Trials@uspto.gov
`571.272.7822
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` Paper No. 12
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` Entered: July 12, 2017
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`
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FAMY CARE LIMITED,
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-00569
`Patent 9,248,191 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 and Denying Motion for Joinder
`35 U.S.C. § 315(c); 37 C.F.R. § 42.108
`
`
`
`
`
`
`
`571.272.7822
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`
`
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` Paper No. 12
`
` Entered: July 12, 2017
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FAMY CARE LIMITED,
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-00569
`Patent 9,248,191 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 and Denying Motion for Joinder
`35 U.S.C. § 315(c); 37 C.F.R. § 42.108
`
`
`
`
`
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`IPR2017-00569
`Patent 9,248,191 B2
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`
`INTRODUCTION
`
`Famy Care Limited (“Petitioner” or “Famy Care”) filed a Petition
`requesting an inter partes review of claims 1–27 of U.S. Patent No.
`9,248,191 B2 (Ex. 1001, “the ’191 patent”). Paper 4 (“Pet.”). Allergan, Inc.
`(“Patent Owner” or “Allergan”) did not file a Preliminary Response to the
`Petition.
`Petitioner also filed a Motion for Joinder pursuant to 35 U.S.C.
`§ 315(c), seeking to join this proceeding with Mylan Pharmaceuticals, Inc.
`v. Allergan, Inc., IPR2016-01132 (“Mylan IPR”). Paper 5. Patent Owner
`opposes Petitioner joinder motion. Paper 9.
`For the reasons stated below, we deny Petitioner’s motion for joinder.
`As for the Petition, 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, we determine that Petitioner has established a
`reasonable likelihood that it would prevail in showing the unpatentability of
`claims 1–27. Accordingly, we institute an inter partes review of those
`claims.
`
`Related Proceedings
`A.
`The parties identify petitions for inter partes review previously filed
`by other petitioners that challenge the claims of the ’191 patent and related
`patents. Pet. 4–5; Paper 8, 2–3. Certain petitions were terminated before
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`decisions on institution were entered. Pet. 5; Paper 8, 2. Other petitions
`have been granted and inter partes review has been instituted for the ’191
`patent and for related U.S. Patents: U.S. Patent No. 9,248,191 (IPR2016-
`01132, IPR2017-00601, IPR2017-00586); U.S. Patent No. 8,633,162
`(IPR2016-01130, IPR2017-00599, IPR2017-00583); U.S. Patent No.
`8,685,930 (IPR2016-01127, IPR2017-00594, IPR2017-00576); U.S. Patent
`No. 8,629,111 (IPR2016-01128, IPR2017-00596, IPR2017-00578); U.S.
`Patent No. 8,642,556 (IPR2016-01129, IPR2017-00598, IPR2017-00579);
`and U.S. Patent No. 8,648,048 (IPR2016-01131, IPR2017-00600, IPR2017-
`00585). Paper 8, 3.
`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. Tex.); Allergan, Inc.,
`v. Innopharma, Inc., No. 2:15-cv-1504 (E.D. Tex.); Allergan, Inc. v. Famy
`Care, Ltd., No. 2:16-cv-0401 (E.D. Tex.); and Allergan, Inc. v. DEVA
`Holding AS, No. 2:16-cv-1447 (E.D. Tex.). Pet. 5; Paper 8, 2.
`Petitioner has also sought inter partes review for related patents in the
`following proceedings: IPR2017-00566 (U.S. Patent No. 8,648,048 B2),
`IPR2017-00567 (U.S. Patent No. 8,629,111 B2), IPR2017-00568 (U.S.
`Patent No. 8,633,162 B2), IPR2017-00570 (U.S. Patent No. 8,642,556 B2),
`and IPR2017-00571 (U.S. Patent No. 8,685,930 B2).
`The ’191 Patent
`B.
`The ’191 patent generally relates to methods of providing therapeutic
`effects using cyclosporin components, and more specifically to a
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`formulation containing cyclosporin-A (“CsA”) and castor oil emulsions for
`treating dry eye syndrome (i.e., keratoconjunctivitis sicca or “KCS”). Ex.
`1001, 1:20–22, 1:60–67, 2:66–67. According to the specification, the prior
`art recognized the use of emulsions containing CsA and CsA-derivatives to
`treat ophthalmic conditions. Id. at 1:28–67. The specification notes,
`however, “[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 2:1–8.
`Accordingly, the specification states that “[i]t has been found that the
`relatively increased amounts of hydrophobic component together with
`relatively reduced, yet therapeutically effective, amounts of cyclosporin
`component provide substantial and advantageous benefits.” Id. at 2:38–41.
`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 2:45–51. Furthermore, using reduced amounts of cyclosporin component
`mitigates against undesirable side effects or potential drug interactions. Id.
`at 2:51–54.
`The patent identifies two particular compositions that were selected
`for further testing, as shown below:
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`Id. at 14:26–38. 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
`14:42–46. The patent indicates “[t]his is surprising for a number of
`reasons.” Id. at 14:47. 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 14:47–50.
`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 14:50–
`55. 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 15:10–
`14.
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`Patent 9,248,191 B2
`
`Illustrative Claim
`C.
`Petitioner challenges claims 1–27 of the ’191 patent, of which
`claims 1, 13, 17, and 21 are independent claims. Claim 1 is
`illustrative, and is reproduced below:
`1. A method of treating dry eye disease, the method
`comprising topically administering to a human eye in need
`thereof a first topical ophthalmic emulsion at a frequency
`of twice a day, wherein the first ophthalmic emulsion
`comprises cyclosporin A in an amount of about 0[.]05%
`by weight, polysorbate 80, acrylate/C10-30 alkyl acrylate
`cross-polymer, water, and castor oil in an amount of about
`1.25% by weight;
`wherein the method is therapeutically effective in
`treating dry eye disease;
`wherein
`the method provides overall efficacy
`substantially equal to administration of a second
`topical ophthalmic emulsion to a human eye in need
`thereof at a frequency of twice a day, the second
`emulsion comprising cyclosporin A in an amount of
`about 0.1% by weight and castor oil in an amount
`of about 1.25% by weight; and
`wherein
`the method results
`in substantially no
`detectable concentration of cyclosporin A in the
`blood of the human.
`Independent claim 13 recites that the concentration of
`cyclosporin A in the blood of the human is less than about 0.1
`ng/ml.
`Independent claim 17 also recites that the first topical
`emulsion breaks down more quickly in the human eye
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`compared to a second emulsion that contains only about 50% as
`much castor oil as the first emulsion.
`Independent claim 21 recites a method of restoring
`tearing comprising administering a topical ophthalmic emulsion
`similar to claim 1.
`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
`1–27
`
`Ding ’979, Sall, and
`Acheampong3
`Ding ’979, Sall, and Glonek4
`
`Ding ’979, Sall, Acheampong,
`and Glonek
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`1–27
`
`17–20
`
`20
`
`
`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).
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`Petitioner also relies on the Declarations of Peter Kador, Ph.D.
`(Ex. 1002) and Michael Lemp, M.D. (Ex. 1003).
`ANALYSIS
`
`A. Motion for Joinder
`Based on authority delegated to us by the Director, we have discretion
`to join an inter partes review to a previously instituted inter partes review.
`35 U.S.C. § 315(c). Section 315(c) provides, in relevant part, that “[i]f the
`Director institutes an inter partes review, the Director, in his or her
`discretion, may join as a party to that inter partes review any person who
`properly files a petition under section 311.” Id. When determining whether
`to grant a motion for joinder we consider factors such as timing and impact
`of joinder on the trial schedule, cost, discovery, and potential simplification
`of briefing. Kyocera Corp. v. SoftView, LLC, Case IPR2013-00004, slip op.
`at 3–4 (PTAB Apr. 24, 2013) (Paper 15).
`Although Famy Care’s Petition is similar to Mylan’s Petition in terms
`of the art relied on for each patentability challenge, it is not a “me-too”
`petition and differs significantly in its presentation of arguments. For
`example, Famy Care’s Petition challenges claims 1–27 over Ding ’979 and
`Sall, and Ding ’979, Sall, and Acheampong. Mylan’s Petition, on the other
`hand, challenges claims 1–16 and 21–27 over the same art. Compare Pet. 6
`with Mylan Pet.5 12. Famy Care relies on the declarations of Dr. Peter
`
`
`5 Mylan IPR, Petition for Inter Partes Review of U.S. Patent No. 9,248,191,
`Paper 3 (filed June 3, 2016) (“Mylan Pet.”).
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`Kador (Ex. 1002) and Dr. Michael A. Lemp (Ex. 1003) to support its
`Petition, whereas Mylan relies on the declaration of Mansoor Amiji, Ph.D.
`Moreover, although both Petitions include claim charts detailing where the
`respective Petitioner contends Ding ’979 and Sall teach each limitation of
`the claims, the claim charts cite different (albeit overlapping) portions of the
`same art for the various claim limitations. Compare, e.g., Pet. 21–25 with
`Mylan Pet. 32–36 (claim 13 claim chart). Famy Care also presents extensive
`additional arguments and evidence regarding secondary considerations.
`Pet. 56–77.
`Allergan asserts that there are “significant differences between Famy
`Care’s petition and Mylan’s petition.” Paper 9, 1. Nevertheless, Allergan
`indicated that it will not oppose joinder if Famy Care agrees to participate in
`the joined proceedings under the following conditions:
`1. Famy Care agrees to rely solely on Mylan’s expert;
`
`2. Famy Care agrees to consolidated briefing subject to the
`word count limits for a single party except for motions that
`involve only Famy Care;
`
`3. Famy Care agrees that cross-examination of Patent Owner’s
`witnesses will occur within the timeframe that the rules allot for
`one party; and
`
`4. Famy Care agrees that Mylan will conduct the oral
`argument.
`
`Id.
`
`In its Reply in support of the Motion for Joinder, Famy Care indicates
`that it only agrees to one of Allergan’s conditions—to conduct the cross-
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`examination of Patent Owner’s witnesses within the timeframe allotted for
`one party. Paper 10, 1. Famy Care, however, states that it cannot agree to
`forgo reliance on its expert declarants because its experts “include a
`distinguished clinician who can provide the Board a valuable perspective on
`the secondary considerations arguments Allergan leans heavily on.” Id. at 2.
`Famy Care also asserts that it cannot agree to limit its briefing in the joined
`proceeding on the basis that it “believes additional briefing, including on its
`secondary considerations arguments, will give [Famy Care] a fair chance to
`present its own arguments and aid the Board in considering the instituted
`grounds.” Id. at 4. Famy Care only agrees to “consolidate its briefing with
`Mylan if permitted separate briefing of up to seven pages (including but not
`limited to arguments on which Mylan lacks standing, or [Famy Care] and
`Mylan disagree).” Id. Finally, with respect to oral arguments, Famy Care
`agrees to have Mylan argue first, but asserts a right to “present its own
`arguments (if necessary) only on issues where the Petitioners disagree, or
`where Mylan has no standing to address, all within the allotted time for one
`party.” Id. at 3.
`Under the circumstances, we determine that joinder of Famy Care to
`IPR2016-01132 is not appropriate. Famy Care argues that if an inter partes
`review is instituted based on its Petition, “but joinder denied, Allergan
`would be compelled to go through duplicative discovery to defend against
`two IPR petitions, and the Board would be required to consider similar
`arguments on the same grounds twice.” Id. at 4. As noted above, however,
`Famy Care does not concede to simply taking a “silent understudy” role with
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`respect to Mylan, and instead seeks the opportunity to present additional
`arguments, briefing, and evidence, including two additional expert
`declarations, beyond what is being considered based on Mylan’s Petition in
`IPR2016-01132. Moreover, to the extent that a denial of joinder would
`result in duplicative proceedings for Allergan, we note that Allergan has
`opposed joinder in this instance. Accordingly, we determine that joinder
`under these conditions would not “secure the just, speedy, and inexpensive
`resolution” of the proceeding. See 37 C.F.R. § 42.1(b). Thus, Famy Care’s
`Motion for Joinder is denied.
`Having determined that joinder is not appropriate, we now consider
`Famy Care’s Petition on the merits.
`Person of Ordinary Skill in the Art
`B.
`Petitioner asserts that as of September 15, 2003, a person of ordinary
`skill in the art would likely have had “some combination of: (a) knowledge
`regarding designing and preparing products intended for ocular
`administration; and/or (b) the ability to understand results and findings
`presented or published by others in the field.” Pet. 11 (citing Ex. 1002 ¶ 60,
`Ex. 1003 ¶ 76). Petitioner further contends that this person typically would
`have had 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.
`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
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`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)).
`
`Claim Construction
`C.
`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).
`“therapeutically effective” and “therapeutic efficacy”
`1.
`Claims 1–16 and 21–27 recite treatment methods utilizing a topical
`ophthalmic emulsion that is “therapeutically effective in treating dry eye
`disease” or achieves “therapeutic efficacy.” Petitioner asserts that the ’191
`patent teaches that cyclosporin A “enhance[s] or restore[s] lacrimal gland
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`tearing” in providing “the desired therapeutic effect.” Pet. 17 (quoting Ex.
`1001, 9:15–17). Petitioner also asserts that the term “therapeutic” includes
`palliative and curative treatments. Id. Petitioner then argues that in the
`context of the ’191 patent, “an emulsion effective to increase tear production
`or reduce symptoms is an emulsion therapeutically effective to enhance and
`restore lactrimal gland tearing and treat dry eye disease.” Id. at 17–18
`(citing Ex. 1002 ¶¶ 71–76; Ex. 1003 ¶¶ 87–92).
`Independent claims 13 and 21 recite an emulsion that achieves as
`much “therapeutic efficacy” as a second emulsion. Petitioner asserts that
`because the plain 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. 19 (citing Ex. 1002
`¶¶ 71–76; Ex. 1003 ¶¶ 87–92).
`At this stage of the proceeding, we are persuaded that Petitioner’s
`arguments and evidence support the broadest reasonable interpretation in
`light of the specification, and find that “therapeutically effective,”
`“therapeutic efficacy,” 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
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`the controversy.’”) (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc.,
`200 F.3d 795, 803 (Fed. Cir. 1999)).
`D. Obviousness over Ding ’979 and Sall
`Petitioner argues that claims 1–27 are unpatentable as obvious over
`the combination of Ding ’979 and Sall. Pet. 28–51. Based on the current
`record, we determine that Petitioner has established a reasonable likelihood
`that it would prevail in showing claims 1–27 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
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`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.
`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:
`
`
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`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
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`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
`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 1–27 of the ’191 patent. Pet. 21–28. For example,
`regarding claim 1, Ding ’979 teaches emulsions that are “made for treatment
`of keratoconjunctivitis sicca (dry eye) syndrome.” Ex. 1006, 5:9–11. Ding
`’979 also teaches that cyclosporins act in the “enhancement or restoring of
`lacrimal gland tearing.” Id. at 1:37–39. Thus, we are persuaded by
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`Petitioner’s assertion that Ding ’979 teaches the emulsion is “therapeutically
`effective in treating dry eye disease,” as recited by the claim.
`Regarding the specific ingredients of the claimed emulsion, as
`Petitioner notes, the emulsion of Ding ’979’s claim 8 recites ranges of
`0.05% to 0.40% CsA; 0.625%–5.0% castor oil; and the other claimed
`ingredients and pH. Ex. 1006, 6:35–42. Dr. Kador testifies that a person of
`ordinary skill in the art would understand that Ding ’979 claim 8 “discloses a
`fully operational invention, and that an emulsion having 0.05% CsA and
`1.25% castor oil is squarely within Ding ’979’s teachings.” Ex. 1002
`¶¶ 162–163.
`Moreover, Example 1D of Ding ’979 teaches every ingredient of the
`emulsion in claim 1, 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.
`Kador, Ding ’979’s teaching that too much CsA in the blood can cause
`unwanted side effects due to systemic circulation would have led a person of
`ordinary skill in the art to use 0.05% CsA and 1.25% castor oil in light of the
`preferred CsA to castor oil ratio taught by Ding ’979. Ex. 1002 ¶¶ 173–174.
`Alternatively, Petitioner asserts that Sall would have motivated a
`person of ordinary skill in the art to use the 0.05% CsA emulsion with
`1.25% castor oil taught by Ding ’979. Pet. 33–36. Sall teaches treating
`patients twice daily with an emulsion containing 0.05% cyclosporin A. Ex.
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`Patent 9,248,191 B2
`1007, 631. Sall concludes 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.” Id. As such, Petitioner asserts that one of ordinary skill in the
`art would have selected the lowest effective dose (0.05% CsA) given Sall’s
`teaching that there was no dose response effect and because such a person
`would have been motivated to keep blood CsA levels as low as possible
`while maintaining efficacy given CsA’s known immunosuppressant
`activities. Pet. 35–36 (citing Ex. 1006, 1:67–2:4; Ex. 1007, 1, 6, 7; Ex. 1002
`¶ 172). Moreover, Petitioner asserts that a person of ordinary skill in the art
`would prefer a 0.05% CsA emulsion with 1.25% castor oil rather than
`0.625% castor oil because Sall taught that castor oil itself provides
`“substantial palliative benefits.” Pet. 35–36 (citing Ex. 1007, 8; Ex. 1002
`¶¶ 174–175).
`Petitioner also addresses four declarations alleging secondary
`considerations that Patent Owner submitted during prosecution of the ’162
`patent application. Pet. 56–76. Patent Owner argues that the evidence of
`unexpected results is “fundamentally flawed.” Id. at 57. Patent Owner also
`asserts that other patents demonstrate near-simultaneous invention using
`1.25% castor oil, including ophthalmic emulsions comprising 1.25% castor
`oil and 0.05% CsA. Id. at 76–77. We have considered Petitioner’s
`arguments and will be able to assess them more fully on a complete trial
`record.
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`Upon considering the arguments set forth in the Petition, we
`determine that Petitioner has shown a reasonable likelihood that it would
`prevail in showing claim 1 is unpatentable as obvious over the combination
`of Ding ’979 and Sall. We have considered Petitioner’s arguments and
`evidence with respect to claims 2–27, and we determine that Petitioner has
`made a sufficient showing as to those claims, as well.
`E. Obviousness over Ding ’979, Sall, and Acheampong
`Petitioner also asserts that claims 1–27 are unpatentable as obvious
`over Ding ’979, Sall, and Acheampong. Pet. 52–53. We incorporate here
`our findings and discussion above regarding the disclosure of Ding ’979 and
`Sall.
`
`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.
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`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.
`Petitioner asserts that claims 1–27 are unpatentable as obvious over
`Ding ’979 and Sall, and that Acheampong further teaches that the CsA blood
`level elements of claims 1–16, 20, 22, and 27 were obvious. According to
`Petitioner, Acheampong would have guided a person of ordinary skill in the
`art to use the 0.05% CsA formulation given the absence of systemic toxicity
`risks. Pet. 52–53. That is, Acheampong teaches an emulsion with 0.05%
`CsA resulted in no detectable CsA in the blood at both peak and trough
`levels. Ex. 1008, Table 1.
`Petitioner further asserts that Acheampong and Sall together would
`give a person of ordinary skill in the art a reasonable expectation of success
`that twice daily administration of 0.05% CsA yields “substantially no
`detectable concentration of cyclosporin A” in the blood. Id. at 53 (citing Ex.
`1002 ¶¶ 231–234; Ex. 1003 ¶ 165–166). According to Petitioner, a skilled
`artisan would have had good reason to combine Acheampong with Ding
`’979 and Sall’s teachings, as Acheampong additionally teaches the safety of
`topically administering CsA emulsions to the eye. Id.
`On the current record, we are persuaded that Petitioner has
`demonstrated a reasonable likelihood that it would prevail in its assertion
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`that claims 1–27 are unpatentable as obvious over the combination of Ding
`’979, Sall, and Acheampong.
`F. Obviousness over Ding ’979, Sall, and Glonek
`Petitioner asserts that claims 17–20 are unpatentable as obvious over
`Ding ’979, Sall, and Glonek. Pet. 54–55. 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
`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.
`Independent claim 17 recites the same emulsion as claims 1, 13, and
`21, but further recites that “the emulsion breaks down more quickly in the
`eye of a human, . . . thereby reducing vision distortion in the human eye as
`compared to a second topical ophthalmic emulsion that contains only 50% as
`much castor oil as the first topical ophthalmic emulsion.” Glonek teaches
`that “[t]he duration of [the blurring] is dependent upon the time required for
`the emulsion to differentiate and form separate layers.” Ex. 1009, 6:37–40.
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`Moreover, Glonek teaches that “it is preferred that the emulsion be stable for
`long term storage, but rapidly differentiate in the eye.” Id. at 6:48–50.
`Accordingly, Petitioner asserts that a skilled artisan would have understood
`that increasing the oil concentration in an emulsion, while holding the
`surfactant concentration constant, results in an increased rate of
`differentiation. Pet. 54–55 (citing Ex. 1009, 10:66–11:3; Ex. 1002 ¶¶ 238–
`240).
`We are persuaded, on the current record, that Petitioner has
`demonstrated a reasonable likelihood that
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