Trials@uspto.gov
`571-272-7822
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` Paper No. 8
` Entered: June 12, 2018
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN TECHNOLOGIES, INC.,
`Petitioner,
`
`v.
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`NOVEN PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
`
`
`
`Case IPR2018-00174
`Patent 9,730,900 B2
`____________
`Before JAMES T. MOORE, SUSAN L. C. MITCHELL, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`SAWERT, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
`
`571-272-7822
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`
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` Paper No. 8
` Entered: June 12, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN TECHNOLOGIES, INC.,
`Petitioner,
`
`v.
`
`NOVEN PHARMACEUTICALS, INC.,
`Patent Owner.
`____________
`
`
`
`Case IPR2018-00174
`Patent 9,730,900 B2
`____________
`Before JAMES T. MOORE, SUSAN L. C. MITCHELL, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`SAWERT, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
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`IPR2018-00174
`Patent 9,730,900 B2
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`INTRODUCTION
`I.
`Mylan Technologies, Inc. (“Petitioner”) requests an inter partes
`review of claims 1–23 of U.S. Patent No. 9,730,900 B2 (“the ’900 patent,”
`Ex. 1001). Paper 2 (“Pet.”). Noven Pharmaceuticals, Inc. (“Patent Owner”)
`filed a Preliminary Response. Paper 6 (“Prelim. Resp.”).
`We have authority to determine whether to institute an inter partes
`review. 35 U.S.C. § 314(b); 37 C.F.R. § 42.4(a). We may not institute an
`inter partes review “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). On April 24, 2018, the Supreme Court
`held that a decision to institute under 35 U.S.C. § 314(b) may not institute
`review on less than all claims challenged in the petition. SAS Inst., Inc. v.
`Iancu, 138 S. Ct. 1348, 1355–56 (2018).
`Applying those standards, and upon consideration of the information
`presented in the Petition and the Preliminary Response, we determine that
`Petitioner has not demonstrated a reasonable likelihood of success in
`proving that any claim of the ’900 patent is unpatentable. We, therefore,
`deny the Petition and do not institute an inter partes review.
`BACKGROUND
`II.
` Related Matters
`Petitioner identifies Noven Pharmaceuticals, Inc. v. Alvogen Pine
`Brook LLC, No. 1:17-cv-01429-LPS (D. Del.) as a related matter under
`37 C.F.R. § 42.8(b)(2). Pet. 20. Petitioner also petitioned for an inter partes
`review of U.S. Patent 9,724,310 B2 (“the ’310 patent”), owned by Patent
`Owner, which has been designated Case IPR2018-00173. Id. at 20.
`Petitioner states that the ’310 and the ’900 patents both claim the benefit of
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`priority to U.S. Application No. 12/216,811, filed on July 10, 2008, now
`U.S. Patent No. 8,231,906 (“the ’906 patent”). Petitioner identifies both
`pending and terminated litigations involving the ’906 patent. See id. at 20–
`21 (identifying Noven Pharmaceuticals Inc. v. Mylan Technologies Inc., No.
`1:15-cv-00328 (D. Del.) (terminated); Noven Pharmaceuticals Inc. v. Mylan
`Technologies Inc., 1:15-cv-00069 (N.D.W.V.) (terminated), Noven
`Pharmaceuticals Inc. v. Actavis Laboratories UT, Inc., Nos. 1:15-cv-00249-
`LPS and 1:16-cv-00465-LPS (D. Del.) (pending); Alvogen Pine Brook LLC
`v. Noven Pharmaceuticals, Inc., No. 1:16-cv-00395-LPS (D. Del.)
`(pending)).
`
` The ’900 Patent
`The ’900 patent, titled “Transdermal Estrogen Device and Delivery,”
`issued on August 15, 2017. Ex. 1001, [45]. The ’900 patent relates to
`transdermal drug delivery systems for the transdermal administration of
`estrogen, and to methods of making and using such systems. Id., Abstract.
`In one embodiment, the transdermal drug delivery system is a patch
`comprising a single adhesive polymer matrix layer of adhesive polymer
`matrix and estradiol. Id. at 2:12–18.
`According to the ’900 patent, “a patch comprising a pressure-sensitive
`adhesive containing a drug, as a means of delivering drug through the skin is
`well known.” Id. at 1:21–23. But formulation of viable commercial
`embodiments has been difficult, in part due to patient preference for patches
`having a small surface area. Id. at 1:56–2:7. The ’900 patent explains that
`“size, e.g., surface area at the site of application, is often dictated and limited
`by other physical and pharmacokinetic requirements, such as desired drug
`delivery rates and daily dosages.” Id. at 1:58–61. Thus, “it is easier to
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`develop a relatively ‘large’ transdermal drug delivery system that will
`achieve drug delivery at target therapeutic levels over an intended duration
`of therapy, than it is to develop a smaller transdermal drug delivery system
`that still exhibits acceptable pharmacokinetic properties.” Id. at 1:61–66.
`The ’900 patent refers to the target delivery rate of a drug as “flux,”
`id. at 3:41, and explains that “Applicant surprisingly discovered that
`increasing the coat weight of the drug-containing adhesive layer resulted in
`an increased flux per unit area, and thus permitted the development of
`smaller transdermal drug delivery systems that achieve comparable daily
`dosages” to larger patches, id. at 3:58–62. Although “it was known in the art
`to increase coat weight to provide delivery over a longer period of time,” the
`’900 patent continues, “it was not known that increasing coat weight could
`increase delivery weight or flux, and thus permit the development of a
`smaller system while maintaining daily dosage.” Id. at 3:65–4:2.
`The ’900 patent provides an example of a polymer matrix composition
`comprising, inter alia, acrylic adhesive, silicone adhesive, povidone (PVP),
`and estradiol. Id. at 15:8–19 (Example 1). In one example, the polymer
`matrix was applied to a release liner at a coat weight of 12.5 mg/cm2
`(Example 1), and in a second sample, at a coat weight of 15 mg/cm2
`(Example 1a). Id. at 15:21–22. Human cadaver permeation studies were
`then performed to compare the estradiol flux of these samples to that of
`commercial embodiment Vivelle-Dot®. Id. at 15:23–43. As shown in
`Figure 1, below, “the systems according to the invention have a greater flux
`than the Vivelle-Dot® product and are able to achieve therapeutic daily
`dosages despite their significantly smaller size.” Id. at 15:44–47.
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`Figure 1 illustrates the estradiol flux (μg/cm2/hr) over time (0–
`81 hours) from transdermal delivery systems according to the
`invention (Examples 1 and 1a) as compared to Vivelle-Dot®.
`Ex. 1001, 3:26–28.
`
` Illustrative Claim
`Of the challenged claims, claim 1 is independent and illustrative of the
`claimed subject matter. Claim 1 recites:
` 1. A method for administering estradiol, comprising applying
`to the skin or mucosa of a subject in need thereof a monolithic
`transdermal drug delivery system consisting of (i) a backing
`layer and (ii) a single adhesive polymer matrix layer defining an
`active surface area and comprising an adhesive polymer matrix
`comprising estradiol as the only drug, wherein the polymer
`matrix has a coat weight of greater than about 10 mg/cm2 and
`includes greater than 0.156 mg/cm2 estradiol, and the system
`achieves an estradiol flux of from about 0.0125 to about 0.05
`mg/cm2/day, based on the active surface area.
`Ex. 1001, 15:49–59.
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` The Prior Art
`Petitioner advances the following references as prior art on which it
`relies for the asserted grounds challenging the claims of the ’900 patent:
`1. Walter Mueller, Patent Application Publication No. US 2003/0099695
`A1 (May 29, 2003) (“Mueller,” Ex. 1005);
`
`2. Center for Drug Evaluation and Research, Approval Package for
`Application No. 20-538/S-015, Vivelle-Dot® Transdermal System
`(Novartis) (May 3, 2002) (“Vivelle-Dot Label,” Ex. 1006);
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`3. David Kanios, Patent Application Publication No. US 2006/0078602
`A1 (Apr. 13, 2006) (“Kanios,” Ex. 1007); and
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`4. Yie W. Chien and Te-Yen Chien, U.S. Patent No. 5,145,682 (Sept. 8,
`1992) (“Chien,” Ex. 1009).
` The Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1–15 of the ’900
`patent on the following grounds:
`Claims
`Basis
`1, 2, 8, 10–16, and
`35 U.S.C. § 102 Mueller
`18–23
`1, 2, and 8–23
`3–7
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`References
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`1–23
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`35 U.S.C. § 103 Mueller and Vivelle-Dot Label
`35 U.S.C. § 103 Mueller, Vivelle-Dot Label, and
`Kanios
`35 U.S.C. § 103 Mueller, Vivelle-Dot Label,
`Kanios, and Chien
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`Pet. 21–22. Petitioner also relies on the Declaration of Keith Brain, Ph.D.
`See Pet. 15 (citing Ex. 1002).
`Patent Owner disputes that Petitioner’s asserted grounds render the
`challenged claims unpatentable. See generally Prelim. Resp. Patent Owner
`relies on the Declaration of Adrian C. Williams, Ph.D. See id. at 7 (citing
`Ex. 2001).
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`III. ANALYSIS
`We organize our analysis into four sections. First, we address the
`level of ordinary skill in the art. Second, we turn to claim construction.
`Third, we provide an overview of the asserted references. Fourth, taking
`account of the information presented, we consider whether the grounds
`asserted in the Petition meet the threshold showing for instituting an inter
`partes review under 35 U.S.C. § 314(a).
` Level of Ordinary Skill in the Art
`We consider the asserted grounds of unpatentability in view of the
`understanding of a person of ordinary skill in the art. Petitioner contends
`and Dr. Brain testifies that, as of July 10, 2008, the earliest filing date in the
`priority chain for the ’900 patent, a person of ordinary skill in the art “would
`likely have an advanced degree, for example a Ph.D., in pharmaceutical
`chemistry, physical chemistry, bioengineering, or a drug delivery related
`discipline,” or, alternatively, “a bachelor’s degree plus two to five years’
`experience in the transdermal delivery industry.” Pet. 15; Ex. 1002
`¶¶ 77–78. Petitioner also asserts that the ordinarily skilled artisan “would
`have familiarity with formulation of drugs for transdermal administration
`and would have been able to understand and interpret the references
`discussed in the field,” including those references discussed and presented in
`the Petition. Pet. 15; see also Ex. 1002 ¶¶ 77–78.
`At this stage of the proceeding, Patent Owner does not dispute
`Petitioner’s proposed level of ordinary skill. Prelim. Resp. 7. Patent Owner
`clarifies, however, “that a POSA who does not have an advanced degree in
`the fields mentioned [by Petitioner] would have a bachelor’s degree in a
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`field related to drug delivery.” Id. (citing Ex. 2001 ¶¶ 26–28). We adopt
`Petitioner’s definition, with Patent Owner’s clarification, for purposes of this
`decision.
`We also find, for purposes of this decision, that the prior art itself is
`sufficient to demonstrate the level of ordinary skill in the art at the time of
`the invention. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir.
`2001) (the prior art, itself, can reflect the appropriate level of ordinary skill
`in art). Further, based on the information presented at this stage of the
`proceeding, we consider each parties’ declarant—Dr. Brain and
`Dr. Williams—qualified to opine from the perspective of an ordinary artisan
`at the time of the invention. See Ex. 1002 ¶¶ 1–11 (Dr. Brain’s
`qualifications); Ex. 1003 (Dr. Brain’s curriculum vitae); Ex. 2001 ¶¶ 4–16
`(Dr. Williams’s qualifications); Ex. 2002 (Dr. Williams’s curriculum vitae).
` Claim Construction
`The Board interprets claims in an unexpired patent using the “broadest
`reasonable construction in light of the specification of the patent.” 37 C.F.R.
`§ 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46
`(2016). “Under a broadest reasonable interpretation, words of the claim
`must be given their plain meaning, unless such meaning is inconsistent with
`the specification and prosecution history.” Trivascular, Inc. v. Samuels,
`812 F.3d 1056, 1062 (Fed. Cir. 2016).
`Petitioner and Patent Owner propose interpretations of the claim terms
`“about,” “coat weight,” “flux,” and “therapeutically effective amount.”
`Pet. 23–28; Prelim. Resp. 25–30. For purposes of this decision, and in order
`to determine whether to institute an inter partes review, we need not
`explicitly interpret every claim term for which the parties propose a
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`construction. See 35 U.S.C. § 314(a); Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly those terms need be
`construed that are in controversy, and only to the extent necessary to resolve
`the controversy.”). We determine that, to resolve whether Petitioner has
`demonstrated a reasonable likelihood of prevailing, we need only address the
`parties’ respective proposed interpretations of “about” and “flux.”
` “about”
`Claim 1 recites “a coat weight of greater than about 10 mg/cm2,” and
`“an estradiol flux of from about 0.0125 to about 0.05 mg/cm2/day.”
`Ex. 1001, 15:55–59 (emphases added). Both Petitioner and Patent Owner
`agree that, based on the written description of the ’900 patent, the term
`“‘about’ will mean up to plus or minus 10% of a particular term.” See
`Pet. 25 (citing Ex. 1001, 4:42–52); Prelim. Resp. 26 (accord). Because the
`written description of the ’900 patent provides an express definition of that
`term, we agree with the parties and find that the broadest reasonable
`interpretation of “about” is “up to plus or minus 10% of a particular term.”
`Ex. 1001, 4:42–52; see also In re Bass, 314 F.3d 575, 577 (Fed. Cir. 2002)
`(“[T]he PTO must apply the broadest reasonable meaning to the claim
`language, taking into account any definitions presented in the
`specification.”).
`
` “flux”
`Claim 1 recites that the monolithic transdermal drug delivery system
`achieves “an estradiol flux of from about 0.0125 to about 0.05 mg/cm2/day.”
`Ex. 1001, 15:57–59 (emphasis added). The written description of the ’900
`patent refers to “flux” as both the “delivery rate” and the “permeation rate.”
`Id. at 3:40–41, 3:67–4:1, 5:24. The written description explains that flux “is
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`defined as the absorption of a drug through skin or mucosal tissue, and is
`described by Fick’s first law of diffusion:
`J= –D(dCm/dx)
`where J is the flux in g/cm2/sec, D is the diffusion coefficient of the drug
`through the skin or mucosa in cm2/sec and dCm/dx is the concentration
`gradient of the drug across the skin or mucosa.” Id. at 5:24–32.
`Petitioner recites the definition of “flux” provided in the specification,
`but also alleges that the ’900 patent is silent on how flux is measured and
`does not require the system to achieve the claimed estradiol flux “for any
`particular time [period].” Pet. 26 (citing Ex. 1002 ¶¶ 86–88). Thus,
`Petitioner alleges, “[u]nder the broadest reasonable interpretation, flux may
`include flux for any time period when the system is applied to the skin.” Id.
`at 27.
`Patent Owner also recites the same definition of “flux” provided in the
`written description, but disagrees with Petitioner that the ’900 patent fails to
`provide a method for measuring flux. Prelim. Resp. 28. Specifically, Patent
`Owner argues that the ’900 patent “illustrates in Example 1 how flux can be
`measured using human cadaver skin permeation studies, a methodology that
`was well-known and conventional.” Id. (citing Ex. 2001 ¶ 124). Patent
`Owner also argues that the Declaration of Richard H. Guy, Ph.D.—
`submitted during prosecution of the application maturing into the ’900
`patent—“provides further information on flux and how flux can be
`measured.” Id. (citing Ex. 1004, 580–581).
`Patent Owner disagrees with Petitioner that flux may relate to any
`time period. Id. at 29. Citing Dr. Williams’s Declaration, Patent Owner
`alleges that an ordinarily skilled artisan would only consider “flux values for
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`a time period once steady state or pseudo steady state is reached.” Id. (citing
`Ex. 2001 ¶ 124). Patent Owner also contends that there is an “essential need
`to account for variations in skin permeability . . . between different skin
`samples.” Id. at 29 (citing Ex. 2001 ¶ 125). An ordinarily skilled artisan
`measuring flux, Patent Owner contends, “would be aware of the impact of
`skin permeation variability on flux measurements, and would implement one
`or more well-known techniques for accounting for skin permeation
`variability, such as the use of an internal control with known flux properties,
`as reflected in Example 1 of the ’900 Patent and discussed in the Guy
`Declaration submitted during prosecution.” Id. at 29–30 (citing Ex. 2001
`¶¶ 126–127; Ex. 1004, 597–99).
`For these reasons, Patent Owner states, the broadest reasonable
`interpretation of the term “flux” “is the rate of absorption of drug through
`skin or mucosal tissue, as may be determined by in vitro human cadaver skin
`permeation studies, appropriately accounting for skin permeation
`variability,” and that the flux achieved by a transdermal delivery system
`“would be reflected by flux values for a period when the flux is at steady
`state or pseudo steady-state.” Id. at 30 (citing Ex. 2001 ¶ 126).
`We agree with the parties that the ’900 patent expressly defines “flux”
`as “the absorption of a drug through skin or mucosal tissue” as described by
`Fick’s first law of diffusion. Ex. 1001, 5:24–32. The parties’ disagreement
`centers on whether additional limitations to that definition are necessary. On
`this record, however, we discern no reason to deviate from the express
`definition set forth in the written description. Phillips v. AWH Corp., 415
`F.3d 1303, 1315 (Fed. Cir. 2005) (en banc) (stating that the specification is
`“the single best guide to the meaning of a disputed term” and “[u]sually, it is
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`dispositive” (citation omitted)). In particular, we determine that Patent
`Owner attempts to cabin the broadest reasonable interpretation of “flux” by
`adding restrictions on the testing methodology that are not found in the
`written description of the ’900 patent. Thus, we determine that flux requires
`no further construction for purposes of this decision. Vivid Techs., 200 F.3d
`at 803.
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` Asserted References
`Before turning to Petitioner’s asserted grounds of unpatentability, we
`provide a brief summary of the asserted references.
` Mueller
`Mueller relates to a “transdermal therapeutic system” (TTS) such as a
`patch, for the administration of estradiol. Ex. 1005 ¶¶ 1, 56–61. Mueller’s
`patches comprise an “active substance-containing matrix,” a backing layer,
`and a “releasable protective layer.” Id. ¶¶ 25–26. In one embodiment, the
`“active substance-containing matrix” “has a single-layer structure and is
`self-adhesive.” Id. ¶ 26. Mueller teaches increasing hydrophilic polymer
`content (e.g., polyacrylate adhesive and PVP) in the matrix layer improves
`the release of the active substance. Id. ¶ 21. “By improving the active
`substance release,” Mueller continues, “the invention enables the
`manufacture of transdermal systems which can have a smaller surface area
`due to the high active substance release rates.” Id. ¶ 22.
`Mueller provides an example of a monolithic TTS comprising silicone
`adhesives with hydrophile additives. Id. ¶¶ 56–61 (Example 3). The patch
`comprises hydroxypropyl cellulose, polyacrylate adhesive, silicone adhesive,
`Kollidon 90F (PVP), and estradiol hemihydrate. Id. ¶ 56. The final film has
`a coat weight of 115 g/m2. Id. ¶ 57. Mueller states that permeation studies
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`were conducted to compare “between samples without hydrophilic additives
`(2a) and samples with hydrophilic additives (3).” Id. ¶ 58. Mueller explains
`that these studies were performed “using Franz diffusion cells and human
`epidermis.” Id. ¶ 60. According to Mueller, Figure 3 (below) shows a
`constant release rate for TSSs of the invention for a period of at least 72
`hours, “whereas in the case of the comparison examples a marked flattening
`of the permeation profile can be seen already after 32 h[ours].” Id. ¶ 61.
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`Figure 3 provides the estradiol permeation of samples with
`hydrophilic additives (●) and without hydrophilic additives (■).
`Ex. 1005 ¶ 58.
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` Vivelle-Dot Label
`The Vivelle-Dot Label describes an estradiol transdermal patch
`comprising a backing, an adhesive layer containing estradiol, and a
`protective layer. Ex. 1006, 12–13. According to the Vivelle-Dot Label, the
`patch “provide[s] nominal in vivo delivery rates of 0.025, 0.0375, 0.05,
`0.075, or 0.1 mg of estradiol per day via the skin” and has active surface
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`areas of “2.5, 3.75, 5.0, 7.5, or 10.0 cm2,” respectively. Id. at 12. The
`Vivelle-Dot Label describes the patch as a “revised formulation with smaller
`system sizes,” which “was shown to be bioequivalent to the original
`formulation, Vivelle.” Id. at 14.
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` Kanios
`Kanios describes a transdermal delivery system “where the drug
`delivery rates, onset and profiles of at least one active agent are controlled
`by selectively manipulating the monomeric make up of an acrylic-based
`polymer in the transdermal drug delivery system.” Ex. 1007, Abstract.
`“The drug carrier composition may be comprised of (a) one or more acrylic-
`based polymers having one or more different monomers selected from the
`group consisting of hard and soft monomers; (b) one or more silicone-based
`polymers; and (c) one or more active agents . . . .” Id.
`Kanios provides examples of dermal compositions comprising, inter
`alia, acrylic-based polymer, silicone-based polymer, PVP, and estradiol.
`Id. ¶ 127 (Examples 1–3). In each example, the proportion of soft
`monomers to hard monomers in the acrylic-based polymer is varied. Id.
`Specifically, the dermal composition of Example 1 comprises 70% soft
`monomers and 30% hard monomers; the dermal composition of Example 2
`comprises 50% soft monomers and 50% hard monomers; and the dermal
`composition of Example 3 comprises 20% soft monomers and 80% hard
`monomers. Id. The average flux profile of each Example is illustrated in
`Figure 1, below. Id. ¶ 128.
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`Figure 1 provides the average flux of dermal compositions
`comprising different proportions of soft and hard acrylic-based
`monomers. Ex. 1007 ¶ 20.
`According to Kanios, “the in-vitro permeation rate for each
`transdermal drug matrix varied depending upon which acrylic polymer was
`utilized in the matrix.” Id. ¶ 135. “These results indicate that drug delivery
`rate and profile can be manipulated by modifying the acrylic monomer
`composition of the acrylic pressure sensitive adhesive in the transdermal
`drug delivery device.” Id.
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` Chien
`Chien discloses “[t]ransdermal absorption dosage units . . . for
`treatment of postmenopausal syndrome.” Ex. 1009, Abstract. The units
`“comprise a backing layer, [and] an adjoining adhesive polymer layer in
`which at least minimum effective daily doses of an estrogen is
`microdispersed.” Id. The adhesive polymer layer also comprises “one or
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`IPR2018-00174
`Patent 9,730,900 B2
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`more transdermal absorption enhancing agents.” Id. at 2:59–62. In
`Example 2, Chien describes various dermal compositions comprising
`estradiol, n-decyl alcohol (a permeation enhancer), and polyacrylate
`adhesive polymer. Id. at 11:22–12:16. The dermal compositions were made
`into patches comprising, in addition to a backing layer and a release layer, an
`adhesive layer with a permeation enhancer, a separating layer, and an
`adhesive layer containing estradiol. Id. at 11:64–12:14. In Tables 1–5,
`Chien provides the permeation rates for estradiol from various samples that
`differ in the thickness of the separating layer (Table 1), the chain length of
`the fatty alcohol (Table 2), the estradiol loading dose (Table 3), the thickness
`of the enhancer-containing upper adhesive layer (Table 4), and the
`concentration of n-decyl alcohol in the upper adhesive layer (Table 5). Id. at
`12:15–13:33.
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` Asserted Anticipation by Mueller
`Petitioner contends that Mueller anticipates claims 1, 2, 8, 10–16, and
`18–23 of the ’900 patent because Mueller “describes as part of a single
`embodiment each element of the challenged claims.” Pet. 28 (citing
`Ex. 1002 ¶ 149). A claim is anticipated and, therefore, unpatentable under
`35 U.S.C. § 102, if all of its limitations are disclosed either explicitly or
`inherently in a single prior art reference. In re Schreiber, 128 F.3d 1473,
`1477 (Fed. Cir. 1997). That single prior art reference must disclose all of the
`limitations of the claim “arranged or combined in the same way as in the
`claim.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1370 (Fed. Cir.
`2008).
`Taking claim 1 as illustrative, Petitioner argues that Mueller teaches
`the preamble (“[a] method for administering estradiol, comprising applying
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`IPR2018-00174
`Patent 9,730,900 B2
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`to the skin or mucosa of a subject in need thereof a monolithic transdermal
`drug delivery system”), by disclosing a monolithic TTS that provides for the
`constant release of estradiol through the skin. Pet. 28–29 (citing Ex. 1005
`¶¶ 1–4, 56–61; Ex. 1002 ¶¶ 150–151, 158). As to claim 1’s backing layer
`and single adhesive polymer matrix layer of adhesive polymer matrix and
`estradiol, Petitioner points out that the monolithic TTS described in
`Mueller’s Example 3 comprises (1) a self-adhesive, single-layer active
`substance matrix that contains estradiol, and (2) a backing layer. Id. at 29
`(citing Ex. 1005 ¶¶ 25, 26, 56, and 57; Ex. 1002 ¶¶ 151–156). Next, as to
`the “coat weight of greater than about 10 mg/cm2” element of claim 1,
`Petitioner asserts that Mueller describes the dried film of Example 3 as
`“having a coating weight of 115 g/m2,” which converts to 11.5 mg/cm2. Id.
`at 29–30 (citing Ex. 1005 ¶¶ 56–57; Ex. 1002 ¶ 153).
`Petitioner contends that Mueller also discloses that the TTS “includes
`greater than 0.156 mg/cm2 estradiol,” as further recited in claim 1. Pet. 30–
`31. Specifically, Petitioner reproduces a table from Dr. Brain’s Declaration
`that sets forth the initial mass (g), the mass in the dried product (g), and the
`percent total dried product (%) for each ingredient of Mueller’s Example 3
`composition. Id. (citing Ex. 1002 ¶¶ 154–157). Dr. Brain calculates the
`amount of estradiol per unit area by first calculating the percent total of
`estradiol in the final dried product (1.50 %), and then multiplying that
`percentage by the final coat weight (11.5 mg/cm2) of Mueller’s dried TTS.
`Ex. 1002 ¶¶ 156–157 (citing Ex. 1005 ¶¶ 56-57). According to Petitioner,
`“[c]oat weight multiplied by the percentage estradiol in the final dried
`product provides an estradiol dose per-unit area of 0.1725 mg/cm2, which is
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`IPR2018-00174
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`greater than 0.156 mg/cm2 estradiol,” as claimed. Id. at 31 (citing Ex. 1005
`¶¶ 56-57; Ex. 1002 ¶¶ 156–57; Ex. 1004, 126).
`Finally, as to claim limitation “and the system achieves an estradiol
`flux of from about 0.0125 to about 0.05 mg/cm2/day, based on the active
`surface area,” Petitioner contends that “results [in Mueller] show an estradiol
`flux achieved by Example 3 of 0.015 and 0.014 mg/cm2/day when measured
`at 32 and 48 hours, respectively.” Id. at 31–32. Both flux values, Petitioner
`asserts, are “well within the range recited in the claim.” Id.
`At this stage of the proceeding, Patent Owner only challenges
`Petitioner’s assertion that Mueller discloses claim 1’s estradiol flux range.
`Patent Owner argues that institution should be denied because Petitioner
`fails to show that Mueller discloses a TTS that achieves the claimed
`estradiol flux of from about 0.0125 to about 0.05 mg/cm2/day. Prelim.
`Resp. 41–48. Having reviewed the evidence and arguments, we agree with
`Patent Owner that Petitioner has not shown on this record a reasonable
`likelihood of prevailing in its assertion that claims 1, 2, 8, 10–16, and 18–23
`of the ’900 patent are anticipated by Mueller. Specifically, we agree with
`Patent Owner that Petitioner fails to show sufficiently for institution that
`Mueller teaches a TTS having the claimed estradiol flux range.
`As explained above, Mueller teaches that a permeation study was
`conducted to compare TTS samples without hydrophilic additives to TTS
`samples with hydrophilic additives. Ex. 1005 ¶ 58. Relying on Figure 3 and
`Dr. Brain’s Declaration, Petitioner asserts that the results of that study “show
`an estradiol flux achieved by Example 3 of 0.015 and 0.014 mg/cm2/day
`when measured at 32 and 48 hours, respectively.” Pet. 31. Petitioner
`provides a table summarizing “[t]he data from Figure 3 for Example 3,
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`provided in units of per hour and per day, and the flux calculated from the
`slope for each permeation data point.” Id. at 32–33. We reproduce that
`table here for ease of reference:
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`Pet. 33 (citing Ex. 1005, Fig. 3; Ex. 1002 ¶¶ 159–62, Ex. 1001, Fig. 1;
`Ex. 1004, 543–44).
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`We note that Petitioner does not provide the calculations necessary to
`calculate flux, but instead directs us to Dr. Brain’s Declaration. Id. at 32–33
`(citing Ex. 1002 ¶¶ 158–62). Dr. Brain states that flux may be calculated by
`first determining the slope at each data point, and then converting the slope
`from units of μg/cm2/hour to units of mg/cm2/day. Ex. 1002 ¶ 159. But
`Dr. Brain does not actually step us through those calculations. Nevertheless,
`both Petitioner and Dr. Brain represent that Mueller’s TTS sample with
`hydrophilic additives has a flux of 0.015 mg/cm2/day at 32 hours and 0.014
`mg/cm2/day flux at 48 hours. Pet. 33; Ex. 1002 ¶ 159.∗
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`∗ Although Petitioner and Dr. Brain do not provide the calculations, we are
`able to obtain Petitioner’s asserted flux value at 32 hours by first subtracting
`the estradiol permeation at 32 hours from that at 24 hours (16–11 = 5), and
`then dividing that number by the change in time (32–24 = 8). We then
`convert the resulting slope, 0.625 μg/cm2/hour (5/8 = 0.625) to the claimed
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`Even putting aside Petitioner’s and Dr. Brain’s failure to fully explain
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`their calculations, we agree with Patent Owner that Petitioner’s reliance on
`Mueller’s Figure 3 for teaching flux values fails to satisfy the reasonable
`likelihood standard.
`Mueller does not disclose any numerical data for the comparative
`permeation studies in the written description, but instead states that the
`results of those permeation studies “are represented in FIG. 3.” Ex. 1005
`¶ 58. Thus, Petitioner must rely on the estradiol permeation values shown
`graphically in Figure 3 to calculate flux values. Pet. 32–33 (citing Ex. 1005,
`FIG. 3). But, as Patent Owner points out and we agree, those estradiol
`permeation values cannot be reasonably ascertained from Figure 3. See
`Prelim. Resp. 42–48.
`First, Petitioner does not establish at this stage of the proceeding that
`Figure 3 provides an accurate scale for estradiol permeation because the x-
`axis and y-axis of that figure are not perpendicular to each another. The
`deficiencies of Figure 3 are readily observable to the naked eye and when
`superimposed onto a grid, as provided in Dr. Williams’s Declaration and
`reproduced below. As shown below, the intersection of the y-axis and the x-
`axis is greater than a 90 degree angle.
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`units of mg/cm2/day by dividing 0.625 by 1000 and multiplying the resulting
`number by 24 (0.625/1000 x 24). This results in the alleged flux of 0.015
`mg/cm2/day flux at 32 hours.
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`IPR2018-00174
`Patent 9,730,900 B2
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