throbber
Trials@uspto.gov
`571-272-7822
`
`
`
` Paper 15
`
`Entered: August 7, 2015
`
`
`
`
`
`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
`
`patent”). Paper 2 (“Pet.”). Patent Owner filed a Preliminary Response.
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`Paper 11 (“Prelim. Resp.”). Also on March 19, 2015, Petitioner filed a
`
`Motion for Joinder (Exhibit 0) of this case with Metrics, Inc. v. Senju
`
`Pharmaceutical Co., Ltd., IPR2014-01041. We address the Motion for
`
`Joinder in an Order filed concurrently herewith.
`
`We have jurisdiction under 35 U.S.C. § 314(a), which provides that an
`
`inter partes review may be instituted upon a showing of “a reasonable
`
`likelihood that the petitioner would prevail with respect to at least 1 of the
`
`claims challenged in the petition.” Petitioner makes that showing with
`
`respect to claims 1–22; therefore, we institute review as to those claims.
`
`Our findings of fact and conclusions of law are based on the record
`
`developed thus far, prior to Patent Owner’s Response. This is not a final
`
`decision as to the patentability of any challenged claim. If a final decision is
`
`issued in this case, it will be based on the full record developed during trial.
`
`A. Related Proceedings
`
`Petitioner identifies eight district court actions involving the ’431
`
`patent, including one that involves Petitioner as a defendant. Pet. 11–12; see
`
`Senju Pharmaceutical Co. v. InnoPharma Licensing, Inc., C.A. No. 1:14-
`
`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
`
`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
`
`essentially of two components: (1) bromfenac (or its salts and hydrates);
`
`and (2) tyloxapol. Ex. 1001, 11:66–12:10. Bromfenac is a non-steroidal
`
`anti-inflammatory drug (“NSAID”). Id. at 1:24–40. The preparation is
`
`
`
`2
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`useful for ophthalmic administration, such as an eye drop to treat blepharitis,
`
`conjunctivitis, scleritis, and postoperative inflammation. Id. at Abstract;
`
`12:5–6. Claim 1 specifies that a quaternary ammonium compound,
`
`specifically, benzalkonium chloride (“BAC”), may be included in the liquid
`
`preparation. Id. at 12:8–9.
`
`An object of the invention is to provide an aqueous liquid preparation
`
`of bromfenac that “is stable within a pH range giving no irritation to eyes”
`
`when preserved with BAC. Id. at 2:15–22. The inventors claim to have
`
`discovered that addition of an alkyl aryl polyether alcohol type polymer,
`
`such as tyloxapol, provides the sought-after stability, giving no irritation to
`
`the eyes. Id. at 2:35–49. The inventors acknowledge that tyloxapol “is a
`
`non-ionic surfactant.” Id. at 4:37–39.
`
`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.
`
`
`
`3
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`
`Claims 3 and 20 specify a tyloxapol concentration that “is from
`
`about 0.01 w/v % to about 0.5 w/v %.” Ex. 1001, 12:13–23, 14:13-16.
`
`None of the claims of the ’431 patent specify a function for tyloxapol in the
`
`preparation. Id. at 11:65–14:22 (claims 1–22).
`
`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
`
`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
`
`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.
`
`
`
`4
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`
`II. ANALYSIS
`
`A. Claim Construction
`
`
`
`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
`
`(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
`
`(Fed. Cir. 2007). If an inventor acts as his or her own lexicographer, the
`
`definition must be set forth in the specification with reasonable clarity,
`
`deliberateness, and precision. Renishaw PLC v. Marposs Societa’ per
`
`Azioni, 158 F.3d 1243, 1249 (Fed. Cir. 1998). The construction that stays
`
`true to the claim language, and most naturally aligns with the inventor’s
`
`description, is likely the correct interpretation. Id. at 1250.
`
`Petitioner addresses the transitional phrase “consisting essentially of”
`
`as applied in claims 1–22. Pet. 15–16. Patent Owner responds that none of
`
`the terms requires express construction, and takes issue with Petitioner’s
`
`discussion of that transitional phrase. Prelim. Resp. 14–15. At this stage of
`
`the proceeding, we determine that the claim terms are clear on their face, and
`
`none is specially defined in the written description of the ’431 patent. No
`
`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
`
`
`
`5
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`patent. At this stage of the proceeding, we consider the applied prior art as
`
`representative of the level of ordinary skill in the art. We discuss facts as
`
`presented thus far in the record. Any inferences or conclusions drawn from
`
`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
`
`the sole pharmaceutical active ingredient, and polysorbate 80. Ex 1004,
`
`10:5–18, 49–57 (for stable aqueous liquid preparation); 10:5–9 (for
`
`bromfenac, as sole pharmaceutical active ingredient, and polysorbate 80);
`
`14:45–50 (Table 11, reporting 100% stability for the Example 6
`
`preparation). The ophthalmic preparation of Ogawa’s Example 6 includes
`
`BAC, which is not excluded by claim 1. Ex. 1004, 10:5–9 (Ogawa); Ex.
`
`1001, 12:6–9 (claim 1). On this record, Petitioner shows sufficiently that the
`
`preparation of Ogawa’s Example 6 meets every limitation of claim 1, but for
`
`the recited use of tyloxapol, in place of polysorbate 80. Ex. 1001, 12:4–5;
`
`see Pet. 21–22 (claim chart for claim 1).
`
`ii. Sallmann (Ex. 1009)
`
`Sallmann discloses tyloxapol as a non-ionic surfactant in an
`
`ophthalmic preparation of an NSAID—although Sallmann discloses
`
`diclofenac potassium, and not bromfenac, as the NSAID. Specifically,
`
`Sallmann’s Example 2 discloses an aqueous ophthalmic preparation that
`
`includes diclofenac, BAC, and tyloxapol. Ex 1009, 8:1–15. Petitioner
`
`shows sufficiently that the remaining ingredients of Sallmann’s Example 2
`
`would not have been expected to adversely affect the stability or
`
`preservative efficacy of the preparation. Ex. 1003 ¶ 54. Bromfenac and
`
`
`
`6
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`diclofenac share several structural similarities, for example, a phenylacetic
`
`acid moiety. Pet. 27 (citing Ex. 1003 ¶¶ 27, 62). Like Ogawa’s Example 6,
`
`Sallmann’s Example 2 discloses a preparation including BAC. Ex. 1009,
`
`8:1–10. Claim 1 places no limit on the concentration of tyloxapol in the
`
`preparation. Ex. 1001, 11:66–12:9.
`
`On this record, Petitioner shows sufficiently that Sallmann’s
`
`Example 2 meets every limitation of claim 1, but for the use of bromfenac in
`
`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
`
`interchangeable based on their similar pharmacological properties).
`
`iii. Fu (Ex. 1011)
`
`
`
`Fu discloses an ophthalmic preparation comprising a NSAID, BAC,
`
`and an ethoxylated octylphenol, e.g., Octoxynol 9 or Octoxynol 40, non-
`
`ionic surfactant. Ex. 1011, 18:5–28, Examples 2, Example 5. Petitioner
`
`shows sufficiently that tyloxapol is an ethoxylated octyphenol non-ionic
`
`surfactant also. Ex. 1003 ¶ 33 (citing Ex. 1024, 1:1:1–2:1:2). Petitioner also
`
`shows sufficiently that Fu “expressly discloses a non-ionic surfactant
`
`concentration of 0.02 w/v %.” Pet. 44–45 (citing Ex. 1011, 18:5–28,
`
`Example 2, Example 5; Ex. 1003 ¶¶ 75, 93). That disclosure bears upon
`
`certain challenged claims, which require a concentration of tyloxapol that “is
`
`about 0.02 w/v %.” Ex. 1001, claims 6, 15–17, and 20–22.
`
`C.
`
`Analysis of the Grounds of Unpatentability
`
`We next turn to whether an ordinary artisan, equipped with the
`
`combined disclosures of Ogawa and Sallman, would have had a reason to
`
`replace polysorbate 80 in Ogawa’s Example 6 with tyloxapol. Alternatively,
`
`
`
`7
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`we consider whether that artisan would have been led to replace diclofenac
`
`with bromfenac in the ophthalmic preparation of Sallmann’s Example 2. On
`
`this record, either substitution results in a preparation that satisfies every
`
`limitation of claim 1.
`
`We then address whether Petitioner has shown sufficiently that the
`
`subject matter of (1) claims 2–5, 7–14, and 18–19 would have been obvious
`
`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
`
`grounds for the remaining claims). We conclude with an analysis of Patent
`
`Owner’s contentions as to secondary considerations of non-obviousness.
`
`i. Replacing Polysorbate 80 with Tyloxapol in Ogawa
`
`We agree with Patent Owner that “Ogawa is completely silent on the
`
`function of polysorbate 80, ascribing no express role to it” in the ophthalmic
`
`preparation of Ogawa’s Example 6. Prelim. Resp. 21; see generally
`
`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
`
`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
`
`the time of the invention, an ordinary artisan would have recognized
`
`polysorbate 80 as a non-ionic surfactant in this art. Prelim. Resp. 10
`
`(referring to “polysorbate 80” and “tyloxapol” as “surfactants”); Prelim.
`
`Resp. 29 (suggesting that polysorbate 80 and tyloxapol are both non-ionic
`
`surfactants, but arguing that how they function in different mediums “is
`
`highly unpredictable”).
`
`
`
`8
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`
`On this record, moreover, Petitioner shows sufficiently that Sallmann
`
`adds tyloxapol to an NSAID-BAC preparation in an amount that falls within
`
`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
`
`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
`
`stage of the proceeding, we accept that a person of ordinary skill in the art,
`
`when replacing polysorbate 80 with tyloxapol in Ogawa’s Example 6, would
`
`have used the concentration of tyloxapol that is disclosed in Sallmann’s
`
`Example 2. Pet. 20–26; Ex. 1003 ¶¶ 47–64.
`
`Patent Owner contends that Ogawa does not add polysorbate 80 to
`
`stabilize the preparation of Example 6 and, on that basis, contends that
`
`Petitioner fails to establish that an ordinary artisan would have included
`
`tyloxapol for a stabilizing purpose. Prelim. Resp. 22–23; compare
`
`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.
`
`
`
`9
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`at 21 (“Ogawa is completely silent on the function of polysorbate 80,
`
`ascribing no express role to it.”) Petitioner, by contrast, directs us to
`
`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
`
`¶¶ 32, 38, 50 (Dr. Laskar’s declaration testimony).
`
`We acknowledge that Patent Owner has not yet filed a Response and
`
`that the Preliminary Response necessarily rests on argument unsupported by
`
`new testimonial evidence. See 37 C.F.R. § 42.107(c) (no new testimonial
`
`evidence may be submitted with a preliminary response). However, the
`
`disclosures in the references advanced in the Preliminary Response, standing
`
`alone, are insufficient to establish Patent Owner’s factual assertions.
`
`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
`
`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
`
`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
`
`
`
`10
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`Petitioner’s assertions are supported by the declaration testimony of
`
`Dr. Laskar.
`
`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
`
`Owner further argues that polysorbate 80 “plays no role in preventing the
`
`oxidative degradation of bromfenac” in Ogawa’s Example 6. Id. Neither of
`
`those facts, however, is adequately supported at this stage of the proceeding.
`
`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.”).
`
`
`
`11
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`
`Based on the information presented, we determine that Petitioner
`
`shows sufficiently that an ordinary artisan would have recognized that
`
`“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”).
`
`That known interchangeability, absent persuasive objective evidence to the
`
`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
`
`Siebentritt, 372 F.2d 566, 568 (CCPA 1967); see also In re Mayne, 104 F.3d
`
`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,
`
`§ 103 likely bars its patentability.”).
`
`
`
`
`
`
`
`12
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`
`ii. Replacing Diclofenac with Bromfenac in Sallmann
`
`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,
`
`disclosing an ophthalmic preparation that meets every limitation of claim 1,
`
`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;
`
`Ex. 1003 ¶¶ 23–24.
`
`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.
`
`Pet. 28–30; Ex. 1003 ¶¶ 60–63. Patent Owner’s counterviews—including
`
`that structural and functional differences between the two NSAIDs would
`
`
`
`13
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`have dissuaded an ordinary artisan from making the proposed substitution—
`
`are not adequately supported on this record and, therefore, are insufficient to
`
`persuade us to deny review. See Prelim. Resp. 33–42.
`
`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
`
`destroyed the entire purpose and essence of Sallmann’s invention.” Id.
`
`at 33. By way of support, Patent Owner avers to “Sallmann’s indisputable
`
`preference for potassium salts.” Id. at 34. Patent Owner also avers that a
`
`person of ordinary skill in the art would have “more likely honed in on
`
`Sallmann’s Examples 8 and 11” instead of Example 2. Id. at 35. Patent
`
`Owner suggests that an ordinary artisan would have recognized that
`
`cyclodextrins in Sallmann’s Example 2 “can unpredictably impact the
`
`stability of a formulation.” Id. Patent Owner argues that the ordinary artisan
`
`“would have recognized from Ogawa that bromfenac degraded via
`
`oxidation.” Id. at 36. Patent Owner also attempts to establish that, as
`
`between bromfenac and diclofenac, a difference in the amine moiety “affects
`
`at least polarity and electron density distribution.” Id. at 41. On the current
`
`record, however, Patent Owner’s conclusion—that these facts show that an
`
`ordinary artisan would not have considered bromfenac and diclofenac to be
`
`interchangeable, ophthalmically-suitable NSAIDs—is based on attorney
`
`argument that is not shown to reflect the perspective of an ordinary artisan.
`
`At this stage of the proceeding, given the evidence before us,
`
`including that discussed above, we are persuaded that Petitioner shows
`
`sufficiently that it would have been obvious to a person of ordinary skill in
`
`the art to replace diclofenac with bromfenac, including bromfenac’s sodium
`
`
`
`14
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`salt as required in some of the challenged claims, in the preparation of
`
`Sallmann’s Example 2, because diclofenac and bromfenac were recognized
`
`as interchangeable, alternative NSAIDs serving the same function in an
`
`ophthalmic preparation. See KSR Int’l Co., 550 U.S. at 417 (a claim likely is
`
`obvious if it is no “more than the predictable use of prior art elements
`
`according to their established functions”).
`
`iii. The Remaining Challenged Claims
`
`a. Claims 2–5, 7–14, and 18–19 over Ogawa and Sallmann
`
`Based on the information presented, there is a reasonable likelihood
`
`that Petitioner also will prevail in showing that the subject matter of
`
`claims 2–5, 7–14, and 18–19 would have been obvious over Ogawa and
`
`Sallmann. Pet. 30–43, 47–50. We have taken account of the
`
`counterarguments presented in the Preliminary Response, but on this record,
`
`we determine that Petitioner has made a showing sufficient to support
`
`institution of an inter partes review of claims 2–5, 7–14, and 18–19.
`
`In particular, on this record, we are satisfied that, to the extent that a
`
`range set forth in the claims is critical, Petitioner shows sufficiently that an
`
`ordinary artisan would have arrived at the specified range using only routine
`
`experimentation. Pet. 40–41; see In re Aller, 220 F.2d 454, 456–58 (CCPA
`
`1955) (“[W]here the general conditions of a claim are disclosed in the prior
`
`art, it is not inventive to discover the optimum or workable ranges by routine
`
`experimentation.” (citations omitted)); In re Peterson, 315 F.3d 1325, 1330
`
`(Fed. Cir. 2003) (“The normal desire of scientists or artisans to improve
`
`upon what is already generally known provides the motivation to determine
`
`where in a disclosed set of percentage ranges is the optimum combination of
`
`percentages.”). For example, claim 3 specifies a concentration of tyloxapol
`
`
`
`15
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`that “is from about 0.01 w/v % to about 0.5 w/v %.” Ex. 1001, 12:13–23,
`
`14:13–16. Petitioner shows sufficiently that Sallmann adds tyloxapol to an
`
`NSAID-BAC preparation in an amount that falls within that concentration.
`
`See Pet. 42 (citing Ex. 1003 ¶ 71) (Sallmann’s Example 2 discloses a
`
`tyloxapol concentration of 0.1 w/v %). Based on the record developed at
`
`this early stage of the proceeding, we accept that a person of ordinary skill in
`
`the art, when replacing polysorbate 80 with tyloxapol in Ogawa’s
`
`Example 6, would have used the concentration of tyloxapol that is disclosed
`
`in Sallmann’s Example 2. Pet. 19–22; Ex. 1003 ¶¶ 50–51.
`
`b. Claims 6, 15–17, and 20–22 over Ogawa, Sallmann, and Fu
`
`Based on the information presented at this stage of the proceeding,
`
`Petitioner also is reasonably likely to prevail in showing that claims 6, 15–
`
`17, and 20–22 are unpatentable over Ogawa, Sallmann, and Fu under
`
`35 U.S.C. § 103. Pet. 44–49. Those claims require a concentration of
`
`tyloxapol that “is about 0.02 w/v %.” See, e.g., Ex. 1001, 12:55 (claim 6);
`
`13:2–3 (claim 15). Petitioner comes forward with evidence sufficient to
`
`show that a person of ordinary skill in the art would have been prompted by
`
`Fu to include tyloxapol, in a concentration of “about 0.02 w/v %,” id., in the
`
`modified composition of Ogawa or Sallmann. Pet. 44–47.
`
`Specifically, Petitioner shows sufficiently that Fu would have
`
`suggested to an ordinary artisan “that ethoxylated octylphenol surfactants,”
`
`the class that includes tyloxapol, would have “worked even better than
`
`polysorbate 80.” Pet. 45 (citing Ex. 1003, ¶¶ 33–35, 38, 64); see Ex. 1011,
`
`Example 5 (Fu, disclosing that the octylphenol surfactant worked better than
`
`polysorbate 80 when “evaluated for their ability to dissolve [an NSAID-
`
`BAC complex] and maintain a physically clear solution over an extended
`
`
`
`16
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`period of time”). Petitioner also shows sufficiently that Fu suggests using
`
`that class of non-ionic surfactants in a concentration of 0.02 w/v % in
`
`aqueous liquid ophthalmic preparations of an NSAID and BAC. Pet. 44–46
`
`(citing Ex. 1011, 18:5–28, Example 2, Example 5; Ex. 1003 ¶¶ 34–35, 60,
`
`75–76).
`
`Alternatively, it appears to us, at this stage of the proceeding, that it
`
`would have been within the grasp of an ordinary artisan to manipulate the
`
`concentration of tyloxapol in the modified preparation of Ogawa or
`
`Sallmann “to discover the optimum or workable ranges by routine
`
`experimentation.” In re Aller, 220 F.2d at 456–57 (CCPA 1955) (“where the
`
`general conditions of a claim are disclosed in the prior art, it is not inventive
`
`to discover the optimum or workable ranges by routine experimentation”);
`
`see Pet. 47–48 (bridging paragraph) (citing In re Aller for that proposition).
`
`iv. Secondary Considerations
`
`We have taken account of the information presented in the
`
`Preliminary Response, but on this record, we determine that Petitioner has
`
`made a showing sufficient to support institution of an inter partes review.
`
`For example, we have taken account of the information advanced by Patent
`
`Owner in support of secondary considerations of non-obviousness. Prelim.
`
`Resp. 49–58. We have noted in particular Petitioner’s concession that “[t]he
`
`subject matter of many of the challenged claims of the ’431 patent is
`
`commercially embodied by Prolensa®, a product marketed by” Patent
`
`Owner. Pet. 9. Nonetheless, at this early stage of the proceeding, before the
`
`filing of Patent Owner’s Response, many of Patent Owner’s factual
`
`assertions, regarding the commercial success of Prolensa®, are not
`
`adequately supported.
`
`
`
`17
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`
`Patent Owner contends that “[t]yloxapol’s stabilization effect
`
`permitted formulating Prolensa® at pH 7.8;” that such a pH is “closer to the
`
`pH of natural tears” than other bromfenac preparations; that the lowered pH
`
`is “less irritating to the patient,” which “improve[s] bromfenac’s intraocular
`
`penetration and permit[s] a lowering of its concentration” compared to a
`
`different product; and that Prolensa®, therefore, “advantageously puts less
`
`drug in contact with surgically compromised ocular tissue without a
`
`reduction in efficacy.” Prelim. Resp. 56. At this stage, however, Patent
`
`Owner refers to entire exhibits, without any pin-cites, and supplies no cogent
`
`explanation of how the exhibits support these fact-laden contentions, or
`
`whether the asserted properties were unexpected or otherwise unobvious.
`
`Id. at 56, n.7 (citing Ex. 2013, Ex. 2026, Ex. 2027, Ex. 2030). Similarly,
`
`Patent Owner refers to sales data for Prolensa®, as projected by a
`
`competitor, but at this stage of the proceeding, comes forward with no
`
`objective evidence of revenues based on actual sales. Id. at 57.
`
`Patent Owner also refers to test results to establish that tyloxapol is a
`
`better stabilizer of bromfenac, compared to polysorbate 80—but advances
`
`no information that the asserted results would have been considered truly
`
`“surprising” or “unexpected” by a person of ordinary skill in the art. Id. at
`
`53. At this early stage, Patent Owner’s position on that point rests entirely
`
`on attorney argument. Id.; see In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir.
`
`1997) (argument of counsel cannot take the place of evidence). The record
`
`is devoid of objective evidence in that regard. Not even the inventors
`
`described tyloxapol as “surprising” or “unexpected” in its stabilizing effect:
`
`When comparing tyloxapol to other alkyl aryl polyether alcohol type
`
`
`
`18
`
`

`

`IPR2015-00903
`Patent 8,129,431 B2
`
`polymers, the inventors described tyloxapol as “especially preferable.”
`
`Ex. 1001, 4:65–67.
`
`In sum, Patent Owner’s information, at this stage of the proceedi

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket