’965 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
`
`5
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`
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`Case IPR2019-00695
`Patent 9,629,965
`
`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 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.
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`May 20, 2019). The Board has denied institution of redundant petitions filed “by
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`the same petitioner and includ[ing] challenges to the same claims . . . of the same
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`patent . . . [where] the differences between the asserted art and arguments [were not]
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`sufficiently material to outweigh the inefficiencies and costs of instituting an
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`additional proceeding.” Id.; see also Comcast Cable Commc’ns, LLC v. Rovi
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`6
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`Case IPR2019-00695
`Patent 9,629,965
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`Guides, Inc., Case IPR2019-00225, Paper 14 at 6–7 (P.T.A.B. June 3, 2019)
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`(denying institution of five of six redundant petitions).
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`Here, the Board should exercise its discretion to deny institution because this
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`Petition is substantially similar to Nalox-1’s petition toward the same patent based
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`on Wyse. See Case IPR2019-00694 (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, would have
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`been motivated to use a 4–6 mg naloxone dose, and would have selected excipients
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`including BZK and EDTA. Compare Pet. at 13–22 with Wyse Petition at 15–24.
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`Both here and in the Wyse Petition, 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. See Pet. at 57–58. In particular, Petitioner repeats
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`an argument about the supposed motivation to use a 4–6 mg naloxone dose, based
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`on the pharmacokinetic data reported in Wyse, in which Petitioner does not even cite
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`Wang—this Petition’s purported lead reference. See Pet. at 18‒19. Petitioner also
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`extensively discusses the pharmacokinetic studies and excipient screening studies
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`disclosed by Wyse in the secondary considerations section. See Pet. at 55–57.
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`Furthermore, Petitioner explicitly relies on Wyse, Djupesland, HPE, and Wermeling
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`’291—references also discussed in the Wyse Petition. Petitioner also submits the
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`same pharmacological expert declaration for the Wyse Petition as for this Petition;
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`7
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`Case IPR2019-00695
`Patent 9,629,965
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`and the formulator expert declarations are identical for the first 233 pages and only
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`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. Wang, the 2005 reference Petitioner tries to contend is its lead
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`reference in this Petition, was ten years old by 2015 and does not even come close,
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`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. 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 IPR proceeding “in view of the overlap
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`between the Petition and [a] Parallel District Court Case.” E-One, Inc. v. Oshkosh
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`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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`and limited exclusive licensee Adapt Pharma Operations Limited (“Adapt Pharma”)
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`against Teva (the “Teva Case”) and Perrigo. Adapt Pharma Operations Ltd., et al.
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`8
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`Case IPR2019-00695
`Patent 9,629,965
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`v. Teva Pharms. USA, Inc., et al., No. 2:16-cv-07721 (D.N.J.) (consolidated); Adapt
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`Pharma Operations Ltd., et al. v. Perrigo UK FINCO Limited Partnership, No. 2:18-
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`cv-15287 (D.N.J.). Institution would be an inefficient use of Board resources, where
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`the Teva Case, involving the same invention and many of the same prior art
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`references, is nearing its final stages, with a bench trial date on August 26, 2019, and
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`less than two months away. This concern is especially pronounced here, because
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`the extensive secondary considerations and third-party discovery record will be
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`onerous, if even 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 FDA approval for an intranasal naloxone product is
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`challenging the same invention before a district court. Under these circumstances,
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`it makes no sense to institute a trial that will not be over until long after the district
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`court’s, particularly given that the district court will have a much more fulsome
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`record to consider.
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`9
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`Case IPR2019-00695
`Patent 9,629,965
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`The specific Petitioner entity, Nalox-1, is a Delaware limited liability
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`company formed on December 12, 2018, that appears to have been created for the
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`sole purpose of challenging the ’965 patent and related patents through IPRs.
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`Petitioner is financially backed by, and appears to be the agent of, Burford Capital
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`Limited—a litigation investment firm—and its affiliate, Burford Capital Investment
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`Management LLC, which recently closed a new $500 million fund “to invest in
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`assets that Burford believes are mispriced and where value can be realized through
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`recourse to litigation and regulatory processes.” Burford Press Release, Ex. 2007.
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`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.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 Patent Owner and Adapt Pharma are currently meeting, and are
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`1 See Neptune Generics, LLC v. Eli Lilly and Company, 921 F.3d 1372 (Fed. Cir.
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`2019) (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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`10
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`Case IPR2019-00695
`Patent 9,629,965
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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 ’965
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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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`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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`11
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`Case IPR2019-00695
`Patent 9,629,965
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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.
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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). 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
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`art and arguments was “nearing its final stages, with expert discovery ending” about
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`seven weeks after the institution decision, “and a 5-day jury trial set to begin” just
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`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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`Intellectual Property GMBH, where “the district court trial is set to occur on April
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`1, 2019, which is more than eight months before our Final Written Decision would
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`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
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`alongside a parallel and advanced district court proceeding “would be contrary to
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`12
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`Case IPR2019-00695
`Patent 9,629,965
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`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. (