Trials@uspto.gov
`571.272.7822
`
`
`
`
`
` Paper No. 8
`
` Entered: December 8, 2016
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`____________
`
`Case IPR2016-01130
`Patent 8,633,162 B2
`____________
`
`
`
`
`Before SHERIDAN K. SNEDDEN, TINA E. HULSE, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`HULSE, Administrative Patent Judge.
`
`
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`571.272.7822
`
`
`
`
`
` Paper No. 8
`
` Entered: December 8, 2016
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`____________
`
`Case IPR2016-01130
`Patent 8,633,162 B2
`____________
`
`
`
`
`Before SHERIDAN K. SNEDDEN, TINA E. HULSE, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`HULSE, Administrative Patent Judge.
`
`
`
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`
`
`INTRODUCTION
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) filed a Petition requesting
`an inter partes review of claims 1–24 of U.S. Patent No. 8,633,162 B2
`(Ex. 1001, “the ’162 patent”). Paper 3 (“Pet.”). Allergan, Inc. (“Patent
`Owner”) filed a Preliminary Response to the Petition. Paper 7 (“Prelim.
`Resp.”).
`We have jurisdiction under 35 U.S.C. § 314, which provides that an
`inter partes review may not be instituted “unless . . . there is a reasonable
`likelihood that the petitioner would prevail with respect to at least 1 of the
`claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering
`the Petition and Preliminary Response, we determine that Petitioner has
`established a reasonable likelihood that it would prevail in showing the
`unpatentability of claims 1–24. Accordingly, we institute an inter partes
`review of those claims.
`
`Related Proceedings
`A.
`The parties identify several petitions for inter partes review
`previously filed by Apotex Corp. and Apotex Inc. and challenging claims of
`the ’162 patent and related patents. Pet. 11; Paper 6, 2 (referring to
`IPR2015-01278, IPR2015-01282, IPR2015-01286, and IPR2015-01283).
`All of the petitions were terminated before institution decisions were
`entered. Pet. 11; Paper 6, 2. The parties also identify several district court
`cases that may affect or be affected by a decision in this proceeding:
`Allergan, Inc. v. Teva Pharmaceuticals USA, Inc., No. 2:15-cv-01455 (E.D.
`
` 2
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`Tex.); Allergan, Inc., v. Innopharma, Inc., No. 2:15-cv-1504 (E.D. Tex.);
`and Allergan, Inc. v. Famy Care, Ltd., No. 2:16-cv-0401 (E.D. Tex.). Pet.
`12; Paper 6, 2.
`Petitioner has also sought inter partes review for related patents in the
`following proceedings: Case IPR2016-01127 (U.S. Patent No. 8,685,930
`B2), Cases IPR2016-01128 and IPR2016-01232 (U.S. Patent No. 8,629,111
`B2), Case IPR2016-01129 (U.S. Patent No. 8,642,556 B2), Case IPR2016-
`01131 (U.S. Patent No. 8,648,048 B2), and IPR2016-01132 (U.S. Patent No.
`9,248,191 B2).
`
`The ’162 Patent
`B.
`The ’162 patent generally relates to methods of providing therapeutic
`effects using cyclosporin components, and more specifically to a
`formulation containing cyclosporin-A (“CsA”) and castor oil emulsions for
`treating dry eye syndrome (i.e., keratoconjunctivitis sicca). Ex. 1001, 1:18–
`20, 1:58–65, 2:63–64. According to the specification, the prior art
`recognized the use of emulsions containing CsA and CsA-derivatives to treat
`ophthalmic conditions. Id. at 1:26–65. The specification notes, however,
`that “[o]ver time, it has become apparent that cyclosporin A emulsions for
`ophthalmic use preferably have less than 0.2% by weight of cylcosporin A.”
`Id. at 1:66–2:1. Moreover, if reduced amounts of cyclosporin are used,
`reduced amounts of castor oil are needed because one of the functions of
`castor oil is to solubilize CsA. Id. at 1:66–2:6.
`Accordingly, the specification states that “[i]t has been found that the
`relatively increased amounts of hydrophobic component together with
`
` 3
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`relatively reduced, yet therapeutically effective, amounts of cyclosporin
`component provide substantial and advantageous benefits.” Id. at 2:36–39.
`The relatively high concentration of hydrophobic component provides for a
`more rapid breaking down of the emulsion in the eye, which reduces vision
`distortion and/or facilitates the therapeutic efficacy of the composition. Id.
`at 2:43–49. Furthermore, using reduced amounts of cyclosporin component
`mitigates against undesirable side effects or potential drug interactions. Id.
`at 2:49–52.
`The patent identifies two particular compositions that were selected
`for further testing, as shown below:
`
`
`
`Id. at 14:20–30. Based on the results of a Phase 3 clinical study, the
`specification concludes that “Composition II . . . provides overall efficacy in
`treating dry eye disease substantially equal to that of Composition I.” Id. at
`14:44–48. The patent indicates that “[t]his is surprising for a number of
`reasons.” Id. at 14:49. According to the specification, a reduced
`concentration of CsA in Composition II would have been expected to result
`in reduced overall efficacy in treating dry eye disease. Id. at 14:49–52.
`
` 4
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`Moreover, although the large amount of castor oil relative to the amount of
`CsA in Composition II might have been expected to cause increased eye
`irritation, it was found to be substantially non-irritating in use. Id. at 14:52–
`57. Accordingly, the specification states that physicians can prescribe
`Composition II “to more patients and/or with fewer restrictions and/or with
`reduced risk of the occurrence of adverse events, e.g., side effects, drug
`interactions and the like, relative to providing Composition I.” Id. at 15:12–
`15.
`
`Illustrative Claim
`C.
`Petitioner challenges claims 1–24 of the ’162 patent, of which
`claims 1, 18, and 23 are independent claims. Claim 23 is illustrative,
`and is reproduced below:
`23. A method of treating dry eye disease, the method
`comprising the step of topically administering to an eye of
`a human in need thereof an emulsion at a frequency of
`twice a day, the emulsion comprising:
` cyclosporin A in an amount of about 0.05% by weight;
`castor oil in an amount of about 1.25% by weight;
`polysorbate 80 in an amount of about 1.0% by weight;
`acrylate/C10-30 alkyl acrylate cross-polymer in an
`amount of about 0.05% by weight;
`glycerine in an amount of about 2.2% by weight;
`sodium hydroxide; and
`water;
`
` 5
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`wherein the emulsion is effective in treating dry eye
`disease.
`Independent claim 1 also recites a method of treating dry
`eye disease with an emulsion comprising 0.05% by weight
`cyclosporin A and 1.25% by weight castor oil.
`Independent claim 18 recites a method of reducing side
`effects in a human being treated for dry eye syndrome with an
`emulsion similar to that recited in claim 23.
`The Asserted Grounds of Unpatentability
`D.
`Petitioner challenges the patentability of claims 1–24 of the ’162
`patent on the following grounds:
`References
`Ding ’9791 and Sall2
`
`Basis
`§ 103(a)
`
`Claim(s) challenged
`1–10, 12–14, 16–20, and
`22–24
`11 and 21
`
`Ding ’979, Sall, and
`Acheampong3
`Ding ’979, Sall, and Glonek4
`
`§ 103(a)
`
`§ 103(a)
`
`15
`
`
`1 Ding et al., US 5,474,979, issued Dec. 12, 1995 (Ex. 1006).
`2 Sall et al., Two Multicenter, Randomized Studies of the Efficacy and Safety
`of Cyclosporine Ophthalmic Emulsion in Moderate to Severe Dry Eye
`Disease, 107 OPHTHALMOLOGY 631–39 (2000) (Ex. 1007).
`3 Acheampong et al., Cyclosporine Distribution into the Conjunctiva,
`Cornea, Lacrimal Gland, and Systemic Blood Following Topical Dosing of
`Cyclosporine to Rabbit, Dog, and Human Eyes, LACRIMAL GLAND, TEAR
`FILM, AND DRY EYE SYNDROMES 2: BASIC SCIENCE AND CLINICAL
`RELEVANCE 1001–04 (David A. Sullivan et al. eds., 1998) (Ex. 1008).
`4 Glonek et al., US 5,578,586, issued Nov. 26, 1996 (Ex. 1009).
`
` 6
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`Petitioner also relies on the Declaration of Mansoor Amiji, Ph.D.
`Ex. 1002.
`
`ANALYSIS
`
`Person of Ordinary Skill in the Art
`A.
`Petitioner asserts that as of September 15, 2003, a person of ordinary
`skill in the art would likely have had “some combination of: (a) experience
`formulating pharmaceutical products; (b) experience designing and
`preparing drug emulsions intended for topical ocular administration; and (c)
`the ability to understand results and findings presented or published by
`others in the field. Pet. 10 (citing Ex. 1002 ¶ 36). Petitioner further
`contends that this person typically would have an advanced degree, such as a
`medical degree, or a Ph.D. in organic chemistry, pharmaceutical chemistry,
`medicinal chemistry, pharmaceutics, physical pharmacy, or a related field, or
`less education but considerable professional experience in these fields. Id.
`(citing Ex. 1002 ¶ 35). Patent Owner does not explicitly address the level of
`ordinary skill in the art in its Preliminary Response.
`On this record, we adopt Petitioner’s definition of the level of
`ordinary skill in the art. We further note that the prior art itself demonstrates
`the level of skill in the art at the time of the invention. See Okajima v.
`Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (explaining that specific
`findings regarding ordinary skill level are not required “where the prior art
`itself reflects an appropriate level and a need for testimony is not shown”)
`(quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158,
`163 (Fed. Cir. 1985)).
`
` 7
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`
`Claim Construction
`B.
`In an inter partes review, the Board interprets claim terms in an
`unexpired patent according to the broadest reasonable construction in light
`of the specification of the patent in which they appear. 37 C.F.R. § 100(b);
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016) (affirming
`applicability of broadest reasonable construction standard to inter partes
`review proceedings). Under that standard, and absent any special
`definitions, we generally give claim terms their ordinary and customary
`meaning, as would be understood by one of ordinary skill in the art at the
`time of the invention. See In re Translogic Tech., Inc., 504 F.3d 1249, 1257
`(Fed. Cir. 2007). Any special definitions for claim terms must be set forth
`with reasonable clarity, deliberateness, and precision. See In re Paulsen, 30
`F.3d 1475, 1480 (Fed. Cir. 1994).
`“effective in treating dry eye disease” and “therapeutically effective”
`1.
`Claims 1–17 and 22–24 recite treatment methods utilizing a topical
`ophthalmic emulsion that is “effective in treating dry eye disease.”
`Petitioner asserts that the ’162 patent teaches that cyclosporin A “acts to
`enhance or restore lacrimal gland tearing in providing the desired therapeutic
`effect.” Pet. 15 (quoting Ex. 1001, 9:14–17). Petitioner then argues that in
`the context of the ’162 patent, “an emulsion that is effective in increasing
`tear production is an example of an emulsion therapeutically effective in
`treating dry eye disease.” Id. Claims 13 and 14 recite an emulsion that is as
`“therapeutically effective” and achieves as much “therapeutic effectiveness”
`as a second emulsion, respectively. Petitioner asserts that because the plain
`
` 8
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`meaning of the word “therapeutic” includes palliative as well as curative
`treatments, the broadest reasonable interpretation of the terms includes
`palliative and curative treatments. Pet. 15 (citing Ex. 1002 ¶¶ 41–42; Ex.
`1022, 7, 4, 5).
`Patent Owner argues that Petitioner’s proposed construction is too
`broad, and that the claims should be construed to require that “the emulsion
`treat the underlying disease,” and not just its symptoms. Prelim. Resp. 21.
`Patent Owner argues that its construction is supported by a dictionary
`definition of “therapeutic,” defined as “[r]elating to therapeutics or to the
`treatment, remediating, or curing of a disease or disorder.” Id. (citing Exs.
`2005, 2006). Patent Owner contrasts this definition of “therapeutic” with the
`definition of “palliative,” defined as “reducing the severity of: denoting the
`alleviation of symptoms without curing the underlying disease,” thereby
`suggesting that the phrase “therapeutically effective” would not include
`palliative effects. Id. at 22 n.2 (citing Ex. 2007). We disagree. The
`definition of “therapeutic” provided by the Patent Owner is not limited to a
`cure of a disease or disorder, but also includes either treatment or
`remediating of a disease or disorder. We thus conclude, on the current
`record, that the ordinary meaning of the phrase “therapeutically effective” is
`not so limited as to exclude palliative effects.
`Patent Owner further argues that the Specification supports its
`construction because “throughout the specification, the ‘162 patent uses the
`word ‘therapeutic’ in connection with the action of cyclosporin. . . . In
`contrast, the ‘162 patent specification does not use the word ‘therapeutic’ to
`
` 9
`
`
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`refer to the activity of the other components of the emulsion, including
`castor oil.” Prelim. Resp. 22. We disagree. Contrary to Patent Owner’s
`assertion, the specification does refer to the “therapeutic effects” of castor
`oil: “it is believed that castor oil includes a relatively high concentration of
`ricinoleic acid which itself may be useful in benefitting ocular tissue and/or
`in providing one or more therapeutic effects when administered to an eye.”
`Ex. 1001, 9:58–62 (emphasis added). Thus, notwithstanding Patent Owner’s
`extrinsic evidence it offers in support of its more-limited construction
`(Prelim. Resp. 22–23), we decline to construe the claims in a manner
`inconsistent with the specification.
`Accordingly, at this stage of the proceeding, we find that “effective in
`treating dry eye disease,” “therapeutically effective,” and similar terms
`encompass both palliative and curative treatments of dry eye disease.
`Remaining Claim Terms
`2.
`Petitioner proposes constructions for a number of additional claim
`terms. At this stage of the proceeding, we determine it is unnecessary to
`expressly construe any other claim terms for purposes of this Decision. See
`Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011)
`(“[C]laim terms need only be construed ‘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)).
`C. Obviousness over Ding ’979 and Sall
`Petitioner argues that claims 1–10, 12–14, 16–20, and 22–24 are
`unpatentable as obvious over the combination of Ding ’979 and Sall.
`
`10
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`Pet. 22–40. Petitioner relies on the testimony of Dr. Amiji in support. Ex.
`1002 ¶¶ 93–116. Patent Owner opposes. Prelim. Resp. 24–33. Based on
`the current record, we determine that Petitioner has established a reasonable
`likelihood that it would prevail in showing claims 1–10, 12–14, 16–20, and
`22–24 are unpatentable over the cited prior art.
`Ding ’979 (Ex. 1006)
`1.
`Ding ’979, assigned to Patent Owner, relates to ophthalmic emulsions
`including cyclosporin, castor oil, and polysorbate 80 that have a high
`comfort level and low irritation potential. Ex. 1006, cover, 1:4–9. Ding
`’979 explains that cyclosporins have “known immunosuppressant activity”
`and have been found “effective in treating immune medicated
`keratoconjunctivitis sicca (KCS or dry eye disease) in a patient suffering
`therefrom.” Id. at 1:10–16. Although the solubility of cyclosporins in water
`is extremely low, cyclosporins have some solubility in oily preparations
`containing higher fatty acid glycerides such as castor oil. Id. at 1:40–41,
`2:39–42. Ding ’979 notes, however, that formulations with a high
`concentration of oils have several drawbacks, including exacerbation of the
`symptoms of dry eyes and low thermodynamic activity of cyclosporin,
`which leads to poorer drug bioavailability. Id. at 2:42–57. Accordingly,
`Ding ’979 “is directed to an emulsion system which utilizes higher fatty acid
`glycerides but in combination with polysorbate 80 which results in an
`emulsion with a high comfort level and low irritation potential suitable for
`delivery of medications to sensitive areas such as ocular tissues.” Id. at
`2:65–3:3.
`
`
`11
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`Ding ’979 discloses that the preferable weight ratio of cyclosporin to
`castor oil is below 0.16, and more preferably between 0.12 and 0.02. Id. at
`3:15–20. Specifically, Ding ’979 discloses several compositions as Example
`1, shown below:
`
`
`
`Id. at 4:32–43. Example 1 identifies compositions A through E, which
`contain varying amounts of cyclosporin A, castor oil, polysorbate 80,
`Pemulen® (an acrylate/C10-30 alkyl acrylate cross-polymer), glycerine,
`sodium hydroxide, and purified water at a pH range of 7.2–7.6. Id.
`According to Ding ’979, the formulations of Example 1 were “made for
`treatment of keratoconjunctivitis sicca (dry eye) syndrome.” Id. at 5:10–12.
`Sall (Ex. 1007)
`2.
`Sall describes the results of two identical clinical trials—supported by
`a grant from Patent Owner—in which patients were treated twice daily with
`either cyclosporin A 0.05% or 0.1% ophthalmic emulsions or vehicle for six
`months. Ex. 1007, Abstract. The study sought to compare the efficacy and
`safety of cyclosporin A 0.05% and 0.1% to vehicle in patients with moderate
`
`12
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`to severe dry eye disease. Id. Sall found that topical treatment with either
`cyclosporin A 0.05% or 0.1% resulted in significantly greater improvements
`than vehicle treatment in two objective signs of dry eye disease. Id. at 637.
`Sall also found that treatment with cyclosporin A 0.05% resulted in
`significantly greater improvements in several subjective parameters. Id.
`Sall also found that trough blood concentrations of cyclosporin A were
`undetectable in all samples of cyclosporin A 0.05%, whereas cyclosporin A
`was quantifiable in only six samples for six different patients in the
`cyclosporin 0.1% group. Id.
`Sall notes that the only treatments available for dry eye disease are
`palliative in nature. Id. at 638. In light of the results of the study, Sall states
`that it “represents the first therapeutic treatment specifically for dry eye
`disease and a significant breakthrough in the management of this common
`and frustrating condition.” Id.
`
`Analysis
`3.
`Petitioner argues that the combination of Ding ’979 and Sall teaches
`each limitation of claims 1–10, 12–14, 16–20, and 22–24 of the ’162 patent.
`For example, regarding claim 23, Petitioner asserts that Ding ’979 teaches
`emulsions for treatment of dry eye syndrome that are “suitable for topical
`application to ocular tissue.” Pet. 24 (citing Ex. 1006, 5:9–11, 6:3–7).
`Petitioner also notes that Ding ’979 teaches that cyclosporin A increases tear
`production in the eye and has been found effective in treating KCS. Id.
`(citing Ex. 1006, 1:10–16, 37–39). Thus, Petitioner asserts that Ding ’979
`
`
`13
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`teaches the “emulsion is effective in treating dry eye disease,” as recited by
`the claim.
`Example 1D of Ding ’979 teaches every ingredient of the emulsion in
`claim 23, except 0.05% cyclosporin A. Ex. 1006, 4:32–43. That is,
`Example 1D teaches an emulsion with 1.25% castor oil, 1.0% polysorbate
`80, 0.05% Pemulen (i.e., acrylate/C10-30 alkyl acrylate cross-polymer),
`2.2% glycerine, sodium hydroxide, and water. Id. Example 1E of Ding
`’979 teaches an emulsion with 0.05% cyclosporin A. Id. According to Dr.
`Amiji, a person of ordinary skill in the art would recognize Ding ’979’s
`emulsions to include an emulsion containing the cyclosporin A/castor oil
`amounts in the claimed combination, i.e., 0.05% cyclosporin A and 1.25%
`castor oil, because such an emulsion would fall within the preferred ratio of
`cyclosporin A to castor oil. Ex. 1002 ¶ 99 (citing Ex. 1006, 3:16–20).
`Petitioner also asserts that Sall teaches treating patients twice daily
`with an emulsion containing 0.05% cyclosporin A. Pet. 28; Ex. 1007, 631.
`Sall concluded that both the 0.05% and the 0.10% cyclosporin A emulsions
`“were safe and effective in the treatment of moderate to severe dry eye
`disease . . . yielding improvements in both objective and subjective
`measures.” Pet. 29 (quoting Ex. 1007, 631). As such, Petitioner asserts that
`one of ordinary skill in the art would have expected the castor oil emulsion
`vehicle containing 0.05% by weight cyclosporin A to be at least as safe and
`effective at treating dry eye disease/KCS and increasing tear production as
`the castor oil emulsion containing 0.10% by weight cyclosporin A. Id. at 30.
`Moreover, Petitioner asserts that Sall provides a strong rationale to deliver
`
`14
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`0.05% cyclosporin A using the 1.25% castor oil vehicle taught by Ding ’979
`(i.e., Example 2C) in light of the preferred ratio of cyclosporin A to castor
`oil taught in Ding ’979. Pet. 31–32; Ex. 1002 ¶ 107.
`In its Preliminary Response, Patent Owner does not argue that the
`combination of references fails to teach any particular limitation of the
`claims. Accordingly, we are persuaded that Petitioner has shown
`sufficiently that the combination of Ding ’979 and Sall teaches each
`limitation of claim 23. That is, Ding ’979 specifically identifies examples
`that include 0.05% CsA and 1.25% castor oil, albeit not as part of the same
`composition. Ex. 1006, 4:32–43. Thus, the only issue before us is whether
`it would have been obvious to use the particular concentrations of 0.05%
`CsA and 1.25% castor oil in the emulsion together, as recited in the
`challenged claims.
`Patent Owner argues that this case is closely analogous to Allergan,
`Inc. v. Sandoz Inc., 796 F.3d 1293, 1302 (Fed. Cir. 2015), in which the court
`addressed the obviousness of claims requiring specific amounts of about
`0.01% bimatoprost and about 200 ppm benzalkonium chloride (BAK) over
`prior art that generally taught a formulation comprising 0.001%–1%
`bimatoprost and 0–1000 ppm BAK. Prelim. Resp. 25–27. We agree that the
`issues are similar. In Allergan, the court reiterated the framework for
`evaluating obviousness in the context of a claimed invention falling within a
`broader range disclosed in the prior art:
`[W]here there is a range disclosed in the prior art, and the claimed
`invention falls within that range, a relevant inquiry is whether
`
`
`15
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`there would have been a motivation to select the claimed
`composition from the prior art ranges. . . . In those circumstances,
`“the burden of production falls upon the patentee to come
`forward with evidence that (1) the prior art taught away from the
`claimed invention; (2) there were new and unexpected results
`relative to the prior art; or (3) there are other pertinent secondary
`considerations.”
`
`796 F.3d at 1304–05 (quoting Galderma Labs., L.P. v. Tolmar, Inc., 737
`F.3d 731, 738 (Fed. Cir. 2013)).
`As discussed above, Petitioner’s evidence of obviousness, in
`accordance with Allergan, shifts the burden of production to Patent Owner
`to come forward with evidence of teaching away, unexpected results, or
`other secondary considerations. Patent Owner argues that increasing the
`amount of castor oil to 1.25% and cutting the amount of cyclosporin in half
`without loss of efficacy was not only unexpected, but counterintuitive to a
`person of ordinary skill in the art. Prelim. Resp. 26–27, 31–32. As support,
`Patent Owner points to results from pharmacokinetic (“PK”) experiments
`presented during prosecution as part of the Declarations of Dr. Rhett
`Schiffman and Dr. Mayssa Attar. Prelim. Resp. 3 (citing Ex. 2004, 188–
`251). Patent Owner asserts that these results predicted that the claimed
`emulsion would have been less effective than the two emulsions disclosed in
`Ding ’979. According to Patent Owner, it was surprising that the claimed
`emulsion was “more effective than the 0.05%/0.625%/1.00% emulsion and
`at least as effective as the 0.1%/1.25%/1.00% emulsion.” Id.
`We have considered the declarations submitted during prosecution,
`but note that neither Dr. Schiffman nor Dr. Attar has been subject to cross-
`
`16
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`examination in this proceeding. Moreover, Petitioner offers the declaration
`of Dr. Amiji, calling into question the alleged unexpected results based on
`the Schiffman and Attar Declarations. Ex. 1002 ¶¶ 128–152. At this
`preliminary stage, we determine that Petitioner has offered sufficient
`evidence to institute trial. That being said, we will be able to evaluate both
`parties’ arguments regarding secondary considerations more thoroughly
`once the record is developed further during trial.
`Patent Owner also argues that Sall would not have motivated a person
`of ordinary skill in the art to combine 0.05% cyclosporin with 1.25% castor
`oil. Prelim. Resp. 27–29. Contrary to Petitioner’s argument, Patent Owner
`asserts that a person of ordinary skill in the art would not have assumed that
`both the 0.05% and 0.10% cyclosporin emulsions in Sall would have
`contained the same amount of castor oil (i.e., 1.25%). Id. at 28. Rather,
`Patent Owner contends that a skilled artisan would have expected the
`emulsions to have the same ratio of cyclosporin to castor oil (i.e., 0.05%
`cyclosporin with 0.625% castor oil, and 0.10% cyclosporin with 1.25%
`castor oil). Id. On the current record, however, we determine that Petitioner
`has shown sufficiently that a skilled artisan reading Ding ’979 and Sall
`would have had a reason to formulate an emulsion with 0.05% cyclosporin
`A and 1.25% castor oil in light of the preferred cyclosporin to castor oil ratio
`taught by Ding ’979. Ex. 1006, 3:17–20.
`Patent Owner further argues that there was no reasonable expectation
`that increasing castor oil concentration would increase therapeutic efficacy.
`Id. at 29–31. In particular, Patent Owner contends that Sall distinguishes
`
`17
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`between therapeutic and palliative treatments, and that the vehicle is not
`responsible for the “clinically significant” effects observed. Id. at 29–30.
`Accordingly, Patent Owner asserts that a person of ordinary skill reading
`Sall would not have expected to achieve this level of efficacy by increasing
`the amount of castor oil relative to the amounts disclosed in Ding ’979. Id.
`at 30. Patent Owner’s argument, however, relies on its construction of
`“therapeutically effective” as excluding palliative treatments. As explained
`above, we decline to so limit the term. Accordingly, we are not persuaded
`by Patent Owner’s argument.
`Upon considering the arguments set forth in the Petition and
`Preliminary Responses, we determine that Petitioner has shown a reasonable
`likelihood that it would prevail in showing claim 23 is unpatentable as
`obvious over the combination of Ding ’979 and Sall. We have considered
`the parties’ arguments and evidence with respect to claims 1–10, 12–14, 16–
`20, 22, and 24, and we determine that Petitioner has made a sufficient
`showing as to those claims, as well.
`D. Obviousness over Ding ’979, Sall, and Acheampong
`Petitioner also asserts that claims 11 and 21 are unpatentable as
`obvious over Ding ’979, Sall, and Acheampong. Pet. 40–41. Patent Owner
`opposes for the same reasons stated above. Prelim. Resp. 34. We
`incorporate here our findings and discussion above regarding the disclosure
`of Ding ’979 and Sall.
`
`
`18
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`
`Acheampong (Ex. 1008)
`1.
`Acheampong describes a study by Patent Owner as part of its
`evaluation of the clinical efficacy of 0.05%–0.4% cyclosporin emulsion for
`the treatment of immuno-inflammatory eye diseases such as dry eye
`syndrome. Ex. 1008, 3. Acheampong describes the results of its research to
`determine the ocular tissue distribution of cyclosporin in rabbits and dogs,
`and to compare tissue concentrations in rabbits, dogs, and humans after
`topical administration. Id.
`In the study of humans, the subjects with dry eye disease received an
`eyedrop of vehicle or 0.05%, 0.1%, 0.2%, or 0.4% cyclosporin emulsions
`twice daily for 12 weeks. Id. at 4. Blood samples were collected from all
`subjects at morning troughs after 1, 4, and 12 weeks of dosing, and from
`certain subjects at 1, 2, and 4 hours after the last dose at week 12. Id.
`Acheampong found that the human blood cyclosporin A concentrations were
`less than 0.2 ng/ml for each emulsion, which is lower than the 20–100 ng/ml
`blood trough concentration used for monitoring the safety of patients
`receiving systemic cyclosporin therapy. Id. at 6.
`Analysis
`2.
`Claims 11 and 21 depend from independent claims 1 and 18,
`respectively, and further recite that “when the emulsion is administered to an
`eye of a human, the blood of the human has substantially no detectable
`concentration of cyclosporin A.” Petitioner asserts that Acheampong
`teaches that an emulsion with 0.05% CsA resulted in no detectable CsA in
`the blood, even at the maximum time point. Pet. 41 (citing Ex. 1008, Table
`
`19
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`1; Ex. 1002 ¶ 120). Petitioner further asserts that a person of ordinary skill
`in the art reading Acheampong and Sall would have had a reasonable
`expectation of success that when the 0.05% cyclosporin A emulsion is
`administered to the eye, there is “substantially no detectable concentration of
`cyclosporin A” in the blood. Id. (citing Ex. 1002 ¶ 121).
`In response, Patent Owner relies on the same reasoning given with
`respect to claim 23. Prelim. Resp. 34. For the same reasons stated above,
`we are persuaded, on the current record, that Petitioner has demonstrated a
`reasonable likelihood that it would prevail in its assertion that claims 11 and
`21 are unpatentable as obvious over the combination of Ding ’979, Sall, and
`Acheampong.
`E. Obviousness over Ding ’979, Sall, and Glonek
`Petitioner asserts that claim 15 is unpatentable as obvious over Ding
`’979, Sall, and Glonek. Pet. 42–43. Patent Owner opposes for the same
`reasons stated with respect to claim 1 above. Prelim. Resp. 34. We
`incorporate here our findings and discussion above regarding the disclosure
`of Ding ’979 and Sall.
`
`Glonek (Ex. 1009)
`1.
`Glonek relates to a composition for augmenting and maintaining a
`stable tear film over the ocular surface and delivering a medicine to the eye
`without causing substantial blurring of vision. Ex. 1009, 1:21–29. Glonek
`explains that an emulsion over the surface of the eye is expected to cause
`blurring, which is likely to occur until the emulsion differentiates. Id. at
`6:37–42. If the emulsion is too stable, excess emulsion will be discharged
`
`20
`
`
`
`
`
`
`
`IPR2016-01130
`Patent 8,633,162 B2
`from the eye. Id. at 6:42–44. Thus, Glonek states that it is preferred that an
`emulsion be stable for long term storage, but rapidly differentiate in the eye.
`Id. at 6:48–50.
`
`Analysis
`2.
`Claim 15 depends from claim 1, and further recites that “the emulsion
`breaks down more quickly in the eye of a human, . . . thereby reducing
`vision distortion in the eye of the human as compared to a second emulsion
`that contains only 50% as much castor oil.” Petitioner asserts that Glonek
`teaches that “an emulsion over the surface of the eye is expected to cause
`blurring. The duration of the blurring is dependent upon the time required
`for the emulsion to differentiate and form separate layers.” Pet. 42 (quoting
`Ex. 1009, 6:37–40). Moreover, Glonek teaches that “it is preferred that the
`emulsion be stable for long term storage, but rapidly differentiate in the
`eye.” Id. at 42–43 (quoting Ex. 1009, 6:48–50). Accordingly, Petitioner
`asserts that “a skilled artisan would have reasonably expected a 1.25% castor
`oil emulsion to break down faster than a 0.625% castor oil emulsion because
`of the increased instability from the higher oil concentration, and that the
`faster differentiation would result in a reduction of blurring.” Id. at 43
`(citing Ex. 1002 ¶¶ 125–127).
`In response, Patent Owner relies on the same reasoning given with
`respect to claim 23. Prelim. Resp. 34. For the same reasons stated above,
`we are persuaded, on the current record, that Petitioner has
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
