UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
` AQUESTIVE THERAPEUTICS, INC.,
`Petitioner,
`
`v.
`
`NEURELIS, INC.,
`Patent Owner.
`____________________
`
`Case IPR2019-00449
`Patent 9,763,876
`____________________
`
`PATENT OWNER PRELIMINARY RESPONSE
`35 U.S.C. 313
`
`1
`
`
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
` AQUESTIVE THERAPEUTICS, INC.,
`Petitioner,
`
`v.
`
`NEURELIS, INC.,
`Patent Owner.
`____________________
`
`Case IPR2019-00449
`Patent 9,763,876
`____________________
`
`PATENT OWNER PRELIMINARY RESPONSE
`35 U.S.C. 313
`
`1
`
`
`
`Table of Contents
`I. Precise Requested Relief ..................................................................................... 1
`II. Statement of Reason to Deny .............................................................................. 1
`A.Background ....................................................................................................... 1
`Epilepsy and epilepsy treatments .............................................................. 1
`1.
`The challenged patent and claims ............................................................. 2
`2.
`B. Claim Construction ........................................................................................... 4
`C. Denial Warranted Under Section 325(d) .......................................................... 6
`D.Denial Warranted Under Section 314(a) ........................................................ 10
`Claims 8-10 and 15 deserve their claimed priority ................................. 15
`1.
`Claims 30-33 deserve their claimed priority ........................................... 17
`2.
`Claims 34-36 deserve their claimed priority ........................................... 21
`3.
`Without Cartt’865 as a reference the petition fails .................................. 25
`4.
`III. Conclusion .........................................................................................................25
`Exhibit List ...............................................................................................................26
`Type-Volume Certificate .........................................................................................27
`Certificate of Service ...............................................................................................28
`
`-i-
`
`IPR2019-00449
`
`
`
`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 REASON TO DENY
`A.
`BACKGROUND
`1.
`Epilepsy and epilepsy treatments
`
`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 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 seizures. EX2004, 3.
`
`Uncontrolled seizures may result in injury, anxiety, depression, brain damage and
`-1-
`IPR2019-00449
`
`
`
`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
`
`Diazepam belongs to a family of drugs (benzodiazepines) that are useful for
`
`treating seizures. EX1001, 1:29-39. While other benzodiazepine formulations are
`
`available for treating seizures, they suffer from solubility problems. EX1001, 1:53-
`
`57. These existing formulations can also be very difficult to administer to a subject
`
`during a seizure, particularly if the person administering therapy is not a health
`
`professional. EX1001, 1:58-2:20. The present inventors realized that while nasal
`
`delivery would address the administration problem, solubility problems pose
`
`challenges for nasal administration. The present inventors developed the use of
`
`tocopherols and tocotrienols with alcohols as substantial fractions of the
`
`formulation to address the solubility problem, while still providing an acceptable
`
`nasal-delivery formulation. Claim 1, from which the challenged claims depend,
`
`defines the invention as (EX1001, 63:26-34):
`
`-2-
`
`IPR2019-00449
`
`
`
`A method of treating a patient with a disorder which is treatable
`with a benzodiazepine drug, comprising:
`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.
`
`Challenged claims 8-10 depend from claim 1 and further specify that “the
`
`solution contains ethanol from 1 to 25% (w/v) and benzyl alcohol from 1 to 25%
`
`(w/v).” EX1001, 63:59-67.
`
`Challenged claim 15 depends from claim 1 and further specifies that “the
`
`solution comprises ethanol from 10 to 22.5% (w/v) and benzyl alcohol from 7.5 to
`
`12.5% (w/v).” EX1001, 64:16-18.
`
`Challenged claims 30 and 31 depend from claim 1 and further specify that
`
`the solution contain “diazepam from 5 to 15% (w/v)” and “vitamin E from 45 to
`
`65% (w/v), ethanol from 10 to 25% (w/v) and benzyl alcohol from 5 to 15%
`
`(w/v)”.
`
`-3-
`
`IPR2019-00449
`
`
`
`Challenged claims 32 depends from claim 1 and further specifies that the
`
`solution contain “vitamin E from 50 to 60% (w/v), ethanol from 15 to 22.5% (w/v)
`
`and benzyl alcohol from 7.5 to 12.5% (w/v)”.
`
`Challenged claims 33 depends from claim 1 and further specifies that the
`
`solution contain “vitamin E from 50 to 60% (w/v), ethanol from 17 to 20% (w/v)
`
`and benzyl alcohol from 10 to 12% (w/v)”.
`
`Challenged claims 34-36 depend from claim 1 and further specify that
`
`“treatment achieves bioavailability that is from about” 80-125%, 90-110%, and
`
`92.5-107.5% , respectively.
`
`The challenged patent (“Cartt’876”) issued in 2017, but claims benefit back
`
`to 2008. EX1001, cover.
`
`CLAIM CONSTRUCTION
`B.
`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
`
`claims. Petition (“Pet.”) 9-13. Aquestive otherwise contends that the claims should
`
`be given their ordinary meaning except to the extent Neurelis has acted as a
`
`lexicographer. Id., 9-10. Surprisingly, Aquestive does not address the claim term
`
`about, even though it is expressly defined in the specification (EX1001, 17:60-65)
`
`as follows:
`
`As used herein, the modifier “about”" is intended to have its regularly
`recognized meaning of approximately. In some embodiments, the term
`-4-
`IPR2019-00449
`
`
`
`may be more precisely interpreted as meaning within a particular
`percentage of the modified value , e.g.[,] “about ” may in some
`embodiments mean ±20%, ±10%, ±5%, ±2%, or ±1% or less.
`
`A proper understanding of the defined meaning of about is critical to determining
`
`how a person of skill would have understood the challenged claims consistent with
`
`the specification. Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (en
`
`banc) (“In such cases, the inventor’s lexicography governs.”). Aquestive’s
`
`oversight is all the more surprising because Aquestive does construe about in its
`
`related petitions (substituting its expert’s opinion for the specification’s
`
`lexicography), indicating the oversight in this petition is intentional. Cf. IPR2019-
`
`00450 Pet. 16-17; IPR2019-00451 Pet. 14; cf. Medtronic, Inc. v. Endotach LLC,
`
`IPR2014-00695, Paper 18, 9 (2014) (denying institution) (“Thus, although
`
`Petitioner suggests it was unaware of Patent Owner’s claim construction position
`
`… until after it filed its First Petition, Petitioner had the burden to anticipate
`
`reasonable claim construction positions, and adequately address such positions in
`
`its Petition as needed.”).
`
`Aquestive further contends that it is not bound by its own constructions in
`
`other proceedings. Pet. 10. 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
`
`-5-
`
`IPR2019-00449
`
`
`
`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).
`
`DENIAL WARRANTED UNDER SECTION 325(D)
`C.
`In Becton Dickinson and Co. v. B. Braun Melsungen AG, IPR2017-01586,
`
`Paper 8 (2017) (informative), 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 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.
`
`-6-
`
`IPR2019-00449
`
`
`
`Aquestive does not address the applicability of section 325(d) to this
`
`petition, yet its proffered grounds indisputably depend on an issue that was
`
`squarely before the examiner. Every ground depends on the availability of the
`
`Cartt’865 application (EX1010) as prior art. Pet. 5-6. Indeed, Aquestive contends
`
`most of the challenged claims are anticipated by Cartt’865. Pet. 5. Yet the
`
`examiner was well aware of the Cartt’865 application: it is both listed as a cited
`
`reference (EX1001, cover 2, right col.) and, in the very first paragraph of the
`
`specification, incorporated by reference into the challenged patent (EX1001, 1:7-
`
`20) as a continuation-in-part antecedent. The examiner could not have been
`
`unaware that the challenged patent is a continuation-in-part and that the Cartt’865
`
`application was cited as a potential prior-art reference. Moreover, the Manual of
`
`Patent Examining Procedure requires examiners to consider whether intervening
`
`prior art should be applied. MPEP §2133.01 (“Rejections of Continuation-In-Part
`
`(CIP) Applications”); see also Paperless Accounting, Inc. v. Bay Area Rapid
`
`Transit System, 804 F.2d 659, 663 (Fed. Cir. 1986) (reversing for improperly
`
`drawing an adverse inference from decision to file a continuation-in-part)
`
`(discussing binding nature of MPEP when noting that with no rejection pending
`
`the patent owner could not and need not contest any possible adverse inference).
`
`Administrative law requires a presumption of regularity in official acts. U.S.
`
`Postal Serv. v. Gregory, 534 U.S. 1, 10 (2001), citing United States v. Chem.
`
`-7-
`
`IPR2019-00449
`
`
`
`Found., Inc., 272 U.S. 1, 14-15 (1926) (“The presumption of regularity supports
`
`the official acts of public officers and, in the absence of clear evidence to the
`
`contrary, courts presume that they have properly discharged their official duties.”).
`
`Instead, Aquestive’s entire case depends on an assumption of irregularity. Despite
`
`the blatant visibility of this pivotal question on the face of the patent and the
`
`prosecution history, Aquestive makes no attempt to explain why the examiner
`
`should be assumed to have departed from the most-applicable written agency
`
`examining protocol—the MPEP—and thus why the Board (and Neurelis) should
`
`address the question again with all of the attendant waste of time and resources.
`
`Similarly, in ground 3, Aquestive relies on the Meezan’962 application
`
`(EX1011) to provide the further limitations of challenged claims 34-36. Pet 6.
`
`However, Meezan’962 was cited by the same examiner for the same purpose
`
`(increased bioavailability) in a rejection for the parent (’942) application.1
`
`EX1004, 2125. Moreover, the examiner rejected the challenged claims for double-
`
`patenting over (meaning he held them to be patentability indistinct from) the
`
`patented claims issuing from the ’942 application. EX1002, 438. In sum, the
`
`examiner has already applied Meezan’962 to claims that he believed were
`
`1 In the rejection, Meezan’962 was combined with Sonne (EX1004, 2125), the
`
`same combination Aquestive proffers in IPR2019-00450. IPR2019-00450 Pet. 5.
`
`-8-
`
`IPR2019-00449
`
`
`
`patentably indistinct from challenged claims 34-36, for the same reason, yet
`
`allowed those claims. Again, Aquestive makes no effort to address the examiner’s
`
`previous consideration of the same reference for the same purpose.
`
`Applying the Becton Dickinson factors to this petition, factors (a), (b)
`
`and (d) weigh heavily against the petition because the same references were in
`
`front of the examiner for the same reasons. Factor (c) weighs against the petition
`
`because Meezan’962 was applied against subsequently-issued claims that the
`
`examiner held were patentably indistinct. While the examiner did not apply
`
`Cartt’865 in a rejection, given its express citation as potential prior art and its
`
`express incorporation as a continuation-in-part parent application, the examiner
`
`could not have been unaware of the possible issue, making the lack of a rejection
`
`very telling. Finally, factors (e) and (f) weigh strongly against the petition because
`
`Aquestive has not even acknowledged the section 325(d) issue, much less provided
`
`any analysis of justification for revisiting these issues. Nor can Aquestive plead
`
`surprise because the problem is apparent from its own exhibits. Aquestive is not
`
`entitled to a do-over on this issue.
`
`The Board has 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
`
`-9-
`
`IPR2019-00449
`
`
`
`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. The lack of exigency perhaps explains why Aquestive
`
`does not address this factor either.
`
`DENIAL WARRANTED UNDER SECTION 314(A)
`D.
`As noted in the previous section, Aquestive’s entire case assumes that the
`
`challenged claims are not entitled to their claimed priority, such that the challenged
`
`patent’s own parent application may be applied as prior art. Pet. 17. Aquestive
`
`goes further and suggests that priority has never been previously considered, citing
`
`Power Oasis, Inc. v. T-Mobile USA, Inc., 522 F.3d 1299, 1305 (Fed. Cir. 2008).
`
`Aquestive (and, in fairness, Power Oasis) posits that if no rejection was made, then
`
`priority must not have been considered. This is, of course, a common logical
`
`fallacy2 that asserts the truth or falsity of what must be proven based solely on the
`
`apparent absence of explicit proof. Aquestive’s assertion ignores the readily-
`
`apparent alternative that priority was properly considered but could not justify a
`
`2 Namely, argumentum ad ignorantiam.
`
`-10-
`
`IPR2019-00449
`
`
`
`proper rejection. Significantly, neither Aquestive nor Power Oasis3 address the
`
`requirement in MPEP §2133.01and the presumption of regularity, which require
`
`the presumption that the examiner considered—and in making no rejection was
`
`satisfied by—the priority claim. Instead, Aquestive implies that the Board must
`
`presume that the examiner flagrantly disregarded directly-applicable written
`
`instructions in the MPEP, or executed those instructions incompetently despite the
`
`clear relevance of the instruction to the prosecution of an application expressly
`
`labeled as a continuation-in-part, all without a shred of evidence. Binding
`
`precedent requires the opposite presumption. Gregory, 534 U.S. at 10; Chem.
`
`Found., 272 U.S. at 14-15. By assuming examiner irregularity, Aquestive
`
`improperly attempts to shift its burden to Neurelis, however, the ultimate burden
`
`on all questions of patentability remains with the petitioner. 35 U.S.C. 316(e).
`
`3 In fairness to the court, the MPEP requirement does not appear to have been
`
`briefed in Power Oasis. Power Oasis is also distinguishable because in that case
`
`the intervening prior art was not before the examiner, 522 F.3d at 1305, while in
`
`this case the purported prior art was expressly cited to the examiner and is listed on
`
`the face of the patent, which amply supports a presumption that the examiner must
`
`have done his job.
`
`-11-
`
`IPR2019-00449
`
`
`
`Aquestive begins its analysis with a chart that excludes claim 1, the
`
`independent claim from which all the other claims depend. Pet. 20-21. In the very
`
`next section, Aquestive misconstrues claim 1 as having a “minimum of 10%
`
`alcohols.” Pet. 21. Significantly, claim 1 requires “ethanol and benzyl alcohol in a
`
`combined amount from about 10% to about 70% (w/w)”. EX1001, 63:33-34. As
`
`Aquestive knows (because it argues it in the other petitions), about is expressly
`
`and very broadly defined in the specification. EX1001, 17:60-65. Indeed, a
`
`disclosed amount may vary by up to 20% if the nature of the embodiment permits.
`
`For example, a disclosure of about 10% would include up to 30%, but logically
`
`could not include -20%. Hence, a person of ordinary skill applying an ordinary
`
`understanding of the claim language in light of the specification would have
`
`reasonably understood a requirement for about 10% alcohol to include any positive
`
`amount of alcohol up to 30%. Phillips, 415 F.3d at 1316 (“In such cases, the
`
`inventor’s lexicography governs.”).
`
`This broad understanding of the invention has existed from the beginning.
`
`For example, the earliest claimed priority is provisional application 61/040,558,
`
`filed 28 March 2008 (well before Cartt’865 was published). EX1001, cover,
`
`item (60). This provisional includes the same definition of about. EX1008, ¶51.
`
`Likewise, Cartt’865, the reference said to anticipate but not support the challenged
`
`claims, also contains the same definition of about. In sum, the scope of the
`
`-12-
`
`IPR2019-00449
`
`
`
`disclosed ranges has always, intentionally, been very broad and has always
`
`included the claimed ranges.
`
`Moreover, the challenged claims require such an understanding. For
`
`example, as noted above, claim 1 requires “ethanol and benzyl alcohol in a
`
`combined amount from about 10% to about 70% (w/w)”. EX1001, 65:33-34. Yet
`
`challenged claim 8, which depends directly from claim 1, requires “ethanol from 1
`
`to 25% (w/v) and benzyl alcohol from 1 to 25% (w/v)”. EX1001, 63:49-51. If one
`
`were to adopt Aquestive’s blinkered reading of the claims and the specification,
`
`this dependency would be impossible. Properly read in light of the specification,
`
`including the disclosure’s express definitions, the dependency makes perfect
`
`sense:4 claim 1 embraces any positive amount of the combination of ethanol and
`
`benzyl alcohol up to 90%, making the further requirement for both ethanol and
`
`4 Because Aquestive ignored the express definition in the present petition, we
`
`cannot guess how it would have explained this dependency other than to suggest
`
`that the examiner either did not read or did not understand the claims he examined.
`
`Once again, precedent requires that we presume that the examiner properly read
`
`claim 8 in light of the specification and thus refrained from rejecting the claim
`
`because it was an appropriate further limitation when properly construed.
`
`-13-
`
`IPR2019-00449
`
`
`
`benzyl alcohol as the specific alcohols, both in ranges of 1-25%, perfectly
`
`appropriate narrowing limitations.5
`
`As noted before, Aquestive has assiduously avoided addressing the express
`
`definition of about in this petition, even though Aquestive relies on it in the related
`
`petitions. Deliberately selective production of evidence warrants an adverse
`
`inference that the withheld expert testimony would have undermined Aquestive’s
`
`case. Cf. Nan Ya Plastics Corp., Ltd. v. United States, 810 F.3d 1333, 1338 (Fed.
`
`Cir. 2016) (affirming Commerce Department application of adverse inferences to
`
`an uncooperative party); cf. 37 CFR §42.51(b)(1)(iii) (requiring production of
`
`inconsistent evidence). At the very least, Aquestive has failed to comply with the
`
`requirement that it lay out its case with particularity, by failing to address the
`
`glaring contrary evidence in its own exhibits. 35 U.S.C. 312(a)(3); 37 CFR
`
`§42.104(b)(3)-(5) (requiring clear statement of case, claim constructions and
`
`exhibits); cf. In re Magnum Oil Tools, Int’l, Ltd., 829 F.3d 1364, 1378 (Fed. Cir.
`
`2016) (making the patent owner “disprove” what the petitioner failed to prove is an
`
`improper burden shift).
`
`5 Aquestive has already stipulated—at least for this petition—that “(w/v)” and
`
`“(w/w)” have effectively the same meaning. Pet. 13.
`
`-14-
`
`IPR2019-00449
`
`
`
`1.
`
`Claims 8-10 and 15 deserve their claimed priority
`
`Aquestive contends that “[w]hile Cartt’865 does disclose that alcohols may
`
`be present in the following ranges (all prefaced with ‘about’), none of the
`
`following disclosed ranges correspond to (or fall within) the ranges recited in
`
`Claims 8-10 and 15”. Pet. 22. The argument fails for two reasons, discussed in
`
`further detail below. First, Aquestive misstates the law, which requires
`
`consideration of the full disclosure for all it fairly teaches to those skilled in the art
`
`rather than restricting the analysis to express disclosure. Second, Aquestive not
`
`only fails to address all of the relevant express disclosure, but also tactically avoids
`
`discussing the key portion of the disclosure even while acknowledging its
`
`relevance. Pet. 22 (“all prefaced with ‘about’”).
`
`The test for sufficiency of support in a parent application is whether the
`
`disclosure of the application relied upon reasonably conveys to the artisan that the
`
`inventor had possession at that time of the later claimed subject matter. Vas-Cath
`
`Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991) (reversing judgment of no
`
`support under 35 U.S.C. 120). Under long-established precedent, express
`
`disclosure is not a requirement. Id. at 1566, citing Ralston Purina Co. v. Far-Mar-
`
`Co, Inc., 772 F.2d 1570, 1575 (Fed. Cir. 1985) (ranges found in applicant's claims
`
`need not correspond exactly to those disclosed in parent application; issue is
`
`-15-
`
`IPR2019-00449
`
`
`
`whether one skilled in the art could derive the claimed ranges from parent's
`
`disclosure).
`
`Aquestive accuses the inventors of disclosing a forest, then trying to claim
`
`specific trees. Pet. 22, quoting General Hospital Corp. v. Sienna Biopharms., Inc.,
`
`888 F.3d 1368, 1372 (Fed. Cir. 2018). Case law permits such flexibility when the
`
`specification provides guidance for the selection. Vas-Cath, 935 F.2d at 1566. Yet
`
`neither Aquestive nor its expert even address the full-scope of the disclosure,
`
`particularly the guidance on how to understand the term about. The specification
`
`clearly indicates that the inventors intended to include permissible ranges within
`
`±20%, providing expressly as examples specific values down to “±1% or less”.
`
`Written description is extremely case-specific. Id. at 1562. The petitioner
`
`(which bears the burden of proof on this issue), however, failed to provide any
`
`evidence of how a person skilled in the art would have understood the pivotal
`
`disclosure. As discussed previously, the conspicuous absence of testimony on this
`
`point (despite Aquestive’s reliance on the same definition in the other petitions)
`
`warrants an adverse inference against Aquestive, but at a minimum demonstrates
`
`that Aquestive has failed to adduce a facially adequate case in its petition for
`
`stripping the claims of their priority. Nan Ya Plastics, 810 F.3d at 1338 (adverse
`
`inferences); §42.51(b)(1)(iii) (inconsistent evidence); 35 U.S.C. 312(a)(3)
`
`-16-
`
`IPR2019-00449
`
`
`
`(insufficient petition); 37 CFR §42.104(b)(3)-(5) (same); Magnum Oil Tools,
`
`829 F.3d at 1378 (improper burden shift).
`
`2.
`
`Claims 30-33 deserve their claimed priority
`
`a. Claims 30 and 31 deserve their claimed priority for the
`diazepam limitations
`
`Aquestive urges that claims 30 and 31 are neither described nor enabled.
`
`These claims require “the solution consists of diazepam from 5 to 15% (w/v)” and
`
`other components. Aquestive contends that only three embodiments are disclosed
`
`(2%, 5% and 7%) and so any other embodiments in the claimed range are neither
`
`described nor enabled. Pet. 25. Yet Aquestive concedes that Cartt’865 itself
`
`discloses ranges encompassing the claimed range. Pet. 25 (“about 0.1-60%, about
`
`1-25%, … respectively”) (converting values given in EX1010, ¶0014). Aquestive
`
`asserts that as a matter of law, these ranges would not disclose the claimed range.
`
`However, as noted in the previous section, written description is extremely case-
`
`specific. See Vas-Cath, 935 F.2d at 1562, citing In re Driscoll, 562 F.2d 1245,
`
`1250 (CCPA 1977) (explaining “compliance with the description requirement of
`
`§112 … must be decided on its own facts. Thus, the precedential value of cases in
`
`this area is extremely limited.”). Once again, Aquestive entirely skips any analysis
`
`of how one skilled in the art would have understood the disclosure of “about 1-
`
`25%” in a context where about expressly permits variance between ±1% and
`
`±20%.
`
`-17-
`
`IPR2019-00449
`
`
`
`Aquestive’s enablement argument is simply that the range is not disclosed
`
`and that the inventors could not make a solution at all of the claimed
`
`concentrations. The first argument confuses enablement and written description,
`
`which are separate requirements in the patent law. Ariad Pharm., Inc. v. Eli Lilly &
`
`Co., 598 F.3d 1336, 1340 (Fed.Cir.2010) (en banc). The second argument lacks
`
`any basis other than Aquestive’s assertion, and again engages in the logical fallacy
`
`that an absence of examples necessarily means that one skilled in the art could not
`
`make the claimed composition. This is not the law: the specification need not
`
`describe how to make and use every possible variant of the claimed invention
`
`because prior art and routine experimentation may fill gaps and even extrapolate
`
`outside the scope of disclosed embodiments, depending on the predictability of the
`
`art. AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244 (Fed. Cir. 2003).
`
`In any case, Cartt’865 itself discloses that “Additional solutions of diazepam
`
`at varying concentrations are made in a similar manner, by varying the amount of
`
`diazepam and the relative amounts of Vitamin E and ethanol.” EX1010, ¶200
`
`(emphasis added). This demonstrates the expectation in Cartt’865 that those skilled
`
`in the art would know what to do. Aquestive has the burden to show the disclosure
`
`is wrong, but only cites a footnote in its expert’s declaration, which simply says
`
`that suspensions and solutions are different. Pet. 25, citing EX1041, ¶242 n.26. The
`
`footnote speculates that—solely due to the lack of solution examples at the higher
`
`-18-
`
`IPR2019-00449
`
`
`
`end of the range—“the inventors of Cartt’865 had not considered 10% solutions as
`
`viable, even though such concentrations in solution clearly were entirely possible
`
`at the time”. EX1041, ¶242 n.26. Where to begin? Not only is the testimony
`
`baseless (and insulting6) speculation about the inventors’ ignorance, it is also
`
`legally irrelevant. Enablement is an objective standard, so it does not matter what
`
`the inventors actually thought. Johns Hopkins Univ. v. CellPro Inc., 152 F.3d
`
`1342, 1360 (Fed. Cir. 1998) (“Because it is imperative when attempting to prove
`
`lack of enablement to show that one of ordinary skill in the art would be unable to
`
`make the claimed invention without undue experimentation, … CellPro's evidence
`
`concerning Civin's subsequent work is insufficient as a matter of law.”). Once
`
`again, Aquestive utterly fails to prove what it must:7 that a person of ordinary skill
`
`in the art could not make a solution with 5-15% diazepam; if anything, Aquestive
`
`proves the opposite.
`
`b. Claims 30-33 deserve their claimed priority for the
`Vitamin E limitations
`
`Vitamin E ranges are “from 45 to 60%” in claims 30 and 31, and are “from
`
`50 to 60%” in claims 32 and 33. Aquestive urges that these ranges are not
`
`6 37 CFR §42.1(c) requires courtesy and decorum from all participants.
`
`7 Significantly, Aquestive never applies any of the Wands factors.
`
`-19-
`
`IPR2019-00449
`
`
`
`supported, even while conceding that Cartt’865 discloses ranges including “about
`
`45-85%, about 50-90%, about 60-75%”. Pet. 26-27, citing EX1010, ¶¶0010, 0015
`
`and 0162. Once again, Aquestive makes no effort to address how a person skilled
`
`in the art would have understood these disclosures in view of the express definition
`
`of about. Aquestive incorrectly asserts that the claims lack written description as a
`
`matter of law with no substantive analysis. Pet. 27, but see Vas-Cath, 935 F.2d at
`
`1562 (written description is fact-intensive and case specific). As discussed
`
`previously, the conspicuous absence of testimony on this point (despite
`
`Aquestive’s reliance on the same definition in the other petitions) warrants an
`
`adverse inference against Aquestive, but at a minimum demonstrates that
`
`Aquestive has failed to adduce a facially adequate case in its petition for stripping
`
`the claims of their priority. Nan Ya Plastics, 810 F.3d at 1338 (adverse inferences);
`
`§42.51(b)(1)(iii) (inconsistent evidence); 35 U.S.C. 312(a)(3) (insufficient
`
`petition); 37 CFR §42.104(b)(3)-(5) (same); Magnum Oil Tools, 829 F.3d at 1378
`
`(improper burden shift).
`
`For enablement, Aquestive simply asserts that the claims are not enabled
`
`without any analysis. Once again, as petitioner, Aquestive is the party with the
`
`burden of proof on all patentability questions. 35 U.S.C. 316(e). A lack of proof is
`
`not proof of unpatentability.
`
`-20-
`
`IPR2019-00449
`
`
`
`c. Claims 30-33 deserve their claimed priority for the
`alcohol limitations
`
`Aquestive asserts that the alcohol ranges for these claims fail for the same
`
`reasons Aquestive provided for claims 8-10 and 15. Pet. 27. Aquestive is wrong for
`
`the same reasons provided above for claims 8-10 and 15. See section II above.D
`
`above1 above.
`
`3.
`
`Claims 34-36 deserve their claimed priority
`
`Aquestive argues that the bioavailability ranges of claims 34-36 are not
`
`described or enabled. Pet. 28-29. Aquestive concedes that Cartt’865 and the ’558
`
`provisional application disclose increased and improved bioavailability. Pet. 28-29,
`
`citing EX1010, ¶¶0074, 0075, 0139 and 0173; see also EX1008, ¶¶058, 059 and
`
`150. Indeed, since 2008, improved bioavailability has been the main point of the
`
`invention, EX1008, ¶058:
`
`It should be recognized by those of skill in the art that additional
`benzodiazepine compounds that have heretofore been considered to
`have marginal or little therapeutic benefit, either because of low
`bioavailability, poor pharmacokinetic properties or poor pharmacody-
`namic properties, may find use throu
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
