throbber
UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`NALOX-1 PHARMACEUTICALS, LLC,
`Petitioner,
`
`v.
`
`ADAPT PHARMA OPERATIONS LIMITED, and
`OPIANT PHARMACEUTICALS, INC.,
`Patent Owners.
`__________________
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`__________________
`
`PATENT OWNERS’ EXHIBIT LIST
`
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`Exhibit
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Declaration of Kenneth A. Williams, M.D.
`
`Short Name
`Williams POPR
`Decl.
`Amphastar Press
`Release
`
`Amphastar Announces the Receipt of a CRL for
`Intranasal Naloxone for the Emergency
`Treatment of Opioid Overdose (Feb. 21, 2017),
`available at http://ir.amphastar.com/
`static-files/19b13150-7ff8-4d3b-8e3f-
`452578083dbb
`Christopher T. Aquina et al., OxyContin® Abuse
`and Overdose, Postgraduate Medicine (2009)
`121(2):163–67
`Catherine T. Baca et al., Take-home Naloxone to
`Reduce Heroin Death, Addiction (2005)
`100:1823–31
`Daniel Belz et al., Naloxone Use in a Tiered-
`Response Emergency Medical Services System,
`Prehosp. Emerg. Care (2006) 10(4):468–71
`Ingebjorg Buajordet, Adverse Events After
`Naloxone Treatment of Episodes of Suspected
`Acute Opioid Overdose, Eur. J. Emerg. Med.
`(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
`Evzio® Label 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/2014/205787Orig
`1s000lbl.pdf
`
`Aquina
`
`Baca
`
`Belz
`
`Buajordet
`
`Burford Press
`Release
`
`2
`
`

`

`
`
`
`
`Exhibit
`2009
`
`2010
`
`2011
`
`2012
`
`2013
`
`2014
`
`2015
`
`2016
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`FDA Teva Press
`Release
`
`Gaddis
`
`Goldfrank’s
`
`Indivior Press
`Release
`
`Description
`FDA Approves First Generic Naloxone Nasal
`Spray to Treat Opioid Overdose (Apr. 19, 2019),
`available at https://www.fda.gov/news-
`events/press-announcements /fda-approves-first-
`generic-naloxone-nasal-spray-treat-opioid-
`overdose
`Gary M. Gaddis et al., Naloxone-Induced Patient
`Violence: An Overlooked Toxicity?, Annals of
`Pharmacotherapy (1992) 26:196–97
`Goldfrank’s Toxicologic Emergencies 579–85
`(9th ed. 2010)
`Indivior Receives Complete Response Letter
`from FDA Not Approving Naloxone Nasal Spray
`New Drug Application for Opioid Overdose
`(Nov. 24, 2015), available at http://www.
`indivior.com/wpcontent/uploads/2015/11/Nasal-
`Naloxone-Final-Release 112415.pdf
`A-M. Kelly et al., Intranasal Naloxone for Life
`Threatening Opioid Toxicity, Emerg. Med. J.
`(2002) 19:375
`Letter from Nydia M. Velasquez et al. to
`Michelle K. Lee, Director, U.S. Patent and
`Trademark Office (Dec. 5, 2016), available at
`http://sls.gmu.edu/cpip/wp-content/uploads/sites/
`31/2016/12/Letter-to-Director-Lee-Regarding-
`IPR-Petitions.pdf
`Loimer 1992 Norbert Loimer et al., Nasal Administration of
`Naloxone for Detection of Opiate Dependence,
`Journal of Psychiatric Research (1992)
`26(1):39–43
`NARCAN® (naloxone hydrochloride) nasal
`spray, Prescribing Information (Revised Jan.
`2017), available at https://www.accessdata.fda.
`gov/drugsatfda_docs/label/2017/208411s001lbl.
`pdf
`
`Kelly 2002
`
`Letter from Ten
`Congressmen to
`Michelle K. Lee,
`Director of U.S.
`PTO
`
`Narcan® Nasal
`Spray Label
`
`3
`
`

`

`
`
`
`
`Exhibit
`2017
`
`2018
`
`2019
`
`2020
`
`2021
`
`2022
`
`2023
`
`2024
`
`2025
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`Osterwalder
`
`Pallasch
`
`Popper
`
`Schwartz
`
`Sporer 1996
`
`Sporer 2007
`
`Stoove
`
`Description
`Joseph J. Osterwalder, Naloxone—For
`Intoxications with Intravenous Heroin and
`Heroin Mixtures—Harmless or Hazardous? A
`Prospective Clinical Study, Journal of
`Toxicology: Clinical Toxicology (1996)
`34(4):409–16
`Thomas J. Pallasch et al., Naloxone-Associated
`Morbidity and Mortality, Oral Surgery, Oral
`Medicine, Oral Pathology and Oral Radiology
`(1981) 52:602–03
`Caroline Popper et al., Naloxone Hazard In Drug
`Abuser, Lancet (1989)
`Jeffrey A. Schwartz et al., Naloxone-Induced
`Pulmonary Edema, Annals of Emergency
`Medicine (1987) 16:1294–96
`Karl A. Sporer et al., Out-of-hospital Treatment
`of Opioid Overdoses in an Urban Setting,
`Academic Emergency Medicine (1996)
`3(7):660–67
`Karl A. Sporer et al., Prescription Naloxone: A
`Novel Approach to Heroin Overdose Prevention,
`Annals of Emergency Medicine (2007)
`49(2):172–17
`Mark A. Stoove et al., Overdose Deaths
`Following Previous Non-Fatal Heroin Overdose:
`Record Linkage of Ambulance Attendance and
`Death Registry Data, Drug and Alcohol Review
`(2009) 28: 347–52
`Terman Slides G. Terman PowerPoint Presentation “Naloxone:
`Effects and Side Effects” at FDA 2012
`Workshop
`Opinion, Adapt Pharma Operations Ltd. v. Teva
`Pharms. USA, Inc., No. 2:16-cv-07721, D.I. 200
`(Apr. 24, 2019)
`
`Teva Case Claim
`Construction
`Opinion
`
`4
`
`

`

`
`
`
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Exhibit
`2026
`
`Short Name
`Teva Case
`Schedule
`Stipulation
`
`2027
`
`van Dorp
`
`2028
`
`Walley
`
`2030
`2031
`
`2032
`
`Yealy
`
`Description
`Stipulation and Order Regarding Expert
`Discovery Schedule, Adapt Pharma Operations
`Ltd. v. Teva Pharms. USA, Inc., No. 2:16-cv-
`07721, D.I. 210 (May 13, 2019)
`Eveline L.A. van Dorp et al., Naloxone
`Treatment in Opioid Addiction: the Risks and
`Benefits, Expert Opinion Drug Safety (2007)
`6(2):125–32
`A.Y. Walley et al., Opioid Overdose Rates and
`Implementation of Overdose Education and
`Nasal Naloxone Distribution in Massachusetts:
`Interrupted Time Series Analysis, BMJ (2013)
`346:174
`2029 Wermeling 2015 Daniel P. Wermeling, Review of Naloxone
`Safety for Opioid Overdose: Practical
`Considerations for New Technology and
`Expanded Public Access, Ther. Adv. Drug Safety
`(2015) 6(1):20-31
`Wermeling ’354 U.S. Patent Application No. 2010/0331354
`Williams
`Kenneth Williams et al., Evidence-Based
`Guidelines for EMS Administration of
`Naloxone, Prehosp. Emerg. Care (2019)
`Donald M. Yealy et al., The Safety of
`Prehospital Naloxone Administration by
`Paramedics, Annals of Emergency Medicine
`(1990) 19(8):902–05
`Zuckerman Matthew Zuckerman et al., Pitfalls of Intranasal
`Narcan – Response to a Letter to the Editor,
`Prehosp. Emerg. Care (2015) 19:138–39
`U.S. Patent No. 9,211,253
`U.S. Patent No. 9,468,747
`U.S. Patent No. 9,561,177
`Minute Entry, Adapt Pharma Operations Ltd. v.
`Teva Pharms. USA, Inc., No. 2:16-cv-07721,
`D.I. 221 (June 26, 2019)
`
`2033
`
`2034
`2035
`2036
`2037
`
`’253 patent
`’747 patent
`’177 patent
`Teva Case Status
`Conference
`Minute Entry
`
`5
`
`

`

`
`
`
`
`Exhibit
`2040
`
`2041
`
`2042
`
`2043
`
`2044
`
`2045
`
`2046
`2047
`2048
`2049
`
`2050
`
`2051
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Ansel’s
`
`Euerby
`
`Hodges
`
`Description
`Short Name
`Iowa Library University of Iowa Libraries, Pharmaceutical
`Sciences & Experimental Therapeutics:
`Compounding (viewed Nov. 19, 2019)
`Ansel’s Pharmaceutical Dosage Forms and Drug
`Delivery Systems (9th ed. 2011)
`Melvin R. Euerby, High Performance Liquid
`Chromatography of Benzalkonium Chloride—
`Variation in Commercial Preparations, J.
`Clinical and Hospital Pharmacy, (1985) 10:73–
`77
`N.A. Hodges et al., Preservative Efficacy Tests
`in Formulated Nasal Products: Reproducibility
`and Factors Affecting Preservative Activity, J.
`Pharm. Pharmacol. (1996) 48:1237–42
`Meda Transcript Transcript of Bench Trial – Volume A, in Meda
`Pharms, Inc. v. Apotex Inc., No. 14-1452-LPS,
`ECF No. 151 (D. Del. Dec. 13, 2016)
`Hospira Naloxone Hydrochloride Label and
`Packaging
`
`Hospira
`Naloxone HCl
`Label
`Evzio® Label Kaléo Evzio® Label and Packaging
`Imitrex Label GlaxoSmithKline Imitrex® Label and Packaging
`Zomig Label AstraZeneca ZOMIG® Label and Packaging
`Rizzo
`Jose Angelo Rizzo et al., Benzalkonium chloride
`and nasal mucociliary clearance: A randomized,
`placebo-controlled, crossover, double-blind trial,
`Am. J. Rhinol. (2006) 20:243–47
`Verse et al., The Tolerability of Nasal Drugs
`With Special Regard to Preservatives and
`Physico-chemical Parameters, Laryngo-Rhino-
`Otol (2003) 82:782–89
`European Pharmacopoeia 6.0, Volume 2 (Jan.
`2008)
`
`Verse
`
`European
`Pharmacopoeia
`6.0
`
`6
`
`

`

`
`
`
`
`Exhibit
`2052
`
`Short Name
`Donovan Alcon
`Deposition
`
`2053
`
`2054
`
`2055
`
`2059
`
`2060
`
`Donovan Alcon
`Report
`
`AHFS
`
`Kabara
`
`Spruill
`
`Hochhaus
`Handbook
`Chapter
`
`2061
`
`Muller
`
`2062
`
`2065
`
`Hochhaus
`Diagram
`Donovan Tr.
`
`2066
`
`Hochhaus Tr.
`
`2067
`
`Altannak
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Deposition Transcript of Maureen Donovan, in
`Alcon Res., Ltd. v. Watson Labs., Inc., No. 16-
`129(LPS)(SRF) (D. Del., Aug. 24, 2018)
`Reply Report of Maureen Donovan, Ph.D., in
`Alcon Res., Ltd. v. Watson Labs., Inc., No. 16-
`129(LPS)(SRF) (D. Del., Apr. 2, 2018)
`American Society of Health System Pharmacists,
`AHFS Drug Information (2009)
`Cosmetic and Drug Preservation: Principles and
`Practice (Jon J. Kabara ed. 1984) (Donovan
`Deposition Exhibit 2046A)
`William J. Spruill et al., Concepts in Clinical
`Pharmacokinetics, Sixth Ed. (2014)
`Günther Hochhaus & Hartmut Derendorf, Dose
`Optimization Based on Pharmacokinetic-
`Pharmacodynamic Modeling, Ch. 4, Handbook
`of Pharmacokinetic/Pharmacodynamic
`Correlation (1995)
`Markus Muller, Current concepts in
`pharmacokinetics and their implications for
`clinical medicine, Wien Klin Wochenschr (2001)
`15/16:566-72
`Diagram of Concentration Time Profile Drawn
`by Dr. Günther Hochhaus
`Transcript of November 22, 2019 Deposition of
`Dr. Maureen Donovan
`Transcript of December 12, 2019 Deposition of
`Dr. Günther Hochhaus
`Naser F. Altannak, Liquid Chromatography-
`Mass Spectrometry Method to Assess Naloxone
`Hydrochloride Photostability Under Artificial
`Light and Sunlight Exposure at Room
`Temperature, Asian K. Pharm. Clin. Res. (2005)
`8(5):309–11
`
`7
`
`

`

`
`
`
`
`Exhibit
`2068
`
`Short Name
`Aungst
`
`2069
`
`Bechgaard
`
`2070
`
`Bernstein
`
`2071
`
`Bommer
`
`2073
`2075
`
`2076
`
`Chiodini
`Davis
`
`EMA Guideline
`on Excipients
`
`2077
`
`EMA
`Presentation
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Bruce J. Aungst and Nancy J. Rogers, Site
`Dependence of Absorption-Promoting Actions
`of Laureth-9, Na Salicylate, Na2EDTA, and
`Aprotinin on Rectal, Nasal, and Buccal Insulin
`Delivery, Pharm. Res. (1988) 5(5):305–08
`Eric Bechgaard et al., Reversibility and clinical
`relevant or morphological changes after nasal
`application of ephedrine nasal drops 1%, Int’l J.
`Pharms. (1997) 152:67–73
`I. Leonard Bernstein, Is the use of benzalkonium
`chloride as a preservative for nasal formulations
`a safety concern? A cautionary note based on
`compromised mucociliary transport, J. Allergy
`Clin. Immunol. (2000) 105:39–44
`Rene Bommer et al., Preservative-Free Nasal
`Drug-Delivery Systems, Medical Device
`Technology (Oct. 2004) 1–5
`Int’l Patent Application No. 93/06854
`Stanley S. Davis and Lisbeth Illum, Absorption
`Enhancers for Nasal Drug Delivery, Clinical
`Pharmacokinetics (2003) 42:1107–1128
`European Medecines Agency, Committee for
`Medicinal Products for Human Use, Guideline
`on Excipients in the Dossier for Application for
`Marketing Authorisation of a Medicinal Product
`(2007), available at https://www.ema.europa.eu/
`en/documents/scientific-guideline/guideline-
`excipients-dossier-application-marketing-
`authorisation-medicinal-product-revision-
`2_en.pdf
`Pjotr Kozarewicz, European Medecines Agency,
`“Preservatives: Are They Safe?” (2010),
`available at https://www.ema.europa.eu/en/
`documents/presentation/presentation-
`preservatives-are-they-safe_en.pdf
`
`8
`
`

`

`
`
`
`
`Exhibit
`2079
`
`2080
`
`2081
`
`2082
`
`2083
`
`2087
`
`2088
`
`2089
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`European Pharmacopoeia, 8th Ed., Vol. 1, 2820-
`22 (2013) – Naloxone Hydrochloride Dihydrate
`
`Short Name
`European
`Pharmacopoeia
`8.0
`Harm Reduction
`Coalition
`
`Ho
`
`Hofmann
`
`Harm Reduction Coalition, How to Give Nasal
`Spray Naloxone, available at
`https://harmreduction.org/issues/overdose-
`prevention/tools-best-practices/od-kit-materials/
`Yin-Ching Ho et al., In vitro effects of
`preservatives in nasal sprays on human nasal
`epithelial cells, A. J. Rhinol. (2008) 22:125–29
`Thiemo Hofmann et al., Influence of
`Preservatives and Topical Steroids on Ciliary
`Beat Frequency In Vitro, Arch. Otolaryngol.
`Head Neck Surg. (2004) 130:440–45
`International Medical Systems, Limited,
`NALOXONE HYDROCHLORIDE – Naloxone
`Hydrochloride Injection Label and Packaging,
`available at https://dailymed.nlm.nih.gov/
`dailymed/getFile.cfm?setid=236349ef-2cb5-
`47ca-a3a5-99534c3a4996&type=pdf.
`Paul Merkus et al., Classification of Cilio-
`Inhibiting Effects of Nasal Drugs, Laryngoscope
`(2001) 111:595–602
`Migranal Label Novartis, Package Insert, Migranal
`(dihydroergotamine mesylate, USP) Nasal
`Spray, available at https://www.accessdata.
`fda.gov/drugsatfda_docs/label/2002/20148s7s8lb
`l.pdf
`European Medicines Agency Committee for
`Medicinal Products for Human Use, Nyxoid
`(Naloxone) Assessment Report, Procedure No.
`EMEA/H/C/004325/0000 (Sept. 14, 2016),
`available at https://www.ema.europa.eu/en/
`documents/assessment-report/nyxoid-epar-
`public-assessment-report_en.pdf
`
`IMS Naloxone
`HCl Label
`
`Merkus
`
`Nyxoid
`Assessment
`Report
`
`9
`
`

`

`
`
`
`
`Exhibit
`2090
`
`2091
`
`2092
`
`2093
`
`2094
`
`2095
`
`2096
`
`2097
`
`2098
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`Okada
`
`Pfeiffer Nasal
`Delivery
`
`Quadir
`
`Remington
`
`Suman
`
`Wang 2012
`
`Description
`Hiroaki Okada et al., Vaginal Absorption of a
`Potent Luteinizing Hormone-Releasing Hormone
`Analogue (Leuprolide) in Rats II: Mechanism of
`Absorption Enhancement with Organic Acids, J.
`Pharm. Sci. (1983) 72:75–78
`Matthias Birkhoff, Nasal Delivery as an
`Alternative to Injection: Science and Technology
`Meet Market Demand, ONdrugDelivery (Apr.
`2008) 13:20–22, available at https://www.
`ondrugdelivery.com/wp-content/uploads/
`2008/04/Apr2008.pdf
`Muhammad Quadir et al., Toxicological
`Implications of Nasal Formulations, Drug
`Delivery (1999) 6:227–42
`Remington: The Science and Practice of
`Pharmacy (20th ed. 2000), Alfonso R. Gennaro
`(Ed.)
`Julie D. Suman, Nasal Drug Delivery, Expert
`Opinion on Biological Therapy (2003) 3:3, 519–
`23
`Chengshuo Wang et al., Effects of
`Benzalkonium Chloride and Potassium Sorbate
`on Airway Ciliary Activity, ORL (2012) 74:149–
`53
`WHO Guide World Health Organization, Substance Use:
`Community Management of Opioid Overdose
`(2014)
`NDA 208411 - Narcan® Nasal Spray Highlights
`of Prescribing Information Rev. 01/2017
`(APT00018727–18744)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 2.3.P.1, Description and
`Composition of Drug Product (APT00018275–
`18276)
`
`
`
`
`
`10
`
`

`

`
`
`
`
`Exhibit
`2099
`
`Short Name
`
`
`2100
`
`2101
`
`2102
`
`2103
`
`2104
`
`2105
`
`2106
`
`2107
`
`2108
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 2.3.P.5, Control of Drug
`Product (APT00018227–18247)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 2.3.P.7, Container
`Closure System (APT00059347–59353)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 2.6.1, Nonclinical
`Introduction (APT00016555–16556)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 3.2.P.5.1, Specifications
`(APT00055005–55008)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 3.2.P.8.1, Stability
`Summary (APT00049472–49496)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 3.2.P.8.3, Stability Data
`(APT00018297–18413)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Clinical Study Report
`(APT00017024–17765)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 3.2.P.3.4, Controls of
`Critical Steps and Intermediates
`(APT00054100–54105)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 2.7.1, Summary of
`Biopharmaceutics Studies and Analytical
`Methods (APT00016558–16596)
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Module 2.7.6, Synopsis of
`Individual Studies (APT00016597–16605)
`
`11
`
`

`

`
`
`
`
`Exhibit
`2109
`
`2113
`2114
`2115
`2116
`2117
`
`2118
`
`2119
`
`2120
`
`2121
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`
`
`Description
`PROTECTIVE ORDER MATERIAL
`NDA 208411 - Validation Report for Standard
`Method of Analysis 73.7822
`(APT00055136–55201)
`Adapt Brochure Adapt Public Interest Segment Brochure
`Adapt Fact Sheet Corporate Communications Fact Sheet to Media
`Adapt Flier
`Adapt Public Interest Segment Flier
`Adapt Website February 2016 Adapt Website
`Prescribe to
`Prescribe to Prevent, Naloxone Product
`Prevent
`Comparison, available at
`https://prescribetoprevent.org/wp2015/wp-
`content/uploads/Naloxone-product-
`chart.17_04_14.pdf (viewed April 1, 2019)
`Naloxone Pricing in the Community As of
`January 2019, available at
`https://www.umassmed.edu/globalassets/
`office-of-undergraduate-medical-education-
`media/naloxone-pricing.pdf (viewed April 11,
`2019)
`Press Release Regarding Surgeon General
`Advisory on Naloxone, available at
`https://www.hhs.gov/about/news/2018/
`04/05/surgeon-general-releases-advisory-on-
`naloxone-an-opioid-overdose-reversing-
`drug.html (viewed March 28, 2019)
`Consumer FAQs, Narcan® Nasal Spray 4mg,
`available at https://www.narcan.com/static/
`NARCAN_Consumer_FAQs.6b96d68e.pdf
`(viewed March 28, 2019)
`How to Get Narcan®, available at
`https://www.narcan.com/patients/how-to-get-
`narcan (viewed April 11, 2019)
`
`UMass
`Naloxone
`Pricing Guide
`
`Surgeon General
`Advisory
`
`Narcan® Nasal
`Spray Consumer
`FAQs
`
`How to Get
`Narcan® Nasal
`Spray
`
`12
`
`

`

`
`
`
`
`Exhibit
`2122
`
`Short Name
`Narcan® Nasal
`Spray Label
`
`2123
`
`Adapt Fast
`Track
`
`2124
`
`Adapt Priority
`Review
`
`2125
`
`Adapt Narcan®
`Nasal Spray
`Approved
`
`2126
`
`Adapt Narcan®
`Nasal Spray
`Available
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Narcan® Nasal Spray Prescribing Information
`(Revised Jan. 2017), available at
`https://www.accessdata.
`fda.gov/drugsatfda_docs/label/2017/
`208411s001lbl.pdf
`Press Release – July 27, 2015, Adapt Pharma
`submits NDA to FDA for NARCAN®
`(Naloxone) Nasal Spray, available at
`http://adaptpharma.com/adapt_press
`_release/july-27-2015/ (viewed March 27, 2019)
`Press Release – September 24, 2015, FDA
`accepts for review Adapt Pharma’s NARCAN®
`(naloxone hydrochloride) Nasal Spray NDA,
`available at http://adaptpharma.com/adapt_press
`_release/september-24-2015/ (viewed April 22,
`2019)
`Press Release – November 19, 2015,
`NARCAN® (naloxone hydrochloride) Nasal
`Spray by U.S. food and drug administration,
`available at http://adaptpharma.com/adapt_press
`_release/november-19-2015/ (viewed March 27,
`2019)
`Press Release – February 25, 2016, NARCAN®
`(Naloxone Hydrochloride) NASAL SPRAY
`Now Available in the United States for
`Emergency Treatment of Known or Suspected
`Opioid Overdose, available at http://
`adaptpharma.com/adapt_press_release/february-
`25-2016/ (viewed March 27, 2019)
`
`13
`
`

`

`
`
`
`
`Exhibit
`2127
`
`Short Name
`Emergent Adapt
`Acquisition
`
`2128
`
`Kaléo Evzio®
`Approved
`
`2129
`
`Kaléo Evzio®
`Available
`
`2130
`
`2131
`
`Kaléo About
`Evzio®
`
`Kaléo
`Evzio2You
`
`2132
`
`Kaléo Cares
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Press Release – October 15, 2018, Emergent
`BioSolutions Completes Acquisition of Adapt
`Pharma and Flagship Product Narcan®
`(naloxone HCl) Nasal Spray, available at
`https://www.emergentbiosolutions
`.com/news/emergent-biosolutions-completes-
`acquisition-adapt-pharma-and-flagship-product-
`narcanr-naloxone (viewed March 26, 2019)
`Press Release – April 3, 2014, FDA Approves
`Kaleo’s EVZIO for the Treatment of Opioid
`Overdose, available at https://kaleo.com/press-
`release/u-s-food-and-drug-administration-
`approves-kaleos-evzio-for-the-emergency-
`treatment-of-opioid-overdose/ (viewed April 1,
`2019)
`Press Release – July 10, 2014, EVZIO (naloxone
`HCl injection) Auto Injector Now Available in
`the United States for Emergency Treatment of
`Opioid Overdose, available at
`https://kaleo.com/press-release/evzio-naloxone-
`hcl-injection-auto-injector-now-available-in-the-
`united-states-for-the-emergency-treatment-of-
`opioid-overdose/ (viewed April 1, 2019)
`Kaléo About Evzio®, available at
`https://www.evzio.com/patient/about-evzio/
`(viewed April 1, 2019)
`Kaléo Evzio2You, available at
`https://evzio.com/patient/in-chronic-
`pain/evzio2you/ (viewed March 28, 2019)
`Kaléo Cares Patient Assistance Program,
`available at https://evzio.com/patient/in-chronic-
`pain/kaleo-cares/ (viewed May 1, 2019)
`
`14
`
`

`

`
`
`
`
`Exhibit
`2133
`
`Short Name
`Kaléo
`Authorized
`Generic
`
`2134
`
`Kaléo Public
`Access
`
`2135
`
`Senate Evzio®
`Report
`
`2136
`
`FDA Narcan®
`Nasal Spray
`Approved
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Press Release – December 12, 2018, Authorized
`Generic for EVZIO (naloxone HCl injection) to
`be Available at a Reduced List Price, available
`at https://kaleo.com/in-the-news/
`authorized-generic-for-evzio-naloxone-hcl-
`injection-to-be-available-at-a-reduced-list-price-
`of-178/ (viewed April 11, 2019)
`Press Release – April 5, 2018, EVZIO®
`(naloxone HCl injection, USP) Auto-Injector
`Now Available to Patients in Select States
`Without a Prescription Through Kaléo’s New
`Virtual Standing Order Pilot Program and to
`Government Agencies at a Direct Purchase
`Price, available at https://www.prnewswire.
`com/news-releases/evzio-naloxone-hcl-injection-
`usp-auto-injector-now-available-to-patients-in-
`select-states-without-a-prescription-through-
`kaleos-new-virtual-standing-order-pilot-
`program-and-to-government-agencies-at-a-
`direct-purchase-price-300624974.html (viewed
`April 11, 2019)
`“Combatting the Opioid Crisis: The Price
`Increase of an Opioid Overdose Reversal Drug
`and the Cost to the U.S. Health Care System,”
`U.S. Senate Permanent Subcommittee on
`Investigations, Committee on Homeland
`Security and Governmental Affairs Staff Report,
`November 2018, available at https://www.hsgac.
`senate.gov/imo/media/doc/Naloxone%20Report
`%20Final%20with%20Annex1.pdf
`FDA News Release: FDA Moves Quickly to
`Approve Easy-to-Use Nasal Spray to Treat
`Opioid Overdose, available at https://wayback.
`archive-it.org/7993/20170404214906/
`https://www.fda.gov/NewsEvents/Newsroom/
`PressAnnouncements/ucm473505.htm (viewed
`December 14, 2019)
`
`15
`
`

`

`
`
`
`
`Exhibit
`2137
`
`2138
`
`2140
`
`2141
`
`2142
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`FDA Evzio® 2
`mg Summary
`Review
`
`FDA Evzio® 2
`mg Orange Book
`
`Description
`“Center for Drug Evaluation and Research
`Application Number: 209862Orig1s000
`Summary Review,” FDA Center for Drug
`Evaluation and Research, available at
`https://www.accessdata.fda.gov/drugsatfda_docs
`/nda/2016/209862Orig1s000SumR.pdf (viewed
`December 14, 2019).
`Orange Book: Approved Drug Products with
`Therapeutic Equivalence Evaluations, Product
`Details for NDA 209862, available at
`https://www.accessdata.fda.gov/
`Scripts/cder/ob/results_product.cfm?
`Appl_Type=N&Ap pl_No=209862 (viewed
`April 2, 2019)
`Press Release – November 18, 2015, FDA
`Approves Naloxone Nasal Spray to Reverse
`Opioid Overdose https://www.drugabuse.gov/
`news-events/news-releases/2015/11/fda-
`approves-naloxone-nasal-spray-to-reverse-
`opioid-overdose (viewed March 27, 2019)
`Wisconsin DOJ Wisconsin Department of Justice, News for
`Immediate Release – December 13, 2017, AG
`Schimel and UW System Team Up with Adapt
`Pharma to Expand Narcan Availability on
`University Campuses, https://www.doj.state.
`wi.us/sites/default/files/newsmedia/12.13.17_Ad
`apt_NARCAN.pdf (viewed December 14, 2019)
`Delaware County Police First in World to Use
`New Lifesaving Drug, available at
`http://www.delconewsnetwork.com/
`ridleytowntalk/news/delaware-county-police-
`first-in-world-to-use-new-lifesaving/article_
`a705efe9-b781-57c8-9469-4266c4c9f7cc.html
`(viewed December 14, 2019)
`
`NIDA Narcan®
`Nasal Spray
`Approved
`
`Delaware
`County
`
`16
`
`

`

`
`
`
`
`Exhibit
`2143
`
`2144
`
`2145
`
`2146
`
`2147
`
`2148
`
`2149
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`Somerset
`County
`
`PAARI About
`Us
`
`Harvard Pilgrim
`About Us
`
`Harvard Pilgrim
`Coverage
`
`Description
`CSC Times, Training on How to Administer
`Life-Saving Narcan Offered Free by the
`Somerset County Health Department, available
`at https://www.csctimes.com/somerset-
`county/2043/ (viewed December 14, 2019)
`Police Assisted Addiction & Recovery Initiative
`(PAARI) – About Us, available at
`https://paariusa.org/about-us/ (viewed December
`14, 2019)
`PAARI Partners Press Release – June 12, 2017, PAARI Law
`Enforcement Partners Hail Ease of Use of Adapt
`Pharma Single-Step Nasal Narcan, available at
`https://paariusa.org/2017/06/12/p-r-law-
`enforcement-partners-hail-ease-use-adapt-
`pharma-single-step-nasal-narcan/ (viewed
`December 14, 2019)
`Harvard Pilgrim Health Care – About Us,
`available at https://www.harvardpilgrim.org/
`public/about-us (viewed April 17, 2019)
`Harvard Pilgrim Health Care – Coverage of
`Narcan Nasal Spray and Evzio, available at
`https://www.harvardpilgrim.org/portal/page?_pa
`geid=253,9059993&_dad=portal&_schema=PO
`RTAL (viewed April 17, 2019)
`Therapeutic Intranasal Drug Delivery:
`Needleless Treatment Options for Medical
`Problems, available at http://intranasal.
`net/information_links/default.htm (viewed
`December 14, 2019)
`Therapeutic Intranasal Drug Delivery: Intranasal
`Naloxone Overview, available at
`http://intranasal.net/OpiateOverdose/
`Opiate_overdose_overview.htm (viewed
`December 14, 2019)
`
`Intranasal.net
`Links
`
`Intranasal.net
`Opiate Overdose
`
`17
`
`

`

`
`
`
`
`Exhibit
`2150
`
`2151
`
`2152
`
`2153
`
`2154
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`NACo Press
`Release
`
`Attorney
`General
`Coffman
`
`Description
`Press Release – State, Local Leaders Expand
`Efforts to Treat Opioid Overdoses, available at
`https://www.naco.org/sites/
`default/files/documents/NARCAN.pdf (viewed
`December 15, 2019)
`Governor Wolf Press Release – October 5, 2017, Governer Wolf
`Announces $5 Million Funding for Naloxone to
`First Responders, available at https://www.
`governor.pa.gov/newsroom/governor-wolf-
`announces-5-million-funding-naloxone-first-
`responders/ (viewed December 15, 2019)
`Press Release – Sept. 19, 2016, Attorney General
`Coffman Announces Initiative to Reverse a
`Deadly Trend by Getting Naloxone into Life
`Saving Hands, available at
`https://www.colorado.gov/pacific/
`post/news/ag-coffman-announces-naloxone-
`initiative-reverse-deadly-trend (viewed
`December 15, 2019)
`Office of the Maine Attorney General – Press
`Release – Aug. 1, 2018, Police Agencies Report
`Over 500 Saves Using Narcan Provided by
`Attorney General’s Office, available at
`https://www.maine.gov/ag/news/article.shtml?id
`=804407 (viewed December 15, 2019)
`Frank S. Abderholden, Chicago Tribune, Fire
`District Teams with Foundation to Purchase
`Opioid-Antidote Kits, available at
`https://www.chicagotribune.com/suburbs/lake-
`county-news-sun/ct-lns-narcan-donation-fills-
`shortage-st-0723-20160722-story.html (viewed
`December 15, 2019)
`
`Attorney
`General Mills
`
`Lake County
`Health
`Department
`
`18
`
`

`

`
`
`
`
`Exhibit
`2155
`
`Short Name
`Davenport Fire
`Department
`
`2156
`
`Stafford County
`Fire & Rescue
`
`2157
`
`Peoria Police
`Department
`
`2158
`
`Martin County
`Sheriff’s Office
`
`2159
`
`Upper Darby
`Police
`Department
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Thomas Geyer, QCTimes.com, Branstad to Sign
`Opioid Overdose Prevention Bill Today,
`available at http://qctimes.com/news/state-and-
`regional/branstad-to-sign-opioid-overdose-
`prevention-billtoday/article_40ceef3a-a43d-
`553c-8157-01451053c69e.html (viewed
`December 15, 2019)
`Kristin Davis, The Free Lance-Star, Stafford
`County Sheriff Deputies Adding Life-Saving
`Opiate Antidote to Arsenal, available
`https://www.fredericksburg.com/
`news/local/stafford/stafford-county-sheriff-
`deputies-adding-life-saving-opiate-antidote-
`to/article_9e2ef5a5-004a-5ae9-9168-
`4837a24740a6.html (viewed December 15,
`2019)
`Trisha Hendricks, KPNX, Body Cam Footage
`Shows Peoria Police Save Heroin Overdose
`Victim with Narcan (December 22, 2017),
`available at https://www.12news.com/article/
`news/local/valley/body-cam-footage-shows-
`peoria-police-save-heroin-overdose-victim-with-
`narcan/75-501882962 (viewed December 15,
`2019)
`25 WPBF News, New Tool for Martin County
`Deputies Saves Lives (Sept. 1, 2016),
`https://www.wpbf.com/article/new-tool-for-
`martin-county-deputies-saves-lives/2107546
`(viewed December 15, 2019)
`Bruce Gordon, FOX29, Upper Darby Police
`Tackle Opioid Epidemic (May 10, 2016),
`available at https://www.fox29.com/news/upper-
`darby-police-tackle-opioid-epidemic (viewed
`December 15, 2019)
`
`19
`
`

`

`
`
`
`
`Exhibit
`2160
`
`Short Name
`Coventry Police
`Department
`
`2161
`
`Smoky
`Mountain News
`
`2162
`
`Brunswick
`County Board of
`Education
`
`2163
`
`Pennsylvania
`Department of
`Health
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Description
`Kendra Leigh Miller, RI Central, Coventry
`Police Switch to One-Step Narcan OD Reversal
`Kit, available at https://www.ricentral.com/
`coventry_courier/news/local_news/
`coventry-police-switch-to-one-step-narcan-od-
`reversal-kit/article_71074c20-5420-11e6-9e7c-
`f726b8405cac.html (viewed December 15, 2019)
`Becky Johnson, Smoky Mountain News, Moving
`Mountains: A Rare Bright Spot in the Relentless
`Fight Against Prescription Pill Abuse (June 1,
`2016), available at
`https://www.smokymountainnews.com/news/ite
`m/17740-moving-mountains-a-rare-bright-spot-
`in-the-relentless-fight-against-prescription-pill-
`abuse (viewed December 15, 2019)
`Hannah Brewer, Brunswick County, Brunswick
`County High Schools to Carry Opioid Overdose
`Reversal Drug (Sug. 17, 2016), available at
`https://spectrumlocalnews.com/nc/coastal/news/
`2016/08/17/brunswick-county-high-schools-
`naloxone- (viewed December 15, 2019)
`Pennsylvania Department of Health, Physician
`General, Montgomery County Commissioner
`and Adapt Pharma Representative Fill Naloxone
`Prescription and Discuss the Fight Against
`Pennsylvania’s Opiod Epidemic, available at
`https://www.prnewswire.com/news-
`releases/physician-general-montgomery-county-
`commissioner-and-adapt-pharma-representative-
`fill-naloxone-prescription-and-discuss-the-fight-
`against-pennsylvanias-opioid-epidemic-
`300389354.html (viewed December 15, 2019)
`
`20
`
`

`

`
`
`
`
`Exhibit
`2164
`
`2165
`
`2166
`
`2167
`
`2168
`
`2169
`
`2170
`
`2171
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`WSJ Overdose
`Deaths
`
`Description
`Jon Kamp, Wall Street Journal, Overdose Deaths
`Likely to Fall for First Time Since 1990 (June
`26, 2019), available at https://www.wsj.com/
`articles/overdose-deaths-likely-to-fall-for-first-
`time-since-1990-11561541406 (viewed June 27,
`2019)
`Rahul Guha, Jian Li, and Andrea L. Scott, “The
`Economics of Commercial Success in
`Pharmaceutical Patent Litigation,” Landslide 1.5
`(2009):8–12
`Ernst R. Berndt, Linda T. Bui, David H.
`Lucking-Reiley and Glen L. Urban, “The Roles
`of Marketing, Product Quality and Price
`Competition in the Growth and Composition of
`the U.S. Anti-ulcer Drug Industry,” NBER
`Working Paper No. 4904, October 1994
`Ernst R. Berndt, “The U.S. Pharmaceutical
`Industry: Why Major Growth In Times of Cost
`Containment?” Health Affairs 20.2 (2001)
`Venkataraman Venkataraman, Sriram, and Stefan Stremersch,
`“The Debate on Influencing Doctors’ Decisions:
`Are Drug Characteristics the Missing Link?”
`Management Science 53.11 (2007):1688–701
`PhRMA, “The Facts About Pharmaceutical
`Marketing & Promotion,” July 2008, at 3,
`available at http://www.phrma.org/sites/
`default/files/pdf/marketing_and_promotion_facts
`_071108_final.pdf (viewed May 6, 2019)
`Don Mogelefsky, “Smooth Operators,” Incentive
`174 (2000):104–05
`Natalie Mizik and Robert Jacobson, “Are
`Physicians ‘Easy Marks’?: Quantifying the
`Effects of Detailing and Sampling on New
`Prescriptions,” INFORMS 50.12 (2004):1704–15
`
`Guha
`
`Berndt 1994
`
`Berndt 2001
`
`PhRMA
`
`Mogelefsky
`
`Mizik
`
`21
`
`

`

`
`
`
`
`Exhibit
`2172
`
`2173
`
`2174
`
`2178
`
`2179
`
`2180
`
`2181
`
`Case IPR2019-00688
`U.S. Patent No. 9,468,747
`
`
`Short Name
`OINDPnews
`Indivior
`Submission
`
`Indivior
`Presentation
`
`Description
`OINDB News, Indivior Announces Submission
`of NDA for Naloxone Nasal Spray, available at
`https://www.oindpnews.com/2015/07/indivior-
`announces-submission-of-nda-for-naloxone-
`nasal-spray/ (viewed April 23, 2019)
`Steve Hebert,

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