Trials@uspto.gov
`Tel: 571-272-7822
`
`Paper 12
`Entered: May 1, 2017
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`
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`
`
`ACRUX DDS PTY LTD. & ACRUX LIMITED,
`Petitioner,
`
`v.
`KAKEN PHARMACEUTICAL CO., LTD. and VALEANT
`PHARMACEUTICALS INTERNATIONAL, INC.,
`Patent Owner.
`
`Case IPR2017-00190
`Patent 7,214,506 B2
`
`
`Before ERICA A. FRANKLIN, SUSAN L. C. MITCHELL, and
`ROBERT A. POLLOCK Administrative Patent Judges.
`
`MITCHELL, Administrative Patent Judge.
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
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`IPR2017-00190
`Patent 7,214,506 B2
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`I. INTRODUCTION
`
`A. Background
`Petitioner Acrux DDS Pty Ltd. and Acrux Limited (“Petitioner”) filed a
`Petition (Paper 1, “Pet.”) requesting an inter partes review of claims 1 and 2 (the
`“challenged claims”) of U.S. Patent No. 7,214,506 B2 (Exhibit 1001, “the ’506
`patent”). See 35 U.S.C. §§ 311–319. Patent Owner Kaken Pharmaceutical Co.,
`Ltd. and Valeant Pharmaceuticals International, Inc. (collectively, “Patent Owner”)
`filed a Preliminary Response. Paper 8 (“Prelim. Resp.”).
`We have authority to determine whether to institute an inter partes review
`
`under 35 U.S.C. § 314 and 37 C.F.R. § 42.4(a). To institute an inter partes review,
`we must determine that the information presented in the Petition shows “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). For the reasons set
`forth below, we conclude that Petitioner has established a reasonable likelihood
`that it would prevail in showing the unpatentability of each of the challenged
`claims of the ’506 patent. Therefore, we institute an inter partes review for claims
`1 and 2 of the ’506 patent on the grounds identified in the Order section of this
`Decision.
`
`B. Related Proceedings
`Both parties indicate that there are no related matters currently pending.
`Pet. 2; Paper 4, 1.
`
`C. The ’506 Patent (Ex. 1001)
`The ’506 patent involves a method for accurately evaluating an effect of an
`antimicrobial agent and a therapeutic agent for onychomycosis which can be
`obtained using this method. Ex. 1001, Abst. The ’506 patent states that an object
`of the invention “is to provide a therapeutic agent for onychomycosis which
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`exhibits the effect on tinea unguium by topical application and which is capable of
`curing tinea unguium [by a] shorter period than that of the marketed oral
`preparation due to good permeability, good retention capacity and conservation of
`high activity in nail plate as well as the potent antifungal activity thereof” and “to
`provide the effective therapeutic agent for onychomycosis exhibiting no side effect
`even if therapeutically effective amounts of it are administered sufficiently.” Id. at
`3:40–51. The ’506 patent lists KP-103 as one of the most preferred antimicrobial
`agents that can be used to cure “disease such as mycosis completely, and prevent[]
`a relapse.” Id. at 9:10–13, 30–31.
`In describing the disease to be cured, the ’506 patent describes
`onychomycosis as a superficial mycosis caused by invading and proliferating in the
`nail of a human by Trichophyton rubrum or Trichophyton mentagrophytes, and in
`rare cases, Microsporum, Epidermophyton, Candida, Aspergillus, or Fusarium. Id.
`at 9:32–39. The ’506 patent includes tinea unguium caused by the Trichophyton
`species in the definition of onychomycosis, the symptoms of which include
`“opacity, tylosis, destruction and deformation of [the] nail plate.” Id. at 2:21–25,
`9:40–43.
`The ’506 patent describes the term “nail” as including “nail plate, nail bed,
`nail matrix, further side nail wall, posterial nail wall, eponychium and
`hyponychium which make up a tissue around thereof.” Id. at 4:65–67.
`
`D. Challenged Claims
`Claim 1 is independent and claim 2 depends from claim 1. Those claims
`recite as follows.
`
`1. A method for treating a subject having onychomycosis wherein the
`method comprises topically administering to a nail of said subject
`having onychomycosis a therapeutically effective amount of an
`antifungal compound represented by the following formula:
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`wherein, Ar is a non-substituted phenyl group or a phenyl group
`substituted with 1 to 3 substituents selected from a halogen
`atom and trifluoromethyl group,
`
`
`R1 and R2 are the same or different and are hydrogen atom, C1-6 alkyl
`group, a non-substituted aryl group, an aryl group substituted
`with 1 to 3 substituents selected from a halogen atom,
`trifluoromethyl group, nitro group and C1-16 alkyl group, C2-8
`alkenyl group, C2-6 alkynyl group, or C7-12 araklyl group,
`m is 2 or 3,
`n is 1 or 2,
`X is nitrogen atom or CH, and
`*1 and *2 mean an asymmetric carbon atom.
`2.
`The method of claim 1, in which the compound represented by
`the formula (II) is (2R, 3R)-2-(2,4-difluorophenyl)-3-(4-
`methylen piperidine-1-yl)-1-(1H-1,2,4-triazole-1-yl)butane-2-
`ol.
`
`Ex. 1001, 17:33–18:32.
`
`E. The Asserted Grounds of Unpatentability
`
`Petitioner contends that the challenged claims are unpatentable based on the
`following grounds. Pet. 4.
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`References
`JP ’6391 and Ogura2
`’367 Patent3 and Ogura
`Hay4 and Ogura
`JP ’639 and Kaken Abstracts5
`’367 Patent and Kaken Abstracts
`Hay and Kaken Abstracts
`
`Basis
`§ 103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`
`Claims Challenged
`1 and 2
`1 and 2
`1 and 2
`1 and 2
`1 and 2
`1 and 2
`
`Petitioner relies also on the Declaration of Kenneth A. Walters, Ph.D.
`Pet. 6–61; see Ex. 1005 (Dr. Walters Declaration).
`
`
`1 Yoichi Ohta and Yukari Tsutsumi, Japanese Pat. App. Pub. No. 10-226639, pub.
`Aug. 25, 1998 (Ex. 1011, “JP ’639”). Petitioner asserts that JP ’639 is prior art
`under 35 U.S.C. § 102(b) because the ’506 patent is not entitled to the priority date
`of the priority document JP 11/214369. Pet. 14–22.
`2 Hironobu Ogura et al., Synthesis and Antifungal Activities of (2R,3R)-2-Aryl-1-
`azolyl-3-(substituted amino)-2-butanol Derivatives as Topical Antifungal Agents,
`47 CHEM. PHARM. BULL. 1417–25 (1999) (Ex. 1012, “Ogura”). Patent Owner is
`disputing whether Ogura is prior art based on a prior reduction to practice of the
`invention. See infra Section II.D.1.
`3 Teresa J. DeVincentis et al., U.S. Patent No. 5,391,367, issued Feb. 21, 1995 (Ex.
`1013, “’367 patent”).
`4R.J. Hay, R.M. Mackie, and Y.M. Clayton, “Tioconazole nail solution—an open
`study of its efficacy in onychomycosis,” 10 CLIN. AND EXPERIMENTAL
`DERMATOLOGY 111–15 (1985) (Ex. 1014, “Hay”).
`5 H. Ogura et al., “KP-103, a Novel Topical Antifungal Triazole: Structure-Activity
`Relationships of Azolylamine Derivatives,” ABSTRACTS OF THE 36TH ICAAC F78
`(1996); Y. Tatsumi et al., “In Vitro Activity of KP-103, a Novel Topical Antifungal
`Triazole,” ABSTRACTS OF THE 36TH ICAAC F79 (1996); Y. Tatsumi et al.,
`“Therapeutic Efficacy of KP-103, a Novel Topical Antifungal Triazole, on
`Experimental Superficial Mycosis,” ABSTRACTS OF THE 36TH ICAAC F80
`(Ex. 1015, collectively, “Kaken Abstracts”).
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`II. ANALYSIS
`
`A. Claim Interpretation
`In an inter partes review, claim terms in an unexpired patent are given their
`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 interpretation approach,
`claim terms are given their ordinary and customary meaning as would be
`understood by one of ordinary skill in the art in the context of the entire disclosure.
`In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
`Patent Owner contends that Petitioner’s failure to construe the terms
`“onychomycosis,” “nail,” or “therapeutically effective amount” as found in
`challenged claims 1 and 2 is fatal to the Petition. Prelim. Resp. 4–5, 20–22. Patent
`Owner asserts:
`Petitioner’s failure to construe the terms “nail” and
`“onychomycosis” is particularly problematic because each alleged
`ground of unpatentability relies on interpreting “nail” as including
`what it characterizes as “skin structures” surrounding the nail, and
`thus implicitly and incorrectly broadens the meaning of
`onychomycosis to include infections that may not involve the nail.
`Prelim. Resp. 4.
`Although Petitioner does not expressly construe any claim term, it does
`identify an express definition of “nail” provided by the ’506 patent upon which it
`relies. Pet. 6, 27 n.6, 44 n.10. Petitioner states that the term “nail” in the ’506
`patent is defined as “including ‘nail plate, nail bed, nail matrix, further side nail
`wall, posterial nail wall, eponychium and hyponychium which make up a tissue
`around thereof.’” Pet. 6 (quoting Ex. 1001, 4:65–67). As discussed in further
`detail below, Petitioner refers to the eponychium and hyponychium as “skin
`structures surrounding the nail.” Id. at 27 n.6, 44 n.10.
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`Petitioner also identifies several statements concerning “onychomycosis” set
`forth in the ’506 patent upon which it relies. Petitioner states:
`Onychomycosis, also referred to as tinea unguium, is one type
`of superficial mycosis affecting humans and animals. Onychomycosis
`is a disease of the nail and is characterized by symptoms such as
`opacity, tylosis (thickening), and destruction and deformation of the
`nail plate. In humans, onychomycosis is caused mainly by the
`microorganism species Trichophyton rubrum and Trichophyton
`mentagrophytes.
`Pet. 5–6 (citing Ex. 1001; Ex. 1005).
`
`Therefore, Petitioner does provide and rely on interpretations of the
`terms “nail” and “onychomycosis” as set forth in the ’506 patent itself.
`The ’506 patent expressly defines the term “nail” as including “nail
`plate, nail bed, nail matrix, further side nail wall, posterial nail wall,
`eponychium and hyponychium which make up a tissue around thereof.”
`Ex. 1001, 4:65–67. Petitioner’s declarant, Dr. Walters, states that “nail” as
`defined in the ’506 patent includes “skin structures surrounding the nail,
`including the eponychium and hyponychium.” Ex. 1005 ¶¶ 103, 113, 122,
`133, 140, 147.
`Patent Owner provides Figure 2, set forth below, that shows where the
`structures that make up the nail as defined by the ’506 patent are found.
`
`As shown in Figure 2 above and as asserted by Petitioner, at least the
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`eponychium and hyponychium, and possibly also the side nail wall and
`posterial nail wall, appear to be part of the skin of a digit. See also Ex. 2015,
`2 (showing schematic structure of the nail apparatus and stating
`hyponychium is the “skin under the free edge of the plate”); Ex. 2013, 239
`(showing diagrammatic drawing of normal nail including hyponychium).
`On the record before us, we find that when read in light of the
`Specification of the ’506 patent, the broadest reasonable construction of the
`claims term “nail” includes “nail plate, nail, bed, nail matrix, further side
`nail wall, posterial nail wall, eponychium and hyponychium which make up
`the tissue around thereof,” that includes skin structures. The fact that the
`’506 patent does not use the term “skin structures” is not dispositive as the
`Specification of the ’506 patent clearly identifies skin structures surrounding
`the nail plate, matrix, and bed, as part of the “nail.”
`Patent Owner further asserts that “even assuming that eponychium
`and hyponychium qualify as ‘skin structures,’ Petitioner’s argument still
`fails because it provides no support for any construction of the term
`‘onychomycosis’ as including infections of just the eponychium and/or
`hyponychium.” Prelim. Resp. 22. This argument lacks merit on the record
`before us because the challenged claims require treating onychomycosis by
`“topically administering to a nail of said subject having onychomycosis a
`therapeutically effective amount of an antifungal compound . . . .” Ex. 1001,
`17:33–18:2. As just discussed, “nail” includes many structures and is not
`limited to the nail plate, matrix, or bed, or the surrounding structures, but
`includes all of them. Also, “onychomycosis” is defined in the ’506 as a kind
`of superficial mycosis, “which is caused by invading and proliferating in the
`nail of human or an animal.” Id. at 9:32–35 (emphasis added).
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`Patent Owner also asserts that “[p]articularly egregious is Petitioner’s
`lack of any explanation as to what constitutes a ‘therapeutically effective
`amount’ of an antifungal agent in the context of onychomycosis, in light of
`the repeated failures of prior topical or even oral treatments to achieve a
`therapeutic effect.” Prelim. Resp. 21. Although the Specification of the
`’506 patent does not expressly define “therapeutically effective amount” as
`it does for “nail” and “onychomycosis,” Petitioner does provide citations to
`references where it alleges a “therapeutically effective amount” is taught.
`See Pet. 22–23, 28–29, 30–31, 34, 35–36, 38–39, 41, 45, 47, 49, 51, 53–54.
`On this record, we find this sufficient to satisfy the requirement to construe
`the claims under Rule 42.204(b)(c).
`
`B. Principles of Law
`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the claimed subject matter 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 said subject matter pertains. KSR
`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). The 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 ordinary skill in the art; and (4) objective evidence
`of nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`In that regard, an obviousness analysis “need not seek out precise teachings
`directed to the specific subject matter of the challenged claim, for a court can take
`account of the inferences and creative steps that a person of ordinary skill in the art
`would employ.” KSR, 550 U.S. at 418; see Translogic, 504 F.3d at 1259. In KSR,
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`the Supreme Court also 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).
`We analyze the asserted grounds of unpatentability in accordance with the
`above-stated principles.
`
`C. Level of Ordinary Skill
`Petitioner and Patent Owner disagree about the breadth of the level of
`ordinary skill in the art. Petitioner states that the level of skill in the art at the time
`of the invention is a person who “would have had familiarity with the biology and
`pathology of common fungal agents that infect the nail and skin, and a familiarity
`with antifungal agents and their clinical use.” Pet. 21. Petitioner also states such a
`person would have had “(i) a bachelor’s or master’s degree in medicinal chemistry,
`biochemistry, pharmacology, and/or biology, and at least 3-5 years of experience
`working with topical antifungal agents, or (ii) a M.D., Pharm.D., or Ph.D. in
`medicinal chemistry, biochemistry, pharmacology, and/or biology and at
`least 1 year of experience working with topical antifungal agents.” Id.
`Patent Owner asserts that the proper field of art for the challenged claims
`should be treatment of fungal infections of the nail alone, because there “is little if
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`any overlap between treatments indicated for fungal infections of the nail and
`treatments for infections of the skin.” Prelim. Resp. 23.
`We are mindful that the level of ordinary skill in the art is reflected by the
`prior art of record. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir.
`2001); In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995). The art asserted
`against the claims in the Petition shows the overlap between treatment of fungal
`infections of skin and nails. See Ex. 1011 (testing antifungal agent on skin and
`hoof wall); Ex. 101 (describing use of KP-103 on skin). Also, the ’506 patent
`defines nail in such a way as to include the skin structures surrounding the nail
`plate, matrix, and bed. See supra Section II.A. Therefore, based on the record
`before us, we apply Petitioner’s stated level of skill set forth above that
`encompasses the field of treatment of fungal infections of nails and skin.
`
`D. Obviousness over the Ogura with JP ’639, the ’367 patent, or Hay
`Petitioner presents three challenges to claims 1 and 2 of the ’506 patent
`based on Ogura with either JP ’639, the ’367 patent, or Hay. As support, Petitioner
`provides detailed explanations as to how each claim limitation is met by the
`references and rationales for combining the references as well as detailed claim
`charts and a declaration of Dr. Walters (Ex. 1005). Pet. 21–40.
`Patent Owner asserts that Petitioner fails to show a reasonable likelihood of
`success that these claims are unpatentable as obvious over these combinations.
`Prelim. Resp. 43–48.
`We have reviewed the parties’ contentions and supporting evidence. Given
`the evidence on this record, especially in light of the breadth of the definition of
`“nail” as used in the challenged claims, we determine that Petitioner has shown a
`reasonable likelihood of prevailing on its assertion that claims 1 and 2 are
`unpatentable as obvious over the combination of Ogura with either JP ’639, the
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`’367 patent, or Hay. Our analysis here focuses on the deficiencies in Patent
`Owner’s arguments in its Preliminary Response as to the claims.
`
`1. Ogura as Prior Art
`As an initial matter, Patent Owner asserts that any challenge to the claims
`based on Ogura should be denied because the invention was reduced to practice
`before Ogura was allegedly published. Prelim. Resp. 17–19. Patent Owner
`presents a May 1999 Report (Ex. 2004) in which it alleges is disclosed results from
`a method for treating a guinea pig by topically administering to the nail a
`therapeutically effective amount of KP-103. Id. at 18. Thus, Patent Owner
`concludes “the inventors had performed a method by May 1999 that met all
`limitations of claims 1 and 2,” and worked for its intended purpose. Id. Patent
`Owner also provides a supporting declaration from inventor Dr. Yoshiyuki
`Tatsumi. Id. at 18–19; Ex. 2003.
`Petitioner has not yet been afforded an opportunity to test the sufficiency of
`Patent Owner’s evidence of a prior reduction to practice. We find that such a
`dispute is best resolved during trial when we are able to assess Petitioner’s and
`Patent Owner’s evidence and arguments upon review of the entire record when
`both parties are afforded an opportunity to challenge the sufficiency of their
`opponent’s case.
`
`2. Ogura (Ex. 1012)
`Ogura studied azolylamine derivatives in an effort to develop “new topical
`antifungal agents with broad spectrum, strong in vitro antifungal activity and
`excellent therapeutic efficacy.” Ex. 1012, 1417.6 Ogura examined the in vitro
`
`
`6 In citing to exhibits, we will refer to the page numbers of the exhibit as opposed
`to those assigned by the party submitting the exhibit.
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`activities of these azolylamine derivatives as compared to the activity of
`clotrimazole against Candida albicans, Cryptococcus neoformans, Aspergillus
`fumigatus, and Trichophyton mentagrophytes as measured by minimum inhibitory
`concentrations (“MIC”). Id. at 1420.
`Ogura could not determine a candidate to pursue based only on MIC values,
`and “next examined the effects of keratin (human hair) on anti-T. mentagrophytes
`activity.” Id. Ogura noted that “[i]n general, the activities of most topical
`antifungal agents are greatly reduced by adsorption to keratin, which is a major
`constituent of the keratinized tissue where fungi reside.” Id. Ogura made the
`following findings.
`The anti-T. mentagrophytes activities of the reference drugs
`clotrimazole and neticonazole were markedly reduced (32-fold) by
`addition of human hair, but the activities of methylenepiperidine
`derivaties (33, 34, 40, 41) were less affected (2––8-fold). . . . .
`Furthermore, we found that the imidazole derivatives (32, 41) were
`more markedly deactivated than corresponding triazole derivatives
`(31, 40). These results indicated that 4-methylenepiperidino triazole
`derivative (40) had low affinity to keratin and could retain a high level
`of activity in the keratinized tissue.
`
`Id.
`To further examine the differences between the imidazole and triazole
`
`derivatives including KP-103, Ogura evaluated their therapeutic efficacy in a
`guinea pig model of Tinea corporis infection. Id. Ogura found that
`
`Triazole derivative (( – )-40) [KP-103] showed high efficacy against
`Tinea corporis both days after infection [day 3 and 4]. On the other
`hand, imidazole derivative (( – )-41) showed high efficacy on day 3
`postinfection but the efficacy was extremely low on day 4
`postinfection. These results suggested that triazole derivative
`(( – )-40) showed better penetration into the hair follicles than
`imidazole derivative (( – )-41) and the triazole group in ( – )-40 was
`necessary for its property. We confirmed that ( – )-40 penetrates
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`easily into the skin by the transfollicular route in addition to
`transepidermal route form the distribution pattern in the skin of guinea
`pigs 24 h after application of the 1% 14C-labelled drug (data not
`shown). Lipophilic compounds generally penetrate well into the skin
`through both the epidermis and hair follicles.
`Id. at 1420–21. Ogura concluded that “the triazole derivative (( – )-40, KP-103),
`which had a 4-methylenepiperidine moiety, was found to have a broad antifungal
`spectrum and showed excellent therapeutic efficacy. The excellent efficacy may
`be attributable to good penetration and low reduction of the activity in the skin in
`addition to its antifungal activity.” Id. at 1421.
`
`3. JP ’639 (Ex. 1011)
`JP ’639 describes a film forming antifungal agent composition that has
`“excellent releasability of the antifungal agent and high penetrability to the
`keratinous layers and is effective in treatment of trichophytosis, especially, tinea
`unguium.” Ex. 1011, Abst. Specifically, JP ’639 states that
`the inventors of the present invention found that, by using a film
`forming compound having a tertiary amine and adjusting the pH value
`of the composition to a pH range wherein the film forming compound
`can be dissolved or partially dissolved, it is possible to obtain
`unexpectedly good film formability and, thus, obtain a film forming
`antifungal agent composition, which has no stickiness after drying
`without being attached to a contact object, is excellent in adhesiveness
`to nails and, further, has high penetrability of the antifungal agent to
`keratin compared with the case wherein the pH value is not adjusted
`to the above described pH range.
`Id. at ¶ 23.
`
`JP ’639 teaches that the antifungal agent preferably is amorolfine
`hydrochloride because it has an extremely high water solubility in an acidic
`region and is thus compatible with the pH-dependency of the film forming
`compound. Id. at ¶ 18. JP ’639 describes testing the penetrability to keratin
`of the antifungal agent in its film on the skin removed from the back of an
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`8-week-old male hairless mouse, see id. at ¶ 37, and testing the penetrability
`to nails using the hoof wall of a pig foot, see id. at ¶ 50. In evaluating its
`film, JP ’639 concludes that “it is possible to effectively treat trichophytosis,
`especially, tinea unguium.” Id. at ¶ 73.
`
`4. The ’367 Patent (Ex. 1013)
`The ’367 patent teaches a topical solution for fungal infections of the nails,
`or onychomycosis. Ex. 1013, 1:5–6. The ’367 patent states “[o]nychomycosis,
`also called ringworm of nails, or tinea unguium, is a fungus infection of the nails
`causing thickening, roughness and splitting usually caused by Trichophyton
`rubrum or Trichophyton mentagrophytes.” Id. at 1:9–12.
`The topical solution as described in the ’367 patent comprises an effective
`amount of the antifungal tioconazole, water, an alcohol, and a gel-forming agent,
`so that when the topical solution is applied to the nails of a human infected with
`onychomycosis, it creates a reservoir from which tioconazole continuously
`penetrates the nail. Id. at 1:44–52. The ’367 patent concludes that “[i]t has now
`been found by in vitro microbiological tests that a topical tioconazole formulation
`is effective in the treatment of onychomycosis.” Id. at 2:27–29.
`
`5. Hay (Ex. 1014)
`Hay involves an open study of the efficacy of a 28% tioconazole nail
`solution as the sole treatment for onychomycosis caused by Trichophyton rubrum,
`Hendersonula toruloidea, and Acremonium. Ex. 1014, 111–12. Hay describes the
`compound as a solution which can be applied to infected nails daily. Id. at 112.
`Hay concludes that “[i]n some patients it is possible to obtain clinical and
`mycological cures in onychomycosis using topical therapy alone. This is of
`potential value to patients because the use of prolonged administration of
`systemically active drugs is thus avoided.” Id. at 115.
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`
`6. Analysis
`Petitioner relies on JP ’639, the ’367 patent, and Hay for teaching “a method
`for treating a subject having onychomycosis wherein the method comprises
`topically administering to a nail of said subject having onychomycosis a
`therapeutically effective amount of an antifungal compound.” Pet. 22–23, 30–31,
`35–36. Petitioner relies on Ogura to teach KP-103 as an antifungal compound
`falling within the scope of the claims. Id. at 24, 31, 36.
`Petitioner asserts that a “person of ordinary skill in the art would have been
`motivated to improve the compositions and topical application method of JP ’639
`using potent azole antifungal compounds that are effective against the
`microorganisms that cause onychomycosis and that are not inactivated by keratin.”
`Pet. 26. Petitioner specifically relies on the broad definition of “nail” set forth in
`the ’506 patent to assert that “Ogura demonstrates that KP-103 is therapeutically
`effective in treating T. mentagrophytes infections of the skin in vivo. Therefore, a
`person of ordinary skill in the art would have been motivated to apply KP-103 to
`treat T. mentagrophytes infections of the nail as nail is broadly defined in the ’506
`patent.” Id. at 27 n.6. Petitioner concludes that “a person of ordinary skill in the
`art would have selected KP-103 to use in the compositions and topical application
`method of JP ’639 for effective treatment of a subject having onychomycosis of the
`nail” with a reasonable expectation of success because Ogura taught that KP-103
`was a highly potent antifungal agent that would not be inhibited by keratin when
`applied to the nail. Id. at 27–28, 32–33 (describing combination with ’367 patent),
`36–39 (describing combination with Hay); see Proctor & Gamble Co. v. Teva
`Pharms. USA, Inc., 566 F.3d 989, 994 (Fed Cir. 2009) (stating may show
`obviousness of a claim by showing “that a skilled artisan would have been
`motivated to combine the teachings of the prior art references to achieve the
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`claimed invention, and that the skilled artisan would have had a reasonable
`expectation of success from doing so” (quoting Pfizer, Inc. v. Apotex, Inc., 480
`F.3d 1348, 1361 (Fed. Cir. 2007))).
`Patent Owner’s response relies on a more narrow definition of “nail” to
`exclude skin structures. For instance, Patent Owner asserts that the Petitioner
`provides insufficient evidence to explain why a POSA would have combined
`Ogura with any of the “nail lacquer” references, JP ’639, the ’367 patent, or Hay,
`because “Petitioner does not provide evidentiary support for why a POSA would
`find motivation from Ogura’s in vitro results or in vivo skin test against T.
`mentagrophytes.” Prelim. Resp. 44. Patent Owner also states “[t]he thrust of
`Ogura was development of antifungal agents for infections of the skin. Ogura’s
`discussion of hair is also in the context of treating skin—skin contains hair
`follicles; nails do not.” Id. at 46 (citation omitted). Patent Owner also points out
`that “Dr. Walters fails to address how the significant structural differences between
`hair and nail would impact a POSA’s interpretation of the Ogura testing and to
`explain why a POSA would not be deterred from using KP-103 in nail.” Id. at 47.
`As we have found for purposes of this decision, “nail” as defined by the ’506
`patent and as used in the claims includes skin structures. Therefore, Patent
`Owner’s arguments relying on a distinction between skin and nails do not persuade
`us that Petitioner has not established a reasonable likelihood of prevailing in
`showing that the challenged claims would have been obvious.
`Patent Owner also relies on secondary considerations to support the
`nonobviousness of the challenged claims. Prelim. Resp. 48–49. Specifically,
`Patent Owner points to a long-felt need for a topical antifungal for treating
`onychomycosis, that researchers were met by decades of failed attempts, and the
`inventors of the ’506 patent found that KP-103 was unexpectedly and
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`unpredictably able to effectively treat onychomycosis. Id. at 49. Patent Owner
`also points to Jublia’s success on the market. Id. Petitioner counters that any
`evidence of unexpected results or alleged commercial success does not overcome
`the strong evidence of obviousness. Pet. 55–56.
`The issue of secondary considerations is highly fact-specific. At this stage of
`the proceeding, the record regarding such secondary considerations is incomplete,
`and Petitioner has not had the ability to fully respond to the specific arguments
`raised by Patent Owner in the Preliminary Response. Our final decision will
`consider the parties’ full record of secondary considerations evidence developed
`during trial as part of our obviousness analysis, as appropriate.
`For the foregoing reasons, we determine that Petitioner has demonstrated a
`reasonable likelihood of prevailing on its assertion that claims 1 and 2 are
`unpatentable over the combinations of Ogura with JP ’639, the ‘367 patent, or Hay.
`
`E. Obviousness over Kaken Abstracts with JP ’639, the ’367 patent, or Hay
`Petitioner presents three challenges to claims 1 and 2 of the ’506 patent
`based on the Kaken Abstracts with either JP ’639, the ’367 patent, or Hay. As
`support, Petitioner provides detailed explanations as to how each claim limitation
`is met by the references and rationales for combining the references as well as
`detailed claim charts and a declaration of Dr. Walters (Ex. 1005). Pet. 40–55.
`Patent Owner asserts that Petitioner fails to show a reasonable likelihood of
`success that these claims are unpatentable as obvious over these combinations.
`Prelim. Resp. 30–43.
`We have reviewed the parties’ contentions and supporting evidence. Given
`the evidence on this record, especially in lig