`571-272-7822
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` Paper 15
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`Entered: August 7, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`INNOPHARMA LICENSING, INC., INNOPHARMA LICENSING LLC,
`INNOPHARMA INC., INNOPHARMA LLC,
`MYLAN PHARMACEUTICALS INC., and MYLAN INC.,
`Petitioner,
`
`v.
`
`SENJU PHARMACEUTICAL CO., LTD., BAUSCH & LOMB, INC., and
`BAUSCH & LOMB PHARMA HOLDINGS CORP.,
`Patent Owner.
`________________
`
`Case IPR2015-00903
`Patent 8,129,431 B2
`_______________
`
`
`Before FRANCISCO C. PRATS, ERICA A. FRANKLIN, and
`GRACE KARAFFA OBERMANN, Administrative Patent Judges.
`
`OBERMANN, Administrative Patent Judge.
`
`
`
`DECISION
`Instituting Inter Partes Review
`37 C.F.R. § 42.108
`
`I. BACKGROUND
`
`On March 19, 2015, Petitioner filed a request for an inter partes
`
`review of claims 1–22 of U.S. Patent No. 8,129,431 B2 (Ex. 1001, “the ’431
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`patent”). Paper 2 (“Pet.”). Patent Owner filed a Preliminary Response.
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`Patent 8,129,431 B2
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`Paper 11 (“Prelim. Resp.”). Also on March 19, 2015, Petitioner filed a
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`Motion for Joinder (Exhibit 0) of this case with Metrics, Inc. v. Senju
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`Pharmaceutical Co., Ltd., IPR2014-01041. We address the Motion for
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`Joinder in an Order filed concurrently herewith.
`
`We have jurisdiction under 35 U.S.C. § 314(a), which provides that an
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`inter partes review may be instituted upon a showing of “a reasonable
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`likelihood that the petitioner would prevail with respect to at least 1 of the
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`claims challenged in the petition.” Petitioner makes that showing with
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`respect to claims 1–22; therefore, we institute review as to those claims.
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`Our findings of fact and conclusions of law are based on the record
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`developed thus far, prior to Patent Owner’s Response. This is not a final
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`decision as to the patentability of any challenged claim. If a final decision is
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`issued in this case, it will be based on the full record developed during trial.
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`A. Related Proceedings
`
`Petitioner identifies eight district court actions involving the ’431
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`patent, including one that involves Petitioner as a defendant. Pet. 11–12; see
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`Senju Pharmaceutical Co. v. InnoPharma Licensing, Inc., C.A. No. 1:14-
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`CV-06893-JBS-KMW (D.N.J. filed Nov. 3, 2014).
`
`Concurrently herewith, we issue a decision to institute in IPR2015-
`
`00902, involving the same parties and directed to U.S. Patent No. 8,669,290
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`B2 (the ’290 patent). The ’290 patent claims priority to the ’431 patent.
`
`B. The ’431 Patent (Ex. 1001)
`
`The ’431 patent relates to an aqueous liquid preparation consisting
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`essentially of two components: (1) bromfenac (or its salts and hydrates);
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`and (2) tyloxapol. Ex. 1001, 11:66–12:10. Bromfenac is a non-steroidal
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`anti-inflammatory drug (“NSAID”). Id. at 1:24–40. The preparation is
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`useful for ophthalmic administration, such as an eye drop to treat blepharitis,
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`conjunctivitis, scleritis, and postoperative inflammation. Id. at Abstract;
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`12:5–6. Claim 1 specifies that a quaternary ammonium compound,
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`specifically, benzalkonium chloride (“BAC”), may be included in the liquid
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`preparation. Id. at 12:8–9.
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`An object of the invention is to provide an aqueous liquid preparation
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`of bromfenac that “is stable within a pH range giving no irritation to eyes”
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`when preserved with BAC. Id. at 2:15–22. The inventors claim to have
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`discovered that addition of an alkyl aryl polyether alcohol type polymer,
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`such as tyloxapol, provides the sought-after stability, giving no irritation to
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`the eyes. Id. at 2:35–49. The inventors acknowledge that tyloxapol “is a
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`non-ionic surfactant.” Id. at 4:37–39.
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`C. Illustrative Claim
`
`Petitioner seeks inter partes review of claims 1–22 of the ’431 patent.
`
`Independent claim 1, reproduced below, is illustrative of the subject matter.
`
`1. An aqueous liquid preparation consisting essentially
`of the following two components, wherein the first
`component is 2-amino-3-(4-bromobenzoyl)-
`phenylaceticacid or a pharmacologically acceptable salt
`thereof or a hydrate thereof, wherein the hydrate is at
`least one selected from a 1/2 hydrate, 1 hydrate, and 3/2
`hydrate and the second component is tyloxapol, wherein
`said liquid preparation is formulated for ophthalmic
`administration, and wherein when a quaternary
`ammonium compound is included in said liquid
`preparation, the quaternary ammonium compound is
`benzalkonium chloride.
`
`Ex. 1001, 11:66–12:10.
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`3
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`Claims 3 and 20 specify a tyloxapol concentration that “is from
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`about 0.01 w/v % to about 0.5 w/v %.” Ex. 1001, 12:13–23, 14:13-16.
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`None of the claims of the ’431 patent specify a function for tyloxapol in the
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`preparation. Id. at 11:65–14:22 (claims 1–22).
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`D. The Applied Prior Art
`
`Petitioner relies upon the following prior art references:
`
`Ogawa et al., U.S. Patent No. 4,910,225, issued Mar. 20, 1990
`(Ex. 1004) (“Ogawa”).
`
`Sallmann et al., U.S. Patent No. 6,107,343, issued Aug. 22,
`2000 (Ex. 1009) (“Sallmann”).
`
`Fu, Austl. Patent Application No. AU-B-22042/88, issued Mar.
`16, 1989 (Ex. 1011 (“Fu”).
`
`E. The Asserted Grounds of Unpatentability
`
`Petitioner asserts that (1) claims 1–5, 7–14, and 18–19 of
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`the ’431 patent are unpatentable under 35 U.S.C. § 103 as obvious
`
`over Ogawa and Sallmann; and (2) claims 6, 15–17, and 20–22 are
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`unpatentable under 35 U.S.C. § 103 as obvious over Ogawa, Sallman,
`
`and Fu. Pet. 19. Petitioner relies on a declaration of Dr. Paul A.
`
`Laskar. Ex. 1003.1
`
`
`
`
`
`
`1 Dr. Laskar has a Ph.D. in Pharmaceutical Sciences and is the founder of a
`pharmaceutical development consulting firm focused on development and
`evaluation of pharmaceuticals, including ophthalmic products. Ex. 1003
`¶¶ 12–13, 17. Dr. Laskar has significant experience in the development and
`assessment of ophthalmic preparations. Ex. 1003 ¶¶ 14, 16. He appears on
`this record to have the requisite familiarity with ophthalmic preparations to
`opine on the views of a hypothetical person of ordinary skill in the art at the
`time of the invention. See id. at ¶¶ 10–17. At this stage of the proceeding,
`we find his testimony credible and persuasive.
`
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`II. ANALYSIS
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`A. Claim Construction
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`
`
`In an inter partes review, claim terms in an unexpired patent are
`
`interpreted according to their broadest reasonable construction in light of the
`
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b); In
`
`re Cuozzo Speed Techs., LLC, No. 2014–1301, 2015 WL 4097949, at *5–*8
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`(Fed. Cir. July 8, 2015). Claim terms are given their ordinary and customary
`
`meaning, as understood by one of ordinary skill in the art in the context of
`
`the entire disclosure. In re Translogic Tech., Inc., 504 F.3d 1249, 1257
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`(Fed. Cir. 2007). If an inventor acts as his or her own lexicographer, the
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`definition must be set forth in the specification with reasonable clarity,
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`deliberateness, and precision. Renishaw PLC v. Marposs Societa’ per
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`Azioni, 158 F.3d 1243, 1249 (Fed. Cir. 1998). The construction that stays
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`true to the claim language, and most naturally aligns with the inventor’s
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`description, is likely the correct interpretation. Id. at 1250.
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`Petitioner addresses the transitional phrase “consisting essentially of”
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`as applied in claims 1–22. Pet. 15–16. Patent Owner responds that none of
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`the terms requires express construction, and takes issue with Petitioner’s
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`discussion of that transitional phrase. Prelim. Resp. 14–15. At this stage of
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`the proceeding, we determine that the claim terms are clear on their face, and
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`none is specially defined in the written description of the ’431 patent. No
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`claim term requires express construction for the purposes of this decision.
`
`B. The Applied Prior Art
`
`We next turn to the prior art references applied in the Petition and, in
`
`particular, to what those references would have conveyed to an ordinary
`
`artisan about the state of the art at the time of the invention of the ’431
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`patent. At this stage of the proceeding, we consider the applied prior art as
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`representative of the level of ordinary skill in the art. We discuss facts as
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`presented thus far in the record. Any inferences or conclusions drawn from
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`those facts are neither final nor dispositive of any issue.
`
`i. Ogawa (Ex. 1004)
`
`Ogawa’s Example 6 discloses a stable aqueous liquid preparation,
`
`formulated for ophthalmic administration, which comprises bromfenac, as
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`the sole pharmaceutical active ingredient, and polysorbate 80. Ex 1004,
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`10:5–18, 49–57 (for stable aqueous liquid preparation); 10:5–9 (for
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`bromfenac, as sole pharmaceutical active ingredient, and polysorbate 80);
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`14:45–50 (Table 11, reporting 100% stability for the Example 6
`
`preparation). The ophthalmic preparation of Ogawa’s Example 6 includes
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`BAC, which is not excluded by claim 1. Ex. 1004, 10:5–9 (Ogawa); Ex.
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`1001, 12:6–9 (claim 1). On this record, Petitioner shows sufficiently that the
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`preparation of Ogawa’s Example 6 meets every limitation of claim 1, but for
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`the recited use of tyloxapol, in place of polysorbate 80. Ex. 1001, 12:4–5;
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`see Pet. 21–22 (claim chart for claim 1).
`
`ii. Sallmann (Ex. 1009)
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`Sallmann discloses tyloxapol as a non-ionic surfactant in an
`
`ophthalmic preparation of an NSAID—although Sallmann discloses
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`diclofenac potassium, and not bromfenac, as the NSAID. Specifically,
`
`Sallmann’s Example 2 discloses an aqueous ophthalmic preparation that
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`includes diclofenac, BAC, and tyloxapol. Ex 1009, 8:1–15. Petitioner
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`shows sufficiently that the remaining ingredients of Sallmann’s Example 2
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`would not have been expected to adversely affect the stability or
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`preservative efficacy of the preparation. Ex. 1003 ¶ 54. Bromfenac and
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`diclofenac share several structural similarities, for example, a phenylacetic
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`acid moiety. Pet. 27 (citing Ex. 1003 ¶¶ 27, 62). Like Ogawa’s Example 6,
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`Sallmann’s Example 2 discloses a preparation including BAC. Ex. 1009,
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`8:1–10. Claim 1 places no limit on the concentration of tyloxapol in the
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`preparation. Ex. 1001, 11:66–12:9.
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`On this record, Petitioner shows sufficiently that Sallmann’s
`
`Example 2 meets every limitation of claim 1, but for the use of bromfenac in
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`place of diclofenac. See Pet. 26– 30 (directing us to information that an
`
`ordinary artisan would have understood that bromfenac was superior to
`
`diclofenac and, moreover, would have recognized those two NSAIDs as
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`interchangeable based on their similar pharmacological properties).
`
`iii. Fu (Ex. 1011)
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`
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`Fu discloses an ophthalmic preparation comprising a NSAID, BAC,
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`and an ethoxylated octylphenol, e.g., Octoxynol 9 or Octoxynol 40, non-
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`ionic surfactant. Ex. 1011, 18:5–28, Examples 2, Example 5. Petitioner
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`shows sufficiently that tyloxapol is an ethoxylated octyphenol non-ionic
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`surfactant also. Ex. 1003 ¶ 33 (citing Ex. 1024, 1:1:1–2:1:2). Petitioner also
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`shows sufficiently that Fu “expressly discloses a non-ionic surfactant
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`concentration of 0.02 w/v %.” Pet. 44–45 (citing Ex. 1011, 18:5–28,
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`Example 2, Example 5; Ex. 1003 ¶¶ 75, 93). That disclosure bears upon
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`certain challenged claims, which require a concentration of tyloxapol that “is
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`about 0.02 w/v %.” Ex. 1001, claims 6, 15–17, and 20–22.
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`C.
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`Analysis of the Grounds of Unpatentability
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`We next turn to whether an ordinary artisan, equipped with the
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`combined disclosures of Ogawa and Sallman, would have had a reason to
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`replace polysorbate 80 in Ogawa’s Example 6 with tyloxapol. Alternatively,
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`we consider whether that artisan would have been led to replace diclofenac
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`with bromfenac in the ophthalmic preparation of Sallmann’s Example 2. On
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`this record, either substitution results in a preparation that satisfies every
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`limitation of claim 1.
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`We then address whether Petitioner has shown sufficiently that the
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`subject matter of (1) claims 2–5, 7–14, and 18–19 would have been obvious
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`over Ogawa and Sallmann; and (2) claims 6, 15–17, and 20–22 would have
`
`been obvious over Ogawa, Sallmann, and Fu. See Pet. 19 (asserting those
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`grounds for the remaining claims). We conclude with an analysis of Patent
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`Owner’s contentions as to secondary considerations of non-obviousness.
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`i. Replacing Polysorbate 80 with Tyloxapol in Ogawa
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`We agree with Patent Owner that “Ogawa is completely silent on the
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`function of polysorbate 80, ascribing no express role to it” in the ophthalmic
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`preparation of Ogawa’s Example 6. Prelim. Resp. 21; see generally
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`Ex. 1004. Notwithstanding that fact, however, the information presented is
`
`sufficient to show that, at the time of the invention, polysorbate 80 and
`
`tyloxapol were added to aqueous ophthalmic preparations as surface-active
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`agents. Pet. 23–24; see Ex. 1003 ¶¶ 32, 38, 50 (Dr. Laskar’s declaration
`
`testimony). At this stage, Patent Owner does not refute adequately that, at
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`the time of the invention, an ordinary artisan would have recognized
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`polysorbate 80 as a non-ionic surfactant in this art. Prelim. Resp. 10
`
`(referring to “polysorbate 80” and “tyloxapol” as “surfactants”); Prelim.
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`Resp. 29 (suggesting that polysorbate 80 and tyloxapol are both non-ionic
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`surfactants, but arguing that how they function in different mediums “is
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`highly unpredictable”).
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`8
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`On this record, moreover, Petitioner shows sufficiently that Sallmann
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`adds tyloxapol to an NSAID-BAC preparation in an amount that falls within
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`the preferred amount disclosed in the ’431 patent. See Pet. 42 (citing
`
`Ex. 1003 ¶ 71) (Sallmann’s Example 2 discloses a tyloxapol concentration
`
`of 0.1 w/v %); Ex. 1001, 5:37–38 (the ’431 patent, disclosing that the
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`tyloxapol range, effective to stabilize a bromfenac-BAC preparation, is from
`
`about 0.01 and 0.5 w/v %). Based on the record developed at this early
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`stage of the proceeding, we accept that a person of ordinary skill in the art,
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`when replacing polysorbate 80 with tyloxapol in Ogawa’s Example 6, would
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`have used the concentration of tyloxapol that is disclosed in Sallmann’s
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`Example 2. Pet. 20–26; Ex. 1003 ¶¶ 47–64.
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`Patent Owner contends that Ogawa does not add polysorbate 80 to
`
`stabilize the preparation of Example 6 and, on that basis, contends that
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`Petitioner fails to establish that an ordinary artisan would have included
`
`tyloxapol for a stabilizing purpose. Prelim. Resp. 22–23; compare
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`Ex. 1003 ¶ 50 (Dr. Laskar’s opinion that polysorbate 80 enhances the
`
`stability of Ogawa’s preparation) to Ex. 1004, 3:7–15 (Ogawa, discussing
`
`the factors that enhance stability, without indicating that polysorbate 80
`
`affects the stability of the preparation). Specifically, Patent Owner directs us
`
`to disclosures suggesting that Ogawa uses a water soluble polymer
`
`(polyvinyl pyrrolidone) and a sulfite (sodium sulfite) to stabilize the
`
`bromfenac preparation. Prelim. Resp. 22 (discussing Experimental
`
`Examples 4–6).
`
`As Patent Owner readily admits, however, those disclosures do not
`
`speak to the function of polysorbate 80 and, accordingly, do not establish
`
`that polysorbate 80 serves no stabilizing function in the preparation. Id.
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`at 21 (“Ogawa is completely silent on the function of polysorbate 80,
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`ascribing no express role to it.”) Petitioner, by contrast, directs us to
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`information that an ordinary artisan would have recognized that
`
`polysorbate 80 is a non-ionic surfactant in Ogawa’s Example 6, and would
`
`have understood that tyloxapol was interchangeable with polysorbate 80 as a
`
`non-ionic surfactant in ophthalmic preparations. Pet. 23–24; see Ex. 1003
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`¶¶ 32, 38, 50 (Dr. Laskar’s declaration testimony).
`
`We acknowledge that Patent Owner has not yet filed a Response and
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`that the Preliminary Response necessarily rests on argument unsupported by
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`new testimonial evidence. See 37 C.F.R. § 42.107(c) (no new testimonial
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`evidence may be submitted with a preliminary response). However, the
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`disclosures in the references advanced in the Preliminary Response, standing
`
`alone, are insufficient to establish Patent Owner’s factual assertions.
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`Specifically, Patent Owner has not refuted adequately, at this stage of the
`
`proceeding, that polysorbate 80 and tyloxapol were used interchangeably as
`
`surfactants in ophthalmic preparations. See Prelim. Resp. 10 (referring to
`
`both “polysorbate 80” and “tyloxapol” as “surfactants”).
`
`Based on the information presented at this stage of the proceeding, the
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`interchangeability of those components is suggested by the combined
`
`teachings of the applied art, where Ogawa includes a non-ionic surfactant,
`
`polysorbate 80, in a stable NSAID-containing ophthalmic preparation, and
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`Sallmann similarly includes a non-ionic surfactant, tyloxapol, in a stable
`
`NSAID-containing ophthalmic preparation. At this early stage, Patent
`
`Owner’s factual contentions, regarding what the applied references would
`
`have conveyed to an ordinary artisan, rest on attorney argument, whereas
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`Petitioner’s assertions are supported by the declaration testimony of
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`Dr. Laskar.
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`For example, Patent Owner argues that the undesirable “red insoluble
`
`particles” in Ogawa’s preparation are caused by dimerization of bromfenac,
`
`rather than complexation of bromfenac and BAC. Prelim. Resp. 21. Patent
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`Owner further argues that polysorbate 80 “plays no role in preventing the
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`oxidative degradation of bromfenac” in Ogawa’s Example 6. Id. Neither of
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`those facts, however, is adequately supported at this stage of the proceeding.
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`None of the challenged claims, moreover, specifies a function for tyloxapol
`
`in the preparation of the invention. See Ex. 1001, 11:65–14:22 (claims 1–
`
`22, which do not specify that tyloxapol must perform a stabilizing function).
`
`On this record, we are not persuaded that Petitioner must establish that an
`
`ordinary artisan would have grasped exactly how polysorbate 80 or
`
`tyloxapol interacts with the components of the aqueous preparation. See
`
`Prelim. Resp. 22 (arguing that Dr. Laskar’s testimony, that polysorbate 80
`
`stabilizes bromfenac in Ogawa’s Example 6 preparation, “is fundamental to”
`
`Petitioner’s challenge).
`
`The issue is whether a person of ordinary skill in the art would have
`
`had a reason (such as a simple substitution) to use tyloxapol, instead of
`
`polysorbate 80, in Ogawa’s Example 6 preparation—whether or not that
`
`artisan would have recognized any stabilizing benefit of doing so. See Ex
`
`parte Obiaya, 227 USPQ 58, 60 (BPAI 1985) (The fact that a patent
`
`applicant may have “recognized another advantage which would flow
`
`naturally from following the suggestion of the prior art cannot be the basis
`
`for patentability when the differences would otherwise be obvious.”).
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`Based on the information presented, we determine that Petitioner
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`shows sufficiently that an ordinary artisan would have recognized that
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`“tyloxapol and polysorbate 80 had previously been used interchangeably as
`
`surfactants in ophthalmic formulations.” Pet. 24 (citing Ex. 1003 ¶¶ 38, 50)
`
`(Dr. Laskar’s testimony that, at the time of the invention, “tyloxapol was a
`
`widely-used surfactant in aqueous liquid preparations comprising anti-
`
`inflammatory agents, and was used interchangeably with polysorbate 80”).
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`That known interchangeability, absent persuasive objective evidence to the
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`contrary, is enough to support the proposed substitution. An express
`
`suggestion to substitute one known equivalent non-ionic surfactant for
`
`another in Ogawa’s ophthalmic preparation is not needed to render the
`
`substitution obvious. See In re Fout, 675 F.2d 297, 301 (CCPA 1982); In re
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`Siebentritt, 372 F.2d 566, 568 (CCPA 1967); see also In re Mayne, 104 F.3d
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`1339, 1340 (Fed. Cir. 1997) (“Because the applicants merely substituted one
`
`element known in the art for a known equivalent, this court affirms [the
`
`conclusion of obviousness].”).
`
` At this stage of the proceeding, absent evidence to the contrary, it
`
`would have been well within the level of ordinary skill in the art to replace
`
`one non-ionic surfactant (polysorbate 80) with another non-ionic surfactant
`
`(tyloxapol) in Ogawa’s Example 6, because both were known to be useful as
`
`surfactants in ophthalmic preparations. See KSR Int’l Co. v. Teleflex Inc.,
`
`550 U.S. 398, 417 (2007) (“If a person of ordinary skill in the art can
`
`implement a predictable variation, and would see the benefit of doing so,
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`§ 103 likely bars its patentability.”).
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`ii. Replacing Diclofenac with Bromfenac in Sallmann
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`Alternatively, Petitioner is reasonably likely to prevail in showing that
`
`an ordinary artisan would have replaced diclofenac with bromfenac in the
`
`ophthalmic preparation of Sallmann’s Example 2. Pet. 26–30; Ex. 1003
`
`¶¶ 23–24, 27, 29, 42, 53–54; see Ex. 1009, 8:1–15 (Sallmann’s Example 2,
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`disclosing an ophthalmic preparation that meets every limitation of claim 1,
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`except that Sallmann uses diclofenac and not bromfenac as the NSAID); see
`
`also Ex. 1003 ¶¶ 60–63 (Dr. Laskar’s testimony that, at the time of the
`
`invention, bromfenac and diclofenac would have been recognized as
`
`interchangeable NSAIDs suitable for use in aqueous liquid ophthalmic
`
`preparations).
`
`Sallmann in Example 2 discloses that diclofenac is useful as the
`
`NSAID in an ophthalmic preparation of an NSAID and BAC. Ex. 1009,
`
`8:1–15. Ogawa in Example 6 discloses that bromfenac is useful as the
`
`NSAID in an ophthalmic preparation of an NSAID and BAC. Ex. 1004,
`
`10:5–9. At the time of the invention, bromfenac and diclofenac were known
`
`to share several structural features. Pet. 27; Ex. 1003 ¶¶ 24, 27.
`
`Furthermore, based on the information presented, a person of ordinary skill
`
`in the art at the time of the invention would have recognized the two
`
`NSAIDs as “suitable and desirable for ophthalmic administration.” Pet. 27;
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`Ex. 1003 ¶¶ 23–24.
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`Accordingly, on the current record, Petitioner shows sufficiently that
`
`an ordinary artisan would have expected diclofenac and bromfenac to work
`
`interchangeably in an ophthalmic preparation of an NSAID and BAC.
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`Pet. 28–30; Ex. 1003 ¶¶ 60–63. Patent Owner’s counterviews—including
`
`that structural and functional differences between the two NSAIDs would
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`have dissuaded an ordinary artisan from making the proposed substitution—
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`are not adequately supported on this record and, therefore, are insufficient to
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`persuade us to deny review. See Prelim. Resp. 33–42.
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`Specifically, Patent Owner contends that a person of ordinary skill in
`
`the art “would not have replaced diclofenac potassium with bromfenac
`
`sodium” because one would have known that “[d]oing so would have
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`destroyed the entire purpose and essence of Sallmann’s invention.” Id.
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`at 33. By way of support, Patent Owner avers to “Sallmann’s indisputable
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`preference for potassium salts.” Id. at 34. Patent Owner also avers that a
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`person of ordinary skill in the art would have “more likely honed in on
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`Sallmann’s Examples 8 and 11” instead of Example 2. Id. at 35. Patent
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`Owner suggests that an ordinary artisan would have recognized that
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`cyclodextrins in Sallmann’s Example 2 “can unpredictably impact the
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`stability of a formulation.” Id. Patent Owner argues that the ordinary artisan
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`“would have recognized from Ogawa that bromfenac degraded via
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`oxidation.” Id. at 36. Patent Owner also attempts to establish that, as
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`between bromfenac and diclofenac, a difference in the amine moiety “affects
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`at least polarity and electron density distribution.” Id. at 41. On the current
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`record, however, Patent Owner’s conclusion—that these facts show that an
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`ordinary artisan would not have considered bromfenac and diclofenac to be
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`interchangeable, ophthalmically-suitable NSAIDs—is based on attorney
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`argument that is not shown to reflect the perspective of an ordinary artisan.
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`At this stage of the proceeding, given the evidence before us,
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`including that discussed above, we are persuaded that Petitioner shows
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`sufficiently that it would have been obvious to a person of ordinary skill in
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`the art to replace diclofenac with bromfenac, including bromfenac’s sodium
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`salt as required in some of the challenged claims, in the preparation of
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`Sallmann’s Example 2, because diclofenac and bromfenac were recognized
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`as interchangeable, alternative NSAIDs serving the same function in an
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`ophthalmic preparation. See KSR Int’l Co., 550 U.S. at 417 (a claim likely is
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`obvious if it is no “more than the predictable use of prior art elements
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`according to their established functions”).
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`iii. The Remaining Challenged Claims
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`a. Claims 2–5, 7–14, and 18–19 over Ogawa and Sallmann
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`Based on the information presented, there is a reasonable likelihood
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`that Petitioner also will prevail in showing that the subject matter of
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`claims 2–5, 7–14, and 18–19 would have been obvious over Ogawa and
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`Sallmann. Pet. 30–43, 47–50. We have taken account of the
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`counterarguments presented in the Preliminary Response, but on this record,
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`we determine that Petitioner has made a showing sufficient to support
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`institution of an inter partes review of claims 2–5, 7–14, and 18–19.
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`In particular, on this record, we are satisfied that, to the extent that a
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`range set forth in the claims is critical, Petitioner shows sufficiently that an
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`ordinary artisan would have arrived at the specified range using only routine
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`experimentation. Pet. 40–41; see In re Aller, 220 F.2d 454, 456–58 (CCPA
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`1955) (“[W]here the general conditions of a claim are disclosed in the prior
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`art, it is not inventive to discover the optimum or workable ranges by routine
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`experimentation.” (citations omitted)); In re Peterson, 315 F.3d 1325, 1330
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`(Fed. Cir. 2003) (“The normal desire of scientists or artisans to improve
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`upon what is already generally known provides the motivation to determine
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`where in a disclosed set of percentage ranges is the optimum combination of
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`percentages.”). For example, claim 3 specifies a concentration of tyloxapol
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`that “is from about 0.01 w/v % to about 0.5 w/v %.” Ex. 1001, 12:13–23,
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`14:13–16. Petitioner shows sufficiently that Sallmann adds tyloxapol to an
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`NSAID-BAC preparation in an amount that falls within that concentration.
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`See Pet. 42 (citing Ex. 1003 ¶ 71) (Sallmann’s Example 2 discloses a
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`tyloxapol concentration of 0.1 w/v %). Based on the record developed at
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`this early stage of the proceeding, we accept that a person of ordinary skill in
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`the art, when replacing polysorbate 80 with tyloxapol in Ogawa’s
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`Example 6, would have used the concentration of tyloxapol that is disclosed
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`in Sallmann’s Example 2. Pet. 19–22; Ex. 1003 ¶¶ 50–51.
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`b. Claims 6, 15–17, and 20–22 over Ogawa, Sallmann, and Fu
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`Based on the information presented at this stage of the proceeding,
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`Petitioner also is reasonably likely to prevail in showing that claims 6, 15–
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`17, and 20–22 are unpatentable over Ogawa, Sallmann, and Fu under
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`35 U.S.C. § 103. Pet. 44–49. Those claims require a concentration of
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`tyloxapol that “is about 0.02 w/v %.” See, e.g., Ex. 1001, 12:55 (claim 6);
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`13:2–3 (claim 15). Petitioner comes forward with evidence sufficient to
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`show that a person of ordinary skill in the art would have been prompted by
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`Fu to include tyloxapol, in a concentration of “about 0.02 w/v %,” id., in the
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`modified composition of Ogawa or Sallmann. Pet. 44–47.
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`Specifically, Petitioner shows sufficiently that Fu would have
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`suggested to an ordinary artisan “that ethoxylated octylphenol surfactants,”
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`the class that includes tyloxapol, would have “worked even better than
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`polysorbate 80.” Pet. 45 (citing Ex. 1003, ¶¶ 33–35, 38, 64); see Ex. 1011,
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`Example 5 (Fu, disclosing that the octylphenol surfactant worked better than
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`polysorbate 80 when “evaluated for their ability to dissolve [an NSAID-
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`BAC complex] and maintain a physically clear solution over an extended
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`period of time”). Petitioner also shows sufficiently that Fu suggests using
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`that class of non-ionic surfactants in a concentration of 0.02 w/v % in
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`aqueous liquid ophthalmic preparations of an NSAID and BAC. Pet. 44–46
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`(citing Ex. 1011, 18:5–28, Example 2, Example 5; Ex. 1003 ¶¶ 34–35, 60,
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`75–76).
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`Alternatively, it appears to us, at this stage of the proceeding, that it
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`would have been within the grasp of an ordinary artisan to manipulate the
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`concentration of tyloxapol in the modified preparation of Ogawa or
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`Sallmann “to discover the optimum or workable ranges by routine
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`experimentation.” In re Aller, 220 F.2d at 456–57 (CCPA 1955) (“where the
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`general conditions of a claim are disclosed in the prior art, it is not inventive
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`to discover the optimum or workable ranges by routine experimentation”);
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`see Pet. 47–48 (bridging paragraph) (citing In re Aller for that proposition).
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`iv. Secondary Considerations
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`We have taken account of the information presented in the
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`Preliminary Response, but on this record, we determine that Petitioner has
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`made a showing sufficient to support institution of an inter partes review.
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`For example, we have taken account of the information advanced by Patent
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`Owner in support of secondary considerations of non-obviousness. Prelim.
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`Resp. 49–58. We have noted in particular Petitioner’s concession that “[t]he
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`subject matter of many of the challenged claims of the ’431 patent is
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`commercially embodied by Prolensa®, a product marketed by” Patent
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`Owner. Pet. 9. Nonetheless, at this early stage of the proceeding, before the
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`filing of Patent Owner’s Response, many of Patent Owner’s factual
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`assertions, regarding the commercial success of Prolensa®, are not
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`adequately supported.
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`Patent Owner contends that “[t]yloxapol’s stabilization effect
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`permitted formulating Prolensa® at pH 7.8;” that such a pH is “closer to the
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`pH of natural tears” than other bromfenac preparations; that the lowered pH
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`is “less irritating to the patient,” which “improve[s] bromfenac’s intraocular
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`penetration and permit[s] a lowering of its concentration” compared to a
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`different product; and that Prolensa®, therefore, “advantageously puts less
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`drug in contact with surgically compromised ocular tissue without a
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`reduction in efficacy.” Prelim. Resp. 56. At this stage, however, Patent
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`Owner refers to entire exhibits, without any pin-cites, and supplies no cogent
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`explanation of how the exhibits support these fact-laden contentions, or
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`whether the asserted properties were unexpected or otherwise unobvious.
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`Id. at 56, n.7 (citing Ex. 2013, Ex. 2026, Ex. 2027, Ex. 2030). Similarly,
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`Patent Owner refers to sales data for Prolensa®, as projected by a
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`competitor, but at this stage of the proceeding, comes forward with no
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`objective evidence of revenues based on actual sales. Id. at 57.
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`Patent Owner also refers to test results to establish that tyloxapol is a
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`better stabilizer of bromfenac, compared to polysorbate 80—but advances
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`no information that the asserted results would have been considered truly
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`“surprising” or “unexpected” by a person of ordinary skill in the art. Id. at
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`53. At this early stage, Patent Owner’s position on that point rests entirely
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`on attorney argument. Id.; see In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir.
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`1997) (argument of counsel cannot take the place of evidence). The record
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`is devoid of objective evidence in that regard. Not even the inventors
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`described tyloxapol as “surprising” or “unexpected” in its stabilizing effect:
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`When comparing tyloxapol to other alkyl aryl polyether alcohol type
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`polymers, the inventors described tyloxapol as “especially preferable.”
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`Ex. 1001, 4:65–67.
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`In sum, Patent Owner’s information, at this stage of the proceedi