UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
` AQUESTIVE THERAPEUTICS, INC.,
`Petitioner,
`
`v.
`
`NEURELIS, INC.,
`Patent Owner.
`____________________
`
`Case IPR2019-00450
`Patent 9,763,876
`____________________
`
`PATENT OWNER PRELIMINARY RESPONSE
`35 U.S.C. 313
`
`

`

`TABLE OF CONTENTS
`
`Patent Owner Preliminary Response ......................................................................... 1
`I.
`Precise Requested Relief ................................................................................. 1
`II.
`Statement of Reasons to Deny ......................................................................... 1
`A. Background ...................................................................................................... 1
`1. Epilepsy and epilepsy treatment ................................................................ 1
`2. The challenged patent and claims ............................................................. 2
`3. Prosecution history .................................................................................... 3
`B. Claim Construction .......................................................................................... 3
`C. Denial Warranted Under Section 325(d) ......................................................... 5
`1. Factors a-c: The Similarities and Material Differences Between the
`Asserted Art and the Prior Art Involved During Examination; the
`Cumulative Nature of the Asserted Art and the Prior Art Evaluated
`During Examination; and the Extent to which the Asserted Art was
`Evaluated During Examination ................................................................. 8
`2. Factor d: The Extent of 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 ........................ 9
`3. Factor e: Whether Petitioner has Pointed Out Sufficiently How the
`Examiner Erred in Its Evaluation of the Asserted Prior Art .................... 20
`4. Factor f: The Extent to which Additional Evidence and Facts
`Presented in the Petition Warrant Reconsideration of the Prior Art or
`Arguments ............................................................................................... 23
`III. Conclusion ..................................................................................................... 24
`Exhibit List ............................................................................................................... 25
`Type Volume Certificate .......................................................................................... 26
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`Certificate of Service ............................................................................................... 27
`
`Certificate of Service ............................................................................................... 27
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`I.
`
`PRECISE REQUESTED RELIEF
`The patent owner (“Neurelis”) requests that institution be denied because the
`
`petitioner (“Aquestive”) has failed to demonstrate a reasonable likelihood that any
`
`challenged claim is unpatentable.
`
`II.
`
`STATEMENT OF REASONS TO DENY
`A. BACKGROUND
`1. Epilepsy and epilepsy treatment
`Epilepsy is a general term for conditions with recurring seizures, involving
`
`abnormal electrical activity in the brain that causes an involuntary change in body
`
`movement or function, sensation, awareness, or behavior. A seizure may last from
`
`a few seconds to a few minutes. Epilepsy causes include head or brain injury, brain
`
`tumor, central nervous system infection, stroke, and genetics, but in most cases the
`
`etiology is unknown. EX2004, 3; EX2001.
`
`Epilepsy actively affects over 3.4 million people in the United States
`
`(about 1.2% of the total population), ranks as the second-most burdensome
`
`neurologic disorder worldwide in terms of disability-adjusted life years, with
`
`associated stigma, psychiatric co-morbidity and high economic costs. EX2004, 3;
`
`EX2001; EX2005, 296. In the United States alone, nearly half a million children
`
`have active epilepsy. EX2001. Medications exist to help prevent seizures, but
`
`success varies and about one-third of epileptics receiving care still experience
`
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`seizures. EX2004, 3. Uncontrolled seizures may result in injury, anxiety,
`
`depression, brain damage and death, while also interfering with normal day-to-day
`
`activities, such as working, going to school, and socializing with friends and
`
`family. EX2004, 3. Better treatments are needed to control epileptic seizures, and
`
`nasal sprays could provide the best solution. EX2003. The United States Food and
`
`Drug Administration granted Neurelis, the patent owner, a Fast Track designation
`
`to develop a diazepam intranasal solution for this very purpose. EX2002.
`
`2. The challenged patent and claims
`Benzodiazepine is a family of drugs that are useful for treating seizures.
`
`EX1001, 1:29-39. While other benzodiazepine formulations for treating seizures
`
`exist, they suffer from solubility problems and can be very difficult to administer
`
`to a subject during a seizure, particularly if the person administering therapy is not
`
`a health professional. EX1001, 1:53-2:20. The present inventors realized that nasal
`
`delivery would address the drug-administration problem, and the use of vitamin E-
`
`analogs and alcohols as substantial fractions of the formulation would address the
`
`solubility problem, while still providing an acceptable nasal-delivery formulation.
`
`The alkyl glycol functions as a penetration enhancer to improve bioavailability.
`
`EX1001, 16:55-56, 34:55-58. Challenged claim 1, from which all the other
`
`challenged claims depend, defines the invention as (EX1001, 63:26-34):
`
`A method of treating a patient with a disorder which is treatable
`with a benzodiazepine drug, comprising:
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`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.
`
`3. Prosecution history
`Aquestive proposes one obviousness ground, relying on a combination of
`
`references, U.S. Patent 6,193,985 (“Sonne”, EX1013) and U.S. Publication
`
`2006/0046962 (“Meezan’962”, EX1011). The examiner (Adam Milligan) was very
`
`familiar with these references, both of which are cited on the face of the challenged
`
`patent. EX1001, cover. Indeed, Aquestive concedes that “both Sonne and
`
`Meezan‘962 were relied on by the Examiner during prosecution of the parent ‘546
`
`patent and grandparent ‘439 application”. Pet. 6-7. The same examiner held the
`
`challenged claims to be patentably indistinct from claims in the ’546 patent,
`
`requiring a terminal disclaimer to overcome the rejection. EX1002, 0169. Hence,
`
`the same examiner had already applied and allowed patentably indistinct claims in
`
`the parent application over the combination of Sonne and Meezan’962.
`
`B. CLAIM CONSTRUCTION
`Aquestive offers constructions for Vitamin E, Bioavailability, % (w/w) and
`
`% (w/v) that are consistent with the use of those terms in the specification and
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`claims. Pet. 9-13. Aquestive also offers a construction for about 56.47% (w/v)
`
`vitamin E, which Aquestive construes to mean “53.65% to 59.29% (w/v) vitamin
`
`E” based on an assumption that “about” means ±5%. Pet. 16-17. Aquestive does
`
`not explain why 5% is the proper amount of variation other than to refer to its
`
`expert’s declaration. Id. The expert simply says that ±5% is a middle range value
`
`for the values provided in the specification and seems right to him. EX1041, ¶98.
`
`The expert’s reasoning is arbitrary. Neurelis notes that the challenged patent
`
`contains a definition of about. EX1001, 17:60-65. Aquestive accepts that an
`
`applicant may act as its own lexicographer. Pet. 12. Yet the petition offers no
`
`reasoning to justify its extrinsic definition. Moreover, to the extent that Aquestive
`
`intends to incorporate the expert’s reasoning into the petition without explanation,
`
`this would be an improper incorporation and a self-help effort to avoid the word-
`
`limit in a petition that Aquestive has certified as being right at the limit. 37 CFR
`
`§42.6(a)(3); Cisco Systs., Inc. v. C-Cation Techs., LLC, IPR2014-00454, Paper 12,
`
`10 (2014) (informative) (impermissible incorporation of arguments into petition
`
`from declaration); Pet. 95 (certifying a word count of 13,985).
`
`Aquestive also contends that it is not bound by its own constructions in other
`
`proceedings. Pet. 12-13. Such reservations are improper and, if accepted, would
`
`undermine the Board’s recent adoption of its present claim-construction standard.
`
`A. Iancu, Changes to the Claim Construction Standard for Interpreting Claims in
`
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`Trial Proceedings Before the Patent Trial and Appeal Board, 83 Fed. Reg. 51340,
`
`51342-43 (2018) (explaining the goals of promoting uniformity and predictability,
`
`while discouraging gamesmanship).
`
`C. DENIAL WARRANTED UNDER SECTION 325(D)
`Aquestive proposes one obviousness ground, relying on a combination of
`
`Sonne and Meezan’962. Aquestive concedes that while “both Sonne and
`
`Meezan‘962 were relied on by the Examiner during prosecution of the parent ‘546
`
`Patent and grandparent ‘439 application”, Aquestive should be permitted to present
`
`the same ground anyway. Pet. 6-7. Significantly, Aquestive makes no attempt to
`
`address the factors set forth in Becton Dickinson and Co. v. B. Braun Melsungen
`
`AG, IPR2017-01586, Paper 8 (2017) (informative).
`
`In Becton, the Board promulgated factors for exercising its discretion under
`
`35 U.S.C. 325(d). Section 325(d) provides a mechanism for limiting harassment of
`
`patent owners by taking previous USPTO reviews of the claims into consideration.
`
`The factors include (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
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`petitioner relies on the prior art or patent owner distinguishes the prior art;
`
`(e) whether petitioner has pointed out sufficiently how the examiner erred in its
`
`evaluation of the asserted prior art; and (f) the extent to which additional evidence
`
`and facts presented in the petition warrant reconsideration of the prior art or
`
`arguments. This discretion “involves a balance between several competing
`
`interests,” including “the interests in conserving the resources of the Office and
`
`granting patent owners repose on issues and prior art that have been considered
`
`previously.” Hospira, Inc. v. Genentech, Inc., IPR2017-00739, Paper 16, 18
`
`(2017) (informative); see also 37 C.F.R. §42.1 (setting policy “to secure the just,
`
`speedy, and inexpensive resolution of every proceeding”).
`
`The Board has also suggested that exigent circumstances might justify
`
`revisiting an issue, such as if a time bar under 35 U.S.C. 315(b) would deprive the
`
`petitioner of any other opportunity to challenge the claims. Ube Maxell Co., Ltd. v.
`
`Celgard, LLC, IPR2015-01511, Paper 10, 11-15 (2016) (“The fact that Ube Maxell
`
`has not been sued, and therefore is not facing a 35 U.S.C. § 315(b) bar, also weighs
`
`in favor of denying institution in this case.”). As even Aquestive concedes, Pet. 1
`
`(“Petitioner is not aware of any [related] matters.”), these claims have not been
`
`asserted against anyone. This lack of exigency perhaps explains why Aquestive
`
`does not address this factor either.
`
`Section 325(d) readily applies here because Aquestive’s proposed
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`obviousness ground relies on the “same or substantially the same prior art or
`
`argument previously [] presented to the Office” during prosecution. Notably, the
`
`same examiner was responsible for examining both the challenged claims and the
`
`earlier applications in which Sonne and Meezan’962 were applied, and the same
`
`examiner held the challenged claims to be patentably indistinct from claims issuing
`
`from these earlier applications and required a terminal disclaimer for the
`
`challenged claims. The Board has declined to institute review under similar
`
`circumstances. See, e.g., Microsoft Corp. v. Koninklijke Philips N.V., IPR2018-
`
`00279, Paper 11, 12 (2018) (“Based on the record before us, we determine that the
`
`same or substantially the same prior art was previously presented to the Office in
`
`connection with the examination of the application of the ’809 patent in a manner
`
`that supports our exercise of discretion to deny institution.”); Edge Endo, LLC v.
`
`Scianamblo, IPR2018-01320, Paper 15, 11-12 (2019) (similar). While Aquestive
`
`put this file history into the record, Aquestive did not acknowledge that the
`
`examiner had already held these claims to be patentably indistinct from claims
`
`already allowed over the identical combination of references.
`
`Instead, Aquestive notes that it has added an expert declaration that was not
`
`available to the examiner. Pet. 6-7. A declaration, however, is not per se sufficient
`
`to transform an old combination of references into a new ground. Sensata
`
`Technologies Inc. v. Danfoss Power Solutions Inc., IPR2017-02069, Paper 8, 16-
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`17 (2018) (denying institution). Aquestive also argues that the applicant misled the
`
`examiner. Pet. 7-10. Yet even assuming arguendo1 that the applicant’s argument
`
`was wrong, Aquestive fails to show that the examiner erred by relying on such
`
`argument to allow the claims. Cf. Innogenetics, N.V. v. Abbott Labs., 512 F.3d
`
`1363, 1379 (Fed. Cir. 2008) (no presumption of materiality from attorney
`
`argument). Finally, Aquestive argues that the examiner mistakenly held that Sonne
`
`does not teach an alkyl glycoside, but failed to note that the examiner relied on
`
`Meezan’962 for this teaching. Pet. 10.
`
`All of the Becton factors weigh in favor of denying institution:
`
`1. Factors a-c: The Similarities and Material Differences
`Between the Asserted Art and the Prior Art Involved
`During Examination; the Cumulative Nature of the
`Asserted Art and the Prior Art Evaluated During
`Examination; and the Extent to which the Asserted Art
`
`1 Neurelis denies that any of the cited examples are objectively misleading in
`
`context, but in any case Aquestive provides no evidence that the applicant intended
`
`to mislead or that the examiner was actually misled. Baseless, derogatory
`
`accusations against the examiner and an opposing party violate USPTO rules.
`
`37 CFR §1.3 (discourteous papers “will not be entered”) (emphasis added) &
`
`§42.1(c) (“Each party must act with courtesy and decorum in all proceedings
`
`before the Board, including interactions with other parties”).
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`was Evaluated During Examination
`As detailed above, both Sonne and Meezan’962 were applied and used as the
`
`basis of an obviousness rejection during prosecution of the ’546 patent and were
`
`used in combination with another reference during the prosecution of the ’439
`
`application. The examiner detailed the disclosures of the Sonne and Meezan’962
`
`references in numerous rejections; rejections that were extensively discussed in a
`
`lengthy back-and-forth between the examiner and applicant. Accordingly, the first
`
`three factors weigh strongly in favor of denying the petition.
`
`2. Factor d: The Extent of 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
`Since the references are the same, Aquestive’s arguments substantially
`
`overlap those made during examination of the ’546 patent and the ’439 application,
`
`which weighs in favor of denying institution under section 325(d). As detailed in
`
`the chart below, the arguments of Aquestive and Dr. Peppas mirror those made
`
`during prosecution.
`
`Aquestive argues:
`
`Examiner argued:
`
`Ground 1: invalidity under 35 U.S.C. §
`
`’439 Application: unpatentable under
`
`103(a) over Sonne and Meezan ’962.
`
`35 U.S.C. § 103(a) over Sonne,
`
`Pet. 5.
`
`EX1007, pp. 0476-79; 0514-15, over
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`Sonne and Meezan ’962, EX1007, pp.
`
`0480-81; 0515-0516, and over Lehat in
`
`view of Sonne and Meezan ’962,
`
`EX1007, pp. 2806-10; 2938-39; 3069-
`
`72; 3095-99; 3313-18; 3472-77.
`
`’546 Patent: unpatentable under 35
`
`U.S.C. § 103(a) over Sonne and Meezan
`
`’962. EX1004, p. 2125-2127.
`
`Sonne teaches a method of treatment by
`
`’439 Application:
`
`delivery of a substantially insoluble or
`
`Sonne teaches tocopherol compositions
`
`sparingly soluble biologically active
`
`for the delivery of biologically active
`
`agent that may be administrated to
`
`agents which are sparingly soluble in
`
`mucosal membranes with nasal
`
`water, such as diazepam . . . One
`
`administration being particularly
`
`particular nasal formulation contains 5g
`
`preferred. Pet. 41.
`
`of diazepam, 44g Tenox GT2 (70%
`
`Sonne further discloses a diazepam, a
`
`tocopherol) . . . the Composition may be
`
`benzodiazepine drug, in an intranasal
`
`in the form of a spray formulation . . .
`
`solution. Pet. 42.
`
`Sonne teaches that “transmucosal
`
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`Sonne discloses alkyl glycoside
`
`delivery is preferred” and “[n]asal . . .
`
`(cetearyl glucoside) in a diazepam
`
`administrations are particularly
`
`emulsion. Pet. 45.
`
`preferred.”
`
`Meezan ’962 discloses a method of
`
`Sonne does not teach the addition of
`
`increasing absorption by nasal
`
`alkyl glycoside in an amount from
`
`administration and encompasses small
`
`0.01% to 1%.
`
`molecule organic drug molecules, small
`
`Meezan ’962 teaches that alkyl
`
`organic molecules, anti-seizure agents
`
`glycoside is an absorption enhancer for
`
`(topiramate, zonisamide), and small
`
`drug administration and demonstrates
`
`molecules. A POSA would also apply
`
`that alkyl glycosides can increase drug
`
`Meezan’962 to benzodiazepines. Pet.
`
`absorption when administered via nasal
`
`42.
`
`spray, where the active ingredient may
`
`be in the form of nanoparticles.
`
`Peppas Declaration:
`
`EX1007, pp. 2806-08.
`
`Sonne teaches 5% diazepam, 65%
`
`It would have been obvious to a POSA
`
`alpha-tocopherol, 19% ethanol, and 11%
`
`administering the nasal spray
`
`benzyl alcohol. A POSA seeking to
`
`formulation of Sonne to use the
`
`optimize the bioavailability of this
`
`surfactant taught by Meezan ’962 to
`
`formulation would look to Meezan ’962
`
`improve the bioavailability of drug
`
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`to add alkyl glycoside. EX1041, ¶¶ 182,
`
`administration via a nasal spray.
`
`264-268.
`
`EX1007, pp. 3070-71.
`
`’546 Patent:
`
`Sonne teaches tocopherol compositions
`
`for the delivery of biologically active
`
`agents which are sparingly soluble in
`
`water, such as diazepam . . . One
`
`particular nasal formulation contains 5g
`
`of diazepam, 44g Tenox GT2 (70%
`
`tocopherol) . . . the Composition may be
`
`in the form of a spray formulation . . .
`
`Sonne teaches that “transmucosal
`
`delivery is preferred” and “[n]asal . . .
`
`administrations are particularly
`
`preferred.”
`
`Meezan ’962 teaches that alkyl
`
`glycosidase is an absorption enhancer
`
`for drug administration and discloses
`
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`use of alkyl glycoside in nasal
`
`administration. Specifically, Meezan
`
`demonstrates that the addition of 0.25%
`
`of alkyl glycoside can increase drug
`
`absorption from about 3%
`
`bioavailability to about 90%
`
`bioavailability when the drug is
`
`administered via a nasal spray. Meezan
`
`further teaches that active ingredients
`
`for the nasal spray may be in the form of
`
`nanoparticles.
`
`It would have been obvious to one of
`
`ordinary skill in the art formulating the
`
`composition of Sonne to incorporate the
`
`alkyl glycosidase of Meezan in order to
`
`increase nasal absorption.
`
`It would have also been obvious to
`
`include the active ingredient in the form
`
`of nanoparticles, given that such a form
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`is taught to be suitable by Meezan ’962.
`
`EX1004, pp. 2125-27.
`
`Sonne’s discloses tocopherols;
`
`’439 Application:
`
`specifically, Sonne’s Example 11
`
`Sonne teaches tocopherol compositions
`
`includes 40% alpha-tocopherol. Pet. 43.
`
`for the delivery of biologically active
`
`agents which are sparingly soluble in
`
`Peppas Declaration:
`
`water, such as diazepam.
`
`Sonne discloses a tocopherol
`
`EX1007, pp. 2806.
`
`formulation. EX1041, ¶¶ 175, 264.
`
`Sonne explicitly teaches “[t]o optimize
`
`the stability of the emulsions, it may be
`
`appropriate to add surfactants such as
`
`Vitamin E TPGS poloxamers (e.g.,
`
`Pluronic RTM), cetearyl glucoside,
`
`polysobrates or sorbitan esters of fatty
`
`acids, or any of the other surfactants
`
`well known in the art.” Given an
`
`explicit teaching to include a surfactant,
`
`there is no reason for one of skill in the
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`art to be taught away from including a
`
`surfactant.
`
`EX1007, p. 3316.
`
`’546 Patent
`
`Sonne teaches tocopherol compositions
`
`for the delivery of biologically active
`
`agents which are sparingly soluble in
`
`water, such as diazepam . . . One
`
`particular nasal formulation contains 5g
`
`of diazepam, 44g Tenox GT2 (70%
`
`tocopherol) . . . the Composition may be
`
`in the form of a spray formulation . . .
`
`Sonne teaches that “transmucosal
`
`delivery is preferred” and “[n]asal . . .
`
`administrations are particularly
`
`preferred.”
`
`EX1004, pp. 2125-27.
`
`Sonne includes 55% ethanol and 0%
`
`’439 Application:
`
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`benzyl alcohol, as well as 19% and
`
`Sonne also teaches that co-solvent such
`
`18.57% ethanol and 11% benzyl
`
`as ethanol, benzyl alcohol, sesame oil or
`
`alcohol. Pet. 44.
`
`propylene glycol can be used in order to
`
`optimize the formulations bioadhesion,
`
`Peppas Declaration:
`
`sprayability and viscosity. When ethanol
`
`Sonne provides a way to solve the
`
`is used in the formulations, it may be
`
`viscosity problem—by adding ethanol in
`
`used in an amount of 11% by weight of
`
`varying concentrations. EX1041, ¶¶
`
`the formulation . . . viscosity can be
`
`176, 269.
`
`reduced by the addition of co-solvents
`
`A POSA would not be dissuaded from
`
`such as ethanol.
`
`adding ethanol despite Sonne teaching
`
`EX1007, p. 2807.
`
`that ethanol is an irritant. EX1041, ¶
`
`177.
`
`To increase viscosity, co-solvents such
`
`as ethanol can be added. Since ethanol
`
`can be irritating to certain mucosal
`
`tissue, Sonne alternatively teaches
`
`emulsification as a means to lower
`
`viscosity. Thus, Sonne teaches three
`
`formulating alternatives, (1) high
`
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`viscosity, (2) co-solvents (i.e., ethanol)
`
`addition and (3) emulsification.
`
`EX1007, pp. 3070-72.
`
`While ethanol addition is not listed as a
`
`most preferred method for viscosity
`
`reduction, it is taught as a suitable
`
`method for such . . . It is further noted
`
`that nasal formulations are not limited to
`
`sprays, which may require higher
`
`amounts of ethanol, but can be in the
`
`form of drops, which can be more
`
`viscous.
`
`EX1007, p. 3098.
`
`Sonne does not teach away from using
`
`ethanol. A reference may be relied upon
`
`for all it would have reasonably
`
`suggested to one having ordinary skill in
`
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`the art, including non-preferred
`
`embodiments.
`
`EX1007, p. 3316-17.
`
`Sonne teaches the inclusion of ethanol,
`
`benzyl alcohol or propylene glycol in an
`
`amount sufficient to provide the desired
`
`formulation bioadhesion, sprayability
`
`and viscosity.
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`Further disagreeing with applicant that
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`Sonne does not disclose 7.5% alcohol:
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`Anticipation may require such a specific
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`embodiment, but the standard for
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`obviousness does not require that a
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`reference provide an exemplary
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`formulation.
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`EX1007, p. 3473, 3475.
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`’546 Patent
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`Sonne teaches a composition that may
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`contain co-solvents such as ethanol,
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`benzyl alcohol, sesame oil and
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`propylene glycol used in order to
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`optimize the formulations bioadhesion,
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`sprayability and viscosity.
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`It would have been obvious to POSITA
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`to optimize the type and amount of co-
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`solvent to provide the desired
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`bioadhesion, sprayability, and viscosity
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`given that Sonne teaches that the
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`purpose of the co-solvents is to modify
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`the bioadhesion, sprayability and
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`viscosity of the formulation.
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`EX1004, 2125.
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`Ultimately, the examiner issued the ’546 Patent and later issued the ’876
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`patent despite its prior arguments that these references rendered the claims
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`unpatentable. Aquestive seeks to rehash those same arguments; hence, the petition
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`should be denied.
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`3. Factor e: Whether Petitioner has Pointed Out Sufficiently
`How the Examiner Erred in Its Evaluation of the Asserted
`Prior Art
`Where a substantially identical reference was previously before the
`
`examiner, the petitioner bears the burden of showing how the examiner materially
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`erred in considering the reference. See Juniper Networks, Inc. v. Mobile
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`Telecomms. Techs., LLC, IPR2017-00642, Paper 31, 10-11 n.6, 19-20 (2018)
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`(collecting cases) (“Consistent with the Office’s need to provide streamlined
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`examination and to utilize Office resources effectively, a petitioner must articulate
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`error in the Examiner’s evaluation of the previously considered prior art.”).
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`Aquestive has failed to carry this burden. While acknowledging that the examiner
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`considered the Sonne and Meezan ’962 references in its prior rejections, Aquestive
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`disparages the examiner’s ultimate decision to issue the ’876 patent based on two
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`flawed theories: (1) that the applicant misled the examiner from proper
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`consideration of Example 11 of Sonne; and (2) that the examiner mistakenly
`
`believed that Sonne did not disclose alkyl glycosides.
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`First, Neurelis did not mislead the examiner from proper consideration of
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`Example 11 of Sonne.2 Aquestive contends the applicant mistakenly argued that
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`2 Indeed, Petitioner’s misrepresentation of the fact raises is of concern in light of
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`37 C.F.R. § 42.1(c) requiring the parties to “act with courtesy and decorum in all
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`Sonne only teaches use of ethanol in emulsions (as opposed to solutions) and
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`further mistakenly characterized Example 11 as an emulsion, instead of a solution.
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`Pet. 8-9. Not so. The applicant did acknowledge that Sonne teaches ethanol in
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`solutions, but argued that
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`Given the general admonition of Sonne [] that ethanol is irritating to
`some mucosal tissues, and the lack of even a single example of an
`intranasal solution containing any ethanol, one of ordinary skill in the
`art would have reasonably concluded that the nasal mucosa is a tissue
`that is irritated by ethanol, and would have thus concluded that
`intranasal administration of the recited formulation, which contain
`alcohol of 10% to 70% (w/w), would not succeed as a therapeutic
`method.
`EX1007, p. 3332; see also EX1004, p. 2149. Additionally, the applicant did
`
`acknowledge that Example 11 is a “solution,” in subsequent responses, but argued
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`that “all of Sonne’s solutions require water and oil. Further, as all of Sonne’s
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`solutions require oil, Sonne fails to provide motivation to prepare the claimed nasal
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`solutions, which do not require oil.” EX1007, pp. 2833-34. The applicant further
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`argued that “Examples 1, 2, 8, 9, 10, 15, 17, and 19 are emulsions (contain water);
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`Example 11 contains triacetin; and Examples 16 and 16 require 59.9% and 44.5%
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`sesame oil, respectively, whereas the formulations recited in the instant claims
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`exclude such additional ingredients.” EX1007, p.3333. Thus, the applicant did not
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`mislead the Examiner from a proper consideration of Sonne and Example 11.
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`proceedings before the Board, including in interactions with other parties.”
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`Yet, even assuming arguendo that these statements were incorrect, the
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`examiner considered the entirety of Sonne, including Example 11, in depth, which
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`the Board has found sufficient in similar circumstances in declining to institute
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`review. See e.g., Exocad GmbH & Exocad America, Inc. v. 3SHAPE A/S,
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`IPR2018-00785, Paper 8, 8-12 (2018) (declining to find persuasive Petitioner’s
`
`argument the Patent Owner submitted erroneous arguments where Petitioner
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`misrepresented what Patent Owner argued and, even assuming the statements were
`
`incorrect, noting that the Examiner considered the entirety of the prior art
`
`disclosure in depth); Edge Endo, LLC v. Maillefer Instruments Holding S.A.R.L.,
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`IPR2018-01349, Paper No. 15 at 13-14 (“In the context before us, where the
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`examiner rejected the claims based on substantially the same prior art, we attribute
`
`less weight to the differences in the arguments raised.”); Argentum Pharm., LLC v.
`
`Merck Patentgesellschaft, IPR2018-00423, Paper 7, 19 (2018) (declining to find
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`persuasive Petitioner’s argument that “Examiner erred by not identifying Example
`
`4 as the closest prior art” where the Examiner identified the patent itself as the
`
`closest prior art, which included Example 4, and finding no persuasive reason for
`
`the Examiner to have narrowed “the closest prior art” to a specific example within
`
`the patent; additionally noting that Petitioner did not sufficiently show that the
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`disclosure was anticipatory).
`
`Second, while Aquestive argues that the examiner mistakenly thought Sonne
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`failed to disclose alkyl glycosides, Aquestive failed to acknowledge the examiner’s
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`subsequent rejections, where he stated “Thus, one of ordinary skill in the art would
`
`have found it obvious to nasally administer a composition that contains only
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`tocopherol or tocotrienol, an alcohol and optionally one or more alkyl glycosides.
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`Sonne does not teach the addition of alkyl glycoside in an amount from 0.01% to
`
`1%.” EX1007, p. 2808.
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`At best, Aquestive is mistaken in its arguments to the Board about the
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`prosecution history. This factor weighs heavily in favor of denying review.
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`4. Factor f: The Extent to which Additional Evidence and
`Facts Presented in the Petition Warrant Reconsideration
`of the Prior Art or Arguments
`The grounds applied to claim 1—the sole independent claim of the ’876
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`patent—contain no additional documentary evidence or facts beyond those the
`
`examiner considered. The declaration of Petitioner’s expert, Dr. Peppas, largely
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`parrots Petitioner’s attorney argument and lacks technical analysis on key issues.
`
`Moreover, the Peppas declaration merely interprets the same references that the
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`examiner interpreted and properly set aside. See Dorco Co., Ltd. v. The Gillette
`
`Co., LLC, IPR2017-00500, Paper 7, 15-20 (2017); Juniper Networks, Inc. v.
`
`Mobile Telecommunications Tech., LLC, IPR2017-00642, Paper 24, 7-13 (2017)
`
`(declining to institute review despite addition of expert testimony where, even
`
`though the declaration provided further explanation of the prior art, finding this
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`factor alone did not overcome the circumstances here, where the prior art was the
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`subject of substantive discussion and studied evaluation in the rejection of the
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`claims); Vestas-American Wind Tech., Inc. v. General Electric Co., IPR2018-
`
`01029, Paper 9, 15-16 (2018) (declining to institute review despite addition of
`
`expert testimony where expert testimony presented little, if any, persuasive
`
`technical evidence or explanation as to why the prior art teaches modification,
`
`instead merely quoting from the reference to make the conclusion). Neither the
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`Petition nor the Peppas declaration warrant re-review of the ’876 patent as the
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`Board would merely be reviewing the same arguments the examiner made and the
`
`applicant overcame during the prosecution.
`
`There is no good reason to reconsider the same prior art and the same
`
`arguments that were extensively analyzed during the multiple, lengthy,
`
`examinations that culminated in the issuance of the ’876 patent. Accordingly, the
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`Board should exercise its discretion under § 325(d) to deny institution o