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
`____________
`
`IPR2019-00687
`U.S. Patent No. 9,211,253
` ____________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,211,253
`AS OBVIOUS OVER DAVIES
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`
`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 Pursuant to 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. 
`
`6 
`4. 
`Service Information Under 37 C.F.R. § 42.8(b)(4) .................................... 7 
`III.  LEVEL OF ORDINARY SKILL IN THE ART .............................................. 7 
`IV.  OVERVIEW OF THE ’253 PATENT ............................................................. 9 
`A.  Summary of the Specification ....................................................................... 9 
`B. 
`Summary of the Claims ............................................................................... 10 
`C. 
`Summary of Relevant Portions of the File History ..................................... 10 
`D.  The ’253 Patent Lacks Priority to the Filing Date of the ’379 Provisional.
`
`11 
`V.  BACKGROUND AND OVERVIEW OF TECHNOLOGY ............................ 13 
`A.  A POSA Would Have Been Motivated to Develop Improved Intranasal
`Naloxone Formulations to Combat the Opioid Epidemic. ................................... 13 
`B.  A POSA Would Have Had the Know-How to Readily Develop an Improved
`Intranasal Naloxone Formulation. ........................................................................ 16 
`The volume of the nasal cavity naturally limits the volume of a naloxone
`1. 
`nasal spray to about 100 µL per spray. ............................................................. 17 
`2.  A POSA would have been motivated to use a 4-6 mg naloxone dose to
`achieve desirable naloxone exposure levels. .................................................... 18 
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`3.  A POSA would have had adequate know-how and ability to select
`commonplace excipients to make a stable, well-tolerated intranasal naloxone
`formulation. ....................................................................................................... 19 
`4.  A POSA would have been motivated to load an intranasal naloxone
`formulation into an easy-to-use single-dose, pre-primed nasal sprayer. .......... 21 
`VI.  CLAIM CONSTRUCTION UNDER 37 C.F.R. § 42.104(b)(3) ................... 22 
`A. 
`“pre-primed” ................................................................................................ 22 
`B. 
`“patient” ....................................................................................................... 23 
`C. 
`“delivery time” ............................................................................................ 23 
`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%”23 
`VII.  SUMMARY OF THE PRIOR ART ............................................................... 24 
`A.  Davies (PCT Patent Publication WO 00/62757) ......................................... 24 
`B.  Additional References ................................................................................. 25 
`C. 
`Public Accessibility of the April 12, 2012 FDA Materials ......................... 26 
`VIII.  THE CHALLENGED CLAIMS ARE UNPATENTABLE ....................... 28 
`A.  Ground 1: Claims 1–4 and 16–24 are obvious over Davies (Nalox1009),
`HPE (Nalox1012), Bahal (Nalox1014), and Kushwaha (Nalox1013). ................ 28 
`1.  Claim 1 ..................................................................................................... 28 
`2.  Claim 2 ..................................................................................................... 36 
`3.  Claim 3 ..................................................................................................... 37 
`4.  Claim 4 ..................................................................................................... 40 
`5.  Claim 16 ................................................................................................... 41 
`6.  Claims 17 and 18 ...................................................................................... 41 
`7.  Claim 19 ................................................................................................... 42 
`8.  Claims 20–23 ............................................................................................ 43 
`9.  Claim 24 ................................................................................................... 44 
`B.  Ground 2: Claims 28 and 29 are obvious over Davies (Nalox1009) in view
`of HPE (Nalox1012), Bahal (Nalox1014), Kushwaha (Nalox1013), and Wyse
`(Nalox1007). ......................................................................................................... 45 
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`C.  Ground 3: Claims 5–7 and 10–14 are obvious over Davies (Nalox1009) in
`view of HPE (Nalox1012), Bahal (Nalox1014), Kushwaha (Nalox1013), and
`Djupesland (Nalox1010). ..................................................................................... 46 
`1.  Claim 5 ..................................................................................................... 47 
`2.  Claim 6 ..................................................................................................... 48 
`3.  Claim 7 ..................................................................................................... 49 
`4.  Claims 10 and 11 ...................................................................................... 49 
`5.  Claims 12–14 ............................................................................................ 50 
`D.  Ground 4: Claims 8 and 9 are obvious over Davies (Nalox1009), HPE
`(Nalox1012), Bahal
`(Nalox1014), Kushwaha
`(Nalox1013), Djupesland
`(Nalox1010), and the ’291 Patent (Nalox1015). .................................................. 51 
`E.  Ground 5: Claims 25–27 are obvious over Davies (Nalox1009), HPE
`(Nalox1012), Bahal
`(Nalox1014), Kushwaha
`(Nalox1013), Djupesland
`(Nalox1010), and Wyse (Nalox1007). ................................................................. 53 
`F.  Ground 6: Claim 15 is obvious over Davies (Nalox1009) in view of
`Djupesland (Nalox1010), HPE (Nalox1012), Bahal (Nalox1014), Kushwaha
`(Nalox1013) and Wyse (Nalox1007) or Wermeling 2013 (Nalox1016) or Wang
`(Nalox1008) and Pharmacologist POSA Knowledge. ......................................... 55 
`IX.  SECONDARY CONSIDERATIONS ............................................................ 58 
`A.  No teaching away ........................................................................................ 58 
`B.  No commercial success ............................................................................... 61 
`C.  No long-felt but unmet need or failure of others ......................................... 62 
`D.  No unexpected superior results ................................................................... 63 
`X.  CONCLUSION ................................................................................................. 64 
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`TABLE OF EXHIBITS
`
`Description
`Exhibit No.
`Nalox1001 U.S. Patent No. 9,211,253 (the ’253 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
`
`iv
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`
`Nalox1016
`
`Nalox1022
`
`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)
`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)
`Bitter, C. et al., Nasal Drug Delivery in Humans, 40 Curr. Probl.
`Dermatol. 20–35 (2011) (Bitter)
`Boyer, E., Management of Opioid Analgesic Overdose, 367(2) N.
`Engl. J. Med. 146–55 (2012) (Boyer)
`CDC, NDA No.
`21-450 Clinical Pharmacology &
`Biopharmaceutics Review (2002) (Zomig Review)
`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)
`
`Nalox1018
`
`Nalox1019
`
`Nalox1020
`
`Nalox1021
`
`Nalox1023
`
`Nalox1024
`
`Nalox1025
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`Nalox1026
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`Nalox1027
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`Nalox1028
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`Nalox1029
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`
`Nalox1030
`
`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)
`
`Nalox1031
`
`Nalox1034
`
`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 &
`Buprenorphine/Naloxone Tablets in Opioid Abusers, 106(8)
`Addiction 1460–73 (2011) (Middleton)
`
`Nalox1036
`
`Nalox1037
`
`Nalox1038
`
`Nalox1040
`
`Nalox1041
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`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`
`Nalox1042
`
`Nalox1043
`
`Nalox1044
`
`Nalox1045
`
`Nalox1047
`
`Nalox1046
`
`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)
`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)
`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)
`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)
`
`Nalox1048
`
`Nalox1049
`
`Nalox1050
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`Nalox1051
`
`Nalox1052
`
`Nalox1053
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`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)
`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
`
`Nalox1062
`
`Nalox1061
`
`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`INTRODUCTION
`Nalox-1 Pharmaceuticals, LLC (“Petitioner”) respectfully petitions for inter
`
`I.
`
`partes Review (“IPR”) of claims 1–29 (the “Challenged Claims”) of U.S. Patent No.
`
`9,211,253 (“the ’253 patent”), purportedly owned by Opiant Pharmaceuticals, Inc.
`
`(“Patent Owner”). Nalox1001. For the reasons addressed below, the Challenged
`
`Claims should be found unpatentable and canceled.
`
`The ’253 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
`
`1
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`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 ’253 patent is a barrier wrongfully and
`
`shamefully preventing broader accessibility to this critically needed naloxone
`
`medication. Removal of the ’253 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 ’253 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.
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`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 ’253 patent for the reasons identified below.
`
`1.
`Statutory Grounds of Challenge
`Petitioner challenges claims 1–29 of the ’253 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. Günther Hochhaus
`
`(Nalox1003):
`
`Ground
`
`Claims
`
`Basis
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`1–4, 16–24
`
`§ 103(a)
`
`28–29
`
`§ 103(a)
`
`5–7, 10–14
`
`§ 103(a)
`
`8–9
`
`§ 103(a)
`
`25–27
`
`§ 103(a)
`
`15
`
`§ 103(a)
`
`References
`Davies in view of HPE, Bahal, and
`Kushwaha
`Davies in view of HPE, Bahal, Kushwaha,
`and Wyse
`Davies in view of HPE, Bahal, Kushwaha,
`and Djupesland
`Davies in view of HPE, Bahal, Kushwaha,
`Djupesland, and the ’291 patent
`Davies in view of HPE, Bahal, Kushwaha,
`Djupesland, and Wyse
`Davies in view of HPE, Bahal, Kushwaha,
`Djupesland, and Wyse or Wang +
`Pharmacologist POSA knowledge or
`Wermeling 2013
`
`3
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`2.
`Statement of Non-Redundancy
`This is Petitioner’s first challenge of the ’253 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 ’253 patent. In particular,
`
`Davies was never fully and substantively considered during the prosecution of
`
`the ’253 patent. While cited, initialed in an Information Disclosure Statement
`
`(“IDS”), and listed on the face of the ’253 patent, Davies was not relied on in making
`
`any substantive rejections in the ’253 patent. In fact, the Office never rejected any
`
`claim during the prosecution of the ’253 patent.
`
`In situations where prior art, relied on in an IPR petition, was cited by Patent
`
`Owner in an IDS and nominally initialed by the Examiner, the Board has rejected
`
`Patent Owner’s 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
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`Davies was merely listed in an IDS and initialed by the Examiner, without
`
`substantive discussion of the references by the Examiner.
`
`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 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
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`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 Owner has
`
`asserted the ’253 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. 9,468,747; 9,561,177; 9,629,965; and 9,775,838, which
`
`are listed in The 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
`
`
`Dr. Yelee Y. Kim (Reg. No. 60,088)
`Telephone: 202.857.6147
`Fax: 202.857.6395
`Yelee.Kim@arentfox.com
`
`
`
`Back-Up Counsel
`
`
`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
`
`
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`
`Lead Counsel
`
`Back-Up Counsel
`
`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.
`
`
`
`
`
`III. LEVEL OF ORDINARY SKILL IN THE ART
`As it relates to the ’253 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. The Formulator POSA would
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`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,
`
`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
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`generally serves as a link between formulators and clinicians, and helps integrate
`
`formulation and clinical aspects of drug development. Id. Such a clinical
`
`pharmacologist would routinely collaborate with others, such as formulators and
`
`clinicians, to achieve a target pharmaceutical profile. Id.
`
`A clinical pharmacologist member of the drug development team (hereinafter
`
`a “Pharmacologist POSA”) would have an advanced degree in pharmacy, clinical
`
`pharmacology, pharmaceutics, or a similar field, and would have several years of
`
`experience in drug development, including the development of solution-based
`
`dosage forms, including nasal spray dosage forms. Hochhaus (Nalox1003), ¶23 The
`
`person would also have an understanding of drug formulation/device combinations,
`
`including the selection of excipients and their relationship to drug exposure and
`
`clinical outcomes. Id.
`
`IV. OVERVIEW OF THE ’253 PATENT
`The ’253 patent, entitled “Nasal Drug Products and Methods of Their Use,”
`
`was filed March 16, 2015, and issued on December 15, 2015 from U.S. Application
`
`No. 14/659,472 (“the ’472 Application”). The ’253 patent claims priority to U.S.
`
`Provisional Application No. 61/953,379 filed on March 14, 2014.
`
`A.
`Summary of the Specification
`The ’253 patent specification is generally directed towards naloxone drug
`
`products for nasal delivery. Nalox1001 at 1:8–12. The ‘253 patent admits the
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`IPR2019-00687
`Petition for Inter Partes Review of U.S. Patent No. 9,211,253
`maturity of naloxone (CAS Reg. No. 357-08-4), in use since at least the 1970s along
`
`with an array of published reports of naloxone’s safe and effective intranasal
`
`delivery as early as at least 1994. Id. at 2:44–47; 9:41–10:3. In particular, the ’253
`
`patent discloses “a single-use, pre-primed device adapted for nasal delivery of a
`
`pharmaceutical composition to a patient by one actuation of the device into the
`
`nostril of the patient.” Id. at 21:5–8. These compositions can be used in methods of
`
`treating opioid overdose or suspected opioid overdose, as well as symptoms such as
`
`respiratory depression resulting from opioid overdose. See id. at 22:52–61.
`
`B.
`Summary of the Claims
`The ’253 patent includes a single independent claim and twenty eight
`
`dependent claims that depend directly or indirectly thereto. The claims of the ’253
`
`patent (recited in full in the Donovan (Nalox1002), ¶¶92–94 and Hochhaus
`
`(Nalox1003), ¶¶38–39 declarations) generally relate to drug products adapted for
`
`nasal delivery comprising a single-use, pre-primed device for delivering a
`
`pharmaceutical composition comprising naloxone hydrochloride or a hydrate
`
`thereof, along with certain inactive ingredients. Nalox1001 at 1:8–12; Hochhaus
`
`(Nalox1003), ¶6; see