Trials@uspto.gov
`Tel: 571-272-7822
`
`
`Paper 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 IPR2017-00566
`Patent 8,648,048 B2
`_______________
`
`
`Before SHERIDAN K. SNEDDEN, TINA E. HULSE, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`SNEDDEN, 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
`
`
`Tel: 571-272-7822
`
`
`Paper 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 IPR2017-00566
`Patent 8,648,048 B2
`_______________
`
`
`Before SHERIDAN K. SNEDDEN, TINA E. HULSE, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`SNEDDEN, 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
`
`
`
`IPR2017-00566
`Patent 8,648,048 B2
`
`I. INTRODUCTION
`
`Famy Care Limited (“Famy Care” or “Petitioner”) filed a Petition to
`institute an inter partes review of claims 1−23 (Paper 3; “Petition” or “Pet.”)
`of US 8,648,048 B2 (Ex. 1001; “the ’048 patent”). Allergan, Inc.
`(“Allergan” or “Patent Owner”) 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., IPR2016-01131 (“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
`consideration of the Petition, we determine that Petitioner has established a
`reasonable likelihood that it will prevail with respect to at least one of the
`challenged claims. We institute an inter partes review as to claims 1−23 of
`the ’048 patent.
`Related Proceedings
`A.
`The parties identify petitions for inter partes review previously filed
`by other petitioners that challenge the claims of the ’048 patent and related
`patents. Pet. 4–5; Paper 8, 2–3. Certain petitions were terminated before
`decisions on institution were entered. Pet. 5; Paper 6, 2. Other petitions
`have been granted and inter partes review has been instituted for the
`following U.S. Patents: U.S. Patent No. 8,633,162 (IPR2016-01130,
`
`2
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`
`
`IPR2017-00566
`Patent 8,648,048 B2
`
`IPR2017-00568, IPR2017-00599, IPR2017-00583); U.S. Patent No.
`8,685,930 (IPR2016-01127, IPR2017-00571, IPR2017-00594, IPR2017-
`00576); U.S. Patent No. 8,629,111 (IPR2016-01128, IPR2017-00567,
`IPR2017-00596, IPR2017-00578); U.S. Patent No. 8,642,556 (IPR2016-
`01129 IPR2017-00570, IPR2017-00598, IPR2017-00579); U.S. Patent No.
`8,648,048 (IPR2016-01131, IPR2017-00600, IPR2017-00585); and U.S.
`Patent No. 9,248,191 (IPR2016-01132, IPR2017-00569, IPR2017-00601,
`IPR2017-00586). Paper 6, 2–3.
`
`B. The ’048 patent (Ex. 1001)
`The ’048 patent generally relates to methods of providing therapeutic
`effects using cyclosporin components, and more specifically to a
`formulation containing, inter alia, cyclosporin-A (“CsA”) and castor oil
`emulsions for treating dry eye syndrome (i.e., keratoconjunctivitis sicca).
`Ex. 1001, 2:55–3:11. 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 been apparent that cyclosporin A emulsions for ophthalmic use
`preferably have less than 0.2% by weight of cyclosporin A.” Id. at 1:66–2:2.
`Moreover, if reduced amounts of CsA are used, reduced amounts of castor
`oil are needed because one of the functions of castor oil is to solubilize
`cyclosporin A. Id. at 2:1–2:6.
`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 2:35–38.
`The relatively high concentration of hydrophobic component provides for a
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`IPR2017-00566
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`more rapid breaking down of the emulsion in the eye, which reduces vision
`distortion and/or facilitates the therapeutic effectiveness of the composition.
`Id. at 2:42–48. Furthermore, using reduced amounts of cyclosporin
`component mitigates against undesirable side effects or potential drug
`interactions. Id. at 2:48–51.
`The patent identifies two particular compositions that were selected
`for further testing, as shown below:
`
`
`Id. at 14:15–30. Based on the results of a Phase III 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
`14:35–40. The patent indicates that “[t]his is surprising for a number of
`reasons.” Id. at 14:41. 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 14:41–44.
`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
`14:44–49. 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
`
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`interactions and the like, relative to providing Composition I.” Id. at 15:4–8.
`
`C. The Asserted Grounds
`
`Petitioner challenges claims 1−23 of the ’048 patent on the following
`grounds. Pet. 6–7.
`Ground
`
`Reference[s]
`
`Ding ’979 1
`
`Basis
`§ 103
`
`Claims challenged
`1− 23
`
`1
`
`2
`
`3
`
`4
`
`§ 103
`
`Ding ’979 and Sall2
`Ding ’979, Sall, and
`Acheampong3
`Ding ’979, Sall, and Glonek4 § 103
`
`§ 103
`
`1− 23
`
`11 and 21
`
`15
`
`Petitioner also relies on the Declarations of Peter Kador, Ph.D. (Ex.
`1002) and Michael Lemp, M.D. (Ex. 1003).
`
`D. Illustrative Claims
`
`Independent claims 1, 18, and 22 are illustrative of the challenged
`claims, and are reproduced below:
`
`
`1 Ding et al., U.S. Patent No. 5,474,979, issued December 12, 1995 (Ex.
`1006, “Ding ’979”).
`2 Kenneth 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 631−639 (2000) (Ex. 1007, “Sall”).
`3 Andrew 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, in
`LACRIMAL GLAND, TEAR FILM, AND DRY EYE SYNDROMES 2, BASIC SCIENCE
`AND CLINICAL RELEVANCE, 1001−1004 (1998) (Ex. 1008, “Acheampong”).
`4 Glonek et al., U.S. Patent No. 5,578,586, issued Nov. 26, 1996. Ex. 1009
`(“Glonek”).
`
`5
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`Patent 8,648,048 B2
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`
`1. A method of increasing tear production in the eye of a human,
`the method comprising topically administering to the eye of the
`human in need thereof an emulsion at a frequency of twice a day,
`wherein the 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; and
`wherein the topical ophthalmic emulsion is effective in
`increasing tear production.
`
`18. A method of treating keratoconjunctivitis sicca, 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;
`a tonicity component or a demulcent component in an
`amount of about 2.2% by weight;
`a buffer; and
`water;
`treating
`in
`effective
`is
`emulsion
`the
`wherein
`keratoconjunctivitis sicca and wherein the topical ophthalmic
`emulsion has a pH in the range of about 7.2 to about 7.6.
`
`22. A method comprising:
`administering an emulsion topically to the eye of a human
`having keratoconjunctivitis sicca at a frequency of twice a day,
`wherein the emulsion comprises:
`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; and
`
`6
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`IPR2017-00566
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`
`wherein the emulsion is effective in increasing tear
`production in the human having keratoconjunctivitis sicca.
`Claims 2–17 depend from claim 1, either directly or indirectly.
`Claims 19–21 depend from claim 18, either directly or indirectly. Claim 23
`depend from claim 22, either directly or indirectly.
`
`II. 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 4 (PTAB Apr. 24, 2013) (Paper 15).
`Although Famy Care’s Petition is similar to Mylan’s Petition in terms
`of the art relied 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 1–23 over Ding ’979 and Sall,
`whereas Mylan’s Petition challenges claims 1–10, 12–14, 16–20, 22, and 23
`over the same art. Compare Pet. 6 with Mylan Pet.5 13. Famy Care relies
`
`
`5 Mylan IPR, Petition for Inter Partes Review of U.S. Patent No. 8,633,162
`Paper 3 (filed June 3, 2016) (“Mylan Pet.”).
`
`7
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`upon the declarations of Dr. Peter Kador (Ex. 1002) and Dr. Michael A.
`Lemp (Ex. 1003) to support its Petition, whereas Mylan relies upon the
`declaration of Mansoor Amiji, Ph.D. 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, 2. 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.
`
`Paper 9, 2.
`
`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-
`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
`2–3. Famy Care also asserts that it cannot agree to limit its briefing in the
`
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`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
`IPR2016-01131 is not appropriate. Famy Care argues that if an inter partes
`review is instituted based on its Petition, “but joinder is 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 ground twice.” Id. at 4. As noted above, however,
`Famy Care does not concede to simply taking a “silent understudy” role with
`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
`IPR2016-01131. 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
`
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`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.
`
`B. Claim Interpretation
`We interpret claims using the “broadest reasonable construction in
`light of the specification of the patent in which [they] appear[].” 37 C.F.R.
`§ 42.100(b); Cuozzo Speed Techs. LLC v. Lee, 136 S. Ct. 2131, 2144–46
`(2016). Under the broadest reasonable construction standard, claim terms
`are given their “ordinary and customary meaning,” as would be understood
`by one of ordinary skill in the art at the time of the invention. In re
`Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007) (quoting
`Phillips v. AWH Corp, 415 F.3d 1303, 1312 (Fed. Cir. 2006)). “Absent
`claim language carrying a narrow meaning, the PTO should only limit the
`claim based on the specification . . . when [it] expressly disclaim[s] the
`broader definition.” In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004)
`(citation omitted). “Although an inventor is indeed free to define the
`specific terms used to describe his or her invention, this must be done with
`reasonable clarity, deliberateness, and precision.” In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994).
`1. “effective”/“therapeutically effective”
`Claims 1–17 and 22–23 recite that the emulsion is “effective in
`increasing tear production,” whereas claims 18–21 recite an emulsion that is
`“effective in treating keratoconjunctivitis sicca.” The dependent claims
`recite other variations such as an emulsion that is “substantially
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`therapeutically effective as a second emulsion” or achieves “at least as much
`therapeutic effectiveness as a second emulsion.”
`Petitioner asserts that the plain meaning of the word “therapeutic”
`includes palliative as well as curative treatments, and as such, emulsions
`effective in increasing tear production is an example of an emulsion
`therapeutically effective in treating dry eye disease/KCS palliative and
`curative treatments. Pet. 18–19 (citing Ex. 1002 ¶¶ 70; Ex. 1003 ¶¶ 82–83,
`85; Ex. 1022, 4–5, 7). We agree that, on the current record, the ordinary
`meaning of the phrase “therapeutically effective” and similar phrases
`includes palliative effects. That being said, at this stage of the proceeding,
`we find that “effective in increasing tear production” does not require further
`construction as its meaning is clear on its face. We also find that “effective
`in treating keratoconjunctivitis sicca” encompasses both the treatment of the
`symptoms of dry eye disease as well as the disease itself.
`2. Remaining Claim Terms
`We determine that no explicit construction of any claim term is
`necessary to determine whether to institute a trial in this case. See, e.g.,
`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)).
`At this stage of the proceeding, we have not made a final
`determination as to the construction of any claim term.
`
`C. Principles of Law
`We analyze the proposed grounds of unpatentability in accordance
`with the following stated principles.
`
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`
`A patent may not be obtained if the differences between the subject
`matter sought to be patented and the prior art are such that the subject matter
`as a whole would have been obvious at the time the invention was made to a
`person having ordinary skill in the art to which the subject matter pertains.
`35 U.S.C. § 103(a). The legal question of obviousness is resolved on the
`basis of underlying factual determinations, including: (1) the scope and
`content of the prior art; (2) any differences between the claimed subject
`matter and the prior art; (3) the level of skill in the art; and (4) objective
`evidence of nonobviousness, i.e., secondary considerations. See Graham v.
`John Deere Co., 383 U.S. 1, 17–18 (1966).
`In KSR International Co. v. Teleflex Inc., the Supreme Court stated
`that an invention may be found obvious if trying a course of conduct would
`have been obvious to a person having ordinary skill:
`
`When there is a design need or market pressure to solve a
`problem and there are a finite number of identified, predictable
`solutions, a person of ordinary skill has good reason to pursue
`the known options within his or her technical grasp. If this leads
`to the anticipated success, it is likely the product not of
`innovation but of ordinary skill and common sense. In that
`instance the fact that a combination was obvious to try might
`show that it was obvious under § 103.
`550 U.S. 398, 421 (2007). “KSR affirmed the logical inverse of this
`statement by stating that § 103 bars patentability unless ‘the improvement is
`more than the predictable use of prior art elements according to their
`established functions.’” In re Kubin, 561 F.3d 1351, 1359−60 (Fed. Cir.
`2009) (citing KSR, 550 U.S. at 417).
`The factual inquiries for an obviousness determination also include
`secondary considerations based on evaluation and crediting of objective
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`evidence of nonobviousness. Graham, 383 U.S. at 17−18. Notwithstanding
`what the teachings of the prior art would have suggested to one with
`ordinary skill in the art at the time of the invention, the totality of the
`evidence submitted, including objective evidence of nonobviousness, may
`lead to a conclusion that the claimed invention would not have been obvious
`to one with ordinary skill in the art. In re Piasecki, 745 F.2d 1468, 1471–72
`(Fed. Cir. 1984).
`Such a conclusion, however, requires the finding of a nexus to
`establish that the evidence relied upon traces its basis to something novel in
`the claim and not to something in the prior art. Institut Pasteur & Universite
`Pierre et Marie Curie v. Focarino, 738 F.3d 1337, 1347 (Fed. Cir. 2013).
`Generally, objective evidence of nonobviousness must be shown to have a
`nexus. In re GPAC Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995) (nexus
`generally); In re Kao, 639 F.3d 1057, 1069 (Fed. Cir. 2011) (unexpected
`results); In re Huang, 100 F.3d 135, 140 (Fed. Cir. 1996) (commercial
`success); Rambus Inc. v. Rea, 731 F.3d 1248, 1256 (Fed. Cir. 2013) (long-
`felt need).
`Objective evidence of nonobviousness also must be reasonably
`commensurate in scope with the claim. Kao, 639 F.3d at 1068. This does
`not mean that the proffered evidence must reach every embodiment within
`the scope of the claim, so long as there is an “adequate basis to support the
`conclusion that other embodiments falling within the claim will behave in
`the same manner.” Id.
`
`D. Content of the Prior Art
`Petitioner relies upon the following prior art in its challenges.
`
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`1. Ding ’979 (Ex. 1006)
`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.
`Ding ’979 discloses that the preferable weight ratio of CsA 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 CsA, castor oil, polysorbate 80, Pemulen®(an
`acrylate/C10-30 alkyl acrylate cross-polymer) (id. at 4:1–5), glycerine,
`sodium hydroxide, and purified water at a pH range of 7.2–7.6. Id. at 4:32–
`43. According to Ding ’979, the formulations of Example 1 was “made for
`treatment of keratoconjunctivitis sicca (dry eye) syndrome.” Id. at 5:10–12.
`2. Sall (Ex. 1007)
`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 CsA 0.05% or 0.1% ophthalmic emulsions or vehicle for six months.
`Ex. 1007, Abstract, 631. The study sought to compare the efficacy and
`safety of CsA 0.05% and 0.1% to vehicle in patients with moderate to severe
`dry eye disease. Id. Sall found that “topical treatment with either CsA
`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 CsA 0.05% resulted in significantly greater
`improvements in several subjective parameters. Id. Sall also found that
`trough blood concentrations of CsA were undetectable in all samples of CsA
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`0.05%, whereas CsA was quantifiable in only six samples for six different
`patients in the CsA 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.
`3. Acheampong (Ex. 1008)
`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, 1001. 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 1002. 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.
`
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`4. Glonek (Ex. 1009)
`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.
`
`E. Asserted Grounds of Unpatentability
`
`1. Obviousness of Claims 1−23 Based on Ding ’979 and Sall
`Petitioner contends that claims 1−23 are rendered obvious by the
`combined teachings of Ding ’979 and Sall. Pet. 29–52. Petitioner sets forth
`the foregoing teachings of Ding ’979 and Sall and provides a detailed
`discussion and claim charts explaining how each claim limitation of the
`challenged claims is disclosed in Ding ’979 and/or Sall. Id. The issue
`before us is whether it would have been obvious to use the particular
`concentrations of 0.05% CsA and 1.25% castor oil recited in the challenged
`claims. Id.
`In its Example 1, Ding ’979 specifically identifies several examples
`(Examples 1A–1E) that include 0.05% CsA and 1.25% castor oil, albeit not
`as part of the same composition. Pet. 29; Ex. 1006, 4:32–43; Ex. 1002 ¶
`156. Petitioner contends that:
`
`The CsA/castor oil amounts in the claimed combination,
`i.e., 0.05% CsA and 1.25% castor oil, would have been obvious
`
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`to an ordinarily-skilled artisan because the CsA/castor oil ratio
`of such formulation uses the identical ratio Ding ’979 Example
`1B (0.04) used, and applies it to a CsA species amount recited in
`Ding ’979 claim 8 and in Ding ‘979 Example 1E. See EX1002,
`¶158; EX1006, 4:33-43, 6:35-41. Applying this ratio also yields
`a specific castor oil amount that same Example 1 also used.
`EX1006, 4:33-43 (Example 1D).
`Pet. 31. Petitioner further contends that:
`
`the ordinarily-skilled artisan, seeking to prepare Ding ’979
`formulations within the scope of claim 8, would retain all
`Example 1 fixed-formulation elements (e.g., Polysorbate 80
`surfactant, Pemulen®, glycerine, NaOH, water), as-is; and
`consider the Example’s existing specific CsA amounts (0.05%,
`0.1%, 0.2%, 0.4%), and castor oil amounts (5%, 2.5%, 1.25%
`and 0.625%). The specific ratios to use of CsA to castor oil would
`be those the Examples already used (0.04 and 0.08), while
`staying within the overall claim 8 ingredient preferences (e.g.,
`not more than 5% by weight castor oil). The ordinarily-skilled
`artisan would be motivated to pursue, reasonably expect to
`prepare, and ultimately use such formulations for dry eye
`disease.
`Id. at 32.
`In an alternate ground, Petitioner combines Ding ’979 with Sall and
`contends that “Sall would have motivated [the ordinarily-skilled artisan]
`person to make and use the 0.05% CsA emulsion with 1.25% castor oil
`taught by Ding ’979.” Id. at 33 (citing Ex. 1002, ¶¶ 166-68). Petitioner
`contends that Sall reports Phase 3 clinical trial results showing that either the
`0.05% or 0.10% CsA emulsion is therapeutically effective in increasing tear
`production and treating dry eye disease/KCS. Id. at 33–34 (citing Ex. 1007,
`1–2, 7–8; EX1002 ¶ 166; Ex. 1003 ¶98–121).
`Petitioner further contends that:
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`The combined teachings of Sall and Ding ’979 would have
`led the ordinarily-skilled artisan to a 0.05% CsA and 1.25%
`castor oil emulsion. An ordinarily-skilled artisan would select the
`lowest effective dose (0.05% CsA) since Sall reported that there
`was no dose response effect; and because the 0.05% CsA
`emulsion appeared to perform better than the 0.1% CsA
`emulsion. Such person also was motivated to keep blood CsA
`levels as low as possible, while maintaining efficacy because
`CsA had known, broad-based immunosuppressant activities.
`EX1006, 1:67-2:4; EX1007-0001, 0006-07; EX1002, ¶169.
`Id. at 35–36.
`Based on the arguments presented and evidence of record, we
`determine that Petitioner has demonstrated a reasonable likelihood that
`claims 1−23 are obvious over the teachings of Ding ’979 alone or in
`combination with Sall. See 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.”); In re Boesch, 617 F.2d 272, 276 (CCPA 1980) (“[D]iscovery
`of an optimum value of a result effective variable in a known process is
`ordinarily within the skill of the art.”).
`2. Obviousness of Claims 11 and 21 over the Combination of
`Ding ’979, Sall, and Acheampong
`Petitioner asserts that claims 11 and 21 are unpatentable as obvious
`over Ding ’979, Sall, and Acheampong. Pet. 53–54. Claims 11 and 21
`depend directly from claims 1 and 18 and further recite as follows:
`“wherein, when the emulsion is administered to the eye of a human in an
`
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`effective amount in treating keratoconjunctivitis sicca, the blood of the
`human has substantially no detectable concentration of the cyclosporin A.”
`We incorporate here our discussion above regarding the teachings of
`Ding ’979 and Sall. With regard to the elements of claims 11 and 12,
`Petitioner asserts that “Acheampong and Sall together teach and give
`the ordinarily-skilled artisan a reasonable expectation that twice daily
`administration of 0.05% CsA yields ‘substantially no detectable
`concentration of cyclosporin A’ in the blood.” Pet. 54 (citing Ex. 1002 ¶
`229; Ex. 1003 ¶¶ 159-60. To support this position, Petitioner asserts as
`follows:
`
`Sall states that humans receiving ophthalmic administrations of
`0.05% CsA emulsions containing castor oil twice a day had,
`“[t]rough blood concentrations of CsA . . . below the limit of
`quantitation (of 0.1 ng/ml) in all samples.” EX1007-0007.
`Acheampong additionally reports on the months-long study
`evaluating both peak and trough concentrations of CsA in the
`blood of humans receiving ophthalmic administrations of
`CsA/castor oil emulsions. EX1008-0004 (“[S]ubjects with KCS
`received an eyedrop of vehicle or 0.05%, 0.10%, 0.20% or 0.40%
`cyclosporine emulsion twice daily … Blood samples were
`collected … at morning troughs … [and] after the last dose
`[(trough levels)].”). Acheampong Table 1 shows that 0.05% CsA
`produced no detectable concentration of CsA in the blood
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