Trials@uspto.gov
`Tel: 571-272-7822
`
`Paper 8
`Entered: August 1, 2019
`
`
`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 B2
`
`
`Before ZHENYU YANG, JON B. TORNQUIST, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`TORNQUIST, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. §§ 314, 325(d)
`
`
`
`
`
`
`
`Tel: 571-272-7822
`
`Paper 8
`Entered: August 1, 2019
`
`
`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 B2
`
`
`Before ZHENYU YANG, JON B. TORNQUIST, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`TORNQUIST, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. §§ 314, 325(d)
`
`
`
`
`
`
`
`
`IPR2019-00450
`Patent 9,763,876 B2
`
`I. INTRODUCTION
`Aquestive Therapeutics, Inc. (“Petitioner”) filed a Petition (Paper 2,
`“Pet.”) requesting an inter partes review of claims 1–36 of U.S. Patent
`No. 9,763,876 B2 (Ex. 1001, “the ’876 patent”). Neurelis, Inc.1 (“Patent
`Owner”) filed a Preliminary Response to the Petition (Paper 6, “Prelim.
`Resp.”).
`For the reasons explained below, we exercise our discretion under
`35 U.S.C. §325(d) and decline to institute an inter partes review on the
`grounds set forth in the Petition.
`
`A. Related Proceedings
`The parties indicate that Petitioner has filed additional petitions
`against the ’876 patent in IPR2019-00449 and IPR2019-00451. Pet. 2;
`Paper 7, 2.
`
`B. The ’876 Patent
`The ’876 patent is directed to nasally administered pharmaceutical
`solutions containing one or more benzodiazepine drugs. Ex. 1001, 9:14–17.
`The ’876 patent explains that solubility challenges associated with
`benzodiazepine drugs previously hindered the development of formulations
`intended for oral, rectal, or parenteral administration. Id. at 1:53–57, 19:12–
`15. It was discovered, however, that vitamin E (which includes tocopherols
`and tocotrienols) is an effective carrier for benzodiazepine drugs, as these
`compounds are soluble, or at least partially soluble, in vitamin E. Id. at
`
`
`1 Patent Owner informs us that subsequent to the filing of the Petition, Hale
`Biopharma Ventures, LLC, the originally named Patent Owner in this case,
`assigned its rights in the ’876 patent to Neurelis, Inc. Paper 7, 2 (citing Reel
`048271; Frame 0304).
`
`2
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`IPR2019-00450
`Patent 9,763,876 B2
`33:8–13, 33:42–45. The ’876 patent also reports that vitamin E “can have
`the added benefit of either avoiding irritation of sensitive mucosal
`membranes and/or soothing irritated mucosal membranes.” Id. at 33:47–49.
`The ’876 patent discloses that one or more lower alcohols, such as
`ethanol and benzyl alcohol, may be used in the formulation. Id. at 2:57–64,
`33:55–67 (noting that to “avoid the drawbacks of emulsions,” the disclosed
`solutions contain vitamin E and “one or more lower alkyl alcohols”).
`In addition, an alkyl glycoside may be added to the formulation to act as a
`penetration enhancer. Id. at 34:2–9.
`
`C. Illustrative Claim
`Petitioner challenges claims 1–36 of the ’876 patent. Independent
`claim 1 is illustrative of the challenged claims and is reproduced below:
`
`1. 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.
`Ex. 1001, 63:26–34.
`D. The Asserted Ground of Unpatentability
`Petitioner contends the subject matter of claims 1–36 of the
`’876 patent would have been obvious in view of the combined disclosures of
`Sonne2 and Meezan.3 Pet. 5–6. In support of its obviousness arguments,
`
`2 US 6,193,985 B1, issued February 27, 2001 (Ex. 1013).
`3 US Pub. No. 2006/0046962 A1, published March 2, 2006 (Ex. 1011).
`3
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`IPR2019-00450
`Patent 9,763,876 B2
`Petitioner relies on the declaration testimony of Dr. Nicholas A. Peppas.
`Ex. 1041; Pet. 5.
`
`II. ANALYSIS
`
`A. Claim Construction
`In an inter partes review, claim terms are construed using the same
`claim construction standard that would be used to construe the claim in a
`civil action under 35 U.S.C. § 282(b). 37 C.F.R. § 42.100(b). Under this
`claim construction standard, claim terms are given their ordinary and
`customary meaning as would be understood by one of ordinary skill in the
`art at the time of the invention. See id.; Phillips v. AWH Corp., 415 F.3d
`1303, 1313 (Fed. Cir. 2005). A patentee may define a claim term in a
`manner that differs from its ordinary and customary meaning; however, any
`special definitions must be set forth in the specification with reasonable
`clarity, deliberateness, and precision. See In re Paulsen, 30 F.3d 1475, 1480
`(Fed. Cir. 1994).
`Petitioner provides proposed constructions for the terms “vitamin E,”
`“bioavailability,” “% (w/w),” “% (w/v),” and “about 56.47% (w/v)
`vitamin E.” Pet. 13–17. Patent Owner contends Petitioner’s constructions
`for “vitamin E,” “bioavailability,” “% (w/w),” and “% (w/v)” are consistent
`with the use of those terms in the specification and claims of the ’876 patent,
`but finds fault with the reasoning and support provided by Petitioner for its
`construction of the term “about 56.47% (w/v) vitamin E.” Prelim. Resp. 3–
`5.
`
`Upon review of the parties’ arguments and supporting evidence, we
`determine that no claim terms require construction for purposes of this
`Decision. See Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co.,
`
`4
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`IPR2019-00450
`Patent 9,763,876 B2
`868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing Vivid Techs., Inc. v. Am. Sci. &
`Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly those terms need be
`construed that are in controversy, and only to the extent necessary to resolve
`the controversy.”)).
`
`B. 35 U.S.C. § 325(d)
`Institution of inter partes review is discretionary. See Harmonic Inc.
`v. Avid Tech, Inc., 815 F.3d 1356, 1367 (Fed. Cir. 2016). Pursuant to
`35 U.S.C. § 325(d), the Board may take into account whether, and reject the
`petition because, “the same or substantially the same prior art or arguments
`previously were presented to the Office.”
`In evaluating whether to exercise our discretion under § 325(d), we
`consider several non-exhaustive factors, including:
`(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.
`
`5
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`IPR2019-00450
`Patent 9,763,876 B2
`Becton, Dickinson and Co. v. B. Braun Melsungen AG, IPR2017-01586, slip
`op. at 17–18 (Paper 8) (PTAB Dec. 15, 2017) (informative). We refer to
`these non-exhaustive factors as the “Becton Dickinson factors.”
`
`Patent Owner requests that we deny institution of inter partes review
`under § 325(d) because Sonne and Meezan were examined in depth by the
`Examiner during prosecution, and all of the Becton Dickinson factors weigh
`in favor of denying institution. Prelim. Resp. 5–24.
`Anticipating Patent Owner’s arguments, Petitioner asserts § 325(d)
`should not bar institution in this case because (1) the Examiner failed to fully
`consider Sonne’s teachings; (2) the Examiner was misled by the Applicants’
`faulty interpretation of Sonne’s disclosures; (3) the Petition presents the
`Sonne and Meezan references “in a new light”; and (4) Petitioner’s
`arguments are accompanied by the declaration testimony of Dr. Peppas,
`which was not before the Examiner during prosecution of the involved
`patent family.4 Pet. 6–11.
`Upon review of the relevant prosecution history and the arguments
`made in the Petition, we find that the Becton Dickinson factors weigh in
`favor of exercising our discretion under 35 U.S.C. § 325(d) to deny
`institution of an inter partes review.
`
`1. Factors (a) and (c)
`Becton Dickinson factor (a) looks to whether the same prior art or
`arguments were previously presented to the Office. Factor (c) looks to
`
`
`4 Petitioner also argues that the Petition applies a different legal theory than
`discussed during prosecution. Pet. 11. It is not clear what legal theory
`Petitioner is referring to, however, as both the Petition and the Examiner
`address obviousness under 35 U.S.C. §103(a). Pet. 5; Ex. 1004, 2124.
`6
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`IPR2019-00450
`Patent 9,763,876 B2
`whether this art was evaluated during examination, including whether it was
`the basis for a rejection. To fully evaluate factors (a) and (c), as well as
`factors (b), (d), (e), and (f) discussed below, we provide a detailed review of
`the prosecution history of record for the ’876 patent family.
`
`a. The ’876 Patent Family
`The ’876 patent was filed as U.S. Application No. 14/527,613
`(“the ’613 application”), and is a continuation of U.S. Application No.
`13/495,942 (“the ’942 application”) (issued as U.S. Patent No. 8,895,546
`(“the ’546 patent”), which is in turn a continuation-in-part (“CIP”) of U.S.
`Application No. 12/413,439 (“the ’439 application”). Ex. 1001, (63).
`Each of the identified patent applications was examined by the same
`patent Examiner. See Ex. 1002, 165; Ex. 1004, 2034; Ex. 1007, 447
`(identifying the Examiner for each application as Adam C. Milligan).5
`
`b. Prosecution History of the ’439 Application
`The ’439 application was filed on March 27, 2009. Ex. 1007, 86;
`Ex. 1001, (63). Pursuant to a restriction requirement, the Applicants elected
`to prosecute original claims 20–47, with independent claim 20 directed to a
`method of treating a patient with a benzodiazepine drug comprising:
`administering to one or more nasal mucosal membranes of a patient
`(1) a benzodiazepine drug, (2) one or more natural or synthetic tocopherols
`or tocotrienols, or any combination thereof, in an amount from about 30% to
`about 95% (w/w), and (3) one or more alcohols or glycols, or any
`
`
`5 Our citations to the prosecution histories in Exhibits 1002, 1004, and 1007
`are to the pages numbers added in the lower right corner of the Exhibits.
`7
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`IPR2019-00450
`Patent 9,763,876 B2
`combinations thereof, in an amount from about 10% to about 70% (w/w).
`Ex. 1007, 459, 464.
`In a March 18, 2011 Office Action, the Examiner rejected pending
`claims 20–24 and 27–45 in view of Sonne, reasoning that Sonne discloses
`compositions containing a benzodiazepine drug in an amount of 0.0001%
`to 40%, tocopherol in an amount from 20 to 99.9%, and the use of one or
`more co-solvents, such as ethanol and benzyl alcohol, to optimize
`bioadhesion, sprayability, and viscosity of the formulation. Id. at 477–478
`(citing Ex. 1013, 1:7–14, 5:56–61, 6:47–53, 8:28–43 (noting that ethanol
`may be used in an amount of about 11% by weight of the formulation),
`11:1–13 (Example 11)).6 The Examiner also rejected pending claims 25, 26,
`46, and 47 in view of the combined disclosures of Sonne and Meezan, noting
`that Meezan discloses the use of nanoparticles (claims 25 and 26) and the
`use of an alkyl glycoside (claims 46 and 47) to improve drug absorption.
`Id. at 480–481.
`Despite the fact that each individual limitation of claim 1 was
`expressly disclosed in Sonne, the Examiner found that Sonne required “too
`much ‘picking and choosing’ to give rise to anticipation.” Id. at 478.
`The Examiner determined, however, that one of ordinary skill in the art
`would have found it obvious to select “the various combinations of features
`claimed from within the prior art disclosure (specifically, diazepam, alcohol
`or glycol, and α-tocopherol) to arrive at the instantly claimed subject
`matter.” Id.
`
`
`6 The Examiner and Applicants did not cite to “Exhibit 1013” when
`discussing Sonne. We do so to aid in identification of the Applicants’ and
`Examiner’s arguments.
`
`8
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`IPR2019-00450
`Patent 9,763,876 B2
`In a September 19, 2011 Response, the Applicants amended pending
`independent claim 20 to require a pharmaceutical “solution” “consisting of”
`the identified ingredients. Id. at 492. The Applicants argued these added
`limitations distinguished the pending claims from the prior art because
`Examples 1–3, 7–11, 17, 19, and 22–23 of Sonne “each describe an oil-in-
`water emulsion of the benzodiazepine,” which is not a “solution” and would
`fall outside the scope of the claim due to the use of the transitional phrase
`“consisting of.” Id. at 501. The Applicants also argued that Sonne discloses
`that nasal administration of active drugs requires the use of “a high
`concentration of the oil (or lipid) phase” and “that addition of co-solvents
`such as ethanol is less desired, since such solutions ‘tend to be irritating to
`certain mucosal tissues.’” Id. at 500–502 (citing Ex. 1013, 3:1–4, 3:65–67,
`4:14–16) (asserting that “Examples 1–3, 7–11, 17, 19, and 22–23 each
`describe an oil-in-water emulsion of a benzodiazepine for nasal
`administration”).
`The Examiner subsequently issued a final rejection of the claims on
`November 21, 2011, disagreeing with the Applicants “teaching away”
`arguments and concluding that “one of ordinary skill in the art would have
`found it obvious to nasally administer a benzodiazepine composition that
`contains only tocopherol or tocotrienol, an alcohol and optionally one or
`more alkyl glycosides.” Id. at 514–515. The Examiner explained that Sonne
`must be interpreted broadly and “relied upon for all that it would have
`reasonably suggested to one having ordinary skill in the art, including
`nonpreferred embodiments.” Id. at 514. As examples of the broad teachings
`of Sonne, the Examiner identified its disclosures that: (1) the “compositions
`of the invention may be used directly as [a] solution of bioactive agents in
`
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`IPR2019-00450
`Patent 9,763,876 B2
`the tocopherol solvent” (id. at 515 (citing Ex. 1013, 3:60–61));
`(2) “[v]iscosity can be reduced by the addition of co-solvents such as
`ethanol” (id. (citing Ex. 1013, 3:65–66)); (3) transmucosal delivery is
`preferred and nasal administration particularly preferred (id. (citing
`Ex. 1013, 3:54, 3:58–59)); (4) compositions of the invention may contain
`from 1–99.99% tocopherol (id. (citing Ex. 1013, 5:55–57)); (5) co-solvents
`such as ethanol can be used to optimize the bioadhesion, sprayability, and
`viscosity of the formulation (id. (citing Ex. 1013, 6:47–53)); and (6) ethanol
`may be present in an amount of about 11% by weight of the formulation (id.
`(citing Ex. 1013, 8:28–43 (Example 3))).
`On May 21, 2012, the Applicants filed a Request for Continued
`Examination (“RCE”), again asserting that Sonne discourages the use of
`ethanol in nasal sprays due to its irritating nature. Id. at 564.
`The Applicants also reiterated that “Examples 1–3, 7–11, 17, 19, and 22–23
`[of Sonne] each describe an oil-in-water emulsion of the benzodiazepine.”
`Id.
`
`On June 19, 2014, the Examiner rejected all pending claims, this time
`with respect to Sonne, Meezan, and Lehat (which was relied on to address
`the Applicants added claim limitations requiring treatment of a seizure
`disorder). Id. at 2806. In so doing, the Examiner again relied on Sonne’s
`broad disclosures, including its disclosure of using ethanol as a co-solvent to
`optimize the bioadhesion, sprayability, and viscosity of the nasal spray. Id.
`at 2807 (citing Ex. 1013, 6:47–53).
`In a November 19, 2014 Response, the Applicants again argued that
`Examples 1–3, 7–11, 17, 19, and 22–23 of Sonne describe oil-in-water
`emulsions containing a benzodiazepine drug, and concluded that because
`
`10
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`IPR2019-00450
`Patent 9,763,876 B2
`each of the benzodiazepine compositions taught by Sonne contains oil, one
`of ordinary skill in the art would not seek to modify the teachings of Sonne
`to practice the claimed methods. Id. at 2832–2833.
`In a March 30, 2016 Response,7 the Applicants correctly noted for the
`first time that Examples 11 and 16 of Sonne are solutions, not emulsions, but
`argued that these solutions do not contain alcohol. Id. at 3085. Applicants
`also argued that in no case does Sonne teach or suggest administering an
`ethanol-containing solution to the nose, and in fact expressly teaches away
`from using such a solution for nasal applications. Id.
`In subsequent Office Actions of July 14, 2016, March 30, 2017, and
`October 19, 2017, the Examiner maintained his position that Sonne’s broad
`disclosures would have led one of ordinary skill in the art to the claimed
`formulations. Id. at 3093–3101, 3309–3320, 3470–3479. Likewise, in
`subsequent responses, Applicants maintained their position that Sonne,
`Meezan, and Lehat did not render the pending claims obvious. Id. at 3113–
`3121, 3323–3335. On June 1, 2018, a Notice of Abandonment was issued
`for the ’439 application for failure to reply to the Office Action of
`October 19, 2017. Id. at 3488.
`
`c. Prosecution History of the ’942 Application
`On June 13, 2012, the Applicants filed the ’942 application, which is a
`CIP of the ’439 application and also claims priority to Provisional
`Application Nos. 61/497,017 and 61/570,110. Ex. 1004, 3; Ex. 1001,
`
`
`7 In an Office Action of March 13, 2015, a Response of September 11, 2015,
`and an Office Action of October 5, 2015, the Applicants and the Examiner
`addressed the implications of the term “consisting of” with respect to
`Sonne’s disclosures. Ex. 1007, 2939, 2958–59, 2965, 3070–3071.
`11
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`IPR2019-00450
`Patent 9,763,876 B2
`(60), (63). Pursuant to a preliminary amendment, independent claim 1 of the
`’942 application recited a pharmaceutical solution for nasal administration
`consisting of (a) a benzodiazepine drug; (b) one or more tocopherols or
`tocotrienols, or any combination thereof, in an amount from about 30% to
`about 95% (w/w); (c) one or more alcohols or glycols, or any combinations
`thereof, in an amount from about 10% to about 70% (w/w); and (d) an alkyl
`glycoside. Ex. 1004, 103.
`In an Office Action of October 1, 2013, the Examiner rejected all
`pending claims as having been obvious over the combined disclosures of
`Sonne and Meezan. Id. at 2122, 2125. In this rejection, the Examiner
`identified the same broad disclosures of Sonne discussed at length during
`prosecution of the parent ’439 application. Id. at 2125–2126.
`In an April 1, 2014 Response, the Applicants amended the claims to
`replace “one or more alcohols or glycols, or any combinations thereof” with
`“ethanol and benzyl alcohol in a combined” amount of from about 10% to
`about 70% (w/w). Id. at 2138–2139. In support of the patentability of these
`amended claims, the Applicants argued that “[n]either Sonne nor Meezan
`teaches or suggests using both ethanol and benzyl alcohol” in the claimed
`amounts and, although Sonne discloses using ethanol as a viscosity-reducing
`agent, this “teaching appears in the context of introducing the purported
`benefits of the therein-described colloidal formulations.” Id. at 2149 (citing
`Ex. 1013, 3:60–67, 4:1–2). Applicants also argued that Sonne’s admonition
`that solutions containing ethanol can be irritating would have counseled one
`of ordinary skill in the art to not use higher concentrations of ethanol than
`are actually used in the Sonne reference. Id.
`
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`On July 24, 2014, the Examiner issued a Notice of Allowance for all
`pending claims of the ’942 application. Id. at 2560–2565; see also id. at
`2583–2584 (issuing a Corrected Notice of Allowance).
`
`d. Prosecution History of the ’613 application
`The ’613 application is a continuation of the ’942 application.
`Ex. 1001, (63). Pursuant to a preliminary amendment, the Applicants chose
`to pursue claims in this application that were drawn to a method of treating a
`patient with a pharmaceutical solution consisting of (a) a benzodiazepine
`drug; (b) one or more tocopherols or tocotrienols, or any combinations
`thereof, in an amount from about 30% to 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. Ex. 1002, 148.
`
`In an Office Action of July 14, 2016, the Examiner rejected the
`pending claims in view of several paragraphs of 35 U.S.C. § 112, and as
`being unpatentable on the grounds of nonstatutory double patenting over
`claims of the ’546 patent and the ’439 application. Id. at 167–170.
`The Examiner did not reject any of the pending claims under
`35 U.S.C. § 103.
`
`In a January 10, 2017 Response, the Applicants amended several
`dependent claims to address the Examiner’s § 112 rejections, and indicated
`they would consider filing a terminal disclaimer should the claims of the
`’613 application be found otherwise allowable. Id. at 186–193.
`
`The Examiner then issued a final rejection of all pending claims on
`the grounds of non-statutory double patenting (id. at 438–439),
`the Applicants filed terminal disclaimers with respect to the ’546 patent, the
`
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`’439 application, and U.S. Application No. 15/470,498 (id. at 478), and the
`Examiner issued a Notice of Allowance (id. at 491–496, 522–524).
`
`e. Conclusion with Respect to Factors (a) and (c)
`As shown above, Sonne was extensively considered during
`prosecution of the ’942 and ’439 applications, and was the basis, either alone
`or in combination with Meezan (and at times Lehat), for every prior art-
`based rejection applied by the Examiner during the eight-year prosecution
`history of this patent family. Thus, factors (a) and (c) favor exercising our
`discretion to deny the Petition under § 325(d).
`
`2. Factor (b)
`Factor (b) looks to the cumulative nature of the asserted art and the
`prior art evaluated during examination. Because the Sonne and Meezan
`references were actually addressed during prosecution, we need not address
`whether they are cumulative to the art that the Examiner considered.
`See NHK Spring Co. v. Intri-Plex Techs., Inc., IPR2018-00752, slip. op.
`at 13 (Paper 8) (PTAB Sept. 12, 2018) (precedential).
`
`3. Factor (d)
`Factor (d) looks to 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.
`
`a. Petitioner’s Arguments with Respect to Sonne and
`Meezan
`Petitioner’s obviousness analysis starts with Example 11 of Sonne,
`reproduced below, which is a “solution of diazepam” that can be used as a
`nose drop.
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`
`
`Ex. 1013, 11:1–12. The solution of Example 11 contains diazepam,
`α-tocopherol, and triacetin. Id.; Pet. 26. Petitioner refers to this solution as
`DS-11. Pet. 26 n.4.
`Petitioner contends that because the nosedrop of DS-11 “may be too
`viscous to spray,” one of ordinary skill in the art would have followed
`Sonne’s teachings and reduced the viscosity of the solution by replacing the
`triacetin co-solvent with ethanol. Id. at 27 (citing Ex. 1013, 3:60–67).
`Petitioner acknowledges that ethanol is “less desired” as a solvent in Sonne
`due to its irritation potential, but contends this does not mean that ethanol is
`“undesirable” or that ethanol could not be used in the nosedrop of
`Example 11. Id. at 27 n.5 (citing Ex. 1013, 1:55–63), 28 n.6 (noting that
`Sonne also identifies triacetin as a nose irritant). Petitioner identifies this
`modified “ethanol-for-triacetin replacement” containing 5% diazepam,
`40% α-tocopherol, and 55% ethanol, as DS11-A. Id. at 28.
`
`In view of Sonne’s disclosure that co-solvents may be used to
`optimize the bioadhesion, sprayability, and viscosity of formulations,
`Petitioner contends that one of ordinary skill in the art seeking to optimize
`the viscosity of DS11-A would have experimented with replacing a portion
`of the ethanol in this solution with benzyl alcohol, thereby forming a
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`solution containing 5% diazepam, 40% α-tocopherol, and a combined
`amount of 55% ethanol and benzyl alcohol. Pet. 29–30 (citing Ex. 1013,
`6:47–53). Petitioner identifies this solution as DS11-B. Id. at 29–30.
`Petitioner contends the precise amounts of ethanol and benzyl alcohol
`in DS11-B would not be critical, as Patent Owner has never demonstrated
`criticality or unexpected results based on the relative amount of ethanol and
`benzyl alcohol in the solution. Id. at 30–31. Thus, Petitioner contends one
`of ordinary skill in the art would have sought to “develop DS11-B solutions
`containing, e.g., 30% ethanol and 25% benzyl alcohol.” Id. at 33. In view
`of Sonne’s disclosure that alcohol is an irritant, however, Petitioner contends
`one of ordinary skill in the art would have sought to replace some of the
`alcohol in the solution with tocopherol, which has a very low irritation
`potential for mucosal tissues. Id. (citing Ex. 1013, 2:55–58). In particular,
`Petitioner contends one of ordinary skill in the art would have increased the
`tocopherol by 25% and reduced the alcohol to 30% to arrive a solution
`containing 5% diazepam, 65% α-tocopherol, and 30% alcohol. Id. at 34–35.
`Within the scope of the 30% alcohol solutions, Petitioner contends
`one of ordinary skill in the art would have created solutions containing
`various combinations of ethanol and benzyl alcohol, including solutions
`containing: 10% ethanol and 20% benzyl alcohol; 15% ethanol and 15%
`benzyl alcohol; 20% ethanol and 10% benzyl alcohol; and 19% ethanol and
`11% benzyl alcohol. Id. Petitioner identifies the solution containing
`5% diazepam, 65% α-tocopherol, 19% ethanol, and 11% benzyl alcohol as
`DS11-C. Id. at 34–35.
`
`Petitioner further argues that because Sonne discloses generally
`increasing bioavailability of its invention, one of ordinary skill in the art
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`IPR2019-00450
`Patent 9,763,876 B2
`would have sought “to add small amounts of dodecyl maltoside, perhaps
`0.25%,” as disclosed in Meezan, to achieve this goal. Pet. 37. Petitioner
`contends ethanol would be reduced in this solution by the same percentage
`as dodecyl maltoside is added, resulting in a solution containing
`5% diazepam, 65% α-tocopherol, 18.75% ethanol, 11% benzyl alcohol, and
`0.25% dodecyl maltoside. Id. Petitioner identifies this solution as DS11-D.
`Id.
`Petitioner relies on hypothetical solutions DS11-A, DS11-B, DS11-C,
`
`and DS11-D in arguing that the challenged claims would have been obvious
`over the combined disclosures of Sonne and Meezan. See, e.g., Pet. 70–71
`(relying on DS11-D for disclosure of a solution containing an alkyl
`glycoside).
`
`b. Analysis
`Petitioner contends “the specific combination of subject matter from
`[the] prior art references relied upon by Petitioner did not form the basis for
`any of the rejections of the ’876 patent.” Pet. 6. Thus, Petitioner asserts it
`presents the Sonne and Meezan references “in a new light.” 8 Id. at 6–7.
`Although the Examiner never explicitly formulated Petitioner’s
`hypothetical DS11-A, DS11-B, DS11-C, and DS11-D solutions, the
`Examiner did identify and rely on nearly every disclosure of Sonne and
`
`
`8 Petitioner also contends the Examiner’s consideration of the ’439 and
`’942 applications is not dispositive because it was directed to different claim
`language. Pet. 11. This is not a persuasive argument because the Examiner
`found that the claims of the ’876 patent “are not patentably distinct from”
`those of the ’942 application, and Petitioner does not argue otherwise.
`See Ex. 1002, 438–439.
`
`
`17
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`IPR2019-00450
`Patent 9,763,876 B2
`Meezan that Petitioner relies on to formulate these solutions. See Prelim.
`Resp. 9–19 (providing a claim chart comparing the arguments made during
`prosecution with those made in the Petition). For example, in rejecting
`claims in the ’942 application, the Examiner relied on Sonne’s disclosures
`that: (1) the formulations may be in the form of solutions; (2) the disclosed
`solutions may be used as a nasal spray; (3) the solutions may contain
`diazepam and tocopherol; (4) the amount of active ingredient may be from
`0.001% to 40% and the amount of tocopherol may be from 20 to 99.9%;
`(5) the bioadhesion, sprayability, and viscosity of the solutions may be
`modified through the addition of co-solvents; (6) ethanol and benzyl alcohol
`may be used as co-solvents; and (7) the total amount of co-solvents may be
`as high as 50-60%, as shown in Examples 11 and 16. Ex. 1004, 2125–2126.
`The Examiner also noted Meezan’s disclosure of using an alkyl glycoside to
`improve bioavailability of an active ingredient. Id. at 2126–2127. These are
`the same general disclosures that are relied upon by Petitioner and
`Dr. Peppas to formulate DS11-A, DS11-B, DS11-C, and DS11-D with
`ethanol, benzyl alcohol, and an alkyl glycoside (DS11-D). Compare, e.g.,
`Pet 27–30 (citing Ex. 1013, 3:60–67, 6:47–53, 11:1–9 (Example 11)) with
`Ex. 1004, 2125–2126 (citing Ex. 1013, 6:47–53, 11:1–13 (Example 11)) and
`Ex. 1007, 515 (quoting Ex. 1013, 3:54–61, 3:65–66, 6:47–53).
`In view of Petitioner’s and the Examiner’s reliance on the same
`general disclosures of Sonne and Meezan, we find that factor (d) also favors
`denying institution under § 325(d).
`
`4. Factor (e)
`Factor (e) asks whether Petitioner has pointed out sufficiently how the
`Examiner erred in its evaluation of the prior art. Petitioner contends the
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`IPR2019-00450
`Patent 9,763,876 B2
`Examiner erred in his consideration of the prior art because he failed to
`consider the full scope of Sonne’s teachings, caused, in part, by the
`Applicants’ incorrect characterization of the content and scope of Sonne’s
`disclosures during prosecution. Pet. 7 (asserting that the Applicants’
`incorrect statements during prosecution ultimately led “the Examiner away
`from a full and fair consideration of Sonne”).
`First, Petitioner contends the Applicants incorrectly argued that
`Sonne’s discussion of using ethanol as a viscosity-reducing agent was only
`in the context of introducing the purported benefits of the colloidal
`formulations. Id. According to Petitioner, this was incorrect, as the
`discussion of using ethanol as a solvent in Sonne was not an introduction to
`the benefits of emulsions, but a specific teaching that ethanol may be used to
`reduce the viscosity of solutions. Id. at 7–8 (citing Ex. 1004, 2149;
`Ex. 1013, 3:60–4:2).
`The arguments identified by Petitioner were made in an April 1, 2014
`Response. Id. at 7 (citing Ex. 1004, 2149). Both before and after these
`assertions were made, the Examiner broadly applied Sonne’s teachings of
`reducing viscosity through the addition of co-solvents. For example, in an
`October 1, 2013 Office Action, the Examiner stated that Sonne discloses that
`ethanol may be used to optimize the viscosity of the formulations. Ex. 1004,
`2125. Likewise, in a July 14, 2016 Office Action in the ’439 application, the
`Examiner stated that Sonne teaches “[v]iscosity can be reduced by the
`addition of co-solvents such as ethanol” and that “[a] co-solvent such as
`ethanol can be used in order to optimize the formulations bioadhesion,
`sprayability, and viscosity.” Ex. 1007, 3096–3097 (citing Ex. 1013, 3:65–
`66, 6:47–53). Thus, even if the Applicants’ arguments regarding Sonne’s
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`IPR2019-00450
`Patent 9,763,876 B2
`ethanol disclosures were incorrect, we are not persuaded that these
`arguments tainted the Examiner’s analysis of Sonne or caused the Examiner
`to narrow his broad understanding of Sonne’s disclosures.
`Second, Petitioner contends Example 11 is “clearly a solution”
`intended for use as a “nosedrop,” yet the Applicants referred to Example 11
`of Sonne as being directed to oil-in-water emulsions with a high
`concentration of oil. Pet. 9–10 (citing Ex. 1007, 501–502, 564,
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