Paper 1
`Filed: February 19, 2019
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`NALOX-1 PHARMACEUTICALS, LLC,
`Petitioner,
`
`v.
`
`ADAPT PHARMA LTD,
` OPIANT PHARMACEUTICALS, INC.,
`Patent Owners
`____________
`
`IPR2019-00692
`U.S. Patent No. 9,561,177
`____________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,561,177
`AS OBVIOUS OVER WANG
`
`
`
`
`
`
`
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`TABLE OF CONTENTS
`
`INTRODUCTION ............................................................................................... 1 
`I. 
`II.  IPR REQUIREMENTS UNDER 37 C.F.R. § 42.104 ........................................ 2 
`A.  Grounds for Standing Under 37 C.F.R. § 42.104(a) ..................................... 2 
`B. 
`Identification of Challenge Under 37 C.F.R. § 42.104(b) ............................ 3 
`1. 
`Statutory Grounds of Challenge ................................................................. 3 
`2. 
`Statement of Non-Redundancy .................................................................. 4 
`3.  Relief Requested ........................................................................................ 5 
`C.  Mandatory Notices Under 37 C.F.R. § 42.8 ................................................. 5 
`1.  Real Party-in-Interest Under 37 C.F.R. § 42.8(b)(1) ................................. 5 
`2.  Related Matters Under 37 C.F.R. § 42.8(b)(2) .......................................... 6 
`Identification of Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`3. 
`
`7 
`4. 
`Service Information Under 37 C.F.R. § 42.8(b)(4) .................................... 7 
`III.  LEVEL OF ORDINARY SKILL IN THE ART ................................................ 8 
`IV.  OVERVIEW OF THE ’177 PATENT .............................................................. 10 
`A.  Summary of the Specification ..................................................................... 10 
`B. 
`Summary of the Claims ............................................................................... 11 
`C. 
`Summary of the Relevant Portions of the File History ............................... 11 
`D.  The ’177 patent Lacks Priority to the Filing Date of the ’379 Provisional . 13 
`V.  BACKGROUND AND OVERVIEW OF TECHNOLOGY ............................ 15 
`A.  A POSA Would Have Been Motivated to Develop Improved Intranasal
`Naloxone Formulations to Combat the Opioid Epidemic. ................................... 15 
`B.  A POSA Would Have Had the Know-How to Readily Develop an Improved
`Intranasal Naloxone Formulation. ........................................................................ 18 
`The volume of the nasal cavity naturally limits the volume of a naloxone
`1. 
`nasal spray to about 100 µL per spray. ............................................................. 19 
`2.  A POSA would have been motivated to use a 4–6 mg naloxone dose to
`achieve desirable naloxone exposure levels. .................................................... 20 
`3.  A POSA would have had adequate know-how and ability to select
`commonplace excipients to make a stable, well-tolerated intranasal naloxone
`formulation. ....................................................................................................... 21 
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`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`4.  A POSA would have been motivated to load an intranasal naloxone
`formulation into an easy-to-use single-dose, pre-primed nasal sprayer. .......... 23 
`VI.  CLAIM CONSTRUCTION UNDER 37 C.F.R. § 42.104(b)(3) ...................... 24 
`A. 
`“pre-primed” ................................................................................................ 25 
`B. 
`“patient” ....................................................................................................... 25 
`C. 
`“wherein no more than about [x]% of the droplets have a diameter less than
`10 μm,” “wherein the median droplet size is between about [x] μm and about [y]
`μm,” and “wherein approximately 90% of droplets have a diameter less than about
`100 μm.” ............................................................................................................... 26 
`“wherein the patient experiences a geometric mean naloxone Cmax” and
`D. 
`“wherein the patient experiences a plasma naloxone concentration such that the
`geometric mean of area under a plasma concentration versus time curve (AUC0-
`∞)” 26 
`E. 
`“bioavailable” .............................................................................................. 27 
`VII. SUMMARY OF PRIOR ART .......................................................................... 28 
`A.  Wang (Chinese Patent Publication CN 1575795) ....................................... 28 
`B.  Additional References ................................................................................. 29 
`C. 
`Public Accessibility of the April 12, 2012 FDA Materials ......................... 30 
`D.  Zomig Review (Nalox1024) was Publicly Accessible ............................... 31 
`VIII.THE
`CHALLENGED
`CLAIMS
`ARE
`UNPATENTABLE .................................................................................................. 32 
`A.  Ground 1: Claims 1–2 are obvious over Wang (Nalox1008) in view of HPE
`(Nalox1012) and Djupesland (Nalox1010). ......................................................... 32 
`1.  Claim 1 ..................................................................................................... 32 
`2.  Claim 2 ..................................................................................................... 36 
`B.  Ground 2: Claims 3–8 are obvious over Wang (Nalox1008) in view of HPE
`(Nalox1012), Djupesland (Nalox1010), Bahal (Nalox1014), and Kushwaha
`(Nalox1013). ......................................................................................................... 36 
`1.  Claim 3 ..................................................................................................... 37 
`2.  Claim 4 ..................................................................................................... 40 
`3.  Claim 5 ..................................................................................................... 40 
`4.  Claim 6 ..................................................................................................... 43 
`5.  Claim 7 ..................................................................................................... 43 
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`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`6.  Claim 8 ..................................................................................................... 43 
`C.  Ground 3: Claim 9 is obvious over Wang (Nalox1008) in view of HPE
`(Nalox1012),
` Djupesland (Nalox1010), Bahal (Nalox1014), Kushwaha
`(Nalox1013) and Wyse (Nalox1007). .................................................................. 44 
`D.  Ground 4: Claims 10–11 are obvious over Wang (Nalox1008) in view of
`HPE (Nalox1012), Djupesland (Nalox1010), and Wyse (Nalox1007). .............. 46 
`E.  Ground 5: Claims 12–15 and 21 are obvious over Wang (Nalox1008) in view
`of HPE (Nalox1012), Djupesland (Nalox1010), and the ’291 patent (Nalox1015).
`
`48 
`1.  Claim 12 ................................................................................................... 48 
`2.  Claim 13 ................................................................................................... 50 
`3.  Claim 14 ................................................................................................... 50 
`4.  Claim 15 ................................................................................................... 50 
`5.  Claim 21 ................................................................................................... 51 
`F.  Ground 6: Claims 16–20, 22–23, and 29 are obvious over Wang (Nalox1008)
`in view of HPE (Nalox1012), Djupesland (Nalox1010), the ’291 patent
`(Nalox1015), and Wyse (Nalox1007). ................................................................. 52 
`1.  Claim 16 ................................................................................................... 52 
`2.  Claim 17 ................................................................................................... 53 
`3.  Claim 18 ................................................................................................... 53 
`4.  Claim 19 ................................................................................................... 55 
`5.  Claim 20 ................................................................................................... 55 
`6.  Claim 22 ................................................................................................... 56 
`7.  Claim 23 ................................................................................................... 57 
`8.  Claim 29 ................................................................................................... 58 
`G.  Ground 7: Claims 24–27 are obvious over Wang (Nalox1008) in view of
`HPE (Nalox1012), Djupesland (Nalox1010), Bahal (Nalox1014), Kushwaha
`(Nalox1013), the ’291 patent (Nalox1015), and Wyse (Nalox1007). .................. 58 
`H.  Ground 8: Claim 28 is obvious over Wang (Nalox1008) in view of HPE
`(Nalox1012), Djupesland (Nalox1010), the ’291 patent (Nalox1015), and Wyse
`(Nalox1007), and optionally Wang (Nalox1008) and Pharmacologist POSA
`knowledge, or Wermeling 2013 (Nalox1016). ..................................................... 59 
`
`iii
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`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`I.  Ground 9: Claim 30 is obvious over Wang (Nalox1008) in view of HPE
`(Nalox1012), Djupesland (Nalox1010), Wyse (Nalox1007), and the ’291 patent
`(Nalox1015), in further view of Zomig Review (Nalox1024). ............................ 60 
`IX.  SECONDARY CONSIDERATIONS .............................................................. 63 
`A.  No teaching away ........................................................................................ 63 
`B.  No commercial success ............................................................................... 66 
`C.  No long-felt but unmet need or failure of others ......................................... 67 
`D.  No unexpected superior results ................................................................... 68 
`X.  CONCLUSION ................................................................................................. 69 
`
`
`
`
`
`iv
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`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`TABLE OF EXHIBITS
`
`Nalox1004
`
`Nalox1005
`
`Nalox1006
`
`Description
`
`Exhibit
`Number
`Nalox1001 U.S. Patent No. 9,561,177 (the ’177 patent)
`Nalox1002 Expert Declaration of Maureen Donovan
`Nalox1003 Expert Declaration of Günther Hochhaus
`Excerpt of File History of U.S. Patent No. 9,561,177, Aug. 22,
`2016 Office Action, Non-Final Rejection (Aug. 22, 2016 Non-
`Final Rejection)
`Excerpt of File History of U.S. Patent No. 9,561,177, Oct. 21,
`2016 Amendment and Response to Office Action (Oct. 21, 2016
`Response to Office Action)
`Excerpt of File History of U.S. Patent No. 9,561,177, Dec. 21,
`2016 Office Action, Notice of Allowance and Fees Due (Notice
`of Allowance)
`Nalox1007 U.S. Patent No. 9,192,570 (Wyse)
`Nalox1008 Chinese Patent No. 1,575,795 (Wang)
`Nalox1009 PCT International App. Pub. No. WO00/62757 (Davies)
`Djupesland, P., Nasal Drug Delivery Device: Characteristics
`and Performance in a Clinical Perspective - A Review, 3 Drug
`Deliv. & Transl. Res. 42–62 (2013) (Djupesland)
`Grassin-Delyle, S. et al., Intranasal Drug Delivery: An Efficient
`and Non-invasive Route for Systemic Administration, Focus on
`Opioids, 134 Pharm. & Ther. 366–79 (2012) (Grassin-Delyle)
`Handbook of Pharmaceutical Excipients, 56–60, 64–66, 78–81,
`220–22, 242–44, 270-72, 441–45, 517–22, 596–98 (Rowe, R. et
`al. eds., 6th ed. 2009) (HPE)
`Nalox1013 Kushwaha, S. et al., Advances in Nasal Trans-Mucosal Drug
`Delivery, (1)7 J. Applied Pharm. Sci. 21–28 (2011) (Kushwaha)
`Nalox1014 U.S. Patent No. 5,866,154 (Bahal)
`Nalox1015 U.S. Patent No. 8,198,291 (the ’291 patent)
`
`Nalox1010
`
`Nalox1011
`
`Nalox1012
`
`v
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`
`Exhibit
`Number
`
`Nalox1016
`
`Description
`Wermeling, D., A Response to the Opioid Overdose Epidemic:
`Naloxone Nasal Spray, 3 Drug Deliv. & Transl. Res. 63–74
`(2013) (Wermeling 2013)
`Nalox1017 Alabama Department of Public Health, Alabama EMS Patient
`Care Protocols (7th ed., Oct. 2013) (Alabama EMS Protocols)
`Aptar Pharma, Press Release, Aptar Pharma Provides Unit-Dose
`Nasal Spray Technology for Treatment of Opioid Overdose
`(Apr. 20, 2016) (Aptar Press Release)
`Ashton, H. et al., Best Evidence Topic Report Intranasal
`Naloxone in Suspected Opioid Overdose, 23(3) Emerg. Med. J.
`221–23 (2006) (Ashton)
`Nalox1020 Barton, E. et al., Intranasal Administration of Naloxone by
`Paramedics, 6 Prehosp. Em. Care 54–58 (Barton 2002)
`Barton, E. et al., Efficacy of Intranasal Naloxone as a Needleless
`Alternative for Treatment of Opioid Overdose in the Prehospital
`Setting, 29(3) J. Emerg. Med. 265–71 (2005) (Barton 2005)
`Nalox1022 Bitter, C. et al., Nasal Drug Delivery in Humans, 40 Curr. Probl.
`Dermatol. 20–35 (2011) (Bitter)
`Nalox1023 Boyer, E., Management of Opioid Analgesic Overdose, 367(2)
`N. Engl. J. Med. 146–55 (2012) (Boyer)
`Nalox1024 CDC, NDA No. 21-450 Clinical Pharmacology &
`Biopharmaceutics Review (2002) (Zomig Review)
`Nalox1025 Excerpt of Commonwealth of Kentucky, Kentucky Patient Care
`Protocols (Mar. 13, 2015) (Kentucky Patient Care Protocols)
`Costantino, H. et al., Intranasal Delivery: Physiochemical and
`Therapeutic Aspects, 337 Int’l. J. of Pharm. 1–24 (2007)
`(Constantino)
`Dowling, J. et al., Population Pharmacokinetics of Intravenous,
`Intramuscular, and Intranasal Naloxone in Human Volunteers,
`30(4) Ther. Drug. Monit. 490–96 (2008) (Dowling)
`FDA, Center for Drug Evaluation and Research, Guidance for
`Industry, Nasal Spray and Inhalation Solution, Suspension, and
`Spray Drug Products – Chemistry, Manufacturing, and Controls
`Documentation (2002) (2002 FDA Guidance)
`
`Nalox1026
`
`Nalox1018
`
`Nalox1019
`
`Nalox1021
`
`Nalox1027
`
`Nalox1028
`
`vi
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`
`Exhibit
`Number
`
`Nalox1029
`
`Nalox1030
`
`Nalox1031
`
`Description
`FDA, Center for Drug Evaluation and Research, Guidance for
`Industry, Bioavailability and Bioequivalence Studies for Nasal
`Aerosols and Nasal Sprays for Local Action (2003) (2003 FDA
`Guidance)
`Freise, K. et al., Naloxone Reversal of an Overdose of a Novel,
`Long-Acting Transdermal Fentanyl Solution in Laboratory
`Beagles, 35(2) J. Vet. Pharmacol. Therap. 45–51 (2012) (Freise)
`Glende, O., Development of non-injectable naloxone for pre-
`hospital reversal of opioid overdose: A Norwegian project and a
`review of international status (May 2016) (unpublished M.A.
`thesis, Norwegian University of Science and Technology) (on
`file with Norwegian University of Science and Technology)
`(Glende)
`Nalox1032 Hertz, S., Naloxone for Outpatient Use: Data Required to
`Support an NDA, PowerPoint Presentation (Hertz Presentation)
`Nalox1033
`Intentionally left blank
`Kelly, A-M. et al., Randomised Trial of Intranasal Versus
`Intramuscular Naloxone in Prehospital Treatment for Suspected
`Opioid Overdose, 182(1) Med. J. Austl. 24–27 (2005) (Kelly)
`Kerr, D. et al., Intranasal Naloxone for the Treatment of
`Suspected Heroin Overdose, 103 Addiction 379–86 (2008) (Kerr
`2008)
`Kerr, D. et al., Randomized Controlled Trial Comparing the
`Effectiveness & Safety of Intranasal & Intramuscular Naloxone
`for the Treatment of Suspected Heroin Overdose, 104 Addiction
`2067–74 (2009) (Kerr 2009)
`Kleiman-Wexler, R. et al., Pharmacokinetics of Naloxone-An
`Insight into the Locus of Effect on Stress-Ulceration, 251(2) J.
`Pharmacol. Exp. Ther. 435–38 (1989) (Kleiman-Wexler)
`Marple, B. et al., Safety Review of Benzalkonium Chloride Used
`as a Preservative in Intranasal Solutions: An Overview of
`Conflicting Data and Opinions, 130 Otolaryngol Head Neck
`Surg. 131–41 (2004) (Marple)
`Nalox1039 Merck Index, Isotonic Solutions, MISC-47–69 (Windholz, M. et
`al. eds., 10th ed. 1983) (Merck Index)
`
`Nalox1034
`
`Nalox1035
`
`Nalox1036
`
`Nalox1037
`
`Nalox1038
`
`vii
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`
`Exhibit
`Number
`
`Nalox1040
`
`Nalox1041
`
`Nalox1042
`
`Nalox1044
`
`Description
`Merlin, M. et al., Intranasal Naloxone Delivery is an Alternative
`to Intravenous Naloxone for Opioid Overdoses, 28 Am. J.
`Emerg. Med. 296–303 (2010) (Merlin)
`Middleton, L. et al., The Pharmacodynamic & Pharmacokinetic
`Profile of Intranasal Crushed Buprenorphine &
`Buprenorphine/Naloxone Tablets in Opioid Abusers, 106(8)
`Addiction 1460–73 (2011) (Middleton)
`Monitto, C. et al., The Optimal Dose of Prophylactic Intravenous
`Naloxone in Ameliorating Opioid-Induced Side Effects in
`Children Receiving Intravenous Patient-Controlled Analgesia
`Morphine for Moderate to Severe Pain: A Dose Finding Study,
`113(4) Anesthesia & Analgesia 834–42 (2011) (Monitto)
`Nalox1043 Pharmacodynamic Agents, in Foye’s Principles of Medicinal
`Chemistry, 670 (Lemke, T. et al. eds., 6th ed. 2008) (Lemke)
`Physicians’ Desk Reference, NARCAN [Naloxone Hydrochloride
`Injection, USP], IMITREX Nasal Spray [Sumatriptan], 1300–02,
`1546–50 (57th ed., 2003) (PDR 2003)
`Nalox1045 Physicians’ Desk Reference, ZOMIG Nasal Spray
`[Zolmitriptan], 768–78 (64th ed., 2010) (PDR 2010)
`Robertson, T. et al., Intranasal Versus Intravenous Naloxone for
`Prehospital Narcotic Overdose, Abstract, 12(5)(1) Acad. Emerg.
`Med. 166–67 (2005) (Robertson 2005)
`Robertson, T. et al., Intranasal Naloxone is a Viable Alternative
`to Intravenous Naloxone for Prehospital Narcotic Overdose, 13
`Prehosp. Emerg. Care 512–15 (2009) (Robertson 2009)
`Role of Naloxone in Opioid Overdose Fatality Prevention;
`Public Workshop; Request for Comments, 76 Fed. Reg. 71,348
`(Nov. 17, 2011) (Role of Naloxone Fed. Reg. Notice)
`Nalox1049 Role of Naloxone in Opioid Overdose Fatality Prevention FDA
`Meeting Transcript (Apr. 12, 2012) (2012 FDA Meeting)
`Rosanske, T., Morphine, in Chemical Stability of
`Pharmaceuticals: A Handbook for Pharmacists, 604–11
`(Connors, K. et al. eds., 2d ed. 1986) (Rosanske)
`Sabzghabaee, A. et al., Naloxone Therapy in Opioid Overdose
`Patients: Intranasal or Intravenous? A Randomized Clinical
`Trial, 10(2) Arch. Med. Sci. 309–14 (2014) (Sabzghabaee)
`
`Nalox1046
`
`Nalox1047
`
`Nalox1048
`
`Nalox1050
`
`Nalox1051
`
`viii
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`
`Description
`
`Exhibit
`Number
`Nalox1052
`
`Nalox1053
`
`Nalox1059
`
`Nalox1060
`
`Intentionally left blank
`Trows, S. et al., Analytical Challenges and Regulatory
`Requirements for Nasal Drug Products in Europe and the U.S., 6
`Pharm. 195–219 (2014) (Trows)
`Nalox1054 United States Pharmacopeia and National Formulary (USP 36-
`NF 31) Vol 1., 54–55, 930–33 (2013) (USP)
`Nalox1055 U.S. Patent Appl. No. 61/918,802 (the ’802 Appl.)
`Nalox1056 U.S. Patent No. 5,307,953 (’953 patent)
`Nalox1057 U.S. Patent No. 5,813,570 (’570 patent)
`Nalox1058 U.S. Provisional Patent Appl. No. 61/953,379 (the ’379
`provisional)
`Wermeling, D., Opioid Harm Reduction Strategies: Focus on
`Expanded Access to Intranasal Naloxone, 30(7)
`Pharmacotherapy 627–31 (2010) (Wermeling 2010)
`Loimer, N. et al, Nasal Administration of Naloxone is as
`Effective as the Intravenous Route in Opiate Addicts, 29(6) Int’l
`J. of Addictions 819–27 (1994) (Loimer)
`Doe-Simkins, M. et al., Saved by the Nose: Bystander-
`Administered Intranasal Naloxone Hydrochloride for Opioid
`Overdose, 99(5) Am. J. Pub. Health 788–91 (2009)
`McDermott, C. & Collins, N., Prehospital Medication
`Administration: A Randomised Study Comparing Intranasal and
`Intravenous Routes, Em. Med. Int’l. 1–5 (2012)
`Nalox1063
`Intentionally left blank.
`Nalox1064 Authenticating Affidavit of Christopher Butler (“Butler
`Affidavit”)
`Nalox1065 Authenticating Affidavits of Rachel J. Watters
`Nalox1066 Authenticating Affidavit of Pamela Lipscomb
`
`Nalox1061
`
`Nalox1062
`
`ix
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`INTRODUCTION
`
`I.
`
`Nalox-1 Pharmaceuticals, LLC (“Petitioner”) respectfully requests inter
`
`partes Review (“IPR”) of claims 1–30 (the “Challenged Claims”) of U.S. Patent No.
`
`9,561,177 (“the ’177 patent”), purportedly owned by Adapt Pharma Limited and
`
`Opiant Pharmaceuticals, Inc. (“Patent Owners”). For the reasons adrressed below,
`
`the Challenged Claims should be found unpatentable and canceled.
`
`The ‘177 patent is listed in the FDA’s Approved Drug Products with
`
`Therapeutic Equivalence Evaluations (a.k.a. “The Orange Book”) as covering
`
`intranasal naloxone sold under the Narcan® name. Naloxone rapidly reverses opioid
`
`overdose -- it is an opioid antagonist and acts to restore normal respiration to a person
`
`whose breathing is impaired from opioid overdose. Naloxone has been available
`
`since 1971 as an injection, and its intranasal administration has been known in the
`
`community since at least 1994 as a safe and effective opiate overdose treatment.
`
`Loimer (Nalox1060) at 819. Narcan® is currently the only FDA-approved single-
`
`use nasal spray indicated for the emergency treatment of known or suspected opioid
`
`overdose. Because of the Patent Owners’ listing of patents in The Orange Book,
`
`there are currently no generic versions of intranasal Narcan® on the market. Patent
`
`Owners’ disingenuous use and abuse of the patent system here is contrary to the
`
`Constitution’s requirement to “promote the progress of science and useful arts” by
`
`1
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`wrongfully monopolizing access to life-saving medicine until 2035, based on
`
`generations-old science and the most obvious applications in this art.
`
`The United States is in the throes of an opioid epidemic. According to the
`
`Centers for Disease Control and Prevention, on average, 130 Americans die each
`
`day from an opioid overdose, and in 2017, the number of overdose deaths involving
`
`opioids was six times higher than in 1999. There is a critical and urgent need in
`
`America for intranasal naloxone products intended for community use and which
`
`can be deployed in life-threatening circumstances -- often by people who are not
`
`medically trained. America cannot afford to wait another day for affordable, safe
`
`and effective intranasal naloxone. The ’177 patent is a barrier wrongfully and
`
`shamefully preventing broader accessibility to this critically needed naloxone
`
`medication. Removal of the ’177 patent (and its relatives) as a barrier will save
`
`American lives by facilitating rapid and expanded access to life-saving naloxone.
`
`II.
`
`IPR REQUIREMENTS UNDER 37 C.F.R. § 42.104
`A. Grounds for Standing Under 37 C.F.R. § 42.104(a)
`
`Petitioner certifies that the ’177 patent is available for IPR and that Petitioner
`
`is not barred or estopped from requesting an IPR challenging the claims on the
`
`grounds identified herein.
`
`2
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`Identification of Challenge Under 37 C.F.R. § 42.104(b)
`
`B.
`
`Petitioner requests that the Patent Trial and Appeal Board (“Board”)
`
`invalidate the Challenged Claims of the ’177 patent for the reasons identified below.
`
`1.
`
`Statutory Grounds of Challenge
`
`Petitioner challenges claims 1–30 of the ’177 patent and requests that each
`
`claim be cancelled based on the following grounds, as supported by the declarations
`
`of Dr. Maureen Donovan (Nalox1002) and Dr. Günther Hochhaus (Nalox1003):
`
`Ground Claims
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`1–2
`
`3–8
`
`9
`
`10–11
`
`12–15, 21
`
`16–20,
`22–23, 29
`
`24–27
`
`§103
`
`§ 103
`
`References
`Basis
`§103 Wang in view of HPE and Djupesland
`Wang in view of HPE, Djupesland, Bahal, and
`Kushwaha
`Wang in view of HPE, Djupesland, Bahal,
`Kushwaha, and Wyse
`§103 Wang in view of HPE, Djupesland, and Wyse
`Wang in view of HPE, Djupesland, and
`the ’291 patent
`Wang in view of HPE, Djupesland, the ’291
`patent, and Wyse
`Wang in view of HPE, Djupesland, Bahal,
`Kushwaha, the ’291 patent, and Wyse
`
`§103
`
`§103
`
`§103
`
`3
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`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`
`Ground Claims
`
`Basis
`
`8
`
`9
`
`28
`
`§103
`
`30
`
`§103
`
`References
`Wang in view of HPE, Djupesland, the ’291
`patent, and Wyse, and optionally Wang and
`Pharmacologist POSA knowledge, or
`Wermeling 2013
`Wang in view of HPE, Djupesland, the ’291
`patent, Wyse, and Zomig Review
`
`Petitioner requests that the Board cancel the Challenged Claims as
`
`unpatentable under these Grounds.
`
`2.
`
`Statement of Non-Redundancy
`
`This is Petitioner’s first challenge of the ’177 patent before the Board.
`
`Petitioner submits the grounds in this Petition are not redundant nor duplicative of
`
`the grounds previously presented to the Office in the ’177 patent. In particular, Wang
`
`was never fully and substantively considered during the prosecution of the ’177
`
`patent. While cited, initialed in an Information Disclosure Statement (“IDS”), and
`
`listed on the face of the ’177 patent, a true and accurate translation of Wang was not
`
`before the Office. Instead, Applicants provided only a machine translation from
`
`Google Patents. Wang was not relied on in making any substantive rejections in
`
`the ’177 patent. In fact, the Office never rejected any claim during the prosecution
`
`of the ’177 patent.
`
`4
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`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`In situations where prior art, relied on in an IPR petition, was cited by Patent
`
`Owners in an IDS and nominally initialed by the Examiner, the Board has rejected
`
`Patent Owners’ arguments in denying institution by declining to invoke 35 U.S.C. §
`
`325(d). See, e.g., Fox Factory, Inc., v. SRAM, LLC, IPR2017-00472, Paper 10 at 8–
`
`9 (PTAB April 21, 2017); Digital Check Corp. d/b/a ST Imaging v. e-Imagedata
`
`Corp., IPR2017-00178, Paper 6 at 12–13 (PTAB April 25, 2017); Limelight
`
`Networks, Inc. v. Mass. Inst. of Tech., IPR2017-00249, Paper 9 at 7 (PTAB May 18,
`
`2017); Microsoft Corp. v. Parallel Networks Licensing, LLC, IPR2015-00486, Paper
`
`10 at 15 (PTAB July 15, 2015). Therefore, recognizing that the Board has discretion,
`
`Petitioner respectfully requests the Board not invoke 35 U.S.C. § 325(d), because
`
`Wang was merely listed in an IDS, provided as a machine-translated English version,
`
`and initialed by the Examiner, without substantive discussion of the reference.
`
`3.
`
`Relief Requested
`
`
`
`Petitioner requests the Board cancel the Challenged Claims as being
`
`unpatentable under AIA 35 U.S.C. § 103(a).
`
`C. Mandatory Notices Under 37 C.F.R. § 42.8
`1.
`Real Party-in-Interest Under 37 C.F.R. § 42.8(b)(1)
`
`Pursuant to 37 C.F.R. § 42.8(b)(1), Petitioner certifies that Nalox-1
`
`Pharmaceuticals, LLC, BCIM Partners III, LP, BCIM General Partner III, LP,
`
`Burford Capital Ireland DAC, BCIM PIII Holdings, LLC, Burford Capital
`
`5
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`Investment Management LLC, Burford Capital Holdings (UK) Limited, and Burford
`
`Capital Limited are the real parties in interest (collectively, “RPI”). Nalox-1
`
`Pharmaceuticals, LLC, a Delaware limited liability company, is 100% owned by
`
`BCIM Partners III, LP, a Delaware limited partnership. BCIM General Partner III,
`
`LLC, a Delaware limited liability company, is the general partner of BCIM Partners
`
`III, LP, and Burford Capital Investment Management LLC is the investment
`
`manager to BCIM Partners III, LP. No other person has authority to direct or control
`
`(i) the timing of, filing of, content of, or any decisions or other activities relating to
`
`this Petition or (ii) any timing, future filings, content of, or any decisions or other
`
`activities relating to the future proceedings related to this Petition. All of the costs
`
`associated with this Petition are expected to be borne by Nalox-1 Pharmaceuticals,
`
`LLC, BCIM Partners III, LP, BCIM General Partner III, LP, Burford Capital
`
`Investment Management LLC and Burford Capital Holdings (UK) Limited.
`
`2.
`
`Related Matters Under 37 C.F.R. § 42.8(b)(2)
`
`Petitioner identifies the following judicial or administrative matters that
`
`would affect, or be affected by, a decision in this proceeding. Patent Owners have
`
`asserted the ’177 patent in the following United States District Court civil actions:
`
`2-18-cv-15287 (D.N.J.), 2-16-cv-07721 (D.N.J.) (consolidated). Petitioner is not a
`
`party to these actions. Petitioner is concurrently filing inter partes review petitions
`
`on related U.S. Patent Nos. 9,211,253; 9,468,747; 9,629,965; and 9,775,838, which
`
`6
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`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`are listed in the FDA’s Orange Book as covering Narcan® nasal spray (naloxone).
`
`3.
`
`Identification of Lead and Back-Up Counsel Under 37 C.F.R.
`§ 42.8(b)(3)
`
`Petitioner provides the following designation of counsel:
`
`Lead Counsel
`
`Back-Up Counsel
`
`
`Dr. Yelee Y. Kim (Reg. No. 60,088)
`Telephone: 202.857.6147
`Fax: 202.857.6395
`Yelee.Kim@arentfox.com
`
`
`
`
`
`
`Janine A. Carlan (Reg. No. 42,387)
`Telephone: 202.715.8506
`Fax: 202.857.6395
`Janine.Carlan@arentfox.com
`
`Richard Berman (Reg. No. 39,107)
`Telephone: 202.857.6232
`Fax: 202.857.6395
`Richard.Berman@arentfox.com
`
`Bradford Frese (Reg. No. 69,772)
`Telephone: 202.857.6496
`Fax: 202.857.6395
`Bradford.Frese@arentfox.com
`
`Christopher Yaen (Reg. No. 66,563)
`Telephone: 202.350.3760
`Fax: 202.857.6395
`Christopher.Yaen@arentfox.com
`
`4.
`
`Service Information Under 37 C.F.R. § 42.8(b)(4)
`
`
`
`Please address all correspondence to above-identified counsel at:
`
`ARENT FOX LLP
`1717 K Street NW
`Washington D.C. 20006
`Petitioner consents to electronic service.
`
`7
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`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`III. LEVEL OF ORDINARY SKILL IN THE ART
`
`As it relates to the ’177 patent, a person of ordinary skill in the art (“POSA”)
`
`would comprise a team of individuals having experience in drug development, and
`
`specifically the development of solution-based dosage forms such as intranasal
`
`dosage forms. Donovan (Nalox1002), ¶38; see also Hochhaus (Nalox1003), ¶22.
`
`This team would include at least one formulator with experience in preformulation
`
`testing for and selection of excipients for a solution-based dosage form (including
`
`intranasal dosage forms) to achieve a target pharmaceutical profile (hereafter
`
`“Formulator POSA”). Donovan (Nalox1002), ¶38. The Formulator POSA would
`
`likely have a Ph.D. in pharmacy, pharmaceutics, pharmaceutical chemistry, or a
`
`similar field involving pharmaceutical formulations, and would have several years
`
`of experience in pharmaceutical formulation development, including development
`
`of solution-based dosage forms, including intranasal dosage forms. Id. Alternatively,
`
`such a Formulator POSA would have a Bachelor’s or Master’s degree in pharmacy,
`
`pharmaceutical chemistry, or a similar field involving pharmaceutical formulations,
`
`and would have many years of experience developing and testing pharmaceutical
`
`formulations. Id. The Formulator POSA would also have an understanding of the
`
`importance, use, and component elements of certain commercially-available
`
`delivery systems for dosage forms, including inhalers, metered-dose nasal sprayers,
`
`8
`
`

`

`IPR2019-00692
`Petition for Inter Partes Review of U.S. Patent No. 9,561,177
`and single-dose nasal sprayers, as well as the importance of the properties of the
`
`spray from such devices (including droplet size and spray plume geometry). Id.
`
`The POSA team would also include drug development professionals with
`
`clinical, clinical pharmacology, and regulatory expertise relevant to the design and
`
`performance of a drug development strategy for solution-based dosage forms such
`
`as intranasal dosage forms, including testing and/or evaluating the fate of the drug
`
`in
`
`the body
`
`(i.e., pharmacokinetics,
`
`including
`
`the physiological and
`
`biopharmaceutical aspects of nasal drug absorption), testing and/or evaluating issues
`
`of safety and efficacy, and evaluating the regulatory requirements of a new dosage
`
`form. Hochhaus (Nalox1003), ¶22. Within the team, the clinical pharmacologist
`
`generally