If the oral argument is held by video conference, Petitioner respectfully requests that the video conference provide the ability for the participants to display demonstrative exhibits and documents of record to all participants.

If the oral argument is held in person at USPTO headquarters in Alexandria or elsewhere, Petitioner respectfully requests that the Board make available audio- visual equipment, including a projector to be connected to a laptop and an ELMO, to display demonstrative exhibits and documents of record.

That a POSITA would have been motivated to combine the applied references and would have had a reasonable expectation of success in so doing.

Any issues raised by Patent Owner in its Request for Oral Argument.

Patent Owner’s contentions (Paper 26) alleging the presence of new or improper arguments in Petitioner’s Reply and/or in Wermeling Declaration.

of Health and Human Services re: IND 112621; NRL-1 (diazepam intranasal solution), Dec. 27, 2016, pp 1-2.

Howard LeWine, M.D., “Quick Injection Helps Stop Epileptic Seizures,” Harvard Health Blog, Feb. 23, 2012; p. 1 “Managing Epilepsy Well Network and Selected Self-Management Programs; Putting Collective Wisdom to Work for People with Epilepsy,” Prevention Research Centers (PRC), CDC , Nov. 2016, pp.1-17 K.M.

Fiest, et al., “Prevalence and Incidence of Epilepsy, A Systematic Review and Meta-Analysis of International Studies,” NEUROLOGY 88, Jan. 17, 2017, pp.296-303 SIGMA Chemical Company Catalog (1988) E. Bechgaard et al., “Solubilization of Various Benzodiazepines for Intranasal Administration, A Pilot Study,” Pharmaceutical Development and Technology 2:293-296 (1997) A. Hussain et al. “Nasal Absorption of Propranolol in Humans,” Journal of Pharmaceutical Sciences 69:1240 (1980) S. Lau and J. Slattery, “Absorption of Diazepam and Lorazepam Following Intranasal Administration,” International Journal of Pharmaceutics, 54:171-174 (1989) M. Schols-Hendriks et al., “Absorption of Clonazepam After Intranasal and Buccal Administration,” British Journal of Clinical Pharmacology 39:449-451 (1995) 2011 Dr. Nicholas Peppas Deposition Transcript, October 24, 2019.

2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 Declaration of Dr. Sveinbjorn Gizurarson, Ph.D. J. Riss et al., “Benzodiazepines in Epilepsy: Pharmacology and Pharmacokinetics,” Acta Neurologica Scandinavica 118:69-86 (2008) D. Wermeling, U.S. Patent No. 6,610,271, issued August 26, 2003 C. Cole et al., “Community Survey of Carer’s: Individual Epilepsy Guidelines (IEG) for Rescue Medication,” Seizure 18:220-224 (2009) D. Terry et al., “Acceptance of the Use of Diazepam Rectal Gel in School and Day Care Settings,” Journal of Child Neurology 22:1135- 1138 (2007) Diastat® Label (2005) “UCB announces NAYZILAM® (midazolam) nasal spray now approved by FDA to treat intermittent, stereotypic episodes of frequent seizure activity in people living with epilepsy in the U.S.,” UCB Press Release, https://www.biospace.com/article/releases/ucb- announces-nayzilam-midazolam-nasal-spray-now-approved-by-fda- to-treat-intermittent-stereotypic-episodes-of-frequent-seizure-activity- in-people-living-with-epilepsy-in-the-u-s-/ (2019) (Accessed October 31, 2019) J. French and T. Pedley, “Initial Management of Epilepsy,” New England Journal of Medicine 359:166-176 (2008) G. Corbo et al. “Measurement of Nasal Mucociliary Clearance,” Archives of Disease in Childhood 64:546-550 (1989) “How does the nose work?

Licenses Aegis Therapeutics' Intravail Drug Delivery Technology” (Business Wire) (April 13, 2005) Handbook of Pharmaceutical Excipients (Pharmaceutical Press and American Pharmacists Association, Publishers) (Fifth Edition, 2006) J. Wyse, U.S. Patent No. 9,192,570 issued November 24, 2015 Daniel P. Wermeling Deposition Transcript, February 26, 2020 “ITI Announces Formation of Scientific Advisory Board Led by the Dean of the University of Iowa’s College of Pharmacy,” ITI Press Release (2006) [SERVED BUT NOT FILED] Declaration of Dr. Sveinbjorn Gizurarson, Ph.D. [SERVED BUT

Pursuant to the scheduling order (Paper 9, 6), Patent Owner (“Neurelis”) requests oral argument on all pending issues, including whether to terminate the review, whether to strike the reply of the Petitioner (Aquestive) or the declaration of its expert Dr. Wermeling, and any motion to exclude.

Because most of its participants are on the West Coast, Neurelis respectfully requests an afternoon (Eastern) argument.

Neurelis anticipates that eight (8) individuals (including counsel) will attend for Neurelis, if in-person attendance becomes feasible.

Date: March 31, 2020 Respectfully submitted,

/Jeffrey W. Guise / Jeffrey W. Guise, Reg. No. 34,613 Counsel for Neurelis

Petitioner, Aquestive Therapeutics, Inc. submits the following objections to evidence of the Patent Owner, Neurelis, Inc. Exhibit 2028: “Intranasal Technology, Inc.

Licenses Aegis Therapeutics' Intravail Drug Delivery Technology” (Business Wire) (April 13, 2005)

The exhibit’s probative value is substantially outweighed by its confusion of the issues to be decided, its waste of the Board’s and the Petitioner’s time, and the danger that it will lead to unfair prejudice if used later in the proceeding or on appeal.

FRE 901 (authentication) Patent Owner failed to provide evidence sufficient to establish the exhibit is what it is purported to be.

The exhibit’s probative value is substantially outweighed by its confusion of the issues to be decided, its waste of the Board’s and the Petitioner’s time, and the danger that it will lead to unfair prejudice if used later in the proceeding or on appeal.

Patent Owner Neurelis, Inc. (Neurelis) submits the following mandatory change-of-information notices for IPR2019-00451.

Related Matters (37 C.F.R. §42.8(b)(2)) – Revised Petitioner (Aquestive) filed two additional inter partes review petitions (IPR2019-00449 and IPR2019-00450) against the involved patent, but both were denied.

Neurelis has an application (15/470,498) that claims benefit under 35 U.S.C. 120 to the application that issued as the involved patent.

Neurelis has filed a tort suit against Aquestive citing the Aquestive petitions as evidence of a pattern of tortious behavior against Neurelis.

Respectfully submitted, /Richard Torczon/ Richard Torczon Reg. No. 34,448 Case IPR2019-00451 Patent No. 9,763,876