Anacor Pharmaceuticals, Inc. v. Flatwing Pharmaceuticals, LLC ( 2020 )

Case: 19-2264 Document: 53 Page: 1 Filed: 08/27/2020
NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
ANACOR PHARMACEUTICALS, INC.,
Appellant
v.
FLATWING PHARMACEUTICALS, LLC,
Appellee
______________________
2019-2264, 2019-2265, 2019-2266, 2019-2267
______________________
Appeals from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in Nos. IPR2018-
00168, IPR2018-00169, IPR2018-00170, IPR2018-00171,
IPR2018-01358, IPR2018-01359, IPR2018-01360,
IPR2018-01361.
______________________
Decided: August 27, 2020
______________________
AARON P. MAURER, Williams & Connolly LLP, Wash-
ington, DC, for appellant. Also represented by DAVID I.
BERL, ANTHONY SHEH.
PHILIP DALE SEGREST, JR., Husch Blackwell LLP, Chi-
cago, IL, for appellee. Also represented by MARC
WEZOWSKI; ERIC RAKESTRAW, St. Louis, MO.
______________________
Case: 19-2264 Document: 53 Page: 2 Filed: 08/27/2020
2 ANACOR PHARMACEUTICALS, INC. v. FLATWING
PHARMACEUTICALS, LLC
Before LOURIE, O’MALLEY, and CHEN, Circuit Judges.
LOURIE, Circuit Judge.
Anacor Pharmaceuticals, Inc., (“Anacor”) appeals from
four final written decisions of the Patent Trial and Appeal
Board (the “Board”) holding all claims of U.S. Patents
9,549,938 (the “’938 patent”), 9,566,289 (the “’289 patent”),
9,566,290 (the “’290 patent”), and 9,572,823 (the “’823 pa-
tent”) unpatentable as obvious. FlatWing Pharm., LLC v.
Anacor Pharm., Inc., No. IPR2018-00168, 2019 WL
2385219 (June 5, 2019); FlatWing Pharm., LLC v. Anacor
Pharm., Inc., No. IPR2018-00169, 2019 WL 2399836 (June
5, 2019); FlatWing Pharm., LLC v. Anacor Pharm., Inc.,
No. IPR2018-00170, 2019 WL 2396792 (June 5, 2019); Flat-
Wing Pharm., LLC v. Anacor Pharm., Inc., No. IPR2018-
00171, 2019 WL 2385222 (June 5, 2019) (“Decision”). Be-
cause the Board’s factual findings are supported by sub-
stantial evidence and its conclusion of obviousness is
correct, we affirm.
BACKGROUND
Anacor markets the compound tavaborole in the form
of a topical solution called KERYDIN®, indicated for the
treatment of onychomycosis, or fungal infection, of the toe-
nails due to Trichophyton rubrum or Trichophyton men-
tagrophytes. KERYDIN® is administered on the toenail
but penetrates through the nail to reach the site of infec-
tion on the nail bed. Tavaborole’s structural formula is il-
lustrated below:
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ANACOR PHARMACEUTICALS, INC. v. FLATWING 3
PHARMACEUTICALS, LLC
J.A. 1502. The Food and Drug Administration approved
KERYDIN® in 2014.
The four patents at issue share a specification that dis-
closes a wide range of boron-containing compounds that are
useful for the treatment of fungal infections. ’823 patent
Abstract. Example 13 indicates formulations of these com-
pounds at concentrations of 10% w/v (weight/volume). ’823
patent col. 186 ll. 20–42. Example 18 reports positive re-
sults from a nail penetrating study of tavaborole formula-
tions at a concentration of 10% w/w. Id. at col. 189 l. 58–
col. 193 l. 5. Example 20 discloses a prophetic study where
tavaborole is applied to nail beds at concentrations of 1%,
2.5%, 5%, 7.5%, 10%, and 15% w/v, and inventors draw the
conclusion that “[t]he optimal dose-response range for pen-
etration into the human nail was determined to be between
1% and 15%.” Id. at col. 193 l. 55–col. 194 l. 4. Claim 2 of
the ’823 patent is representative of all the claims at issue
in this appeal, but, as it is dependent upon claim 1, both
claims are shown as follows:
1. A method of delivering a compound, in a human,
from a dorsal layer of a nail plate to a nail bed to
treat onychomycosis caused by Trichophyton
rubrum or Trichophyton mentagrophytes, the
method comprising:
contacting the dorsal layer of the nail plate
with a pharmaceutical composition com-
prising a compound that penetrates the
nail plate, the compound being [tavaborole]
or a pharmaceutically acceptable salt
thereof, thereby treating onychomycosis
due to Trichophyton rubrum or Tri-
chophyton mentagrophytes.
2. The method of claim 1, wherein the pharmaceu-
tical composition is in the form of a topical solution
comprising 5% w/w of [tavaborole], and wherein
Case: 19-2264 Document: 53 Page: 4 Filed: 08/27/2020
4 ANACOR PHARMACEUTICALS, INC. v. FLATWING
PHARMACEUTICALS, LLC
the pharmaceutical composition further comprises
ethanol and propylene glycol.
’823 patent col. 317 l. 51–col. 318 l. 53 (emphasis added). 1
Previously, the Board held claims of two related pa-
tents—U.S. Patents 7,582,621 (the “’621 patent”) and
7,767,657—unpatentable as obvious in two final written
decisions. See Coal. for Affordable Drugs X LLC v. Anacor
Pharm., Inc., No. IPR2015-01776 (P.T.A.B. Feb. 23, 2017),
Paper 70; Coal. for Affordable Drugs X LLC v. Anacor
Pharm., Inc., No. IPR2015-01780 (P.T.A.B. Feb. 23, 2017),
Paper 70; Coal. for Affordable Drugs X LLC v. Anacor
Pharm., Inc., No. IPR2015-01785 (P.T.A.B. Feb. 23, 2017),
Paper 70. In relevant part, the Board concluded that the
claims were obvious in view of two published patent appli-
cations, WO1995/033754 (“Austin”) and U.S. Patent App.
Pub. 2002/0165121 (“Brehove”). Austin is directed to the
use of organoboron compounds (including tavaborole) as
fungicides for industrial uses and teaches that tavaborole
shows antifungal activity against several fungi. J.A. 3214–
15 (Example 64). Brehove discloses topical compositions of
organoboron compounds and results from an in vitro test
showing inhibition of a common fungus, J.A. 3231
(¶¶[0030–33]), and in vivo tests showing nail penetration
and antifungal activity for compositions of organoboron
compounds formulated in petroleum jelly or mineral oil at
10% or 25% concentration, J.A. 3231–32 at ¶¶[0034–38].
Anacor appealed to this court in that case only with re-
spect to claim 6 of the ’621 patent, which was directed to a
method of treating onychomycosis by administration of a
1 The Board held all claims of each patent unpatent-
able. Anacor appeals here only with respect to claims 3, 5,
and 6 of the ’938 patent; claims 10 and 12–15 of the ’289
patent; claims 2, 5, 6, 8, and 11 of the ’290 patent; and claim
2 of the ’823 patent. Appellant Br. 4.
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PHARMACEUTICALS, LLC
“therapeutically effective amount” of a tavaborole composi-
tion. This court affirmed. See Anacor Pharm., Inc. v.
Iancu, 889 F.3d 1372, 1385 (Fed. Cir. 2018). We rejected
Anacor’s argument that a skilled artisan would not have
expected tavaborole to be effective against multiple fungi
species. We concluded that substantial evidence supported
the Board’s finding of a reason to combine Austin and Bre-
hove because the “structural and functional similarities”
between tavaborole and Brehove’s compounds provided a
reason to expect a similar tavaborole composition to be use-
ful for treating onychomycosis. Id.Meanwhile, FlatWing Pharmaceuticals, LLC (“Flat-
Wing”), petitioned for inter partes review of the four pa-
tents at issue here on the ground of obviousness. The
Board issued final written decisions concluding that the
challenged claims—which further limit the claimed compo-
sitions to those formulated at a concentration of 5% by
weight—would have been obvious over a combination of
Austin, Brehove, and U.S. Patent 6,224,887 (“Samour”),
which discloses topical formulations of other antifungal
compounds, such as econazole, at concentrations of 5% by
weight. Decision, 2019 WL 2385222, at *6. The Board
found that Austin, Brehove, and Samour each teach anti-
fungal compositions at concentration ranges that overlap
5%, id. at *7, that a skilled artisan would have been able to
make the claimed composition of tavaborole using known
techniques, and that formulation of tavaborole, even as a
boron-containing compound, would not have been unpre-
dictable, id. at *11–13. And it rejected Anacor’s argument
that Samour teaches away from a 5% concentration, as
Samour does not “criticize or otherwise discourage the use
of 5% w/w of antifungal agent.” Id. at *9.
Anacor timely appealed from each of the Board’s deci-
sions. We have jurisdiction pursuant to 28 U.S.C.
§ 1295(a)(4)(A).
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6 ANACOR PHARMACEUTICALS, INC. v. FLATWING
PHARMACEUTICALS, LLC
DISCUSSION
We review the Board’s legal determinations de novo, In
re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), but we re-
view the Board’s factual findings underlying those deter-
minations for substantial evidence, In re Gartside, 203 F.3d
1305, 1316 (Fed. Cir. 2000). A finding is supported by sub-
stantial evidence if a reasonable mind might accept the ev-
idence as adequate to support the finding. Consol. Edison
Co. v. NLRB, 305 U.S. 197, 229 (1938).
The sole issue presented in this appeal is obviousness.
Obviousness is a question of law that “lends itself to several
basic factual inquiries,” Graham v. John Deere Co., 383
U.S. 1, 17 (1966) (citing Great Atl. & Pac. Tea Co. v. Super-
market Equip. Corp., 340 U.S. 147, 155 (1950)), including
the scope and content of the prior art, the level of ordinary
skill in the art, differences between the prior art and the
claimed invention, and any relevant secondary considera-
tions, id. at 17–18. The Supreme Court has held that “a
patent composed of several elements is not proved obvious
merely by demonstrating that each of its elements was, in-
dependently, known in the prior art.” KSR Int’l Co. v. Te-
leflex Inc., 550 U.S. 398, 418 (2007). Instead, there must
have been “an apparent reason to combine the known ele-
ments in the fashion claimed by the patent at issue.” Id. at
417–18. Such a reason exists if the claimed invention
“simply arranges old elements with each performing the
same function it had been known to perform and yields no
more than one would expect from such an arrangement.”
Id. (internal quotation marks and citation omitted).
Anacor argues that the Board erred in determining
that the claimed composition would have been obvious as
the product of routine optimization. It asserts that the
mere existence of screening techniques for assessing an an-
tifungal composition’s efficacy and nail penetration is in-
sufficient evidence that it would have been obvious to
formulate the claimed composition, as organoborons are
Case: 19-2264 Document: 53 Page: 7 Filed: 08/27/2020
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PHARMACEUTICALS, LLC
quite reactive. Appellant Br. 28–31. Anacor also contends
that skilled artisans would have been discouraged from
creating a 5%-tavaborole composition because Samour
teaches away from a 5%-econazole composition in favor of
a 10%-econazole composition.
Flatwing responds that the Board reasonably found
that Samour teaches successful nail penetration with a 5%
econazole composition, and since tavaborole is a smaller
molecule than econazole, a skilled artisan would have ex-
pected that a similar tavaborole composition would per-
form as well or better. Flatwing adds that there is a clear
relationship between antifungal concentration and nail
penetration, making tavaborole concentration a result-ef-
fective variable, and merely selecting a concentration from
a known range is obvious. Flatwing also denies Anacor’s
teaching-away claim.
We agree with Flatwing. As an initial matter, we reject
Anacor’s teaching-away argument. Samour discloses sev-
eral small experiments to determine the effect of econazole
concentration on nail penetration. J.A. 3279–82 (Examples
4–9). The results indicate that 10%-econazole compositions
provide greater nail penetration than the 5%-econazole
compositions, but the effect is modest overall and depends
on other variables, such as excipients. J.A. 3281–82 (Ta-
bles 11–14) (showing 5%-econazole compositions achieving
nail penetration between 1.067 and 2.176 µg/mg and 10%-
econazole compositions between 1.984 and 2.166 µg/mg).
Samour finds “no significant benefit” from increasing the
concentration to 20% econazole, J.A. 3281 col. 24 ll. 54–56,
concludes that the “especially preferabl[e]” range of concen-
trations is “from about 5 to 20%,” J.A. 3275 col. 12 ll. 25–
26, and ultimately claims compositions with concentra-
tions of 1 to 10% econazole, J.A. 3285 col. 32 ll. 26–33. 2
2 While Anacor protests the Board’s decision to cite
Samour’s claims, as that portion of Samour was not
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PHARMACEUTICALS, LLC
Thus, Samour’s teachings barely even suggest a “prefer-
ence for an alternative” approach, DePuy Spine, Inc. v.
Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed.
Cir. 2009) (citation omitted)—let alone discourage a skilled
artisan from pursuing a 5%-antifungal composition, as is
required for a reference to teach away, see, e.g., United
States v. Adams, 383 U.S. 39, 52 (1966). The Board’s find-
ing is therefore amply supported by substantial evidence.
The remainder of Anacor’s challenge fares no better.
As the Board found, the references teach all elements of the
claimed invention. See Decision, 2019 WL 2385222, at *6–
7. Austin teaches that tavaborole is an effective antifungal
agent outside the clinical context, J.A. 3214–15, and Bre-
hove and Samour each suggest methods of formulating dif-
ferent antifungal compounds in topical compositions to
achieve nail penetration. J.A. 3231–32, 3281–82. Each ref-
erence suggests compositions with a range of concentra-
tions overlapping 5%, and Samour discloses several 5%-
econazole topical compositions that attained nail penetra-
tion. J.A. 3281–82 (Examples 9–10).
Yet Anacor argues that tavaborole would have pre-
sented special challenges as an organoboron molecule, and
a skilled artisan would not have simply used the formula-
tion techniques in Brehove and Samour to create the
claimed 5%-tavaborole composition.
specifically cited in Flatwing’s petition or expert testimony,
the Board was entitled to do so because the entirety of
Samour was before it as evidence, both parties discussed
Samour’s claims at the hearing, and Samour’s claims are
cumulative in view of its multiple experiments showing
nail penetration with a 5%-econazole composition. See In
re NuVasive, 841 F.3d 966, 971 (Fed. Cir. 2016) (“[T]he
Board is not limited to citing only portions of the prior art
specifically drawn to its attention . . . .”).
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We find Anacor’s arguments unpersuasive. The Board
reasonably credited testimony from Flatwing’s expert that
the claimed composition could have been made according
to well-known formulation techniques, and tavaborole’s po-
tential reactivity as an organoboron compound would not
have been an important consideration. Decision, 2019 WL
2385222, at *10 (declining to credit Anacor’s expert’s testi-
mony because he did not consider the rate of tavaborole hy-
drolysis or oxidation in a topical composition). And the
existence of the Brehove reference describing in vivo inhi-
bition of a common fungus with organoboron composi-
tions—formulated in either mineral oil or petroleum jelly—
is especially damaging to Anacor’s arguments.
As the Board noted, the inventors evidently did not
consider formulating organoborons a great challenge, as
the specification does not offer any guidance beyond cita-
tion of well-known guides to pharmaceutical formulation.
See ’823 patent col. 161 ll. 19–29 (“Those skilled in the art
will recognize various synthetic methodologies that may be
employed to prepare non-toxic pharmaceutical formula-
tions incorporating the compounds described herein.”), col.
186 ll. 40–42 (“The preparation of these formulations is
well known in the art and is found in references such as
Remington: The Science and Practice of Pharmacy . . . .”);
cf. Lincoln Eng’g Co. v. Stewart-Warner Corp., 303 U.S.
545, 550 (1938) (“If this were so vital an element in the
functioning of the apparatus, it is strange that all mention
of it was omitted.”). Thus, the Board did not err in deter-
mining that creating a tavaborole topical composition
would have been obvious.
Furthermore, there is no dispute that a skilled artisan
would have appreciated that concentration is a result-ef-
fective variable, Reply Br. 2, such that one could optimize
nail penetration by routine experimentation within a pre-
dictable range of concentrations. Decision, 2019 WL
2385222, at *7, *10 (crediting Flatwing’s expert’s testi-
mony that tavaborole’s lower molecular weight would
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10 ANACOR PHARMACEUTICALS, INC. v. FLATWING
PHARMACEUTICALS, LLC
indicate its suitability for diffusion across the nail at lower
concentrations). We conclude, as the Board did, that the
selection of 5% as the concentration of a tavaborole compo-
sition would have been obvious to a skilled artisan. See In
re Aller, 220 F.2d 454, 456 (CCPA 1955) (“[W]here the gen-
eral conditions of a claim are disclosed in the prior art, it is
not inventive to discover the optimum or workable ranges
by routine experimentation.” (collecting cases)).
CONCLUSION
We have considered Anacor’s further arguments but
find them unpersuasive. For the foregoing reasons, the de-
cisions of the Board are
AFFIRMED