`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
`____________
`
`IPR2019-00697
`U.S. Patent No. 9,775,838
`____________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,775,838
`AS OBVIOUS OVER WYSE
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`
`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 .................................................................. 3
`3. Relief Requested ........................................................................................ 7
`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) .......................................... 8
`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 ’838 PATENT ........................................................... 11
`A. Summary of the Specification ..................................................................... 11
`B.
`Summary of the Claims ............................................................................... 12
`C.
`Summary of the Relevant Portions of the File History ............................... 13
`D. The ’838 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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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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” ................................................................................................ 25
`B.
`“patient” ....................................................................................................... 25
`C.
`“delivery time” ............................................................................................ 25
`D.
`“wherein the patient experiences a geometric mean naloxone Cmax” and
`“wherein the patient experiences a plasma naloxone concentration such that the
`geometric mean of area under a plasma concentration versus time curve (AUC0-
`∞)”
` ..................................................................................................................... 26
`VII. SUMMARY OF PRIOR ART CONSIDERED ............................................. 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
`D. Zomig Review Was Publicly Accessible .................................................... 30
`VIII. THE CHALLENGED CLAIMS ARE UNPATENTABLE ....................... 31
`A. Ground 1: Claims 1–4, 18–23, 25–29, 30–34, 36, and 39–40 are obvious
`over Wyse (Nalox1007) in view of HPE (Nalox1012). ....................................... 31
`1. Claim 1 ..................................................................................................... 31
`2. Claim 2 ..................................................................................................... 35
`3. Claim 3 ..................................................................................................... 35
`4. Claim 4 ..................................................................................................... 38
`5. Claim 18 ................................................................................................... 39
`6. Claims 19 and 20 ...................................................................................... 39
`7. Claim 21 ................................................................................................... 40
`8. Claims 22 and 23 ...................................................................................... 40
`9. Claims 25–29 ............................................................................................ 42
`10. Claim 30 ................................................................................................... 43
`11. Claim 31 ................................................................................................... 44
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`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`12. Claim 32 ................................................................................................... 44
`13. Claim 33 ................................................................................................... 45
`14. Claim 34 ................................................................................................... 46
`15. Claim 36 ................................................................................................... 46
`16. Claims 39 and 40 ...................................................................................... 48
`B. Ground 2: Claims 5–12 are obvious over Wyse (Nalox1007) in view of HPE
`(Nalox1012) and Wang (Nalox1008). .................................................................. 49
`1. Claims 5–9 ................................................................................................ 49
`2. Claims 10–12 ............................................................................................ 50
`C. Ground 3: Claims 13–17 and 41–46 are obvious over Wyse (Nalox1007) in
`view of HPE (Nalox1012) and the ’291 patent (Nalox1015)............................... 51
`1. Claims 13–17 ............................................................................................ 51
`2. Claim 41 ................................................................................................... 52
`3. Claims 42–44 ............................................................................................ 55
`4. Claim 45 ................................................................................................... 56
`5. Claim 46 ................................................................................................... 56
`D. Ground 4: Claims 24, 35, and 37 are obvious over Wyse (Nalox1007) in
`view of HPE (Nalox1012) and Djupesland (Nalox1010). ................................... 57
`1. Claim 24 ................................................................................................... 57
`2. Claim 35 ................................................................................................... 58
`3. Claim 37 ................................................................................................... 58
`E. Ground 5: Claim 38 is obvious over Wyse (Nalox1007) in view of HPE
`(Nalox1012), Djupesland (Nalox1010), and Zomig Review (Nalox1024).......... 59
`IX. SECONDARY CONSIDERATIONS ............................................................ 61
`A. No teaching away ........................................................................................ 61
`B. No commercial success ............................................................................... 64
`C. No long-felt but unmet need or failure of others ......................................... 65
`D. No unexpected superior results ................................................................... 66
`X. CONCLUSION ................................................................................................. 67
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`TABLE OF EXHIBITS
`
`Exhibit
`Number
`
`Description
`
`Nalox1004
`
`Nalox1005
`
`Nalox1006
`
`Nalox1001 U.S. Patent No. 9,775,838 (the ’838 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
`
`
`
`iv
`
`
`
`Nalox1016
`
`Nalox1018
`
`Nalox1019
`
`Nalox1021
`
`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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
`
`
`
`v
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`Nalox1030
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`Nalox1031
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`Nalox1034
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`Nalox1036
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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 &
`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
`vi
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`Nalox1037
`
`Nalox1038
`
`Nalox1040
`
`Nalox1041
`
`Nalox1042
`
`
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`
`
`Nalox1044
`
`Nalox1046
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`Nalox1047
`
`Nalox1048
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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)
`Nalox1057 U.S. Patent No. 5,813,570 (’570 Patent)
`
`Nalox1050
`
`Nalox1051
`
`Nalox1052
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`Nalox1053
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`vii
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`Nalox1059
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`Nalox1060
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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
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`Nalox1062
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`INTRODUCTION
`
`I.
`
`Nalox-1 Pharmaceuticals, LLC (“Petitioner”) respectfully requests Inter
`
`Partes Review (“IPR”) of claims 1–46 (the “Challenged Claims”) of U.S. Patent No.
`
`9,775,838 (“the ’838 patent”), purportedly owned by Adapt Pharma Limited and
`
`Opiant Pharmaceuticals, Inc. (“Patent Owners”). For the reasons addressed below,
`
`the Challenged Claims should be found unpatentable and canceled.
`
`The ’838 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
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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
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`America for intranasal naloxone products intended for community use and which
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`can be deployed in life-threatening circumstances – often by people who are not
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`medically trained. America cannot afford to wait another day for affordable, safe
`
`and effective intranasal naloxone. The ’838 patent is a barrier wrongfully and
`
`shamefully preventing broader accessibility to this critically needed naloxone
`
`medication. Removal of the ’838 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 ’838 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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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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 ’838 patent for the reasons identified below.
`
`1.
`
`Statutory Grounds of Challenge
`
`Petitioner challenges claims 1–46 of the ’838 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
`
`Basis
`
`Reference
`
`1–4, 18–23, 25–29,
`30–34, 36, 39–40
`5–12
`
`13–17, 41–46
`
`24, 35, 37
`
`38
`
`§ 103 Wyse in view of HPE
`
`§ 103 Wyse in view of HPE, and Wang
`§ 103 Wyse in view of HPE and
`the ’291 patent
`§ 103 Wyse in view of HPE and
`Djupesland
`§ 103 Wyse in view of HPE,
`Djupesland, and Zomig Review
`
`1
`
`2
`
`3
`
`4
`
`5
`
`
`
`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 relating to the ’838 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
`3
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`of the ’838 patent. In addition, although Wyse—the primary reference cited in this
`
`Petition—was used in a rejection of certain claims of a related patent (U.S. 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.
`
`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 ’177 patent. 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
`
`
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`4
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`(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
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`17–18 (P.T.A.B. Dec. 15, 2017).
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`Becton–Dickinson factors (a), (b), and (c), which analyze the cumulative or
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`overlapping nature of the proceedings, support institution here. During prosecution
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`of the ’838 patent, the Examiner never cited Wyse. While primary reference Wyse
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`(in combination with a secondary reference, Djupesland1) was cited by the Examiner
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`in a rejection of certain claims during the prosecution of the parent ’177 patent,
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`which issued prior in time to the ’838 patent, HPE was not a reference of record
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`during prosecution of either the ’177 or ’838 patent.2 Thus, the Petition’s
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`combination of Wyse and HPE, which together, or in combination with certain
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`additional references, renders obvious the challenged claims, was never evaluated
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`during examination. This Petition thus presents non-cumulative grounds and
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`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
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`1 The Djupesland reference cited during prosecution is the same reference included
`in Grounds 4 and 5 of this Petition.
`2 HPE is not cumulative to any reference cited during the prosecution of the ’838
`patent.
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`5
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`
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`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
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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
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`13 at 13 (P.T.A.B. June 24, 2015). Further, where the Petition is supported by
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`evidence that was not available in prosecution that further elucidates what a POSA
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`would have understood from a reference’s disclosure, Becton-Dickinson factors (d)–
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`(f) support institution. See Parsons XTreme Golf v. Taylor Made Golf Co.,
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`PGR2018-00074, Paper No. 7 at 43 (P.T.A.B., Jan. 24, 2019). In prosecution of the
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`related ’177 patent, the Examiner erred in finding that Wyse teaches away from the
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`use of one of the claimed ingredients, benzalkonium chloride (BAC). See Notice of
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`Allowance (Nalox1006) at 8. As Petitioner shows in this Petition, and as supported
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`by the Declarations of Dr. Donovan and Dr. Hochhaus, HPE would have motivated
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`a POSA to use BAC, and a POSA would not have considered Wyse to teach away
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`from its use in the claimed naloxone solution. Thus, this Petition presents new
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`evidence and testimony not previously available to the Examiner during prosecution.
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`In view of the above, Petitioner respectfully requests the Board decline to use its
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`discretion under 35 U.S.C. § 325(d).
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`6
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`
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`Relief Requested
`
`3.
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`
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`Petitioner requests the Board cancel the Challenged Claims as being
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`unpatentable under AIA 35 U.S.C. § 103(a).
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`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
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`Pharmaceuticals, LLC, BCIM Partners III, LP, BCIM General Partner III, LP,
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`Burford Capital Ireland DAC, BCIM PIII Holdings, LLC, Burford Capital
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`Investment Management LLC, Burford Capital Holdings (UK) Limited, and Burford
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`Capital Limited are the real parties in interest (collectively, “RPI”). Nalox-1
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`Pharmaceuticals, LLC, a Delaware limited liability company, is 100% owned by
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`BCIM Partners III, LP, a Delaware limited partnership. BCIM General Partner III,
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`LLC, a Delaware limited liability company, is the general partner of BCIM Partners
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`III, LP, and Burford Capital Investment Management LLC is the investment
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`manager to BCIM Partners III, LP. No other person has authority to direct or control
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`(i) the timing of, filing of, content of, or any decisions or other activities relating to
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`this Petition or (ii) any timing, future filings, content of, or any decisions or other
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`activities relating to the future proceedings related to this Petition. All of the costs
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`associated with this Petition are expected to be borne by Nalox-1 Pharmaceuticals,
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`LLC, BCIM Partners III, LP, BCIM General Partner III, LP, Burford Capital
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`
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`7
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`
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`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`Investment Management LLC and Burford Capital Holdings (UK) Limited.
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`2.
`Related Matters Under 37 C.F.R. § 42.8(b)(2)
`Petitioner identifies the following judicial or administrative matters that
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`would affect, or be affected by, a decision in this proceeding. Patent Owners have
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`asserted the ’838 patent in the following United States District Court civil actions:
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`2:18-cv-15287 (D.N.J.), 2:16-cv-07721 (D.N.J.) (consolidated). Petitioner is not a
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`party to these actions. Petitioner is concurrently filing inter partes review petitions
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`on related U.S. Patent Nos. 9,211,253; 9,468,747, 9,561,177; and 9,629,965, which
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`are listed in The FDA’s Orange Book as covering Narcan® nasal spray (naloxone).
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`3.
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`Identification of Lead and Back-Up Counsel Under 37 C.F.R.
`§ 42.8(b)(3)
`Petitioner provides the following designation of counsel:
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`Lead Counsel
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`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
`
`Bradford Frese (Reg. No. 69,772)
`Telephone: 202.857.6496
`Fax: 202.857.6395
`Bradford.Frese@arentfox.com
`
`
`
`
`8
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`
`
`IPR2019-00697
`Petition for Inter Partes Review of U.S. Patent No. 9,775,838
`Christopher Yaen (Reg. No. 66,563)
`Telephone: 202.350.3760
`Fax: 202.857.6395
`Christopher.Yaen@arentfox.com
`
`
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`4.
`Service Information Under 37 C.F.R. § 42.8(b)(4)
`Please address all correspondence to above-identified counsel at:
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`ARENT FOX LLP
`1717 K Street NW
`Washington D.C. 20006
`Petitioner consents to electronic service.
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`
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`
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`III. LEVEL OF ORDINARY SKILL IN THE ART
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`As it relates to the ’838 patent, a person of ordinary skill in the art (“POSA”)
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`would comprise a team of individuals having experience in drug development, and
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`specifically the development of solution-based dosage forms such as intranasal
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`dosage forms. Donovan (Nalox1002), ¶35; see also Hochhaus (Nalox1003), ¶22.
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`This team would include at least one formulator with experience in preformulation
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`testing for and selection of excipients for a solution-based dosage form (including
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`intranasal dosage forms) to achieve a target pharmaceutical profile (hereafter
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`“Formulator POSA”). Donovan (Nalox1002), ¶35. The Formulator POSA would
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`likely have a Ph.D. in pharmacy, pharmaceutics, pharmaceutical chemistry,