`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`COALITION FOR AFFORDABLE DRUGS X LLC,
`Petitioner,
`v.
`ANACOR PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`Case IPR2015-01780
`Patent 7,767,657 B2
`
`
`
`Before GRACE KARAFFA OBERMANN and MICHAEL P. TIERNEY,
`Vice Chief Administrative Patent Judges, and TINA E. HULSE,
`Administrative Patent Judge.
`
`TIERNEY, Vice Chief Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`Inter Partes Review
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
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`MYLAN - Ex. 1017, p. 1
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`I.
`
`INTRODUCTION
`Coalition for Affordable Drugs X, LLC (“Petitioner”), filed a Petition
`requesting an inter partes review of claims 1–24 of U.S. Patent 7,767,657
`B2 (Ex. 1001, “the ’657 patent”). Paper 3 (“Pet.”). Patent Owner, Anacor
`Pharmaceuticals Inc. (“Patent Owner”), filed a Preliminary Response.
`Papers 7 and 17 (“Prelim. Resp.”). We determined that there was a
`reasonable likelihood that Petitioner would prevail in challenging those
`claims as unpatentable. Pursuant to 35 U.S.C. § 314, we authorized an inter
`partes review to be instituted on February 23, 2016. Paper 24 (“Dec. on
`Inst.”).
`After institution, Patent Owner filed a Patent Owner Response. Paper
`32 (“PO Resp.”). Petitioner filed a Reply. Paper 47 (“Reply”). Patent
`Owner filed Motions for Observations Regarding the Cross-Examination
`Testimony of Stephen B. Kahl, Ph.D. (Paper 55) and S. Narasimha Murthy,
`Ph.D. (Paper 56), and Petitioner filed Responses (Papers 61 and 62,
`respectively). With Board authorization, Patent Owner filed an
`Identification of New Arguments and Evidence in Petitioner’s Reply (Paper
`53), and Petitioner filed a Response (Paper 60).1 Patent Owner also filed a
`Motion to Exclude Evidence (Paper 57), Petitioner filed a Response (Paper
`63), and Patent Owner filed a Reply (Paper 65).
`
`1 We do not find the arguments identified by Patent Owner to be
`impermissible new arguments and evidence in the Reply. Rather, we
`determine that the arguments were each in response to those set forth by
`Patent Owner in its Response, for the reasons stated by Petitioner. Paper 60,
`1–3; see 37 C.F.R. § 42.23(b) (“A reply may only respond to arguments
`raised in the corresponding . . . patent owner response.”).
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`MYLAN - Ex. 1017, p. 2
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`An oral hearing was held on November 3, 2016. A transcript of the
`hearing has been entered into the record of the proceedings as Paper 69
`(“Tr.”).
`We have jurisdiction under 35 U.S.C. § 6. This Final Written
`Decision is issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73.
`For the reasons that follow, we determine that Petitioner has shown by a
`preponderance of the evidence that claims 1–24 are unpatentable.
`
`A. Related Proceeding
`The claims of the ’657 patent have been challenged in related inter
`partes review proceeding IPR2015-01785. Additionally, the ’657 patent
`claims to be a continuation-in-part of U.S. Patent 7,582,621, which is
`involved in inter partes review IPR2015-01776. Pet. 4.
`
`B. The ’657 Patent
`The ’657 patent is titled “Boron-Containing Small Molecules.” Ex.
`1001. The ’657 patent describes compounds useful for treating fungal
`infections, in particular, for topical treatment of onychomycosis and/or
`cutaneous fungal infections. Id. at Abstract. The compounds are said to
`have physiochemical properties that help facilitate the penetration of the nail
`plate. Id.
`The ’657 patent describes pharmaceutical formulations that include a
`pharmaceutically acceptable excipient and a compound of said invention.
`Id. at 139:35–37. According to the ’657 patent “Summary of the Invention,”
`said invention provides a structure that is described as having the following
`formula:
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`MYLAN - Ex. 1017, p. 3
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`in which R1 and R2 are members independently selected from
`H, substituted or unsubstituted alkyl, substituted or
`unsubstituted heteroalkyl, substituted or unsubstituted
`cycloalkyl, substituted or unsubstituted heterocycloalkyl,
`substituted or unsubstituted aryl, and substituted or
`unsubstituted heteroaryl. R1 and R2, together with the atoms to
`which they are attached, can be optionally joined to form a 4- to
`7-membered ring. Z1 is a member selected from
`
`
`
`
`R3a and R4a are members independently selected from H,
`cyano, substituted or unsubstituted alkyl, substituted or
`unsubstituted heteroalkyl, substituted or unsubstituted
`cycloalkyl, substituted or unsubstituted heterocycloalkyl,
`substituted or unsubstituted aryl, and substituted or
`unsubstituted heteroaryl. R5 is a member selected from halogen
`and OR8. R8 is a member selected from H, substituted or
`unsubstituted alkyl, substituted or unsubstituted heteroalkyl,
`substituted or unsubstituted cycloalkyl, substituted or
`unsubstituted heterocycloalkyl, substituted or unsubstituted
`aryl, and substituted or unsubstituted heteroaryl. A is a member
`selected from CR9a and N. D is a member selected from CR10a
`and N. E is a member selected from CR11a and N. G is a
`member selected from CR12a and N. R9a, R10a, R11a and
`R12a are members independently selected from H, OR*,
`NR*R**, SR*, —S(O)R*, —S(O)2R*, —S(O)2NR*R**, nitro,
`halogen, cyano, substituted or unsubstituted alkyl, substituted
`or unsubstituted heteroalkyl, substituted or unsubstituted
`cycloalkyl, substituted or unsubstituted heterocycloalkyl,
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`MYLAN - Ex. 1017, p. 4
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`substituted or unsubstituted aryl, and substituted or
`unsubstituted heteroaryl. Each R* and R** are members
`independently selected from H, substituted or unsubstituted
`alkyl, substituted or unsubstituted heteroalkyl, substituted or
`unsubstituted cycloalkyl, substituted or unsubstituted
`heterocycloalkyl, substituted or unsubstituted aryl, and
`substituted or unsubstituted heteroaryl. R9a and R10a, along
`with the atoms to which they are attached, are optionally joined
`to form a ring. R10a and R11a, along with the atoms to which
`they are attached, are optionally joined to form a ring. R11a and
`R12a, along with the atoms to which they are attached, are
`optionally joined to form a ring. The combination of nitrogens
`(A+D+E+G) is an integer selected from 0 to 3.
`
`
`Id. at 4:6–5:2. Example 4.2.j identifies the compound 1,3-dihydro-5-
`fluoro-1-hydroxy-2,1-benzoxaborole as “C10,” which has the
`following structure:
`
`
`Id. at 180:20–27. The ’657 patent provides several examples
`describing the antifungal activity of compound C10 and its ability to
`penetrate human nails. Id. at 189:15–196:46.
`The ’657 patent states that preferred compounds will have desirable
`pharmacological properties, including oral bioavailability, low toxicity, low
`serum binding, and desirable in vitro and in vivo half-lives. Id. at 165:66–
`166:2. According to the ’657 patent, “[a]ssays may be used to predict these
`desirable pharmacological properties.” Id. at 166:6–7. For example,
`“[t]oxicity to cultured hepatocyctes may be used to predict compound
`toxicity.” Id. at 166:9–10.
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`MYLAN - Ex. 1017, p. 5
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`C. Illustrative Claim
`The ’657 patent contains twenty-four claims, all of which are
`challenged by Petitioner. All twenty-four claims are directed to a
`pharmaceutical formulation. Claim 1 is the sole independent claim.
`Claim 1 is illustrative of the challenged claims and is reproduced
`below:
`1. A pharmaceutical formulation, comprising:
`(a) 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a salt
`thereof; and
`(b) a pharmaceutically acceptable excipient
`wherein said pharmaceutical formulation is for topical
`administration to an animal suffering from an infection by a
`microorganism.
`
`
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`D. Prior Art Relied Upon
`Petitioner relies upon the following prior art:
`
`U.S. 6,143,794 Chaudhuri Nov. 4, 2000
`U.S. 6,224,887 Samour
` May 1, 2001
`U.S. 7,074,392 Friedman
` Jul. 11, 2006
`U.S. 5,498,407 Atlas
`
`
`Mar. 12, 1996
`U.S. 3,816,472 Shapiro
`
`
`June 11, 1974
`US 2002/0165121 A1 Brehove
`Nov. 7, 2002
`WO 95/33754 Austin
`
`
`Dec. 14, 1995
`
`(Ex. 1004)
`(Ex. 1005)
`(Ex. 1006)
`(Ex. 1007)
`(Ex. 1008)
`(Ex. 1003)
`(Ex. 1002)
`
`Petitioner contends that the challenged claims are unpatentable under
`
`35 U.S.C. § 103 based on the following specific grounds (Pet. 21–60):
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`MYLAN - Ex. 1017, p. 6
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`References
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`Austin and Brehove
`
`Austin, Brehove, and Chaudhuri
`Austin, Brehove, and Samour
`Austin, Brehove, Friedman, and Atlas
`Austin, Brehove, Friedman, and Samour
`Austin, Brehove, and Shapiro
`
`Basis Claim(s) challenged
`
`§ 103
`
`§ 103
`§ 103
`§ 103
`§ 103
`§ 103
`
`1–5, 10–16, and 18–
`24
`6
`7
`8
`9
`17
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`Level of Ordinary Skill in the Art
`E.
`Factors that may be considered in determining the level of
`ordinary skill in the art include, but are not limited to, the types of
`problems encountered in the art, the sophistication of the technology,
`and the educational level of active workers in the field. In a given
`case, one or more factors may predominate. In re GPAC, 57 F.3d
`1573, 1579 (Fed. Cir. 1995). Here, the challenged claims are directed
`to pharmaceutical compositions for topical administration to an
`animal suffering from an infection by a microorganism that
`comprise1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole and a
`pharmaceutically acceptable excipient. The ’657 patent provides
`examples of lacquer and solvent formulations, and states that “the
`preparation of these formulations is well known in the art.” Ex. 1001,
`188:25–50.
`Petitioner contends that a person of ordinary skill in the art
`“would have an advanced degree (Master’s or Ph.D.) or equivalent
`experience in chemistry, pharmacology, or biochemistry, and at least
`two years of experience with the research, development or production
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`MYLAN - Ex. 1017, p. 7
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`of pharmaceuticals.” Pet. 22 (citing Ex. 1009 ¶¶ 20–22, Ex. 1011
`¶¶ 35–37). Patent Owner argues that Petitioner’s proposed definition
`“excludes necessary expertise in mycology and in clinical
`dermatology.” PO Resp. 20. According to Patent Owner, a person of
`ordinary skill in the art “would have needed knowledge and
`experience in several areas,” including “medicinal chemistry; the
`development of potential drug candidates suitable for treating
`onychomycosis; and in assessing, together with others, the toxicology,
`pharmacology, and clinical utility of such candidates, including
`parameters relating to transungual penetration.” Id. (citing Ex. 2034
`¶ 108).
`Based on the record presented, we hold that the cited prior art is
`representative of the level of ordinary skill in the art. See Okajima v.
`Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001). The cited prior art
`is consistent with Petitioner’s broader description of the level of
`ordinary skill in the art. We are not persuaded that additional
`experience in mycology, clinical dermatology, medicinal chemistry,
`the development of drug candidates for treating onychomycosis, and
`the assessment of the toxicology, pharmacology, and clinical utility of
`drug candidates is required, as Patent Owner suggests, as it is unclear
`as to why the claimed subject matter is beyond the abilities of
`someone that has Petitioner’s proposed qualifications.
`
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`MYLAN - Ex. 1017, p. 8
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`II. ANALYSIS
`
`A.
`Claim Interpretation
`In an inter partes review, the Board interprets claim terms in an
`unexpired patent according to the broadest reasonable construction in light
`of the specification of the patent in which they appear. 37 C.F.R. § 100(b);
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016). Under
`that standard, and absent any special definitions, we give claim terms their
`ordinary and customary meaning, as would be understood by one of ordinary
`skill in the art at the time of the invention. See In re Translogic Tech., Inc.,
`504 F.3d 1249, 1257 (Fed. Cir. 2007).
`For purposes of the Decision on Institution, we interpreted the claim
`term “1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole” to include “5-
`fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole” and “tavaborole.” Dec.
`on Inst. 9. The parties do not dispute this interpretation, and we see no
`reason to modify it in light of the record developed at trial. Accordingly, for
`ease of reference, we refer to the claimed compound as “tavaborole” in this
`Final Written Decision.
`Patent Owner contends that the claim term “wherein said
`pharmaceutical formulation is for topical administration to an animal
`suffering from an infection by a microorganism” should be construed to
`mean that the formulation must be suitable for administration to an animal
`suffering from the type of infection recited in a given claim. PO Resp. 23.
`We agree with Patent Owner’s construction that certain challenged claims,
`for example, claims 18, 20 and 22, are directed compositions where the
`composition is suitable for use in topical administration of specific
`infections.
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`MYLAN - Ex. 1017, p. 9
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`Based on our review of the complete record, and the claim
`construction arguments raised by the parties, for purposes of this Final
`Written Decision we determine that it is unnecessary to construe explicitly
`any other claim terms. See Wellman, Inc. v. Eastman Chem. Co., 642 F.3d
`1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only be construed ‘to the
`extent necessary to resolve the controversy.’”) (quoting Vivid Techs., Inc. v.
`Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
`
`
`Expert Qualifications to Testify as to the
`B.
`Knowledge of One of Ordinary Skill in the Art
`
`In support of the Petition, Petitioner submitted the Declarations of
`Stephen Kahl, Ph.D. (Ex. 1009 and Ex. 1069) and S. Narasimha Murthy,
`Ph.D. (Ex. 1011 and Ex. 1070). Patent Owner asserts that “there are huge
`holes in the expertise of Petitioner’s declarations,” in particular, that
`Dr. Murthy is not a chemist, and neither Dr. Kahl nor Dr. Murthy is a
`mycologist. PO Resp. 21–22. Patent Owner’s argument is based on its
`contention that a person of ordinary skill in the art “would have needed
`knowledge and experience in several areas,” including “medicinal
`chemistry; the development of potential drug candidates suitable for treating
`onychomycosis; and in assessing, together with others, the toxicology,
`pharmacology, and clinical utility of such candidates, including parameters
`relating to transungual penetration.” Id. at 20.
`As set forth above, we are not persuaded that the additional
`qualifications enumerated by Patent Owner are necessary, and determined
`that the level of ordinary skill in the art is reflected by the cited prior art.
`Dr. Murthy has a Ph.D. in pharmaceutics, has been an assistant professor of
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`MYLAN - Ex. 1017, p. 10
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`pharmaceutics at various universities, and has received research grants
`relating to the topical administration of therapeutics, including ungual
`delivery, which has resulted in 85 publications in peer-reviewed journals.
`Ex. 1011 ¶¶ 4–8; Ex. 1012; Ex. 1070 ¶¶ 6–9. We also note that, although
`Dr. Murthy acknowledges that he is “not a synthetic chemist by profession,”
`he does have “extensive course work in the fields of organic chemistry,
`physical chemistry, medicinal chemistry and pharmaceuticals.” Ex. 1070
`¶ 10. Dr. Kahl has a Ph.D. in chemistry, is a professor in the department of
`pharmaceutical chemistry at the University of California, San Francisco, has
`served as an ad hoc reviewer for 20 journals, and has conducted research
`related to bioactive boron molecules that are specifically targeted to
`biological systems, which has resulted in over 65 publications in books and
`peer-reviewed journals. Ex. 1009 ¶¶ 4–8; Ex. 1010. Based on the facts in
`this record, we determine that Drs. Murthy and Kahl are qualified to testify
`as to the knowledge of a person of ordinary skill in the art in this proceeding.
`
`Section 103 Obviousness Challenge
`C.
`Petitioner contends that the challenged claims represent a combination
`of known prior art elements (tavaborole and topical formulations), used for
`their known purpose (antifungal treatment and topical delivery formulation)
`to achieve a predictable result (treat or inhibit the growth of fungus in an
`animal). Pet. 21–60. In support of its contentions, Petitioner relies on the
`Declarations of Dr. Kahl and Dr. Murthy. Id. Patent Owner disagrees with
`Petitioner’s contentions, and relies on the Declarations of Paul J. Reider,
`Ph.D. (Ex. 2034), Mahmoud A. Ghannoum, Ph.D., E.M.B.A. (Ex. 2035),
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`MYLAN - Ex. 1017, p. 11
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`Majella Lane, Ph.D. (Ex. 2036), and Howard I. Maibach, M.D., Ph.D.
`(Ex. 2037). PO Resp. 28–64.
`
`
`1. Background on Obviousness
`A claimed invention is not patentable under 35 U.S.C. § 103 if it is
`obvious. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 427 (2007). In
`Graham v. John Deere, Co., the Supreme Court established the factors
`underlying an obviousness inquiry:
`Under § 103, the scope and content of the prior art are to be
`determined; differences between the prior art and the claims at
`issue are to be ascertained; and the level of ordinary skill in the
`pertinent art resolved. Against this background, the
`obviousness or nonobviousness of the subject matter is
`determined.
`
`
`383 U.S. 1, 17 (1966). In addressing the findings of fact, “[t]he combination
`of familiar elements according to known methods is likely to be obvious
`when it does no more than yield predictable results.” KSR, 550 U.S. at 416.
`As explained in KSR:
`If a person of ordinary skill can implement a predictable
`variation, § 103 likely bars its patentability. For the same reason,
`if a technique has been used to improve one device, and a person
`of ordinary skill in the art would recognize that it would improve
`similar devices in the same way, using the technique is obvious
`unless its actual application is beyond his or her skill.
`Id. at 417. Accordingly, a central question in analyzing obviousness is
`“whether the improvement is more than the predictable use of prior art
`elements according to their established functions.” Id.
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`MYLAN - Ex. 1017, p. 12
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`2. Scope and Content of the Prior Art
`a. Austin
`Austin relates to the use of oxaboroles as industrial biocides, and
`especially as fungicides for the protection of plastic materials. Ex. 1002,
`Abstract. The Abstract states that “[p]referred compounds are 5- and 6-
`fluoro or bromo-1,3-dihydro-1-hydroxy-2,1-benzoxaborole including O-
`esters thereof.” Id. Austin notes that it has been found that compounds
`containing an oxaborole ring are “particularly effective against micro-
`organisms such as bacteria, algae, yeasts and particularly fungi, especially
`fungi which cause degradation of plastics materials.” Id. at 1:35–38.
`Austin tested three compounds falling within the scope of its preferred
`5- and 6-fluoro or bromo-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles,
`including tavaborole. Specifically, Austin discloses tavaborole as Example
`64, along with the results of a study showing tavaborole has effective
`antifungal activity against five different fungi: Aspergillus niger,
`Aureobasidium pullulans, Candida albicans, Gliocladium roseum, and
`Penicillium pinophylum. Id. at 37 (Table 9). Of the three preferred
`compounds tested, tavaborole demonstrated the lowest Minimum Inhibitory
`Concentration (“MIC”) values against several pathogens, including Candida
`albicans. Id. In other words, tavaborole inhibited the visible growth of
`Candida albicans at the lowest level of concentration of the three preferred
`compounds tested. Ex. 1009 ¶ 35.
`Austin teaches that its compounds may be used with water-miscible
`organic solvents such as ethanol or glycols, including propylene glycol.
`Ex. 1002, 6:34–37. According to Austin, the concentration of the oxaborale
`in its biocide composition may range from 10 to 20% by weight relative to
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`MYLAN - Ex. 1017, p. 13
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`the total weight of the biocide composition, which for tavaborole an ethanol
`solution would be 7.9%–15.8% w/v. Ex. 1011 ¶¶ 167–169.
`
`
`b. Brehove
`Brehove relates to the topical treatment of nail infections such as
`onychomycosis caused by bacteria, fungi, and other pathogens. Ex. 1003
`¶ 3. Brehove explains that onychomycosis is a nail disease typically caused
`by Candida albicans, Trichophyton mentagrophytes, Trichophyton rubrum,
`or Epidermpophyton floccusum. Id. ¶ 5. Brehove states that Candida
`albicans is the most common pathogen causing onychomycosis. Id. ¶ 18.
`Brehove teaches that to be effective for onychomycosis, the topical
`treatment should exhibit a powerful potency for pathogens, be permeable
`through the nail barrier, and be safe for patient use. Id. ¶ 6. According to
`Brehove, “[t]here exists a need in the art for a topical application that
`combines these traits in high degree.” Id.
`Brehove states that the “safety and non-toxicity of organo-boron
`compounds has been questioned.” Id. ¶ 13. On the one hand, Brehove
`describes one reference that states that boron compounds are “very toxic,”
`and may be considered an industrial poison. Id. ¶ 14. On the other hand,
`Brehove describes references that found the toxicity of a certain boron-
`containing compound to be “very low,” and a boron containing antifungal
`fuel additive called Biobor JF, when combined with naptha, is said to cause
`“mild irritation.” Id. ¶¶ 14–15 and 23.
`Biobor JF contains a combination of 2,2’-(1-methyltrimethylene
`dioxy) bis-(4-methyl-1, 3, 2-dioxaborinane) (referred to by Brehove as “S1”)
`and 2,2’-oxybis (4, 4, 6-trimethyl-1, 3, 2-dioxaborinane) (referred to by
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`MYLAN - Ex. 1017, p. 14
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`Brehove as “S2”). Ex. 1003 ¶¶ 15, 30. Brehove describes the results of both
`in vitro testing of the antifungal activity of S1 and S2 against C. albicans
`and in vivo treatment of patients with onychomycosis using S1 and S2. Id.
`¶¶ 30–38.
`
`Brehove describes several topical treatment formulations including
`one that is applied nightly in a petroleum jelly or mineral oil base and
`another formulation that is applied once per week in a cellulose acetate
`lacquer base. Id. ¶ 18. Brehove teaches that its active ingredient may be
`used in combination with penetration enhancers to increase the permeability
`of the skin to a drug. Id. ¶ 27. According to Brehove, its formulations
`achieve efficacy in treating onychomycosis without skin irritation or
`noticeable side effects. Id. ¶ 18. For example, Brehove states that a male
`volunteer with onychomycosis on both feet applies the solution to his entire
`toenail and 250 days later, the nail is fully-grown and completely free of
`infection with no skin irritation observed. Id. ¶ 35.
`
`
`c. Chaudhuri
`Chaudhuri is directed to topical formulations for treating nail fungal
`diseases. Ex. 1004. Chaudhuri states that treating onychomycosis can be
`difficult and that it would be advantageous to have a topical formulation
`capable of penetrating the nail barrier and treating nail fungal diseases. Id.
`at 1:55–65. Chaudhuri states that suitable solvents for its composition
`include lower alkanols, such as ethanol, and dihydroxyalcohols, such as
`propylene glycol. Id. at 6:2–7. In particular, Chaudhuri provides an
`example containing 5–20% weight propylene glycol, 20–80% weight
`ethanol, and 0.5 to 15% weight antifungal. Id. at 8:57–9:10, Table B. One
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`MYLAN - Ex. 1017, p. 15
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`skilled in the art would have understood Chaudhuri’s Table B proportions as
`equating to a ratio of 1:4 propylene glycol to ethanol and 1:10 weight per
`volume of antifungal. Ex. 1011, ¶¶ 100, 193.
`
`
`d. Samour
`Samour describes a nail lacquer formulation that is effective for the
`treatment or prevention of fungal infections, such as onychomycosis.
`Samour’s nail lacquer formulation incorporates an antifungal agent and,
`when applied to nails, yields a hard, durable, substantially clear, long-lasting
`film that is effective in treating fungal infestations associated with nails.
`Ex. 1005, 3:5–13. Samour teaches that an effective amount of active
`antifungal agent preferably ranges from 1 to 10% by weight of the
`composition. Id. at 12:9–14. Suitable film-forming polymers for the
`composition include acrylic polymers such as Gantrez ES-425 (poly(vinyl
`methyl ether-alt-maleic acid monobutyl ester)). Id. at 7:54–62; Ex. 1011
`¶¶ 103, 208; Ex. 1035, 5. Samour teaches that an effective amount of film-
`forming polymer is preferably 15 to about 50%, and especially from 20 to
`40% by weight of composition. Id. at 8:38–44; Ex. 1011 ¶¶ 103, 208.
`Samour exemplifies a number of lacquer formulations including a
`formulation having 71% ethanol, 24% film-forming polymer and 5%
`antifungal. Ex. 1005, 9:31–49, 22:20–36.
`
`
`e. Friedman
`Friedman describes a topical sustained release composition for
`delivery of antifungal agents to nails. Friedman describes a number of
`methacrylic polymers for use as a film-forming polymer and describes
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`MYLAN - Ex. 1017, p. 16
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`plasticizers, such as dibutyl sebacate, with a preferable weight ratio of
`plasticizer to polymer of about 0.4:1 to about 0.3:1. Ex. 1006, 5:51–64.
`Friedman teaches that a suitable solvent includes ethanol, preferably about
`60 to 90% w/w of the composition. Id. at 6:1–9. Dr. Murthy testifies that
`60% to about 90% w/w ethanol corresponds to 47.4% to about 71.1% w/v
`ethanol. Ex. 1011 ¶ 225 n.8.
`
`
`f. Atlas
`Atlas describes the use of hydrogel polymers as excellent carriers for
`the release of drugs. Ex. 1007, 1:5–14. Atlas states that poly(2-
`hydroxyethyl methacrylate) (“P-HEMA”) was the most widely used
`hydrogel. Id. at Abstract. Atlas teaches that the P-HEMA hollow fibers act
`as a reservoir and matrix for diffusion-controlled delivery to skin and nails.
`Id. at 2:58–64. Atlas Example 4 describes a cosmetic nail polish
`composition having P-HEMA. Id. at 3:57–4:7.
`
`
`g. Shapiro
`Shapiro describes antifungal compounds for treating fungal infections.
`Ex. 1008, 1:15–16. Shapiro teaches that its antifungal compounds are
`effective against fungi including Trichophyton rubrum, Trichophyton
`mentagrophytes, Trichophyton verrucosum, and Microsporum gypseum. Id.
`at 2:3–14.
`
`
`
`3. Austin and Brehove: Claims 1–5, 10–16 and 18–24
`Petitioner contends that Austin teaches tavaborole “as a preferred
`fungicide” that “has significant antifungal activity against Candida albicans
`
`MYLAN - Ex. 1017, p. 17
`
`
`
`(CA), a fungus often associated with onychomycosis, at the lowest
`concentration tested (5 parts per million).” Pet. 30. Petitioner notes that
`Austin “identifies a number of organic solvents to form solvates with”
`tavaborole, including ethanol and polyethylene glycol. Id. Petitioner further
`contends that Brehove teaches “the topical application of boron compounds
`to ‘treat and prevent the spread of nail infections or onychomycosis caused
`by bacteria, fungi and other pathogens.’” Id. (quoting Ex. 1003 ¶ 3).
`Petitioner notes that Brehove states that onychomycosis typically is caused
`by Candida albicans, Trichophyton mentagrophytes, and Trichophyton
`rubrum, and that “boron-based topical formulations have ‘powerful potency
`against Candida albicans . . . effectively kill[ing] the most common
`pathogen causing onychomycosis.’” Id. at 30–31 (quoting Ex. 1003 ¶ 18).
`Petitioner also contends that Brehove describes boron-based topical
`formulations that effectively cure onychomycosis without skin irritation and
`apparent side effects. Id. at 31.
`Petitioner contends that a person of ordinary skill in the art “would
`have had several reasons to combine” Austin and Brehove “with a
`reasonable expectation of success.” Pet. 32. According to Petitioner, both
`Austin and Brehove “teach the use of boron-based compounds as
`fungicides,” both also “disclose the use of boron-based compounds to
`specifically inhibit Candida albicans,” and Austin describes “the claimed
`boron-based compound having a lower molecular weight than the successful
`compounds” described in Brehove, which is “more likely to effectively
`penetrate the nail barrier in similar topical formulations.” Id. at 32–33.
`Petitioner contends that a person of ordinary skill in the art “seeking to
`develop a therapeutic treatment for onychomycosis before February 2005
`
`MYLAN - Ex. 1017, p. 18
`
`
`
`would have understood that boron compounds were effective fungicides
`safely applied to humans,” and “would have also understood from Brehove
`that boron-based industrial fungicides had successfully treated
`onychomycosis with little skin irritation or side effects.” Id. at 33.
`Petitioner also contends that a person of ordinary skill in the art “would have
`expected that 5-fluoro benzoxaborole, which shares similar structural
`features with the compounds of Brehove, would likely share similar
`functional features.” Id. at 34.
`Patent Owner makes three main arguments in response: (1) Austin is
`not analogous art to the ’657 patent; (2) a person of ordinary skill in the art
`would not have been motivated to combine Austin and Brehove; and (3) the
`combination of Austin and Brehove does not disclose every element of the
`challenged claims. We address each in turn below.
`
`
`a. Whether Austin is Analogous Art
`Patent Owner argues that Austin is not analogous art because it is
`neither from the same field of endeavor nor reasonably pertinent to the
`problem solved by the ’657 patent. PO Resp. 28–34. The test for
`determining whether a prior art reference constitutes analogous art to the
`claimed invention is whether the prior art is from the same field of endeavor,
`regardless of the problem addressed, or, if the reference is not from the same
`field of endeavor, whether the reference still is reasonably pertinent to the
`particular problem with which the inventor is involved. In re Bigio, 381
`F.3d 1320, 1325 (Fed. Cir. 2004). “A reference is reasonably pertinent if . . .
`it is one which, because of the matter with which it deals, logically would
`have commended itself to an inventor’s attention in considering his
`
`MYLAN - Ex. 1017, p. 19
`
`
`
`problem.” Innovation Toys, LLC v. MGA Entm’t, Inc., 637 F.3d 1314, 1321
`(Fed. Cir. 2011). The scope of analogous art is to be construed broadly,
`because “familiar items may have obvious uses beyond their primary
`purposes, and a person of ordinary skill often will be able to fit the teachings
`of multiple patents together like pieces of a puzzle.” Wyers v. Master Lock
`Co., 616 F.3d 1231, 1238 (Fed. Cir. 2010) (quoting KSR, 550 U.S. at 398).
`Patent Owner contends that Austin is not reasonably pertinent to the
`problem solved by the ’657 patent because “[m]edicinal chemists would not
`look to industrial biocides for pharmaceutical leads.” PO Resp. 32. Patent
`Owner argues that a person of ordinary skill in the art “would have
`understood that the requirements for a useful biocide are different from the
`requirements for a useful drug,” and “would have sought out compounds
`with at least low in vivo toxicity, high in vivo activity against medically
`relevant targets, corresponding high selectivity, and chemical and metabolic
`stability.” Id. at 32–33. According to Patent Owner, a person of ordinary
`skill in the art reading Austin would have learned “that these characteristics
`are not relevant to an industrial biocide.” Id. at 33.
`Based upon our review of the complete record, we find that Austin is
`reasonably pertinent to the problems the inventors of the ’657 patent sought
`to solve. Both the inventors and Austin sought to inhibit microorganisms,
`including Candida albicans. Ex. 1001, 128:13–129:28; Ex. 1002, 33:7–
`38:2. Further, as noted by Petitioner, a person of ordinary skill in the art
`would have recognized that industrial fungicides may have therapeutic uses,
`including in some cases, topically treating a human for Candida albicans.
`Pet. 18–20; Ex. 1024 ¶¶ 14–15, 23, 30–38; Ex. 1025, 2:9–15, 3:12–16, 6:45–
`50; Ex. 1026, 1:18–26, 13:32–48; Ex. 1027, 1:25-40, 3:73–4:36; Ex. 1028,
`
`MYLAN - Ex. 1017, p. 20
`
`
`
`12:52–54, 16:63–17:46; Ex. 1029, Abstract, 15:12–16:16. For example,
`Pfiffner2 describes its antifungal compounds as suitable for combating fungi
`in agriculture and horticulture but also as suitable for use in ointments where
`the active compound completely prevented the growth of Candida albicans
`in vitro. Ex. 1028, 12:52–54, 17:9-46. As another example, Grier describes
`its compounds as suitable for the treatment of fungal infections caused by
`Candida albicans and T. rubrum, as well as for industrial applications, such
`as mildew-proofing paint. Ex. 1026, 1:18–
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