UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`PADAGIS US LLC
`Petitioner,
`v.
`NEURELIS, INC.
`Patent Owner.
`
`Case No. IPR2025-00464
`Patent 8,895,546
`________________
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 8,895,546
`UNDER 35 U.S.C. §§ 311–319 AND 37 C.F.R. § 42.100 et seq.
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`V.
`
`TABLE OF CONTENTS
`INTRODUCTION ......................................................................................... 1
`I.
`II. MANDATORY NOTICES ........................................................................... 3
`A.
`Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) ................................ 3
`B.
`Related Matters (37 C.F.R. § 42.8(b)(2)) ........................................... 3
`C.
`Lead and Backup Counsel (37 C.F.R. § 42.8(b)(3)) ......................... 4
`D.
`Service Information (37 C.F.R. § 42.8(b)(4)) .................................... 4
`E.
`Payment of Fees (37 C.F.R. §§ 42.15(a) and 42.103(a)) ................... 4
`F.
`Certification of Word Count Under 37 C.F.R. § 42.24(d) ............... 5
`III. GROUNDS FOR STANDING UNDER 37 C.F.R. § 42.104(a) ................. 5
`IV.
`IDENTIFICATION OF GROUNDS FOR WHICH REVIEW IS
`REQUESTED UNDER 37 C.F.R. § 42.104(b)(1) ....................................... 5
`Patent owner is COLLATERALLY estopped from raising issues
`that WERE ADJUDICATED in IPR2019-00451 ....................................... 6
`VI. OVERVIEW OF THE ’546 Patent ............................................................10
`A.
`Summary of Claimed Subject Matter .............................................10
`B.
`Filing History and Priority Claims for the ’546 Patent .................10
`C.
`Prosecution History of the ’546 Patent ............................................11
`D.
`Earliest Priority Date and Support for the ’546 Patent
`Claims .................................................................................................12
`Claim Construction of “vitamin E” .................................................16
`E.
`VII. State of Technology AT THE TIME OF THE INVENTION .................16
`A.
`Summary ............................................................................................16
`B.
`Product Design Considerations ........................................................17
`C.
`Intranasal Delivery Of Benzodiazepines For Treatment Of
`Seizures Prior To 2009 ......................................................................19
`VIII. SUMMARY OF PRIOR ART ....................................................................21
`A.
`Gwozdz (EX1009) ..............................................................................21
`B. Meezan (EX1010) ..............................................................................23
`
`i
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`IX. Level of SKill in the Art ..............................................................................23
`X.
`Gwozdz in view of Meezan renders obvious claims 1-22 of the ’546
`Patent ............................................................................................................24
`A. Motivation to Combine and Expectation of Success ......................25
`B.
`Application of the Combined Teachings of Gwozdz and
`Meezan to claims 1-22 of the ’546 Patent ........................................40
`XI. The Board Should Not Exercise its Discretion to Deny Institution ........66
`A.
`35 U.S.C. § 325(d) ..............................................................................66
`B.
`Fintiv ...................................................................................................67
`XII. CONCLUSION ............................................................................................68
`
`ii
`
`

`

`Exhibit No.
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`PETITIONER’S EXHIBITS
`Exhibit Description
`U.S. Patent No. 8,895,546, Administration Of
`Benzodiazepine Compositions, filed June 13, 2012 (“’546
`Patent”)
`File History for ’546 Patent, Ser. No. 13/495,942 (“’546
`FH”)
`Part 1: Pages 1-350
`Part 2: Pages 351-700
`Part 3: Pages 701-1050
`Part 4: Pages 1051-1400
`Part 5: Pages 1401-1750
`Part 6: Pages 1751-2100
`Part 7: Pages 2101-2450
`Part 8: Pages 2451-2681
`
`U.S. Patent No. 9,763,876, Administration Of
`Benzodiazepine Compositions, filed October 29, 2014
`(“’876 Patent”)
`File History for 9,763,876 Patent, Ser. No. 14/527,613
`(“’876 FH”)
`Part 1: Pages 1-270
`Part 2: Pages 271-530
`
`Provisional Patent Application No. 61/497,017, filed June
`14, 2011 (“’017 Provisional”)
`Provisional Patent Application No. 61/570,110, filed
`December 13, 2011 (“’110 Provisional”)
`File History for Non-Provisional Patent Application Serial
`No. 12/413,439, filed March 27, 2009 (“’439 FH”)
`Part 1: Pages 1-400
`Part 2: Pages 401-800
`Part 3: Pages 801-1200
`Part 4: Pages 1201-1600
`Part 5: Pages 1601-2000
`Part 6: Pages 2001-2400
`Part 7: Pages 2401-2800
`Part 8: Pages 2801-3200
`
`iii
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Exhibit No.
`
`Exhibit Description
`Part 9: Pages 3201-3488
`
`Provisional Patent Application No. 61/040,558, filed March
`28, 2008 (“’558 Provisional”)
`Gwozdz et al., WO 2009/120933, Pharmaceutical Solutions
`And Method For Solubilizing Therapeutic Agents, published
`October 1, 2009, International Filing Date March 27, 2009
`(PCT/US2009/038518) (“Gwozdz”)
`Meezan et al., U.S. Patent Publication No. US
`2006/0046962, Absorption Enhancers for Drug
`Administration, Serial No. 11/127,786, published March 2,
`2006 (“Meezan”)
`Ritschel, Handbook of Basic Pharmacokinetics, Chapter 36
`(Bioavailability and Bioequivalence), Drug Intelligence
`Publications, Illinois, 1992 (“Ritschel”)
`Osborne et al., Skin Penetration Enhancers Cited in the
`Technical Literature, Pharmaceutical Technology,
`November 1997 (“Osborne”)
`Lindhardt et al., Electroencephalographic effects and serum
`concentrations after intranasal and intravenous
`administration of diazepam to healthy volunteers, Blackwell
`Science Ltd Br J Clin Pharmacol, 52, 521-527, 2001
`(“Lindhardt”)
`Illum L, Nasal drug delivery-possibilities, problems and
`solutions, Journal of Controlled Release 87 (2003) 187198
`(“Illum I”)
`Ivaturi et al., Pharmacokinetics and tolerability of
`intranasal diazepam and midazolam in healthy adult
`volunteers, Acta Neurol Scand. 2009 Nov;120(5):353-7.
`doi: 10.1111/j.1600-0404.2009.01170.x. Epub 2009 May 14
`(“Ivaturi”)
`Rowe et al., editors, Handbook of Pharmaceutical
`Excipients, Fourth Edition (2003), Monographs for
`“Alcohol” (i.e., ethanol), “Alpha Tocopherol”, “Benzyl
`Alcohol”, “Glycerin”, “Olive Oil”, “Polyethylene Glycol”,
`“Propylene Glycol”, “Sesame Oil”, and
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`iv
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Exhibit No.
`
`Exhibit Description
`“Triacetin”, American Pharmaceutical Association,
`Washington DC (“Rowe”)
`
`PDR 54th Edition 2000, DIASTAT® (diazepam rectal gel);
`MIACALCIN® (Calcitonin Nasal Spray); VALIUM®
`(diazepam injection), Physicians’ Desk Reference (“PDR”)
`
`Knoester PD, Jonker DM, Van Der Hoeven RT, et al.
`Pharmacokinetics and pharmacodynamics of midazolam
`administered as a concentrated intranasal spray. A study in
`healthy volunteers. Br J Clin Pharmacol. 2002; 53: 501-507
`(“Knoester”)
`Florida Regional Common EMS Protocols Field Guide,
`Jones and Barlett Publishers, MA (2005) (“EMS”)
`Valium® Tablet Label, Roche, January 2008 (“Valium
`label”)
`Wolfe T, Macfarlane T. Intranasal midazolam therapy for
`pediatric status epilepticus. Am J Emerg Med 2006; 24:43-
`346 (“Wolfe”)
`
`Holsti M, Sill B, Firth S, et al., Prehospital intranasal
`midazolam for the treatment of pediatric seizures. Ped
`Emerg Care 2007; 23: 148-153 (“Holsti”)
`
`Greenblatt D, Gan L, Harmatz, et al. Pharmacokinetics and
`pharmacodynamics of single-dose triazolam: EEG
`compared with digital symbol substitution test. Br J Clin
`Pharmacol 2005; 60: 244-248 (“Greenblatt”)
`O’Regan M, Brown J, Clarke M. Nasal rather than rectal
`benzodiazepines in the management of acute childhood
`seizures. Develop Med and Child Neurol 1996; 38: 1037-
`1045 (“O’Regan”)
`Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam
`vs rectal diazepam in acute childhood seizures. Pediatric
`Neurology 2006; 34: 355-359 (“Bhattacharyya”)
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`v
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Exhibit Description
`SIGMA Chemical Company Catalog (1988) (“Sigma
`Catalog”)
`Wermeling DP, et al., Intranasal Delivery of Antiepileptic
`Medications for Treatment of Seizures, Neurotherapeutics:
`The Journal of the American Society for Experimental
`Neurotherapeutics, Vol. 6, 352-353, April 2009
`(“Wermeling I”)
`Hardman, et al., Editors, Goodman & Gilman’s, The
`Pharmacological Basis of Therapeutics, 10th Edition (2001)
`(“Goodman & Gilman”)
`Loftsson T, Gudmundsdottir H, Sigurjonsdittur JF, et al.
`Cyclodextrin solubilization of benzodiazepines: formulation
`of midazolam nasal spray. Int J Pharm 2001; 212:29-40
`(“Loftsson”)
`Gudmundsdottir H, Sigurjonsdottir JF, Masson M, et al.
`Intranasal administration of midazolam in a cyclodextrin
`based formulation: bioavailability and clinical evaluation in
`humans. Pharmazie 2001; 56: 963-966 (“Gudmundsdottir”)
`Dale O., Nilsen T., Loftsson T. Intranasal midazolam: a
`comparison of two delivery devices in human volunteers. J
`Pharmacy Pharmacol 2006; 58: 1311-1318 (“Dale”)
`Burstein AH, Modica R, Hatton M, et al. Pharmacokinetics
`and pharmacodynamics of midazolam after intranasal
`administration. J Clin Pharmacol 1997; 37: 711-718
`(“Burstein”)
`Wermeling, D, Record K, Kelly T, et al., Pharmacokinetics
`and pharamcodynamics of a new intranasal midazolam
`formulation in healthy volunteers. Anesth Analg 2006; 103:
`344-349 (“Wermeling II”)
`Schols-Hendriks MWG, Lohman JJHM, Janknegt R, et al.
`Absorption of clonazepam after intranasal and buccal
`administration. Br J Clin Pharmacol, 1995; 39: 449-451
`(“Schols-Hendricks”)
`Lau SWJ, Slattery JT. Intl J Pharmaceutics. Absorption of
`diazepam and lorazepam following intranasal
`administration. Int J Pharmaceutics 1989; 54: 171-174
`(“Lau”)
`
`Exhibit No.
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`vi
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Exhibit Description
`Wermeling DP, Miller JL, Archer SM, et al. Bioavailability
`and pharmacokinetics of lorazepam after intranasal,
`intravenous, and intramuscular administration. J Clin
`Pharmacol, 2001; 41: 1225-1231 (“Wermeling III”)
`Budavari, et al., Editors, The Merck Index, 12th Edition
`(1996) (“Merck Index”)
`USP 26/NF 21 2003, The Official Compendia of Standards,
`Ethanol, Copyright 2002 (“USP 26/NF 21”)
`U.S. App. No. 12/413,439, filed March 27, 2009 (“’439
`Application”)
`Final Written Decision issued in IPR 2019-00451,
`Aquestive Therapuetics, Inc. v. Neuelis, Inc., Paper 44
`(issued , August 6, 2020) (“IPR 2019-00451 Final Written
`Decision”)
`Lowenstein DH, Alldredge BK. Status epilepticus, N Eng J
`Med 1998; 338:970-976 (“Lowenstein I”)
`Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise
`the definition of status epilepticus. Epilepsia 1999: 40:120-
`122 (“Lowenstein II”)
`Wang HC, Chang WN, Chang HW, et al., Factors
`predictive of outcome in postraumatic seizures. J Trauma
`2008; 64: 883-888 (“Wang”)
`Stavem K, Bjornaes H, Langmoen IA. Long-term seizures
`and quality of life after epilepsy surgery compared with
`matched controls. Neurosurgery 2008; 62: 326-334
`(“Stavem”)
`Logroscino G, Hessdorffer DC, Cascino G, et al., Time
`Trends in incidence, mortality, and case-fatality after first
`episode of status epilepticus, Epilepsia 2001; 42:1031-1035
`(“Logroscino”)
`Feen ES, Bershad EM, Suarez JI, Status Epilepticus, South
`Med J 2008; 101: 400-406 (“Feen”)
`Pang T, Hirsch L, Treatment of convulsive and
`nonconvulsive status epilepticus, Cur Treat Options Neurol
`2005; 7:247-259 (“Pang”)
`Smith B, Treatment of status epilepticus, Neurol Clin 2001;
`19:347-369 (“Smith”)
`
`Exhibit No.
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`vii
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Exhibit Description
`Ericksson K, Kalviainen R. Pharmacologic management of
`convulsive status epilepticus in childhood, Expert Rev
`Neurotherapeutics 2005; 5:777-783 (“Ericksson”)
`Meierkord H, Engelsen B, Gocke K, et al., EFNS guideline
`on the management of status epilepticus, Eur J Neurol 2006;
`13: 445-450 (“Meierkord”)
`Prasad K, Krishman P, Al-Roomi K, et al., Anticonvulsant
`therapy for status epilepticus, Br J Clin Pharmacol 2007;
`63:640-647 (“Prasad”)
`Illum L., Nasal Clearance in Health and Disease, J Aerosol
`Med 2006; 19:92-99 (“Illum II”)
`Constantino HR, Illum L, Brandt G et al., Intranasal
`delivery: Physicochemical and therapeutic aspects, Intl J
`Pharmaceutics 2007; 337:1-24 (“Constantino”)
`Rudy AC, Coda BA, Archer SM, et al., A multiple dose
`phase I study of intranasal hydromorphone hydrochloride in
`healthy volunteers, Anesth Analg 2004; 99:1379-1386
`(“Rudy”)
`Mittal P, Manohar R, Rawat A, Comparative study of
`intranasal midazolam and intravenous diazepam sedation
`for procedures and seizures, Ind J Pediatrics 2006; 73:975-
`78 (“Mittal”)
`Mahmoudian T, Zadeh M, Comparison of intranasal
`midazolam with intravenous diazepam for treating acute
`seizures in children, Epilepsy and Behavior 2004; 5:253-
`255 (“Mahmoudian”)
`Lahat E, Goldman M, Barr J, et al., Comparison of
`intranasal midazolam with intravenous diazepam in treating
`febrile seizures in children: prospective randomized study,
`BMJ 2000; 321:83-87 (“Lahat”)
`Sharma S, et al., Permeation enhancers in the transmucosal
`delivery of macromolecules, Pharmazie 2006; 61(6): 495-
`504 (“Sharma”)
`Ahsan F. et al., Effects of the permeability enhancers,
`tetradecylmaltoside and dimethyl-β-cyclodextrin, on insulin
`movement across human bronchial epithelial cells, Eur J
`Pharm Sciences 2003; 20:27-34 (“Ahsan”).
`
`Exhibit No.
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`1059
`
`viii
`
`

`

`Exhibit No.
`1060
`
`1061
`1062
`1063
`
`1064
`
`1065
`1066
`1067
`1068
`
`1069
`
`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Exhibit Description
`U.S. Patent No. 5,661,130 to Meezan and Pillion (“Meezan
`II”)
`U.S. Patent No. 6,610,271 to Wermeling (“Wermeling IV”)
`Declaration of Dr. Maureen Donovan, Ph.D.
`Complaint filed in Neurelis, Inc. v. Padagis LLC et al., Civil
`Action No. 1:24-cv-11637 (D. Mass) (complaint filed on
`June 25, 2024).
`U.S. Provisional Patent App. No. 61/040,281 (“’281
`Provisional”)
`Not Used
`Not Used
`Not Used
`Neurelis, Inc. v. Aquestive Therapeutics, Inc., No. 2021-
`1038, (Fed. Cir. Oct. 7, 2021)
`Chart comparing claims 1-22 of the ’546 Patent to claims 1-
`16 and 24-36 of the ’876 Patent
`
`ix
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`I.
`
`INTRODUCTION
`Padagis US LLC (“Petitioner”) hereby respectfully requests inter partes
`
`review of claims 1-22 (“Challenged Claims”) of U.S. Patent No. 8,895,546 (“the
`
`’546 Patent”) pursuant to 35 U.S.C. §§ 311-319.
`
`Notably, the issues presented in this Petition are substantially the same as the
`
`issues the Board previously considered in IPR2019-00451 when issuing a Final
`
`Written Decision findings all claims of U.S. Patent No. 9,763,876 (“the ’876
`
`Patent”) were unpatentable. See EX1040 at 69 (copy of final decision in IPR2019-
`
`00451, Aquestive Therapeutics, Inc. v. Neurelis, Inc.). The ’876 Patent is a
`
`continuation of the ’546 Patent and recites substantially the same limitations as the
`
`’546 Patent. The primary difference between the ’876 Patent claims found to be
`
`unpatentable in IPR2019-00451 and the claims of the ’546 Patent is that the former
`
`are directed to a method of treatment using a specific pharmaceutical solution while
`
`the latter are to the pharmaceutical solution itself.
`
`To illustrate, a comparison of claim 1 of the ’876 Patent and claim 1 of the
`
`’546 Patent is provided below:
`
`Claim 1 of 9,763,876 Found
`Unpatentable in IPR 2019-00451
`
`Claim 1 of 8,895,546
`
`1. A method of treating a patient with a
`disorder which is treatable with a
`benzodiazepine drug, comprising:
`
`1. A pharmaceutical solution for nasal
`administration consisting of:
`(a) a benzodiazepine drug;
`
`1
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`(b) one or more natural or synthetic
`tocopherols or tocotrienols, or any
`combinations thereof, in an amount
`from about 30% to about 95% (w/w);
`(c) ethanol and benzyl alcohol in a
`combined amount from about 10% to
`about 70% (w/w); and
`(d) an alkyl glycoside.
`
`administering to one or more nasal
`mucosal membranes of a patient
`a pharmaceutical solution for nasal
`administration consisting of
`a benzodiazepine drug,
`one or more natural or synthetic
`tocopherols or tocotrienols, or any
`combinations thereof, in an amount
`from about 30% to about 95% (w/w);
`ethanol and benzyl alcohol
`in a
`combined amount from about 10% to
`about 70% (w/w); and
`an alkyl glycoside.
`
`See EX1069 (comparing claims 1-22 of the ’546 Patent to claims 1-16 and 24-36 of
`
`the ’876 Patent).
`
`The present IPR relies on the same prior art and substantially same arguments
`
`that the Board considered already in IPR2019-00451 to find the claims there were
`
`unpatentable. The Board having already found a method of treatment using the
`
`claimed pharmaceutical formulation being obvious, there is no patentable distinction
`
`in claiming the pharmaceutical formulation itself. As such, Neurelis, Inc. (“Patent
`
`Owner”) is collaterally estopped from contesting the issues previously addressed in
`
`IPR2019-00451.
`
`2
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Even assuming Patent Owner is not collaterally estopped from contesting the
`
`patentability of the claims over the prior art cited in this Petition, the reasoning and
`
`analysis of the Board’s decision in IPR2019-00451 why the claim pharmaceutical
`
`compound is obvious would apply equally in the instant IPR.
`
`For the reasons provided by the Board in IPR2019-00451 and as explained in
`
`detail below, there is a reasonable likelihood that claims 1-22 of the ’546 Patent are
`
`unpatentable, and the Board should institute IPR based on this Petition.
`
`II. MANDATORY NOTICES
`Pursuant to 37 C.F.R. § 42.8, Petitioner provides the following disclosures:
`
`Real Party-In-Interest (37 C.F.R. § 42.8(b)(1))
`A.
`The real parties-in-interest are Padagis US LLC, Padagis LLC, and Padagis
`
`Israel Pharmaceuticals Ltd.
`
`B.
`
`Related Matters (37 C.F.R. § 42.8(b)(2))
`
` The ’876 Patent, which is a continuation of the ’546 Patent, was the
`
`subject of IPR2019-00451 which resulted in a Final Written Decision
`
`determining that claims 1-36 of the ’876 Patent are unpatentable.
`
`EX1040.
`
` The ’546 Patent is involved in district court litigation captioned
`
`Neurelis, Inc. v. Padagis LLC et al. Civil Action No. 1:24-cv-00562 (D.
`
`Del.) (complaint filed on May 8, 2024). See EX1063.
`
`3
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`C.
`
`Lead and Backup Counsel (37 C.F.R. § 42.8(b)(3))
`
`Lead Counsel
`
`Backup Counsel
`
`James P. Murphy
`Reg. No. 55,474
`Polsinelli PC
`1000 Louisiana Street
`Suite 6400
`Houston, Texas 77002
`Tel: (713) 374-1631
`jpmurphy@polsinelli.com
`
`Corey Casey
`Reg. No. 66,950
`Polsinelli PC
`900 West 48th Place
`Suite 900
`Kansas City, Missouri 64112
`Tel: (816) 572-4439
`ccasey@polsinelli.com
`
`Pursuant to 37 C.F.R. § 42.10(b), Powers of Attorney have been filed with
`
`this Petition.
`
`Service Information (37 C.F.R. § 42.8(b)(4))
`D.
`Petitioner consents to service by e-mail at the above e-mail addresses provided
`
`above for lead and backup counsel. Physical mailing service information is as
`
`follows:
`
`James Murphy
`Polsinelli PC
`1000 Louisiana Street
`Suite 6400
`Houston, Texas 77002
`Payment of Fees (37 C.F.R. §§ 42.15(a) and 42.103(a))
`E.
`All required fees have been paid with the filing of this Petition. Petitioner
`
`further authorizes the U.S. Patent & Trademark Office to charge Deposit Account
`
`No. 50-1662 for any fees, including the fee set forth in 37 C.F.R. § 42.15(a) for this
`
`Petition.
`
`4
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`Certification of Word Count Under 37 C.F.R. § 42.24(d)
`F.
`Petitioner certifies that the word count in this Petition, including all footnotes,
`
`is 13,944 words as counted by the word-processing program (Microsoft Word for
`
`Office 365) used to generate this Petition, where such word count excludes the table
`
`of contents, mandatory notices, certificate of service, list of exhibits, and this
`
`certificate of word count. This Petition is in compliance with the 14,000 word limit
`
`set forth in 37 C.F.R. § 42.24(a)(1)(i).
`
`III. GROUNDS FOR STANDING UNDER 37 C.F.R. § 42.104(A)
`Petitioner certifies that the ’546 patent is available for inter partes review.
`
`Petitioner is not barred or estopped from requesting an inter partes review of the
`
`’546 patent claims on the grounds identified in this Petition. 37 C.F.R. § 42.104(a).
`
`IV.
`
`IDENTIFICATION OF GROUNDS FOR WHICH REVIEW IS
`REQUESTED UNDER 37 C.F.R. § 42.104(B)(1)
`Petitioner asserts that claims 1-22 of the ’546 patent are unpatentable based
`
`on the following grounds:
`
`Ground 1: Claims 1-22 are obvious over Gwozdz1 in view of Meezan2.
`
`1 PCT Pub. No. WO 2009/120933 A2, published October 1, 2009 (Ex. 1009,
`“Gwozdz”).
`2 U.S. Pub. No. 2006/0046962 A1, published March 2, 2006 (Ex. 1010, “Meezan”).
`
`5
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`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`V.
`
`IS COLLATERALLY ESTOPPED FROM
`PATENT OWNER
`RAISING ISSUES THAT WERE ADJUDICATED IN IPR2019-00451
`“It is well established that collateral estoppel applies to IPR proceedings.”
`
`Google LLC v. Hammond Dev. Int'l, 54 F.4th 1377, 1381 (Fed. Cir. 2022); see also
`
`Nestle USA, Inc. v. Steuben Foods, Inc., 884 F.3d 1350, 1352 (Fed. Cir. 2018). The
`
`party seeking to invoke collateral estoppel must show:
`
`(1) the issue is identical to one decided in the first action;
`
`(2) the issue was actually litigated in the first action;
`
`(3) resolution of the issue was essential to a final judgment in the first action;
`
`and
`
`(4) the party against whom collateral estoppel is being asserted had a full and
`
`fair opportunity to litigate the issue in the first action.
`
`Id. All four prongs of this test are indisputably met here in view of IPR2019-00451.
`
`The Patent Owner in the instant IPR, Neurelis Inc., is the same Patent Owner
`
`that participated in IPR2019-00451 and there is little dispute that Patent Owner had
`
`a full and fair opportunity to litigate the issues in IPR2019-00451. The Board issued
`
`a final written decision in IPR2019-00451 related to U.S. Patent No. 9,763,876 (“the
`
`’876 Patent”), which is a continuation of the ’546 Patent. In the final written decision
`
`in IPR2019-00451, the PTAB determined that claims 1-16 and 24-36 are
`
`6
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`unpatentable over the combination of Gwozdz in view of Meezan3. EX1040. The
`
`Board’s decision was appealed by Patent Owner but affirmed by the Federal Circuit.
`
`See EX1068 (Fed Circuit affirmance of IPR2019-00451 decision). As such, the
`
`Board’s final decision in IPR2019-00451 provided final resolution of invalidity
`
`issues related to the Gwozdz and Meezan combination that was essential to the
`
`judgment. XY, LLC v. Trans Ova Genetics, L.C., 890 F.3d 1282, 1294 (Fed. Cir.
`
`2018) (“[A]n affirmance of an invalidity finding, whether from a district court or the
`
`Board, has a collateral estoppel effect on all pending or co-pending actions.”).
`
`In addition, collateral estoppel applies even when claims are not identical so
`
`long as the issues are materially the same. Nestle., 884 F.3d at 1352; Finjan LLC v.
`
`SonicWall, Inc., 84 F.4th 963, 969 (Fed. Cir. 2023) (“collateral estoppel applies
`
`where the issues of patentability are identical, i.e., where the differences between the
`
`unadjudicated patent claims and adjudicated patent claims do not materially alter the
`
`question of invalidity.”) (internal quotations omitted).
`
`Here, the question of patentability of claims 1-16 and 24-36 of the ’876 Patent
`
`that was previously adjudicated and the patentability of claims 1-22 in the instant
`
`3 In IPR2019-00451 the Board refers to Meezan as “Meezan ’962.” Both Meezan in
`
`this this IPR Petition and Meezan ’962 in IPR2019-00451 are the same reference,
`
`namely U.S. Patent Publication No. US 2006/0046962.
`
`7
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`IPR are substantially the same. See EX1069. The primary difference between the
`
`’876 claims found unpatentable in IPR2019-00451 and the claims of the ’546 Patent
`
`is that the former are directed to a method of treatment using a specific
`
`pharmaceutical solution while the latter are to the pharmaceutical solution itself.
`
`This difference does not materially alter the question of invalidity. Rather, if a
`
`method of treatment using a pharmaceutical solution is obvious, the pharmaceutical
`
`solution itself must likewise be obvious for substantially the same reasons.
`
`There are a number of issues in the instant IPR that Patent Owner is precluded
`
`from contesting as they are materially identical to issues the Patent Owner actually
`
`raised and were fully resolved by the Board in IPR2019-00451. In particular,
`
`Petitioner notes that the Patent Owner is precluded from contesting the following
`
`findings made by the Board in IPR2019-00451:
`
`1. U.S. Prov. App. No. 61/040,558 (“the ’558 provisional”) “does not provide
`
`adequate written description support for the ‘alkyl glycoside’ limitation.”
`
`See EX1040 at p. 23 (finding that “after reviewing all of the evidence, we
`
`find that the ’558 provisional does not provide adequate written description
`
`support for the ‘alkyl glycoside’ limitation. Therefore, the claims of the
`
`’876 patent are not entitled to the benefit of priority to the ’558
`
`provisional.”)
`
`8
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`2. Gwozdz is entitled to the filing date of the ’281 Provisional. See EX1040
`
`at p. 14 (finding “Petitioner has shown that the claims of Gwozdz are
`
`supported by the Gwozdz provisional, ‘at least because Gwozdz’s claims
`
`are literally identical to the claims filed in [the] Gwozdz provisional.’”.)
`
`3. “a person of ordinary skill in the art would have had reason to add alkyl
`
`glycoside as a penetration enhancer, as disclosed in Meezan ’962, with a
`
`formulation of benzodiazepine, tocopherol, ethanol, and benzyl alcohol, as
`
`disclosed in Gwozdz.” EX1040 at p 47.
`
`4. “each limitation of claims 1–16 and 24–36 [of the ’876 Patent] are taught
`
`or suggested by the combination of Gwozdz and Meezan ’962 and further
`
`that the skilled artisan would have had reason to make the suggested
`
`combination with a reasonable expectation of success.” EX1040 at p. 51
`
`(emphasis added); see also id. at p. 54 (“On this record, we also find that
`
`the evidence of secondary considerations of non-obviousness is weak, at
`
`best. As discussed above, we find that Patent Owner has not established
`
`the requisite nexus between the challenged claims and any of the asserted
`
`secondary considerations”)
`
`(emphasis added); see also EX1069
`
`(comparing claims of the ’546 Patent and the ’876 Patent).
`
`9
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`The findings in IPR2019-00451 above are materially identical to issues to be
`
`determined in this IPR.
`
`VI. OVERVIEW OF THE ’546 PATENT
`A.
`Summary of Claimed Subject Matter
`The ’546 Patent describes pharmaceutical compositions (primarily solutions)
`
`for the intranasal administration of benzodiazepine drugs. EX1001, 8:62-65. The
`
`’546 Patent explains that the pharmaceutical composition for nasal administration
`
`comprises (1) a benzodiazepine drug; (2) one or more natural or synthetic
`
`tocopherols or tocotrienols in an amount of from about 30% to about 95% w/w; and
`
`(3) one or more alcohols or glycols in an amount of from about 10% to about 70%
`
`w/w. Id., 8:66 to 9:5. As reflected in the claims of the ’546 Patent, the pharmaceutical
`
`compositions (solutions) are focused on solutions consisting of a benzodiazepine
`
`drug (including diazepam); about 30% to about 95% (w/w) of one or more natural
`
`or synthetic tocopherols or tocotrienols (including alpha-tocopherol, i.e., vitamin E);
`
`ethanol and benzyl alcohol in a combined amount of from about 10% to about 70%
`
`(w/w); and an alkyl glycoside (including dodecyl maltoside in amounts ranging from
`
`0.01% to 1% (w/w)). See id., claims 1, 2, 5, 16, and 17.
`
`B.
`
`Filing History and Priority Claims for the ’546 Patent
`
`The ’546 Patent is a continuation-in-part of application No. 12/413,439 (“the
`
`’439 Application”), filed on March 27, 2009, which in turn claims priority to U.S.
`
`10
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`provisional application No. 61/040,558 (“the ’558 Provisional”), filed March 28,
`
`2008. The ’546 Patent also states that it claims priority to U.S. provisional
`
`application No. 61/497,017 (“the ’017 Provisional”), filed on June 14, 2011, and
`
`U.S. provisional application No. 61/570,110 (“the ’110 Provisional”), filed
`
`December 13, 2011.
`
`C.
`
`Prosecution History of the ’546 Patent
`
`The ’546 Patent was subject to an abbreviated prosecution, consisting of only
`
`a restriction requirement, and a single non-final rejection, which the ‘546 Patent
`
`Applicant was able to overcome. Specifically, after the issuance of an
`
`election/restriction requirement (see EX1002, pp. 2036-2039), the Examiner issued
`
`a non-final rejection, finding the claims obvious over U.S. Patent No. 6,193,985 to
`
`Sonne et al. (“Sonne”) in view of U.S. Patent Publication No. 2006/0046962 to
`
`Meezan (“Meezan”). See id., pp. 2125-2127.
`
`In response, Applicant amended independent Claim 1 to recite the presence
`
`of “ethanol and benzyl alcohol in a combined amount from about 10% to about 70%
`
`(w/w).” See id., pp. 2139. In the comments submitted with the claim amendments
`
`that led to allowance, Applicant stated that “[t]he pending claims also require both
`
`ethanol and benzyl alcohol in a combined amount of from 10% to 70% (w/w).
`
`Neither Sonne nor Meezan teaches or suggests using both ethanol and benzyl alcohol
`
`11
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`in such amounts. Thus, the combination of references fails to teach or suggest the
`
`claimed invention.” Id., pp. 2148-2149.
`
`D.
`
`Earliest Priority Date and Support for the ’546 Patent Claims
`
`The claims of the ’546 Patent are entitled to an earliest effective filing date of
`
`no earlier than the filing date of the parent ’439 Application on March 27, 2009.
`
`Every claim of the ’546 Patent requires the presence of an alkyl glycoside (or
`
`specific alkyl glycoside compounds, e.g., dodecyl maltoside), as Claim 1, which is
`
`the only independent claim of the ’546 Patent, recites the requirement of “an alkyl
`
`glycoside.” Certain dependent claims (i.e., claims 17-22) require dodecyl maltoside
`
`as a species compound of the claimed “alkyl glycoside” genus. Consequently, for
`
`the ’546 Patent to be entitled to an effective filing date of the earliest priority
`
`application (i.e., the ’558 Provisional filed March 28, 2008), the ’558 Provisional
`
`must provide support for the claimed “alkyl glycoside” limitation. The ’558
`
`Provisional provides no such support, and, consequently, the ’546 Patentee is
`
`entitled to an effective filing date no earlier than the ’439 Application.
`
`In IPR2019-00451, the same question was at issue, namely, whether the “alkyl
`
`glycoside” limitation present in the claims of the ’876 Patent was supported by the
`
`’558 Provisional. EX1040 at 13-14. Based on all the evidence submitted during the
`
`proceeding, the PTAB concluded that “the ’558 Provisional does not provide
`
`adequate written description support for the ‘alkyl glycoside’ limitation.” Id., p. 23.
`
`12
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,895,546
`
`(emphasis added). Patent Owner is collaterally estopped from contesting this finding
`
`as discussed previously. Even if collateral estoppel did not apply, the Board here
`
`should adopt the analysis and findings of the Final Decision in IPR2019-00451 on