`
`
`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 IPR2015-01776
`Patent 7,582,621 B2
`____________
`
`
`Before GRACE KARAFFA OBERMANN and MICHAEL P. TIERNEY,
`Vice Chief Administrative Patent Judges, and TINA E. HULSE,
`Administrative Patent Judge.
`
`
`
`HULSE, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`
`
`
`FlatWing Ex. 1014, p. 1
`
`

`

`
`INTRODUCTION
`
`Coalition for Affordable Drugs X LLC (“Petitioner”) filed a Petition
`requesting an inter partes review of claims 1–12 of U.S. Patent No.
`7,582,621 B2 (Ex. 1001, “the ’621 patent”). Paper 1 (“Pet.”). Anacor
`Pharmaceuticals, Inc. (“Patent Owner”) filed a Preliminary Response to the
`Petition. Paper 17 (“Prelim. Resp.”).
`On February 23, 2016, we instituted an inter partes review of claims
`1–12 of the ’621 patent on two grounds of obviousness. Paper 24 (“Dec.
`Inst.”), 15. Patent Owner filed a Response to the Petition. Paper 32 (“PO
`Resp.”). Petitioner filed a Reply to Patent Owner’s Response. Paper 47
`(“Pet. Reply”).
`Patent Owner filed a motion to exclude certain exhibits. Paper 57.
`Petitioner filed an opposition (Paper 63) and Patent Owner filed a reply
`(Paper 65). Pursuant to authorization from the Board, Patent Owner also
`filed an Identification of New Arguments and Evidence in Petitioner’s Reply
`(Paper 53) and Petitioner filed a response (Paper 60).1
`Patent Owner filed observations on the cross-examinations of
`Petitioner’s declarants, Stephen B. Kahl, Ph.D. (Paper 55) and S. Narasimha
`Murthy, Ph.D. (Paper 56). Petitioner filed responses to Patent Owner’s
`observations. Paper 61 (Kahl); Paper 62 (Murthy).
`
`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; 37 C.F.R. § 42.23(b) (“A reply may only respond to arguments raised
`in the corresponding opposition or patent owner response.”).
`
`FlatWing Ex. 1014, p. 2
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`

`

`An oral hearing was held on November 3, 2016, a transcript of which
`has been entered in the record. Paper 69 (“Tr.”).
`We have jurisdiction under 35 U.S.C. § 6(c). 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 1–12 of the ’521 patent are
`unpatentable.
`
`Related Proceedings
`A.
`Petitioner has filed concurrently two other petitions for inter partes
`review of the claims of related U.S. Patent No. 7,767,657 B2 in IPR2015-
`01780 and IPR2015-01785. Pet. 5.
`The ’621 Patent
`B.
`The ’621 patent relates to boron-containing compounds useful for
`treating fungal infections, including infections of the nail and hoof known as
`ungual and/or periungual infections. Ex. 1001, Abstract, 1:12–13. One type
`of ungual and/or periungual fungal infection is onychomycosis. Id. at 1:15–
`17. According to the Specification, current treatment for ungual and/or
`periungual infections generally falls into three categories: systemic
`administration of medicine; surgical removal of the nail or hoof followed by
`topical treatment of the exposed tissue; or topical application of medicine
`with bandages to keep the medication in place on the nail or hoof. Id. at
`1:17–24.
`Each of the approaches have major drawbacks. Systemic
`administration of medicine typically requires long-term, high-dose therapy,
`which can have significant adverse effects on, for example, the liver and
`testosterone levels. Id. at 1:28–45. Surgical treatment is painful and
`undesirable cosmetically (or not realistic for animals such as horses). Id. at
`
`FlatWing Ex. 1014, p. 3
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`

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`1:46–52. And topical dosage forms cannot keep the drug in contact with the
`infected area for therapeutically effective periods of time. Moreover,
`because of the composition of the nail, topical therapy for fungal infections
`have generally been ineffective. Id. at 1:53–2:11. Accordingly, the
`Specification states that “there is a need in the art for compounds which can
`effectively penetrate the nail. There is also need in the art for compounds
`which can effectively treat ungual and/or periungual infections.” Id. at
`2:36–39.
`The ’621 patent claims a method of treating an infection using 1,3-
`dihydro-5-fluoro-l-hydroxy-2, 1-benzoxaborole, which is referred to as
`either compound 1 (see id. at 32:10–17) or compound C10 (see id. at 51:55–
`61) in the Specification, and has the following chemical structure:
`
`
`
`
`
`Illustrative Claim
`C.
`Petitioner challenges claims 1–12 of the ’621 patent. Claim 1 is
`illustrative and is reproduced below:
`1. A method of treating an infection in an animal, said method
`comprising administering to the animal a therapeutically
`effective amount of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-
`benzoxaborole, or a pharmaceutically acceptable salt thereof,
`sufficient to treat said infection.
`Claims 2–4 and 10 depend directly or indirectly from claim 1 and further
`recite specific infections that are treated with the claimed method. Claims 5
`and 7 depend from claim 1 and further recite specific animals that are treated,
`
`FlatWing Ex. 1014, p. 4
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`

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`including humans. Claims 8 and 9 depend from claim 1 and further recite the
`site of administration of the drug. And claims 11 and 12 are independent
`claims that are similar to claim 1, but recite a method of treating
`onychomycosis in a human (claim 11) and a method of inhibiting growth of a
`fungus in a human (claim 12).
`
`D. Grounds of Unpatentability Instituted for Trial
`We instituted trial based on the following grounds of unpatentability:
`References
`Basis
`Claim(s) challenged
`Austin2 and Brehove3
`§ 103
`1–12
`
`Austin and Freeman4
`
`§ 103
`
`1–12
`
`
`
`ANALYSIS
`
`Person of Ordinary Skill in the Art
`A.
`The level of ordinary skill in the art is a factual determination that
`provides a primary guarantee of objectivity in an obviousness analysis. Al-
`Site Corp. v. VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966) and Ryko Mfg. Co. v.
`Nu-Star, Inc., 950 F.2d 714, 718 (Fed. Cir. 1991)).
`Petitioner asserts that a person of ordinary skill in the art at the time
`the ’621 patent was filed would have had 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 of pharmaceuticals. Pet. 23 (citing Ex. 1006
`
`2 Austin et al., WO 95/33754, published Dec. 14, 1995 (Ex. 1002).
`3 Brehove, US 2002/0165121 A1, published Nov. 7, 2002 (Ex. 1003).
`4 Freeman et al., WO 03/009689 A1, published Feb. 6, 2003 (Ex. 1004).
`
`FlatWing Ex. 1014, p. 5
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`¶ 21; Ex. 1008 ¶ 34). Patent Owner asserts that a person of ordinary skill in
`the art would have “needed knowledge and experience in several areas:
`medicinal chemistry; the development of potential drug candidates suitable
`for treating onychomyosis; and in assessing, together with others, the
`toxicology, pharmacology, and clinical utility of such candidates, including
`parameters relating to transungual penetration.” PO Resp. 21–22 (citing Ex.
`2034 ¶ 108). Patent Owner further asserts that Petitioner’s definition is
`incorrect because it excludes “necessary expertise in mycology and in
`clinical dermatology.” Id. at 22.
`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) (explaining that specific
`findings regarding ordinary skill level are not required “where the prior art
`itself reflects an appropriate level and a need for testimony is not shown”)
`(quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158,
`163 (Fed. Cir. 1985)). 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.
`Claim Construction
`B.
`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);
`
`FlatWing Ex. 1014, p. 6
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`

`

`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016)
`(affirming applicability of broadest reasonable construction standard to inter
`partes review proceedings). 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). Any special definitions for claim terms must be set forth with
`reasonable clarity, deliberateness, and precision. See In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994).
`In our Decision to Institute, we determined that the broadest
`reasonable interpretation of 1,3-dihydro-5-fluoro-1-hydroxy-2,1-
`benzoxaborole includes “5-fluoro-1,3-dihydro-1-hydroxy-2,1-
`benzoxaborole” and “tavaborole.” Dec. Inst. 6. Neither party contested this
`construction during trial. Accordingly, because nothing in the full record
`developed during trial persuades us to deviate from our prior construction,
`we adopt the construction for purposes of this Decision. For ease of
`reference, we refer to the claimed compound as “tavaborole” in this
`Decision.
`
`“therapeutically effective amount”
`1.
`Each of the claims of the ’621 patent recites administering a
`“therapeutically effective amount of tavaborole.” According to Petitioner,
`“therapeutically effective amount” means “an amount of the claimed
`compound needed to reach the desired therapeutic result.” Pet. 12. Patent
`Owner asserts the claim phrase should be construed as expressly defined in
`the ’621 patent specification: “‘therapeutically effective’ amount refers to
`the amount of drug needed to effect the desired therapeutic result.” PO
`Resp. 25; Ex. 1001, 9:57–58.
`
`FlatWing Ex. 1014, p. 7
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`Because the ’621 patent specification defines the phrase with clarity,
`deliberateness, and precision, we determine the broadest reasonable
`interpretation of “therapeutically effective amount” is “the amount of drug
`needed to effect the desired therapeutic result.” See In re Paulsen, 30 F.3d
`at 1480.
`
`Credibility of Petitioner’s Experts
`C.
`As an initial matter, Patent Owner contends that we should not credit
`the testimony of Petitioner’s declarants because they are not qualified to
`opine from the perspective of a person of ordinary skill in the art. PO Resp.
`21–24. For the reasons that follow, we are not persuaded.
`Petitioner relies on the testimony of two declarants: S. Narasimha
`Murthy, Ph.D. and Stephen Kahl, Ph.D. Both Dr. Murthy and Dr. Kahl
`provide their background and experience in their respective declarations,
`along with a curriculum vitae, which provides further detail regarding each
`declarant’s experience. Ex. 1008 (Murthy) ¶¶ 4–8; Ex. 1009 (Murthy CV);
`Ex. 1006 (Kahl) ¶¶ 4–8; Ex. 1007 (Kahl CV). For example, Dr. Murthy has
`a Ph.D. in pharmaceutics, has been an assistant professor of pharmaceutics
`at various universities, and has received research grants relating to the
`topical administration of therapeutics, including ungual nail delivery, which
`has resulted in 85 publications in peer-reviewed journals. Ex. 1008 ¶¶ 4–8.
`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. 1006 ¶¶ 4–8. Based on these qualifications, we
`
`FlatWing Ex. 1014, p. 8
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`determine that the Drs. Murthy and Kahl are competent to opine on the
`matters in this proceeding.
`Patent Owner contends that there are “huge holes” in the expertise of
`Petitioner’s declarants. PO Resp. 23. For example, Patent Owner argues
`that Dr. Murthy’s testimony should be disregarded because he allegedly
`conceded he is not a chemist. Id. We are persuaded by Dr. Murthy’s
`testimony in response that, although he is not a synthetic chemist by
`profession, he is an expert in pharmaceutics with extensive coursework in
`various fields of chemistry. Ex. 1044 ¶ 10. Patent Owner also argues that
`neither declarant is a mycologist or has expertise in treating patients. PO
`Resp. 23. As explained above, we do not agree with Patent Owner’s
`argument that a person of ordinary skill in the art is required to have
`expertise in mycology or clinical dermatology.
`Thus, we are not persuaded by Patent Owner’s argument that we
`should uphold the challenged claims because Petitioners’ declarants are not
`qualified to opine from the perspective of a person of ordinary skill in the art
`in this proceeding. Id. at 24.
`Principles of Law
`D.
`To prevail in this inter partes review of the challenged claims,
`Petitioner must prove unpatentability by a preponderance of the evidence.
`35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d).
`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 the
`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
`
`FlatWing Ex. 1014, p. 9
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`factual determinations, including: (1) the scope and content of the prior art;
`(2) any differences between the claimed subject matter and the prior art;
`(3) the level of skill in the art; and (4) objective evidence of nonobviousness.
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`“[A] patent composed of several elements is not proved obvious
`merely by demonstrating that each of its elements was, independently,
`known in the prior art.” KSR, 550 U.S. at 418. “[I]t can be important to
`identify a reason that would have prompted a person of ordinary skill in the
`relevant field to combine elements in the way the claimed new invention
`does.” Id. Moreover, a person of ordinary skill in the art must have had a
`reasonable expectation of success of doing so. PAR Pharm., Inc. v. TWi
`Pharms., Inc., 773 F.3d 1186, 1193 (Fed. Cir. 2014).
`We analyze the instituted grounds of unpatentability in accordance
`with the above-stated principles.
`E. Obviousness over Austin and Brehove
`Petitioner asserts that claims 1–12 are unpatentable as obvious over
`Austin and Brehove. Pet. 23–42. Petitioner relies on the Declarations of
`Stephen Kahl, Ph.D (Ex. 1006) and S. Narasimha Murthy, Ph.D. (Ex. 1008).
`Patent Owner opposes Petitioner’s assertion, relying on the Declarations of
`Paul J. Reider, Ph.D. (Ex. 2034), Mahmoud A. Ghannoum, Ph.D., E.M.B.A.
`(Ex. 2035), Majella Lane, Ph.D. (Ex. 2036), and Howard I. Maibach, M.D.,
`Ph.D. (Ex. 2037). PO Resp. 35–54. Based on the full trial record, we
`determine that Petitioner has established by a preponderance of the evidence
`that claims 1–12 are unpatentable as obvious over Austin and Brehove.
`Austin (Ex. 1002)
`1.
`Austin relates to the use of oxaboroles as industrial biocides, and
`especially as fungicides for the protection of plastic materials. Ex. 1002,
`
`FlatWing Ex. 1014, p. 10
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`

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`Abstract. The Abstract further 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.
`Along with a number of different preferred oxaboroles, Austin
`discloses tavaborole as Example 64, as well as the results of a study showing
`tavaborole has effective antifungal activity against five different fungi:
`Aspergillus niger, Aureobasidium pullulans, Candida albicans (“C.
`albicans”), Gliocladium roseum, and Penicillium pinophylum. Id. at 37
`(Table 9).
`
`Brehove (Ex. 1003)
`2.
`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 C. albicans, Trichophyton mentagrophytes, Trichophyton rubrum (“T.
`rubrum”), or Epidermpophyton floccusum. Id. ¶ 5. Brehove states that C.
`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,”
`
`FlatWing Ex. 1014, p. 11
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`

`

`while on the other hand, Brehove describes references that found the toxicity
`of a certain boron-containing compound to be “very low” and another
`industrial fungicide compound called Biobor® JF to cause “mild irritation.”
`Id. ¶¶ 14–15.
`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
`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.
`
`Analysis
`3.
`a. Whether Austin Is Analogous Art
`Patent Owner first argues that Petitioner’s arguments fail because
`Austin is not analogous art. PO Resp. 27–32. Prior art is analogous if it
`either (1) “is from the same field of endeavor, regardless of the problem
`addressed,” or (2) “is reasonably pertinent to the particular problem with
`which the inventor is involved.” Unwired Planet, LLC v. Google Inc., 841
`F.3d 995, 1000 (Fed. Cir. 2016) (quoting In re Clay, 966 F.2d 656, 658–59
`(Fed. Cir. 1992)). “A reference is reasonably pertinent if, even though it
`may be in a different field from that of the inventor’s endeavor, 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 problem.” In
`re ICON Health & Fitness, Inc., 496 F.3d 1374, 1380–81 (Fed. Cir. 2007).
`Patent Owner argues that medicinal chemists would not look to
`industrial biocides for pharmaceutical leads because the requirements for a
`useful biocide are different from the requirements for a useful drug. PO
`
`FlatWing Ex. 1014, p. 12
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`Resp. 31 (citing Ex. 2034 ¶¶ 121–126). Patent Owner further asserts that a
`person of ordinary skill in the art would have sought out compounds with at
`least low in vivo toxicity, high in vivo activity against medicinally relevant
`targets, high selectivity, and chemical and metabolic stability. Id.
`Accordingly, Patent Owner contends that a person of ordinary skill in the art
`“would have learned from Austin that these characteristics are not relevant to
`an industrial biocide.” Id. We are not persuaded.
`Based on our review of the complete record, we find that Austin is
`reasonably pertinent to the particular problem the inventors sought to solve.
`Both the inventors and Austin sought to inhibit microorganisms, including
`C. albicans. Ex. 1001, 25:5–55; 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 C. albicans. Pet. 15–17; see, e.g., Ex. 1003
`¶¶ 14–15, 23, 30–38; Ex. 1021, 2:9–15, 3:12–16, 6:45–50; Ex. 1022, 1:18–
`26, 13:32–48; Ex. 1023, 1:25–40, 3:73–4:36; Ex. 1026, 12:52–54, 16:63–
`17:46; Ex. 1029, Abstract, 15:12–16:16. For example, Pfiffner5 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 C. albicans in vitro.
`Ex. 1026, 12:52–54, 17:9-46. As another example, Grier describes its
`compounds as suitable for the treatment of fungal infections caused by C.
`albicans and T. rubrum, as well as for industrial applications, such as
`mildew-proofing paint. Ex. 1022, 1:18–26, 13:32–48, 17:38–18:45.
`
`5 Albert Pfiffner, US 4,202,894, issued May 13, 1980 (Ex. 1026).
`
`FlatWing Ex. 1014, p. 13
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`Moreover, Brehove describes the topical use of an industrial
`fungicide, BioBor, to treat onychomycosis “without skin irritation or
`noticeable side effects.” Ex. 1003 ¶ 24; Ex. 1044 ¶¶ 50, 52. Brehove also
`notes that the materials safety data sheet of BioBor states, “Skin Contact:
`May cause slight to mild irritation. Prolonged or repeated contact may dry
`the skin and lead to irritation (i.e. dermatitis).” Id. ¶ 15. Patent Owner and
`its declarant assert that Brehove mischaracterizes the dangers associated
`with contacting the skin with BioBor based on the product label and other
`warnings in the safety data sheet to wear protective clothing and clean the
`skin if contact occurs. PO Resp. 32; Ex. 2034 ¶ 155. We do not find those
`other warnings identified by Dr. Reider to be inconsistent with or to
`outweigh the warning stated in Brehove that BioBor may cause skin
`irritation.
`Thus, based on the record presented, we find that Austin logically
`would have commended itself to the problem facing the inventors of the
`’657 patent. See Scientific Plastic Products, Inc. v. Biotage AB, 766 F.3d
`1355 (Fed. Cir. 2014); see also In re ICON Health, 496 F.3d at 1379–80
`(holding that reference may be reasonably pertinent as analogous art where
`the matter it deals with logically would have commended itself to the
`inventor’s attention).6
`
`6 Petitioner points to a paper published in 2006 by the inventors of the ’657
`patent that published “their ‘discovery’ of a ‘new’ boron-containing
`compound (tavaborole) for the treatment of onychomycosis,” and “also
`reported on the synthesis of benzoxaborole derivatives, including the 7-
`fluoro derivative,” which was synthesized using a scheme disclosed in
`Austin. Reply 11–12 (citing Ex. 2157, 3, 6). Petitioner argues that the
`inventors’ citation to Austin as a reference relied upon during the drug
`discovery process “prov[es] that a [person of ordinary skill in the art] would
`
`FlatWing Ex. 1014, p. 14
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`Independent Claims
`b.
`Petitioner provides a claim chart identifying where each limitation is
`taught in the cited references. Pet. 38–42. We have considered the claim
`chart and find that the combination of Austin and Brehove teaches each
`limitation of independent claims 1, 11, and 12. For example, regarding
`claim 1, Brehove teaches a method of treating an infection in an animal by
`disclosing that the invention relates to the treatment of human fingernails
`and toenails to cure or prevent the spread of nail infections such as
`onychomycosis, caused by bacteria, fungi and other pathogens. Ex. 1003
`¶ 3. Brehove also teaches administering a therapeutically effective amount
`of a pharmaceutical composition to the toenail of a patient suffering from
`onychomycosis in an amount sufficient to treat the infection. Id. ¶ 35.
`Finally, Austin teaches that tavaborole is effective against C. albicans. Ex.
`1002, Abstract, 37 (Example 64).
`Patent Owner argues that there is no basis to conclude that a person of
`ordinary skill in the art would have selected tavaborole from among the
`millions of compounds disclosed in Austin. PO Resp. 33–35. As Petitioner
`notes, however, Austin discloses tavaborole (i.e., 5-fluoro benzoxaborole) as
`a preferred fungicide. Pet. 27 (citing Ex. 1002, Abstract); Ex. 1006 ¶ 34;
`Ex. 1008 ¶ 61. Moreover, of the preferred compounds tested, tavaborole
`demonstrated the lowest Minimum Inhibitory Concentration (“MIC”) tested
`
`find Austin directly relevant, and at minimum, analogous art.” Id. at 11.
`Additionally, the examiner of the ’621 patent application “also
`independently identified Austin in 2008 and rejected the pending claims over
`Austin.” Id. at 12. Although we do not rely on the inventors’ citation to
`Austin or the examiner’s rejection over Austin in finding that Austin is
`analogous art, we note that both facts are consistent with our finding.
`
`FlatWing Ex. 1014, p. 15
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`(5 ppm) against several pathogens, including C. albicans. Pet. 28; Ex. 1002,
`37 (Table 9, Example 64); Ex. 1006 ¶ 34; Ex. 1008 ¶ 63. That is, tavaborole
`inhibited the growth of C. albicans—which is a cause of onychomycosis—at
`the lowest level of concentration. Ex. 1008 ¶¶ 63–64. Accordingly,
`evaluating Austin for all that it teaches, we determine that one of ordinary
`skill in the art would have recognized that tavaborole is a preferred fungicide
`for effectively inhibiting C. albicans, which causes onychomycosis.
`Patent Owner contends that Petitioner’s argument is flawed because
`Austin describes tens of thousands of structures as “preferred” and
`“particularly preferred,” including the O-esters of 5- and 6-fluoro or bromo-
`1,3-dihydro-1-hydroxy-2,1-benzoxaborole. PO Resp. 33–34 (citing Ex.
`2034 ¶¶ 114, 148, 150); Ex. 1002, Abstract. Patent Owner also asserts that a
`person of ordinary skill in the art would not select tavaborole among the
`many disclosed compounds given that Table 8 identifies numerous
`benzoxaborole O-esters with the same MIC of 5 ppm as tavaborole. PO
`Resp. 34 (citing Ex. 1002, 5; Ex. 2034 ¶ 151).
`We are not persuaded by Patent Owner’s argument. Although Austin
`may encompass millions of compounds, Patent Owner’s declarant, Dr.
`Reider, testifies that Austin disclosed test results for only sixteen compounds
`identified as “preferred compounds”—nine O-esters from Table 8 and seven
`simple benzoxaboroles, including tavaborole, from Table 9. Ex. 1048,
`304:4–308:11. We are persuaded that a person of ordinary skill in the art
`would have looked to compounds in Table 9 over the O-esters of Table 8
`because the Table 9 compounds have a lower molecular weight that is more
`likely to penetrate the nail. Pet. Reply 14–15; Ex. 1043 ¶¶ 10–11; Ex. 1044
`¶¶ 44–45.
`
`FlatWing Ex. 1014, p. 16
`
`

`

`During oral argument, Patent Owner argued that because almost all of
`the “particularly preferred” compounds of Table 8 have the lowest MIC for
`C. albicans and an average molecular weight of 219 Da, which is less than
`the molecular weights of the compounds of Brehove and Freeman, a person
`of ordinary skill in the art would turn to the compounds of Table 8, rather
`than Table 9, when reading Austin as a whole. Tr. 24:11–29:16. Even if
`true, we do not find Patent Owner’s argument detracts from what Austin
`reasonably suggests to a person of ordinary skill in the art. See Merck & Co.
`v. Biocraft Labs, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (“That the [prior
`art] discloses a multitude of effective combinations does not render any
`particular formulation less obvious.”). In other words, that Austin also
`points to the compounds of Table 8 does not preclude a person of ordinary
`skill in the art from considering tavaborole when reading Austin as a whole.
`See id. (“[I]n a section 103 inquiry, ‘the fact that a specific [embodiment] is
`taught to be preferred is not controlling, since all disclosures of the prior art,
`including unpreferred embodiments, must be considered.’”) (quoting In re
`Lamberti, 545 F.2d 747, 750 (CCPA 1976)). This is particularly true where
`tavaborole has a lower molecular weight than the compounds of Table 8 and
`was the most effective against C. albicans of the preferred compounds in
`Table 9.
`In sum, Austin teaches that tavaborole was known as a preferred
`fungicide that was effective against C. albicans. Although Austin describes
`a broad class of preferred compounds, Austin tested only sixteen of its
`preferred compounds where nine of the sixteen compounds were “O-esters”
`in Table 8 and seven of the sixteen compounds, including tavaborole, were
`listed in Table 9. Ex. 1002, Abstract, Tables 8 and 9; Ex. 1048, 304:4–
`308:11. Of the preferred compounds tested with the most potent activity,
`
`FlatWing Ex. 1014, p. 17
`
`

`

`tavaborole was the simplest and lowest molecular weight compound, which,
`as explained further below, is the most important factor in predicting
`whether a molecule will penetrate a nail plate. Ex. 1043 ¶¶ 10–11; Ex. 1044
`¶¶ 44–45. Accordingly, we find that a person of ordinary skill in the art
`would have chosen tavaborole as a potential candidate for treating
`onychomycosis. Pet. Reply 15; Ex. 1043 ¶¶ 10–11; Ex. 1044 ¶¶ 44–47.
`Patent Owner also argues that neither reference discloses
`“administering to the animal [or human] a therapeutically effective amount
`of [tavaborole],” as required by each claim. PO Resp. 35–36. We are not
`persuaded. Patent Owner attacks each reference separately and does not
`acknowledge what the art fairly teaches in combination. In re Merck & Co.,
`800 F.2d 1091, 1097 (Fed. Cir. 1986) (stating the prior art “must be read, not
`in isolation, but for what it fairly teaches in combination with the prior art as
`whole”). Here, Austin and Brehove together suggest administering to a
`human a therapeutically effective amount of tavaborole.
`The parties also dispute whether a person of ordinary skill in the art
`would have had a reason to combine Austin and Brehove to reach the
`claimed invention with a reasonable expectation of success. We determine
`that Petitioner has shown that it would.
`In particular, we are persuaded by Petitioner’s detailed explanation
`supported by the testimony of its two declarants as to why a person of
`ordinary skill in the art would have administered Austin’s tavaborole in
`Brehove’s method of treating onychomycosis with a reasonable expectation
`of success. Pet. 31–38. Specifically, Petitioner asserts that a person of
`ordinary skill in the art would have combined Austin and Brehove because:
`(1) both references teach the use of boron-based compounds as
`fungicides; (2) both references also disclose the use of boron-
`
`FlatWing Ex. 1014, p. 18
`
`

`

`based compounds to specifically inhibit Candida albicans,
`which is one of the fungi responsible for onychomycosis; and (3)
`Austin discloses boron-based compounds that have lower
`molecular weight than the successful compounds of Brehove and
`are therefore likely to effectively penetrate the nail barrier.
`
`Pet. 31 (citing Ex. 1006 ¶¶ 33-34, 36; Ex. 1008 ¶¶ 86, 93-96, 116).
`In response, Patent Owner first argues that an ordinary artisan would
`not have found Brehove credible and, therefore, would not have combined it
`with Austin with a reasonable expectation of success. PO Resp. 36–40.
`Specifically, Patent Owner criticizes Brehove for failing to provide further
`det