`
`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.
`OPIANT PHARMACEUTICALS, INC.,
`Patent Owner
`
`
`
`IPR2019-00694
`U.S. Patent No. 9,629,965
` ____________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,629,965
`AS OBVIOUS OVER WYSE
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`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) ............................ 2 
`1. 
`Statutory Grounds of Challenge ................................................................. 3 
`2. 
`Statement of Non-Redundancy .................................................................. 3 
`3.  Relief Requested ........................................................................................ 6 
`C.  Mandatory Notices Under 37 C.F.R. § 42.8 ................................................. 7 
`1.  Real Party-in-Interest Pursuant to 37 C.F.R. § 42.8(b)(1) ......................... 7 
`2.  Related Matters Under 37 C.F.R. § 42.8(b)(2) .......................................... 7 
`Identification of Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3)
`3. 
`
`8 
`4. 
`Service Information under 37 C.F.R. § 42.8(b)(4) .................................... 9 
`III.  LEVEL OF ORDINARY SKILL IN THE ART .............................................. 9 
`IV.  OVERVIEW OF THE ’965 PATENT ........................................................... 11 
`A.  Summary of the Specification ..................................................................... 11 
`B. 
`Summary of the Claims ............................................................................... 12 
`C. 
`Summary of Relevant Portions of the File History ..................................... 12 
`D.  The ’965 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 
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`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 
`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” ................................................................................................ 24 
`B. 
`“patient” ....................................................................................................... 25 
`C. 
`“delivery time” ............................................................................................ 25 
`D. 
`“90% confidence interval for dose delivered per actuation is ± about 2.0%”
`and “95% confidence interval for dose delivered per actuation is ± about
`2.5%” .................................................................................................................... 25 
`“yields, when intranasally administered to a patient, a mean naloxone plasma
`E. 
`concentration” and “yields a mean naloxone plasma concentration… in said
`patient” .................................................................................................................. 26 
`VII.  SUMMARY OF THE PRIOR ART ............................................................... 27 
`A.  Wyse (U.S. Patent No. 9,192,570) .............................................................. 27 
`B.  Additional References ................................................................................. 28 
`C. 
`Public Accessibility of the April 12, 2012 FDA Materials ......................... 29 
`VIII.  THE CHALLENGED CLAIMS ARE UNPATENTABLE ....................... 30 
`A.  Ground 1: Claims 1-22, 25-26, and 29-30 are obvious over Wyse
`(Nalox1007) in view of HPE (Nalox1012) .......................................................... 31 
`1.  Claim 1 ..................................................................................................... 31 
`2.  Claim 2 ..................................................................................................... 36 
`3.  Claim 9 ..................................................................................................... 37 
`4.  Claims 10–12 ............................................................................................ 37 
`5.  Claims 3–5 and 14–16 .............................................................................. 38 
`6.  Claims 6–8 and 13 .................................................................................... 40 
`7.  Claim 17 ................................................................................................... 41 
`8.  Claims 18 and 19 ...................................................................................... 42 
`9.  Claim 20 ................................................................................................... 42 
`10.  Claims 21, 22, and 26 ............................................................................... 44 
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`11.  Claim 25 ................................................................................................... 45 
`12.  Claims 29 and 30 ...................................................................................... 46 
`B.  Ground 2: Claims 23–24 are obvious over Wyse (Nalox1007) in view of
`Djupesland (Nalox1010) and HPE (Nalox1012). ................................................ 47 
`1.  Claim 23 ................................................................................................... 47 
`2.  Claim 24 ................................................................................................... 48 
`C.  Ground 3: Claims 27–28 are obvious over Wyse (Nalox1007) in view of
`HPE (Nalox1012), and the ’291 patent (Nalox1015). .......................................... 49 
`IX.  SECONDARY CONSIDERATIONS ............................................................ 50 
`A.  No teaching away ........................................................................................ 51 
`B.  No commercial success ............................................................................... 54 
`C.  No long-felt but unmet need or failure of others ......................................... 55 
`D.  No unexpected superior results ................................................................... 56 
`X.  CONCLUSION ................................................................................................. 56 
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`TABLE OF EXHIBITS
`
`Description
`
`Exhibit
`Number
`Nalox1001 U.S. Patent No. 9,629,965 (the ’965 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)
`
`Nalox1004
`
`Nalox1005
`
`Nalox1006
`
`Nalox1010
`
`Nalox1011
`
`Nalox1012
`
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`Nalox1016
`
`Nalox1018
`
`Nalox1019
`
`Nalox1021
`
`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)
`21-450 Clinical
`Pharmacology &
`Nalox1024 CDC, NDA No.
`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)
`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)
`
`Nalox1026
`
`Nalox1027
`
`Nalox1028
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`Nalox1029
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`
`Nalox1030
`
`Nalox1031
`
`Nalox1034
`
`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)
`Nalox1035 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)
`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 &
`in Opioid Abusers, 106(8)
`Buprenorphine/Naloxone Tablets
`Addiction 1460–73 (2011) (Middleton)
`Nalox1042 Monitto, C. et al., The Optimal Dose of Prophylactic Intravenous
`Naloxone in Ameliorating Opioid-Induced Side Effects in Children
`
`Nalox1036
`
`Nalox1037
`
`Nalox1038
`
`Nalox1040
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`Nalox1041
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`
`Nalox1044
`
`Nalox1046
`
`Nalox1047
`
`Nalox1048
`
`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)
`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)
`
`Nalox1050
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`Nalox1051
`
`Nalox1052
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`Nalox1053
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`Nalox1059
`
`Nalox1060
`
`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)
`Excerpt of File History of U.S. Patent No. 9,629,965, March 17,
`2017 Office Action, Notice of Allowance and Fees Due (’965
`Notice of Allowance)
`Nalox1064 Authenticating Affidavit of Christopher Butler (“Butler Affidavit”)
`Nalox1065 Authenticating Affidavits of Rachel J. Watters
`Nalox1066 Authenticating Affidavit of Pamela Lipscomb
`
`Nalox1061
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`Nalox1062
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`Nalox1063
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`INTRODUCTION
`Nalox-1 Pharmaceuticals, LLC (“Petitioner”) respectfully petitions for inter
`
`I.
`
`partes Review (“IPR”) of claims 1–30 (the “Challenged Claims”) of U.S. Patent No.
`
`9,629,965 (“the ’965 patent”), purportedly owned by Opiant Pharmaceuticals, Inc.
`
`(“Patent Owner”). Nalox1001. For the reasons addressed below, the Challenged
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`Claims should be found unpatentable and canceled.
`
`The ’965 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 Owner’s listing of patents in The Orange Book,
`
`there are currently no generic versions of intranasal Narcan® on the market. Patent
`
`Owner’s 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
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`wrongfully monopolizing access to life-saving medicine until 2035, based on
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`1
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`

`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`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 ’965 patent is a barrier wrongfully and
`
`shamefully preventing broader accessibility to this critically needed naloxone
`
`medication. Removal of the ’965 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 ’965 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.
`
`B.
`Identification of Challenge Under 37 C.F.R. § 42.104(b)
`Petitioner requests that the Patent Trial and Appeal Board (“Board”)
`
`
`
`invalidate the challenged claims of the ’965 patent for the reasons identified below.
`
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`Petition for Inter Partes Review of US. Patent No. 9,629,965
`
`IPR2019-00694
`
`1.
`
`Statutory Grounds of Challenge
`
`Petitioner challenges claims 1—30 of the ’965 patent and requests that each
`
`claim be cancelled based on the following grounds, which are supported by the
`
`declarations of Dr. Maureen Donovan (Nalox1002) and Dr. Gunther Hochhaus
`
`(Nalox1003):
`
`Ground
`
`Claims
`
`
`
`
`
`
`
`29—30
`
`
`1—22, 25—26,
`
`
`
`§ 103(a) Wyse in view of HPE
`
`
`
`
`
`2
`§ 103(a) Wyse in view of Djupesland and HPE
`Wyse in view of HPE and the ’291
`
`27—28
`§ 103(a)
`
`
`
`
`
`
`
`patent
`
` 3
`
`23—24
`
`2.
`
`Statement of Non—Redundancy
`
`This is Petitioner’s first challenge relating to the ’965 patent before the Board.
`
`Petitioner submits that the grounds provided in this petition are not redundant nor
`
`duplicative of the grounds previously presented to the Office during the examination
`
`of the ’965 patent. In addition, although Wyse—the primary reference cited in this
`
`Petition—was cited in the Reasons for Allowance of the ’965 patent and used in a
`
`rejection of certain claims of a related patent (US. Patent No. 9,561,177, or the
`
`177
`
`patent”), this Petition submits new evidence and arguments that are non-cumulative
`
`to those considered by the Office.
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`

`

`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`Petitioner respectfully submits that new evidence and arguments provided
`
`here are not “the same or substantially the same” previously considered by the Office
`
`during prosecution of the ’965 and ’177 patents. When evaluating whether
`
`previously presented prior art or arguments are “the same or substantially the same,”
`
`the Board examines several non-exclusive factors to guide its decision under 35
`
`U.S.C. § 325(d). The non-exclusive factors, also referred to as the “Becton-
`
`Dickinson factors” are:
`
`(a) the similarities and material differences between the
`asserted art and the prior art involved during examination;
`(b) the cumulative nature of the asserted art and the prior
`art evaluated during examination;
`(c) the extent to which the asserted art was evaluated
`during examination, including whether the prior art was
`the basis for rejection;
`(d) the extent of the overlap between the arguments made
`during examination and the manner in which Petitioner
`relies on the prior art or Patent Owner distinguishes the
`prior art;
`(e) whether Petitioner has pointed out sufficiently how the
`Examiner erred in its evaluation of the asserted prior art;
`and
`(f) the extent to which additional evidence and facts
`presented in the Petition warrant reconsideration of the
`prior art or arguments.
`Becton, Dickinson & Co. v. B. Braun Melsungen AG, IPR2017-01586, Paper 8 at
`
`17–18 (P.T.A.B. Dec. 15, 2017).
`
`
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`4
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`Becton Dickinson factors (a), (b), and (c), which analyze the cumulative or
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`overlapping nature of the proceedings, support institution here. Wyse was never
`
`relied on in any substantive rejection by the Examiner during prosecution of the ’965
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`patent, but instead cited in an IDS and addressed in the Examiner’s Reasons for
`
`Allowance as being the closest prior art. ’965 Notice of Allowance (Nalox1063).
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`Further, while Wyse (in combination with a secondary reference, Djupesland1) was
`
`cited by the Examiner in a rejection of certain claims during the prosecution of the
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`related ’177 patent, which issued prior in time to the ’965 patent, HPE was not a
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`reference of record during prosecution of either the ’177 or ’965 patents.2 Thus, the
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`Petition’s combination of Wyse and HPE, which together, or in combination with
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`certain additional references, renders obvious the challenged claims, was never
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`evaluated during examination. This Petition thus presents non-cumulative grounds
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`and arguments not presented during prosecution.
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`Remaining Becton Dickinson factors (d), (e), and (f) also strongly support
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`institution. Those factors analyze whether the Petitioner has sufficiently made a case
`
`for reconsidering the prior art. Where the Petition “sufficiently shows that the
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`Examiner’s decision not to reject the claims” was “based on an erroneous finding by
`
`
`1 The Djupesland reference cited during prosecution is the same reference included
`in Ground 2 of this Petition.
`2 HPE is not cumulative to any reference cited during the prosecution of the ’177
`or ’965 patents.
`
`
`
`5
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`the Examiner,” particularly regarding the prior art’s disclosure, institution is
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`warranted. See Black & Decker (U.S.) Inc. v. Christy, Inc., IPR2015-00468, Paper
`
`13 at 13 (P.T.A.B. June 24, 2015). Further, where the Petition is supported by
`
`evidence that was not available in prosecution that further elucidates what a POSA
`
`would have understood from a reference’s disclosure, Becton-Dickinson factors (d)–
`
`(f) support institution. See Parsons XTreme Golf v. Taylor Made Golf Co., Paper
`
`No. 7, PGR2018-00074, 43 (P.T.A.B. Jan. 24, 2019). In prosecution of both the ’177
`
`and ’965 patents, the Examiner erred in finding that Wyse teaches away from the
`
`use of one of the claimed ingredients, benzalkonium chloride (BAC). See (Notice
`
`of Allowance (Nalox1006), page 8; Nalox1063). As Petitioner shows in this Petition,
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`and as supported by the Declarations of Dr. Donovan and Dr. Hochhaus, HPE would
`
`have motivated a POSA to use BAC, and a POSA would not have considered Wyse
`
`to teach away from its use in the claimed naloxone solution. Thus, this Petition
`
`presents new evidence and testimony not previously available to the Examiner
`
`during prosecution. In view of the above, Petitioner respectfully requests the Board
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`decline to use its discretion under 35 U.S.C. § 325(d).
`
`3.
`Relief Requested
`Petitioner requests the Board cancel the Challenged Claims as being
`
`
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`unpatentable under AIA 35 U.S.C. § 103(a).
`
`
`
`6
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`C. Mandatory Notices Under 37 C.F.R. § 42.8
`1.
`Real Party-in-Interest Pursuant to 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
`
`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
`
`
`
`7
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`

`Petition for Inter Partes Review of US. Patent No. 9,629,965
`
`IPR2019-00694
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`would affect, or be affected by, a decision in this proceeding. Patent Owner has
`
`asserted the ’965 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 US. Patent Nos. 9,211,253, 9,468,747, 9,561,177, and 9,775,838, which
`
`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.
`:5 423mm
`
`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
`
`Janine A. Carlan (Reg- No. 42,387)
`Telephone: 202-715.8506
`Fax: 202.857.6395
`
`Yelee.Kim@arentfox.com
`
`Janine.Carlan@arentfox.com
`
`Christopher.Yaen@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
`
`

`

`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
`
`
`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.
`
`
`
`
`
`III. LEVEL OF ORDINARY SKILL IN THE ART
`As it relates to the ’965 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), ¶26; 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), ¶¶26–27. 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.
`
`Donovan (Nalox1002), ¶26 Alternatively, such a Formulator POSA would have a
`
`Bachelor’s or Master’s degree in pharmacy, pharmaceutical chemistry, or a similar
`
`
`
`9
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`IPR2019-00694
`Petition for Inter Partes Review of U.S. Patent No. 9,629,965
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`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,
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`including inhalers, metered-dose nasal sprayers, 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
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`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 serves as a link between formulators and clinicians, and helps integrate
`
`f