throbber
Trials@uspto.gov
`571-272-7822
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`Paper No. 13
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` Entered: October 16, 2019
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`NALOX-1 PHARMACEUTICALS, LLC,
`Petitioner,
`
`v.
`
`ADAPT PHARMA LIMITED, and
`OPIANT PHARMACEUTICALS, INC.,
`Patent Owners.
`____________
`
`IPR2019-00697
`Patent 9,775,838 B2
`____________
`
`
`
`Before ERICA A. FRANKLIN, ZHENYU YANG, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`FRANKLIN, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
`
`
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`
`

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`IPR2019-00697
`Patent 9,775,838 B2
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`I. INTRODUCTION
`Nalox-1 Pharmaceuticals, LLC (“Petitioner”), filed a Petition
`requesting inter partes review of claims 1–46 (“the challenged claims”) of
`U.S. Patent No. 9,775,838 B2 (Ex. 1001, “the ’838 patent”). Paper 1
`(“Pet.”). Adapt Pharma Limited and Opiant Pharmaceuticals, Inc.
`(collectively, “Patent Owner”) timely filed a Preliminary Response. Paper 9
`(“Prelim. Resp.”).
`Under 35 U.S.C. § 314(a), an inter partes review may not be instituted
`unless the information presented in the petition “shows that there is a
`reasonable likelihood that the petitioner would prevail with respect to at
`least 1 of the claims challenged in the petition.” Having considered the
`evidence and arguments of record, we agree with Patent Owner that the prior
`art teaches away from the claimed invention, and, therefore, decline to
`institute inter partes review.
`A. Related Matters
`The parties identify the following district court cases involving the
`’838 patent: Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA,
`No. 2:16-cv-07721 (D.N.J.); Adapt Pharma Operations Ltd. v. Perrigo UK
`FINCO Limited Partnership, No. 2:18-cv-15287 (D.N.J.). Pet. 8; Paper 6, 2.
`Petitioner is not a party in either of those cases. Petitioner additionally
`challenges claims 1–46 of the ’838 patent in two other petitions concurrently
`filed in IPR2019-00698 and IPR2019-00699.
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`The ’838 patent is one of five patents listed in the Orange Book for
`intranasal naloxone sold under the brand name NARCAN. Pet. 1; Paper 9,
`1. Petitioner has also filed petitions for inter partes review of claims of each
`of those other four patents. Paper 6, 1–2.
`B. The ’838 Patent
`The ’838 patent is directed to “pharmaceutical compositions
`comprising an opioid receptor antagonist, medical devices for delivery of the
`pharmaceutical compositions, and methods of using the compositions and
`the medical devices.” Ex. 1001, 1:35–39. In particular, the Specification
`discloses what is described as an “improved single-use, pre-primed device
`adapted for nasal delivery of a pharmaceutical solution to a patient”
`comprising naloxone hydrochloride or a hydrate thereof. Id. at 2:66–3:2.
`Naloxone is an opioid receptor antagonist approved for use by injection for
`the reversal of opioid overdose. Id. at 2:9. According to the Specification,
`the improvement derives from administering naloxone nasally with a device
`being adapted to spray a round plume with an ovality ratio less than about
`two. Id. at 3:3–5. Additionally, the Specification explains that nasal
`delivery of naloxone is “considered an attractive route for needle-free,
`systemic drug delivery, especially when rapid absorption and effect are
`desired. In addition, nasal delivery may help address issues related to poor
`bioavailability, slow absorption, drug degradation, and adverse events (AEs)
`in the gastrointestinal tract and avoids the first-pass metabolism in the liver.”
`Ex. 1001, 10:52–58.
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`The disclosed compositions comprise benzalkonium chloride
`(“BAC”). Id. at 13:67–14:16. The Specification explains that BAC “can
`function as a preservative (even in low amounts), a permeation/penetration
`enhancer, and/or a cationic surfactant (typically at a higher amount for these
`latter two).” Id. at 14:16–19.
`C. Illustrative Claim
`Claims 1 and 41 are the only independent claims of the ’838 patent.
`Claim 1, reproduced below, is illustrative of the claimed subject matter.
`1. A method of treating opioid overdose, the method comprising:
`delivering a 25–200 μL spray of a pharmaceutical solution from
`a pre-primed device into a nostril of a patient,
`wherein the device is adapted for nasal delivery,
`wherein the spray delivers between about 4 mg and about 10 mg
`naloxone, an isotonicity agent, and between about 0.005%
`and about 0.015% (w/v) of benzalkonium chloride.
`
`
`Ex. 1001, 63:5–13 (emphasis added).
`Independent claim 41 recites a method of treating narcotic-induced
`respiratory depression, wherein the method similarly requires the spray of a
`pharmaceutical solution from a pre-primed device into a nostril of a patient
`to deliver between about 4 mg and about 10 mg naloxone, an isotonicity
`agent, and “between about 0.005% and about 0.015% (w/v) of benzalkonium
`chloride.” Id. at 65:16–19.
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`D. Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1–46 under 35 U.S.C.
`§ 103 on the following grounds:
`
`Claim(s)
`1–4, 18–23, 25–29, 30–34,
`36, 39–40
`5–12
`13–17, 41–46
`24, 35, 37
`38
`
`References
`Wyse1 and HPE2
`Wyse, HPE, and Wang3
`Wyse, HPE, and the ’291 patent4
`Wyse, HPE, and Djupesland5
`Wyse, HPE, Djupesland, and Zomig
`Review6
`
`Petitioner also relies on the Declarations of Maureen D. Donovan,
`Ph.D. (Ex. 1002) and Günther Hochhaus, Ph.D. (Ex. 1003) to support its
`challenge.
`
`
`1 Wyse et al., U.S. Patent No. 9,192,570 B2, issued Nov. 24, 2015 (“Wyse”)
`(Ex. 1007).
`2 Handbook of Pharmaceutical Excipients, 56–60, 64–66, 78–81, 220–22,
`242–44, 270–72, 441–45, 517–22, 596–98 (Rowe et al. eds., 6th ed. 2009)
`(“HPE”) (Ex. 1012).
`3 Wang et al., Chinese Patent Publication No. CN 1575795 A, published
`February 9, 2005 (“Wang”) (Ex. 1008).
`4 Wermeling, U.S. Patent No. 8,198,291 B2, issued June 12, 2012 (“the ’291
`patent”) (Ex. 1015).
`5 Djupesland, Nasal Drug Delivery Device: Characteristics and
`Performance in a Clinical Perspective - A Review, 3 DRUG DELIV. &
`TRANSL. RES. 42–62 (2013) (“Djupesland”) (Ex. 1010).
`6 CDC, NDA No. 21-450 Clinical Pharmacology & Biopharmaceutics
`Review (2002) (“Zomig Review”) (Ex. 1024).
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`II. ANALYSIS
`A. Claim Construction
`In an inter partes review based on a petition filed after November 13,
`2018, such as the present Petition, the Board interprets a claim term by
`applying “the standard used in federal courts, in other words, the claim
`construction standard that would be used to construe the claim in a civil
`action under 35 U.S.C. [§] 282(b), which is articulated in Phillips.”7 83 Fed.
`Reg. 51,340, 51,343. Under that standard, the words of a claim “are
`generally given their ordinary and customary meaning,” which is “the
`meaning that the term would have to a person of ordinary skill in the art in
`question at the time of the invention, i.e., as of the effective filing date of the
`patent application.” Phillips v. AWH Corp., 415 F.3d 1303, 1312–13 (Fed.
`Cir. 2005) (en banc) (citations omitted). Any special definitions for claim
`terms must be set forth with reasonable clarity, deliberateness, and precision.
`In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`Petitioner proposes constructions for certain claim terms and phrases.
`Pet. 25–27. Patent Owner does not address Petitioner’s proposed claim
`constructions or offer its own in the Preliminary Response. Based upon our
`review, there is no controversy regarding the construction of any claim term.
`For purposes of this Decision, we interpret the challenged claims according
`to their ordinary meaning as understood by one skilled in the art at the time
`
`
`7 See Changes to the Claim Construction Standard for Interpreting Claims in
`Trial Proceedings Before the Patent Trial and Appeal Board, 83 Fed.
`Reg. 51,340, 51,340, 51,344 (Oct. 11, 2018) (to be codified at 37 C.F.R.
`pt. 42).
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`of invention. Thus, we do not find it necessary to provide any express claim
`constructions. Further, we note that this Decision declining to institute trial
`does not turn on the adoption of any particular claim construction. See
`Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co., 868 F.3d 1013,
`1017 (Fed. Cir. 2017) (noting that “we need only construe terms ‘that are in
`controversy, and only to the extent necessary to resolve the controversy’”)
`(quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803
`(Fed. Cir. 1999)).
`
`B. Level of Ordinary Skill in the Art
`The level of ordinary skill in the art is a factual determination that
`provides a primary guarantee of objectivity in an obviousness analysis. Al-
`Site Corp. v. VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966); Ryko Mfg. Co. v. Nu-
`Star, Inc., 950 F.2d 714, 718 (Fed. Cir. 1991)).
`According to Petitioner, a person with ordinary skill in the art
`(“POSA”) at the time of the invention of the ’838 patent “would comprise a
`team of individuals having experience in drug development, and specifically
`the development of solution-based dosage forms such as intranasal dosage
`forms.” Pet. 9 (citing Ex. 1002 ¶ 35; Ex. 1003 ¶ 22). Petitioner asserts that
`this team would include a “Formulator POSA” as well as a “Pharmacologist
`POSA.” Pet. 9–11. Petitioner explains that the Formulator POSA would
`have “experience in preformulation testing for and selection of excipients for
`a solution-based dosage form (including intranasal dosage forms) to achieve
`a target pharmaceutical profile.” Id. at 9 (citing Ex. 1002 ¶ 35). Petitioner
`explains that the Pharmacologist POSA would have
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`clinical, clinical pharmacology, and regulatory expertise relevant
`to the design and performance of a drug development strategy for
`solution-based dosage forms such as intranasal dosage forms,
`including testing and/or evaluating the fate of the drug in the
`body (i.e., pharmacokinetics, including the physiological and
`biopharmaceutical aspects of nasal drug absorption), testing
`and/or evaluating issues of safety and efficacy, and evaluating
`the regulatory requirements of a new dosage form.
`Id. at 10 (citing Ex. 1003 ¶ 22).
`For purposes of this Decision, we adopt Petitioner’s definition of the
`level of ordinary skill in the art, as it is supported by declaration testimony,
`undisputed by Patent Owner in the Preliminary Response, and consistent
`with the level of skill in the art reflected in the prior art of record. See
`Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001).
`C. Obviousness
`Each ground presented in the Petition challenges claims of the ’838
`patent as obvious over a combination of references including Wyse. Pet. 3.
`Patent Owner asserts that Wyse teaches away from the claimed invention.
`Prelim. Resp. 48. As that assertion relates to each ground presented, and is
`potentially dispositive of each ground, we begin our obviousness analysis by
`considering whether Wyse teaches away from the claimed inventions.
`1. Wyse
`Wyse teaches “compositions containing an opioid antagonist such as
`naloxone and one or more pharmaceutically acceptable excipients. The
`compositions may be used for intranasal delivery of Naloxone for the
`treatment of, for example, opioid overdose in an individual in need thereof.”
`Ex. 1007, Abstract.
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`Of particular relevance here, Wyse discloses the results of preliminary
`formulation screening studies for 13 naloxone formulations, each including
`20 mg/ml naloxone HCl and a different combination of excipients.
`Ex. 1007, 26:26–29, Table 13. BAC was present in five of the formulations
`tested. Id. at Table 13. Wyse reports that the study “surprisingly showed”
`that the use of BAC “resulted in an additional degradant” in four of those
`formulations. Id. at 27:29–32. In this regard, Wyse remarks that “[a]part
`from the preservative [i.e., BAC,] Formulation 7”––one of the
`BAC-containing formulations that unexpectedly resulted in degradant––
`“was believed to be ideal for nasal delivery because the excipients were
`expected to increase the residence time in the nasal cavity (HPMC), prevent
`oxidation (EDTA), and create a hyperosmotic solution that facilitates
`diffusion across the cell membrane.” Id. at 27:32–37.
`Wyse explains that “[i]n this initial study, the preliminary conclusion
`was that benzyl alcohol and paraben preservatives were acceptable, but
`benzalkonium chloride was not, due to increased observed degradation.” Id.
`at 27:41–44. Wyse concludes:
`Net, Applicant found that, surprisingly, commonly used
`excipients
`including one or more
`[of] ascorbic acid,
`hypromellose, propylene glycol 400, sorbitol, glycerine,
`polypropylene
`glycol, methylparaben,
`propylparaben,
`benzylalkonium chloride, were found to increase degradation of
`naloxone.
` While some of
`the excipients might work
`individually, the combination of many of these was found to be
`unacceptable for various reasons as outlined above. Equally
`surprising was that the disclosed compositions, which lack
`commonly used excipients and combinations of commonly used
`excipients, had superior stability as compared to more complex
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`formulations and remained stable for a period of up to 36 months
`under ambient conditions.
`Id. at 28:23–35.
`
`2. HPE
`HPE discloses that “[b]enzalkonium chloride is a quaternary
`ammonium compound used in pharmaceutical formulations as an
`antimicrobial preservative in applications similar to other cationic
`surfactants, such as cetrimide.” Ex. 1012, 56. According to HPE, in nasal
`formulations, BAC is used in “a concentration of 0.002–0.02% w/v.” Id.
`HPE notes that BAC is “[i]ncluded in the FDA Inactive Ingredients
`Database” for nasal preparations. Id. at 57 (citation omitted).
`3. Wang
`Wang describes a naloxone hydrochloride nasal spray. Ex. 1008, 7.
`Wang states that
`[t]he inventors have found through intensive studies that a novel
`nasal spray administration dosage form is formed by mixing
`naloxone hydrochloride with an optional preservative, osmotic
`pressure regulator, penetration enhancer and water. The
`preparation has a single-dose and multi-dose nasal spray with
`rapid absorption, high bioavailability and low irritation. The
`preparation is suitable for scale production and storage.
`Id. According to Wang, “the preservative used in the nasal spray of the
`present invention is selected from methyl, ethyl, propyl, or butyl
`para-hydroxybenzoate, sorbic acid, benzoic acid, sodium benzoate, benzyl
`alcohol, benzalkonium chloride, benzalkonium bromide, chlorobutanol,
`resorcinol, sodium ethylenediamine tetraacetate and the like.” Id.
`
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`4. The ’291 Patent
`The ’291 patent discloses the spray pattern function for an intranasal
`butorphanol composition when sprayed from the Pfeiffer Unitdose Second
`Generation device onto an impaction plate from various distances.
`Ex. 1015, 11:46–12:15. For example, the ’291 patent describes the spray
`diameter, ovality, and droplet size distribution observed at several spray
`distances. Id.
`
`5. Djupesland
`Djupesland describes the Pfeiffer/Aptar single-dose intranasal
`delivery device used to administer certain migraine medications. Ex. 1010,
`49. Djupesland explains that “[t]o emit 100 μl, a volume of 125 μl is filled
`in the device (Pfeiffer/Aptar single-dose device) used for the intranasal
`migraine medications Imitrex (sumatriptan) and Zomig (zolmitriptan).” Id.
`6. Zomig Review
`Zomig Review discloses a unit dose delivery device designed to
`administer zolmitriptan, a selective 5-HT 1B/1D receptor agonist for the
`acute treatment of migraine headaches, to the nasal cavity. Ex. 1024, 4, 5.
`7. Analysis
`Having considered the record before us, we are not persuaded that
`Petitioner has demonstrated a reasonable likelihood of prevailing in
`establishing that at least one of the challenged claims is unpatentable. Each
`independent claim of the ’838 patent requires a naloxone formulation that
`comprises BAC. For the reasons set forth below, we find that Wyse teaches
`away from the use of BAC in intranasal naloxone formulations, and,
`therefore, we determine that Petitioner has not demonstrated sufficiently for
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`institution that a person of ordinary skill in the art would have had a
`reasonable expectation of successfully using BAC in an intranasal naloxone
`formulation, in view of Wyse.
`Petitioner contends that the combination of Wyse and HPE teaches or
`suggests the inclusion of BAC in an intranasal formulation in an amount
`falling within the ranges specified by independent claims 1 and 41. Pet. 33–
`35, 53.8 According to Petitioner, Wyse discloses that an intranasal naloxone
`formulation “can contain an antimicrobial agent—i.e., a preservative—in an
`amount of 0.1% to 2% by weight of the formulation.” Id. at 33 (citing
`Ex. 1007, 7:21–28). Petitioner recognizes that Wyse discloses the use of
`benzyl alcohol as a preservative, but points out that Wyse also teaches that
`“[o]ther suitable antimicrobial agents may be readily understood by one of
`ordinary skill in the art.” Id. (citing Ex. 1007, 7:26–28). Petitioner reasons
`that a person having ordinary skill in the art “would have looked to
`pharmaceutical compendiums like HPE to determine what other
`antimicrobial agents would be acceptable; BAC would have been one such
`antimicrobial agent.” Id. at 33–34 (citing Ex. 1012, 56–57). In particular,
`Petitioner asserts that such artisan would have selected BAC for use in an
`intranasal naloxone formulation because it has a wide range of antimicrobial
`
`
`8 Petitioner points to the analysis of Wyse and HPE set forth in its discussion
`of the patentability of claim 1 to support its contention that the prior art
`teaches or suggests including BAC in a naloxone formulation in the amounts
`recited by independent claim 41. Pet. 53. Because Petitioner focuses its
`analysis on claim 1 with regard to the BAC requirement set forth in each
`challenged independent claim, we do the same.
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`activity at low concentrations, is FDA-approved for, and commonly used in
`nasal sprays, and is more effective than other nasal spray preservatives
`against certain bacteria and fungi. Id. at 34 (citing Ex. 1002 ¶¶ 73, 75, 151).
`Petitioner acknowledges Wyse’s teaching that BAC is not acceptable
`for inclusion in intranasal naloxone formulations due to increased observed
`degradation. Pet. 61 (citing Ex. 1007, 27:30–34, 27:41–44). Petitioner
`asserts, however, that an ordinarily skilled artisan would not have given
`Wyse’s teachings regarding the unacceptable use of BAC with naloxone
`“much merit.” Id. According to Petitioner, because “Wyse performed
`degradation testing on multiple different formulations combining multiple
`different excipients, it cannot be conclusively determined that any individual
`excipient was responsible for any instability issues in the disclosed
`formulation.” Pet. 61–62 (citing Ex. 1002 ¶¶ 80–82). In addition, Petitioner
`argues that Wyse does not indicate that the inclusion of BAC “specifically
`resulted in additional naloxone degradation, rather than degradation of
`another component,” id. at 62 (citing Ex. 1002 ¶ 83), and points out that out
`that one of the five BAC-including formulations tested by Wyse did not
`result in additional degradant, id. (citing Ex. 1002 ¶¶ 84–87). Further,
`Petitioner contends that an unpublished Norwegian graduate thesis by
`Glende9 that discusses the “WIPO publication equivalent of Wyse,” but
`undisputedly does not qualify as prior art, demonstrates that “others reading
`
`
`9 Glende, Development of Non-Injectable Naloxone for Pre-Hospital
`Reversal of Opioid Overdose: A Norwegian Project and a Review of
`International Status (May 2016) (unpublished M.A. thesis, Norwegian
`University of Science and Technology) (“Glende”) (Ex. 1031).
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`the disclosure of Wyse have concluded that it does not teach away from
`using BAC.” Id. at 62–63 (citing Ex. 1031, 76; Ex. 1002 ¶¶ 76–87).
`We are not persuaded by Petitioner’s contentions. Wyse explicitly
`and unambiguously discourages the use of BAC in intranasal naloxone
`formulations. Petitioner has not demonstrated persuasively for institution
`that an ordinarily skilled artisan seeking to develop an intranasal naloxone
`formulation would not have taken heed of Wyse’s teaching that BAC is
`unacceptable for use as an excipient in such a formulation. Indeed, as
`Petitioner acknowledges, such an artisan “would have been concerned about
`naloxone degradation,” and would have “been motivated to choose
`ingredients to render the formulation chemically and microbiologically
`stable.” Pet. 21; see also id. (“Ideally, nearly all of the naloxone active
`ingredient would remain present after storage; the solution would have
`resisted any changes in color or formation of particulate matter; and the
`solution would have been free of microbial growth or ingress.” (citing
`Ex. 1002 ¶ 59)).
`Wyse is the only reference of record that compares naloxone
`formulations having different excipient combinations, and provides stability
`data for intranasal naloxone formulations. See Parts II.C.1–6 (summarizing
`the asserted references), supra. As the only data of record concerning the
`use of excipients in intranasal naloxone formulations, Petitioner has not
`demonstrated for institution that an ordinarily skilled artisan interested in
`determining what “antimicrobial agents would be acceptable,” i.e.,
`successful, in a naloxone formulation, Pet. 33–34, would not have given
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`significant weight to the naloxone formulation stability data disclosed by
`Wyse.
`Petitioner’s argument that Wyse cannot be said to teach away because
`it does not “conclusively” establish that BAC causes naloxone degradation
`or demonstrate that BAC is “incompatible with naloxone,” Pet. 62,
`misapprehends the standard for evaluating whether a reference teaches
`away. A reference teaches away “when a person of ordinary skill, upon
`reading the reference, would be discouraged from following the path set out
`in the reference, or would be led in a direction divergent from the path that
`was taken” in the claim. Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d
`731, 738 (Fed. Cir. 2013). “[I]n general, a reference will teach away if it
`suggests that the line of development flowing from the reference’s
`disclosure is unlikely to be productive of the result sought by the applicant.”
`In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
`Such is the case here. Wyse states that BAC was “found to increase
`degradation of naloxone,” Ex. 1007, 28:23–25 (emphasis added), and
`explains that BAC is not acceptable for use in intranasal naloxone
`formulations, id. at 27:41–44. In addition to teaching that BAC-containing
`naloxone formulations are unstable, Wyse discloses that other antimicrobial
`preservatives, such as benzyl alcohol, are stable in combination with
`naloxone. Ex. 1007, 27:29–37, 28:23–25, 28:41–29:27, Tables 14–15.
`These disclosures expressly teach away from the use of BAC in intranasal
`naloxone formulations, and directly counter Petitioner’s assertion, Pet. 61–
`62, that Wyse does not sufficiently specify the nature or importance of the
`observed BAC-associated degradant.
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`Wyse’s rejection of BAC as a viable excipient for use in naloxone
`formulations is further underscored by the fact that Wyse expressly excluded
`BAC from the naloxone formulations chosen for further study. Ex. 1007,
`28:41–47, Table 14. Significantly, Wyse reports that the use of BAC as a
`preservative rendered an otherwise “ideal” naloxone formulation unstable.
`Id. at 27:29–37, 28:41–29:27, Tables 14–15. In particular, the
`BAC-containing version of the otherwise “ideal” formulation produced
`undesirable degradant in a preliminary screening study, while the benzyl
`alcohol-containing version of that formulation was stable. Id. at 27:29–32,
`Table 15. In addition, Wyse ultimately determined that two formulations
`using benzyl alcohol (and excluding BAC) as a preservative were stable and
`warranted further development. Id. at 29:18–40, Tables 15–16.
`Contrary to Petitioner’s assertion, the explicit teaching away in Wyse
`is not undermined by its disclosure of naloxone formulations comprising
`combinations of “multiple different excipients,” or by its disclosure that one
`out of the five of the BAC-containing naloxone formulations tested did not
`show additional degradant. See Pet. 62. As explained above, a teaching
`away need not be established by irrefutable proof or scientific certainty; it is
`sufficient that a reference discourages the skilled artisan from one path, or
`leads her down a divergent one. Galderma, 737 F.3d at 738. Here, Wyse
`does both. Not only does Wyse present experimental results demonstrating
`that BAC is unacceptable for use in naloxone formulations, Ex. 1007,
`27:41–44, 28:23–25, but it also provides data indicating that other
`preservatives, in particular, benzyl alcohol, are stable, and, thus, useful, in
`such formulations, id. at 29:18–40, Tables 15–16. Accordingly, even if an
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`ordinarily skilled artisan might have contemplated including BAC in an
`intranasal naloxone formulation because it was a preservative known for use
`in nasal formulations, see Ex. 1012, 56–57, such an artisan would have been
`dissuaded from using BAC based on Wyse’s express teachings that BAC is
`unacceptable for use in intranasal naloxone formulations. See Allergan, Inc.
`v. Sandoz Inc., 796 F.3d 1293, 1305–1306 (Fed. Cir. 2015) (affirming a
`finding of teaching away even though the claimed amounts of active and
`preservative fell within ranges disclosed by a prior art reference because the
`prior art as a whole taught that the amount of the claimed preservative
`should be minimized to avoid safety problems). In other words, based on
`the teachings of Wyse, a person of ordinary skill in the art would not have
`had a reasonable expectation of successfully using BAC in such an
`intranasal naloxone formulation.
`Petitioner’s reliance on Glende does not dictate a different result.
`First, as Petitioner acknowledges, Glende is not prior art. Pet. 62. Second,
`Petitioner’s reliance on Glende as suggesting that an ordinarily skilled
`artisan would have disregarded Wyse’s teaching away is circular. Glende
`considered the WIPO publication equivalent of Wyse (“Wyse PCT”)10 in
`light of the WIPO publication equivalent of the parent to the ’838 patent
`(“the ’373 PCT”).11,12 Ex. 1031, 52; see also Prelim. Resp. 53–54
`
`
`10 Dehart and Wyse, PCT Publication No. WO/2015/095644, published June
`25, 2015.
`11 Crystal, et al., PCT Publication No. WO/2015/136373, published Sept. 17,
`2015.
`12 The ’838 patent is a continuation-in-part of U.S. Patent No. 9,211,253 B2.
`17
`
`

`

`IPR2019-00697
`Patent 9,775,838 B2
`
`(explaining the relationship between the WIPO publications discussed by
`Glende and their U.S. counterparts). Glende recognizes that the Wyse PCT
`teaches that BAC “was found to further increase . . . degradation” of
`intranasal naloxone formulations. Ex. 1031, 63. Glende subsequently
`observes, however, that the ’373 PCT discloses that BAC-containing
`formulations were “storage-stable.” Id. at 64. After reviewing the thesis, we
`agree with Patent Owner that “Glende’s statement that BZK ‘should not be
`depreciated based on [Wyse] solely,’ id. at 76—the very point for which
`Petitioner tries to use it—was thus based on knowledge of the patented
`invention.” Prelim. Resp. 54.
`We are also unpersuaded, for institution, by Petitioner’s reliance on
`HPE to overcome Wyse’s teaching away. Unlike HPE, Wyse discloses the
`results of stability studies on BAC-containing intranasal naloxone
`formulations. HPE’s general teaching that BAC is an antimicrobial that may
`be used in, and is FDA approved for, nasally administered pharmaceutical
`formulations in general, Ex. 1002, 56–57, is insufficient to defeat Wyse’s
`teaching away because HPE does not address the use of BAC in intranasal
`naloxone formulations, much less the effect of BAC on the stability of such
`formulations. See Tec Air, Inc. v. Denso Mfg. Mich. Inc., 192 F.3d 1353,
`1360 (Fed. Cir. 1999) (“There is no suggestion to combine, however, if a
`reference teaches away from its combination with another source.”). Indeed,
`HPE also teaches that the antimicrobial preservative benzyl alcohol—used in
`lieu of BAC in the formulations identified by Wyse as stable and appropriate
`
`
`Ex. 1001, code (63).
`
`18
`
`

`

`IPR2019-00697
`Patent 9,775,838 B2
`
`for further development (Ex. 1007, Table 15)—is safe, effective, and
`commonly used in pharmaceutical formulations. Ex. 1012, 10–11.
`Accordingly, based on the record before us, we find that Wyse teaches
`away from using BAC in intranasal naloxone formulations. Because each of
`the challenged claims requires a naloxone formulation that includes BAC,
`Petitioner has not shown a reasonable likelihood in prevailing in its assertion
`that these claims would have been obvious.
`
`III. CONCLUSION
`Having reviewed the record before us, we are not persuaded that
`Petitioner has demonstrated a reasonable likelihood of prevailing with
`respect to any one of the challenged claims. Therefore, we do not institute
`the requested inter partes review.
`
`ORDER
`
`Accordingly, it is:
`ORDERED that Petitioner’s request for an inter partes review of
`claims 1–46 of the ’838 patent in this case is denied.
`
`
`
`19
`
`

`

`IPR2019-00697
`Patent 9,775,838 B2
`
`PETITIONER:
`
`Yelee Y. Kim
`Janine A. Carlan
`Richard Berman
`Bradford Frese
`Christopher Yaen
`ARENT FOX LLP
`Yelee.Kim@arentfox.com
`Janine.Carlan@arentfox.com
`Richard.Berman@arentfox.com
`Bradford.Frese@arentfox.com
`Christopher.Yaen@arentfox.com
`
`
`PATENT OWNER:
`
`Robert F. Green
`Jessica Tyrus Mackay
`GREEN, GRIFFITH & BORG-BREEN LLP
`rgreen@greengriffith.com
`jmackay@greengriffith.com
`
`
`Jessamyn S. Berniker
`David M. Krinsky
`Anthony H. Sheh
`WILLIAMS & CONNOLLY LLP
`jberniker@wc.com
`dkrinsky@wc.com
`asheh@wc.com
`
`20
`
`

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