Trials@uspto.

gov
571.272.7822

Paper No. 24
Filed: February 23, 2016

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 IPR2015-01785
Patent 7,767,657 B2

Before MICHAEL P. TIERNEY, GRACE KARAFFA OBERMANN, and

TINAE. HULSE, Administrative Patent Judges.
TIERNEY, Administrative Patent Judge.

DECISION
Institution of Inter Partes Review
37 C.F.R. 42.108

IPR2015-01785
Patent 7,767,657 B2
I.
INTRODUCTION
Coalition for Affordable Drugs X, LLC (Petitioner), filed a Petition
requesting an inter partes review of claims 124 of U.S. Patent 7,767,657
(Ex. 1001, the 657 patent). Paper 1 (Pet.). Patent Owner, Anacor
Pharmaceuticals Inc. and Sandoz Inc., (Patent Owner) filed a Preliminary
Response. Papers 7 and 17 (Prelim. Resp.).
We have jurisdiction under 35 U.S.C. 314. The standard for
instituting an inter partes review is set forth in 35 U.S.C. 314(a), which
provides:
THRESHOLD.The Director may not authorize an inter partes
review to be instituted unless the Director determines that the
information presented in the petition filed under section 311 and
any response filed under section 313 shows that there is a
reasonable likelihood that the petitioner would prevail with
respect to at least 1 of the claims challenged in the petition.
Upon consideration of the Petition and Preliminary Response, we
conclude that the information presented in the Petition demonstrates that
there is a reasonable likelihood that Petitioner would prevail in challenging
claims 124 as unpatentable. Pursuant to 35 U.S.C. 314, we hereby
authorize an inter partes review to be instituted as to claims 124 of the 657
patent.

A.

Related Proceeding

The claims of the 657 patent have been challenged in related inter
partes review proceeding IPR2015-01780. Additionally, the 657 patent
claims to be a continuation-in-part of U.S. Patent 7,582,62, which is
involved in inter partes review IPR2015-01776. Pet. 4.

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Patent 7,767,657 B2
B. The 657 Patent
The 657 patent is titled Boron-Containing Small Molecules. Ex.
1001. The 657 specification describes compounds useful for treating fungal
infections, in particular, 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 includes a
pharmaceutically acceptable excipient and a compound of said invention.
Id. at 139:3537. According to the 657 patent Summary of the Invention,
said invention provides a structure that is described as having the following
formula:

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

IPR2015-01785
Patent 7,767,657 B2
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,
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 4:65:2. Example 4.2.j of the 657 patent identifies the
compound 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole as
C10, which has the following structure:

IPR2015-01785
Patent 7,767,657 B2

Id. at 180:2027. The 657 patent provides several examples

describing the antifungal activity of compound C10 and its ability to
penetrate human nails. Id. at 189:15196:46.
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 165:66166:2. According to the 657 patent,
[a]ssays may be used to predict these desirable pharmacological
properties. Id. at 166:67. For example, [t]oxicity to cultured
hepatocyctes may be used to predict compound toxicity. Id. at
166:910.

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

(Ex. 1004)

U.S. 6,224,887 Samour

May 1, 2001

(Ex. 1005)

U.S. 7,074,392 Friedman

Jul. 11, 2006

(Ex. 1006)

U.S. 5,498,407 Atlas

Mar. 12, 1996

(Ex. 1007)

U.S. 3,816,472 Shapiro

June 11, 1974

(Ex. 1008)

WO 95/33754

Austin

Dec. 14, 1995

(Ex. 1002)

WO 03/009689

Freeman

Feb 6, 2003

(Ex. 1003)

Petitioner contends that the challenged claims are unpatentable under

35 U.S.C. 103 based on the following specific grounds (Pet. 2160):

References

Basis

Claims challenged

Austin and Freeman

103

Austin, Freeman, and Chaudhuri

Austin, Freeman, and Samour
Austin, Freeman, Friedman, and Atlas
Austin, Freeman, Friedman, and Samour
Austin, Freeman, and Shapiro

103
103
103
103
103

12, 45, 1016 and

1824
6
3, 7
8
9
17

E.

Level of Ordinary Skill in the Art

Petitioners declarants, Dr. Stephen Kahl (Ex. 1009) and Dr. S.

Narasimha Murthy (Ex. 1011), testify that, based on their experience
in pharmacology, a person of ordinary skill in the art at the time of the
invention had an advanced degree, Masters or Ph.D. or equivalent
experience in chemistry, pharmacology or biochemistry and at least
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two years of experience with the research, development, or production
of pharmaceuticals. Ex. 1009, 21 and Ex. 1011, 36. Patent Owner
goes further than Petitioner and states that a person of ordinary skill in
the art would also possess knowledge and experience in medicinal
chemistry and development of potential drugs candidates suitable for
treating onychomycosis and ungula and other infections. Prelim.
Resp. 1516. We need not decide at this time whether one skilled in
the art would have possessed the additional knowledge identified by
Patent Owner for purposes of this Decision. Moreover, Patent Owner
acknowledges that Petitioners declarants purport to have experience
in the additional fields, and the prior art itself is sufficient to
demonstrate the level of skill in the art at the time of the invention.
See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (the
prior art itself can reflect the appropriate level of ordinary skill in the
art).

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);
In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 127879 (Fed. Cir. 2015),
cert. granted sub nom. Cuozzo Speed Techs., LLC v. Lee, 84 U.S.L.W. 3218
(U.S. Jan. 15, 2016) (No. 15-446). 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
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Patent 7,767,657 B2
(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).
Petitioner identifies several claim terms in the challenged claims and
provides definitions for those terms. Pet. 1015. Patent Owner states that,
where the specification does not already state the meaning of the identified
claim terms, Petitioner has failed to provide sufficient reason why the
ordinary and customary meanings of the claim terms should not be adopted.
Prelim. Resp. 1620.
At this stage of the proceeding, except for the term 1,3-dihydro-5fluoro-1-hydroxy-2,1-benzoxaborole, we determine that it is unnecessary to
construe explicitly the claim terms for purposes of this Decision. 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. & Engg, Inc.,
200 F.3d 795, 803 (Fed. Cir. 1999)).

1.

1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole

Independent claim 1 recites the compound 1,3-dihydro-5-fluoro-1hydroxy-2,1-benzoxaborole. 1,3-dihydro-5-fluoro-1-hydroxy-2,1benzoxaborole has the following structure:

IPR2015-01785
Patent 7,767,657 B2
The parties agree that the claimed compound may also be referred to as 5fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole. Pet. 1011; Prelim.
Resp. 1718. Patent Owner further notes that the claimed compound is also
known as tavaborole. Id.
We determine that the broadest reasonable interpretation of 1,3dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole includes 5-fluoro-1,3dihydro-1-hydroxy-2,1-benzoxaborole and tavaborole. Accordingly, for
ease of reference, we refer to the claimed compound as tavaborole in this
Decision.

D.

Section 103 Obviousness Challenge

Petitioner raises six (6) challenges based on 35 U.S.C. 103.

Generally, 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. 2160. Patent Owner opposes
Petitioners assertions. Prelim. Resp. 2060. Based on the current record,
we determine that Petitioner has established a reasonable likelihood that it
would prevail in showing claims 124 are unpatentable as obvious over the
cited art.

1. Background on Obviousness
An invention is not patentable under 35 U.S.C. 103 if it is obvious.
KSR Intl Co. v. Teleflex Inc., 550 U.S. 398, 427 (2007). 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
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Patent 7,767,657 B2
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.
Graham v. John Deere Co., 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.

2. Austin and Freeman: Claims 12, 45, 1016 and 1824

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 further states that [p]referred compounds are 5- and
6-fluoro or bromo-1,3-dihydro-1-hydroxy-2,1-benzoxaborole including Oesters thereof. Id. Austin notes that it has been found that compounds
containing an oxaborole ring are particularly effective against microorganisms such as bacteria, algae, yeasts and particularly fungi, especially
fungi which cause degradation of plastics materials. Id. at 1:3538.
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,
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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 at 6:3437. According to Austin, the concentration of the oxaborale in
its biocide composition may range from 10 to 20% by weight relative to the
total weight of the biocide composition, which for tavaborole an ethanol
solution would be 7.9%15.8% w/v. Ex. 1011, 167169.
Freeman discloses phenyl boronic acid and related boronic acid
compounds that are used for treating fungal infections such as
onychomycosis. Ex. 1003, Abstract, 1. Freeman identifies Trichophyton
rubrum (T. rubrum) as one of the most common dermatophyte causes of
onychomycosis. Id. 8. Freeman also identifies non-dermatophytes,
especially Candida Sp., as another cause of onychomycosis. Id.
According to Freeman, phenyl boronic acids have been found to be
particularly useful in treating nail fungal infections. Id. 22.
Freeman also discloses results of in vitro testing of the fungicidal
activity of phenyl boronic acid. Id. 3134. In particular, Freeman notes
that phenyl boronic acid exhibited fungicidal effect on T. rubrum. Id. 34.
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Freeman also notes that the compounds tested had a fungicidal effect on
Candida parapsylosis at 10 mg/ml. Id.
Freeman teaches that its water-soluble phenyl boronic acid can be
administered topically in the form of a buffered solution, lotion or ointment.
Id. at 30. Suitable carriers include, among other things, water, alcohols
and polyethylene glycols. Id. at 38. The amount of the acid in the overall
formulation will depend on the type of application but ranges from 2% to
50% are most preferred. Id. at 64.

a. Analysis
Petitioner argues that claims 12, 45, 1016 and 1824 are
unpatentable as obvious over the combination of Austin and Freeman.
Through claim charts and its declarants testimony, Petitioner asserts that the
combination teaches each limitation of the claims. Pet. 2235; Ex. 1009,
1011. For example, Petitioner relies upon Austins teaching that tavaborole
is a compound that is effective in inhibiting Candida albicans and boron
compositions for topical application directly to the nails of humans to
effectively treat onychomycosis. Pet. 2232, Ex. 1002, 37 (Table 9) and Ex.
1003, 1, 8, 22, 30, 37, 64, and 68.
Having reviewed the arguments and evidence, we are persuaded that
Petitioner has shown sufficiently that each limitation of the challenged
claims is taught by the combination of Austin and Freeman.
Petitioner then provides a detailed explanation supported by the
testimony of its two declarants as to why a person of ordinary skill in the art
would have employed Austins tavaborole with Freemans topical
formulations for treating onychomycosis with a reasonable expectation of
success. Pet. 3235. Dr. Murthy testifies in support of Petitioner and
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testifies that a person of ordinary skill in the art would have had reason to
combine Austins tavaborole with Freemans topical formulations as both
Austin and Freeman describe boron-based compounds for inhibiting
Candida albicans, and as Freeman teaches topical formulations that deliver a
boron-based compound for treating onychomycosis, which is predominantly
caused by Candida albicans. Ex. 1011 147148.
Patent Owner disagrees with Petitioners analysis of the prior art. In
its Preliminary Response, Patent Owner does not appear to challenge that the
combination of references teaches each limitation of the claims. Instead,
Patent Owner argues that Petitioner has failed to meet its burden to show
that a person of ordinary skill in the art would have combined Austin and
Freeman in the manner recited in the claims with a reasonable expectation of
success. Patent Owner argues that Petitioner has failed to explain why a
person of ordinary skill in the art would have chosen any compound from
Austin as a starting point for further investigation. Prelim. Resp. 22.
According to Patent Owner, a person of ordinary skill in the art would have
understood that biocides, such as taught by Austin, are designed to kill living
organisms. Id. at 23. Patent Owner states that nothing in Austin discloses or
suggests that its industrial biocides may be used for therapeutic purposes in
or on humans or animals. Id. at 24.
Austin teaches that tavaborole, as well as other biocides, inhibit
Candida albicans, which is the most common pathogen causing
onychomycosis. Freeman teaches that a phenyl boronic acid, a boron based
compound, was effective in inhibiting onychomycosis of the fingernail and
toenail and the boron-based compound into a topical composition for
treatment of nail infections.
Dr. Murthy testifies one skilled in the art would have understood that
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Austins industrial biocides are effective in treating Candida albicans, and
that boron-based compounds were well known in the art as biocides. Ex.
1011, e.g., 161162. Dr. Murthy further testifies that Freeman
demonstrated to one of ordinary skill in the art topical applications of a
boron-based compound to a human was effective in treating onychomycosis.
Id. at 153. We credit Dr. Murthys testimony at this stage of the
proceeding as it is consistent with the cited prior art. Based on the current
record, we hold that one of ordinary skill in the art would have had sufficient
reason to select a compound from Austin for therapeutic purposes.
Patent Owner contends that one skilled in the art would have expected
the following of boron-containing compounds:
Given Austins focus on effective industrial biocides, it is not
surprising that the reference provides no information at all
about the toxicity or therapeutic efficacy of its boron-containing
compounds in humans or animals. To a POSA in 2005
considering compounds for use in humans and animals, this
would have been a glaring omission, especially when the art,
including Dr. Kahls article, taught a POSA to expect boroncontaining compounds to be toxic. See, e.g., Exs. 2002, 20052013, 2017 & 2028.
Prelim. Resp. 24. Patent Owner, at this stage of the proceeding, does not
provide a sufficient explanation for why one skilled in the art would have
been led to expect that boron-containing compounds are toxic, and would
not have been led to use such compounds. Additionally, Patent Owners
allegations of a glaring omission of toxicity appear to be inconsistent with
Patent Owners 657 specification and prosecution history, which described
and claimed millions of boron-containing compounds for pharmaceutical
formulations but as to toxicity merely stated that [t]oxicity to cultured
hepatocyctes may be used to predict compound toxicity. Ex. 1001 at
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166:910, Ex. 1013 at 102104. Further, Petitioners declarant, Dr. Kahl,
testifies that [b]oron-containing compounds are generally considered safe.
Ex. 1006 31. Thus, at this stage of the proceeding, we are persuaded that
Petitioner has made a sufficient showing that a person of ordinary skill in the
art would not have been dissuaded from Austins boron-containing
compounds.
Patent Owner also argues that a person of ordinary skill in the art
would not have selected tavaborole from the millions of compounds
disclosed in Austin. Prelim. Resp. 2531. It is well settled that a reference
may be relied upon for all that it would have reasonably suggested to one
having ordinary skill in the art. Merck & Co., Inc. v. Biocraft Labs., Inc.,
874 F.2d 804, 807 (Fed. Cir. 1989). Here, Austin discloses 5-fluoro
benzoxaboroles as preferred fungicides in the Abstract and tavaborole is one
of three preferred compounds tested that effectively inhibits Candida
albicans, which is a cause of onychomycosis. Pet. 23, Ex. 1011, 189
190. Accordingly, evaluating Austin for all that it teaches, we conclude on
the present record that one skilled in the art would have recognized that
tavaborole is a preferred fungicide for inhibiting Candida albicans, which is
a cause of onychomycosis.
Patent Owner argues that Freeman would not supply a reasonable
expectation of success because a skilled artisan would not have been
convinced that phenyl boronic acids are not toxic, given an alleged lack of
data in Freeman. Id. at 3234, 3839. Patent Owner also argues that a
skilled artisan would not have combined the references given the structural
differences between tavaborole and phenyl boronic acids. Id. at 3336.
Petitioner, however, offers the testimony of its declarant, Dr. Murthy, who
states that both Austin and Freeman disclose boron-based cyclic compounds
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and that a person of ordinary skill in the art would have expected that
compounds that share sufficient similar structural features would likely share
similar functional features, such as the inhibition of additional fungi
responsible for onychomycosis. Ex. 1011 155156. Further, Patent
Owners 657 specification and prosecution history described and claimed
millions of boron-containing compounds for pharmaceutical formulations
but likewise did not provide in vivo testing for each of the compounds
falling within the scope of its claimed pharmaceutical formulations. Ex.
1001 at 166:910, Ex. 1013 at 102104. Thus, although we acknowledge
Patent Owners arguments, on this record and at this stage of the proceeding,
we determine that Petitioner has set forth sufficient evidence to show that a
person of ordinary skill in the art would have had a reason to employ
Austins tavaborole in Freemans topical formulations with a reasonable
expectation of success in treating onychomycosis caused by Candida
albicans. See Pet. 2935.
Claims 13, 18, 19 and 22 are dependent claims directed to
pharmaceutical formulations where the formulation is for a topical
administration to skin, nail or hair (claim 13), to an animal suffering from a
dermatophyte (claim 18) or Tinea unguium, Trichophyton rubrum and
Trichophyton mentagrophytes (claim 19) and where the infection is
onychomycosis (claim 22). Patent Owner contends that Petitioner has failed
to demonstrate that one of ordinary skill in the art following the teachings of
Austin and Freeman would have treated onychomycosis and other infections
requiring nail infection such as recited in claims 13, 18, 19, and 22. Prelim.
Resp. 4147. Patent Owner alleges that one of ordinary skill in the art
would have understood that 9095% of onychomycosis infections are caused
by dermatophytes. Id. at 41. Patent Owner contends that Austin does not
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suggest, or provide data to support, that the boron-containing compounds it
discloses would be effective against dermatophytes as Austin presents data
on Candida albicans and other non-dermatophytes and Freeman fails to
remedy this deficiency. Id. at 42.
Claims 13, 18, 19, and 22 are composition claims, as opposed to
method claims. On this record, Patent Owner does not provide a sufficient
explanation as to how its composition claims for treating dermatophytes,
Tinea unguium, Trichophyton rubrum and Trichophyton mentagrophytes,
which can cause onychomycosis, differ from a composition arrived at from
the teachings of Austin and Freeman for treating onychomycosis. See Pet.
2936. Additionally, Freeman describes its invention as curing or
preventing the spread of nail infections, such as onychomycosis, and fungal
infections by treating with a boron-containing compound. Ex. 1003, 19
20 and 22. Dr. Murthy testifies that a person of ordinary skill in the art
would have expected that compounds that share sufficient similar structural
features, such as the boron cyclic compounds of Austin and Freeman, would
likely share similar functional features. Ex. 1011 155.
Patent Owner also contends that a person of ordinary skill in the art
would have expected compounds to exhibit poor nail penetration absent data
evidencing low keratin binding. Prelim. Resp. 4344. Dr. Murthy testifies
that one skilled in the art would have recognized that tavaborole has a
similar molecular weight to the boron-containing compounds of Freeman
and would have been expected to have better penetration of the nail plate.
Ex. 1011 153. Further, Freeman teaches that its boron-containing active
ingredient was effective in treating onychomycosis and Freeman states
explicitly that its composition was for treating onychomycosis of the
fingernail and toenail. Ex. 1003 1 and 3437. Based upon the evidence
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of record, we conclude at this stage that one skilled in the art would have
understood that a composition containing tavaborole in combination with the
nail treatment ingredients of Freeman would have had a reasonable
expectation of success of treating onychomycosis.
Accordingly, we determine that Petitioner has established a
reasonable likelihood that it would prevail in showing claims 12, 45, 10
16 and 1824 are unpatentable as obvious over Austin and Freeman.

3. Austin, Freeman, and Chaudhuri: Claim 6

Claim 6 depends from claim 1 and requires that the pharmaceutical
composition of claim 1 comprise propylene glycol and ethanol in a ratio of
about 1:4 and about 1:10 weight per volume of tavaborole.
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 1:5565. Chaudhuri states that suitable solvents for its composition
include lower alkanols, such as ethanol, and dihyxdroxyalcohols, such as
propylene glycol. Id. at 6:27. In particular, Chaudhuri provides an
example containing 520% weight propylene glycol and 2080% weight
ethanol and 0.5 to 15% weight antifungal. Id. at 8:579:10, Table B. One
skilled in the art would have understood Chaudhuris Table B proportions as
equating to a ratio of 1:4 propylene glycol to ethanol and 1:10 wt/volume of
antifungal. Ex. 1011, 100, 193.
Petitioner cites Austin for its description of organic solvents, such as
ethanol and propylene glycol in combination with a biocide, with preferably
10 to 20% by weight concentration of biocide. Pet. 37. Petitioner relies
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upon Chaudhuri for its teaching that an effective nail treatment formulation
for onychomycosis would employ a 1:4 ratio of propylene glycol to ethanol
and 1:10 wt/volume antifungal. Pet. 3738.
Patent Owner contends that one skilled in the art would have
recognized that Chaudhuri does not describe compounds that are structurally
similar to the boron-containing compounds of Austin and Freeman. Prelim.
Resp. 5051. Patent Owner also contends that one of ordinary skill in the art
would not have combined the teachings of Austin, Freeman and Chaudhuri
as Chaudhuri does not report on antifungal activity for its compounds in the
same manner as Austin. Id. at 51.
Based on the record presented, we credit the testimony of Dr. Murthy
as it is consistent with the teachings of the prior art of record and find that
Petitioner has shown sufficiently that nail treatment formulations containing
ethanol, propylene glycol and antifungal compounds in the claim
proportions were known in the art and effective in treating onychomycosis.
We conclude, on this record, that Petitioner has provided sufficient and
credible evidence to demonstrate that one skilled in the art would have
combined the known antifungal tavaborole with the known nail treatment
formulations for their known use (treating nail onychomycosis) to achieve a
predictable result (an antifungal nail treatment composition for treating
onychomycosis).

4. Austin, Freeman, and Samour: Claims 3 and 7

Claim 3 depends from claim 1 and requires the formulation be a
lacquer. Claim 7 depends from claim 1 and requires that the pharmaceutical
composition of claim 1 comprises 70% ethanol, about 20% poly(vinyl
methyl ether-alt-maleic acid monobutyl ester) and about 10% tavaborole.
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Samour describes a nail lacquer formulation that is effective for the
treatment or prevention of fungal infections, such as onychomycosis.
Samours 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, 3:513. Samour teaches that an effective amount of active antifungal
agent preferably ranges from 1 to 10% by weight of the composition. Id. at
12:914. Suitable film forming polymers for the composition include
acrylic polymers such as Gantrez ES-425 (poly(vinyl methyl ether-altmaleic acid monobutyl ester)). Id. at 7:5462, Ex. 1011 103, 208 and Ex.
1035 at 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 8:3844, Ex. 1011, 101, 208. Samour exemplifies a
number of lacquer formulations including a formulation having 71%
ethanol, 24% film-forming polymer and 5% antifungal. Ex. 1005, 9:3149,
22:2036.
According to Dr. Murthy, formulating a pharmaceutical composition,
such as that recited in claim 7, requires nothing more than routine
experimentation. Ex. 1011, 212. Petitioner cites Austin for its description
of organic solvents, such as ethanol and propylene glycol in combination
with a biocide, with preferably 10 to 20% by weight concentration of
biocide. Pet. 4041. Petitioner relies upon Freeman for its teaching that
onychomycosis treatments can be formulated with evaporating solvents,
such as alcohols. Pet. 40. Petition cites Samour for teaching one skilled in
the art that an effective nail treatment formulation for onychomycosis can be
formulated using 20 to 40% film-forming polymer such as Gantrez ES-425,
a solvent such as ethanol in an amount of about 71% and an antifungal agent
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in an amount of from 1 to 10% of the composition. Id. at 4044. Based on
the teachings of Austin, Freeman and Samour, Dr. Murthy concludes that
one skilled in the art would have had a reasonable expectation of success of
formulating an effective onychomycosis treatment using tavaborole with the
improved nail lacquer formulation described in Samour. Ex. 1011 211
216.
Patent Owner contends that Samour fails to describe a boroncontaining compound and does not provide the effectiveness or toxicity of
any antifungal compound. Prelim. Resp. 53. Patent Owner further contends
that Samour describes the use of skin penetration enhancers but does not
provide data on penetration data containing tavaborole. Id. at 54.
Based on the record presented, we credit the testimony of Dr. Murthy
as it is consistent with the teachings of the prior art of record. We conclude,
on this record, that Petitioner has provided sufficient and credible evidence
to demonstrate that one skilled in the art would have combined the known
antifungal tavaborole with the known nail treatment formulations for their
known use (treating nail onychomycosis) to achieve a predictable result
(penetrating a nail with an antifungal compound to treat onychomycosis).

5. Austin, Freeman, Friedman, and Atlas: Claim 8

Claim 8 depends from claim 1 and requires that the pharmaceutical
composition comprises about 56% ethanol; about 14% water; about 15%
poly(2-hydroxyethyl methacrylate); about 5% dibutyl sebacate and about
10% of tavaborole.
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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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, 5:5164.
Friedman teaches that a suitable solvent includes ethanol, preferably about
60 to 90% w/w of the composition. Id. at 6:19. 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.7.
Atlas describes the use of hydrogel polymers as excellent carriers for
the release of drugs. Ex. 1007 at 1:514. Atlas states that poly(2hydroxyethyl methacrylate) (P-HEMA) was the most widely used
hydrogel. Id. at Abstract. Atlas teaches that P-HEMA hollow fibers act as a
reservoir and matrix for diffusion-controlled delivery to skin and nails. Id.
at 2:5864. Atlas Example 4 describes a cosmetic nail polish composition
having P-HEMA. Id. at 3:574:7.
Dr. Murthy testifies that one of ordinary skill in the art would have
understood that the composition of claim 8 represents nothing more than
routine experimentation using well known pharmaceutical components. Ex.
1011 230234. Dr. Murthy further testifies that one of ordinary skill in
the art would have had a reasonable expectation of success of combining the
known components given that it was known that high-swelling polymers
were preferred for pharmaceutical lacquer formulations and that the use of
P-HEMA was a well-known high-swelling hydrogel. Id. at 235236.
Patent Owner contends that one would not have combined the
teachings of the cited references due, among other things, to the structural
differences between Austin and Freeman and that Friedman fails to teach a
boron-containing compound. Prelim. Resp. 5557.
Based on the record presented, we credit the testimony of Dr. Murthy
as it is consistent with the teachings of the prior art of record. We conclude,
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on this record, that Petitioner has provided sufficient and credible evidence
to demonstrate that one skilled in the art would have combined the known
antifungal tavaborole with the known nail treatment formulations for their
known use (nail drug delivery systems and treating nail onychomycosis) to
achieve a predictable result (forming an effective nail lacquer delivery
composition with an antifungal compound to treat onychomycosis).

6. Austin, Freeman, Friedman, and Samour: Claim 9

Claim 9 depends from claim 1 and requires that the pharmaceutical
composition comprises about 56% ethanol; about 14% water; about 15%
poly(2-hydroxyethyl methacrylate); about 5% dibutyl sebacate and about
10% of tavaborole.
Regarding claim 9, Petitioner and Patent Owner present essentially the
same reasons as provided above with respect to claims 7 and 8. For the
reasons stated above regarding the challenges with respect to claims 7 and 8,
we likewise determine that Petitioner has made a sufficient showing as to
why a person of ordinary skill in the art would have combined the teachings
of Austin, Freeman, Friedman and Samour and arrived at the composition of
claim 9.

7. Austin, Freeman, and Shapiro: Claim 17

Claim 17 depends from claim 14, which depends from claim 1. Claim
17 requires the fungus or yeast be selected from Trichophyton concentricum,
Trichophyton violaceum, Trichophyton schoenleinii, Trichophyton
verrucosum, Trichophyton soudanense, Microsporum gypseum,
Microsporum equinum, Candida guilliermondii, Malassezia globosa,

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Malassezia obtuse, Malassezia restricta, Malassezia slooffiae and
Aspergillus flavus.
Shapiro describes antifungal compounds for treating fungal infections.
Ex. 1008, 1:1516. Shapiro teaches that its antifungal compounds are
effective against fungi including Trichophyton rubrum, Trichophyton
mentagrophytes, Trichophyton verrucosum, and Microsporum gypseum. Id.
at 2:314.
Petitioner states that one skilled in the art would have combined the
teachings of Austin, Freeman and Shapiro because Freeman and Shapiro
teach treating or inhibiting onychomycosis in humans with pharmaceutical
drug formulations and Shapiro describes antifungal compounds that have
cross-activity against a number of different fungi linked to onychomycosis.
Pet. 60.
Patent Owner contends that Shapiros compounds are structurally
different than those of Austin and Freeman. Prelim. Resp. 5960. Patent
Owner states that one skilled in the art would not have expected a
formulation of tavaborole for topical application would succeed. Id. at 60.
Claims 17 is a composition claim, as opposed to a method claim. On
this record, Patent Owner does not provide a sufficient explanation as to how
its composition claims for treating the recited fungi differs from a
composition arrived at from the teachings of Austin and Freeman for treating
onychomycosis caused by Candida albicans. See Pet. 2936. Further,
Shapiro teaches one skilled in the art that antifungal drugs may exhibit
cross-activity between fungi linked to onychomycosis and fungi linked to
other fungal infections. Ex. 1011, 272.

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III. CONCLUSION
For the foregoing reasons, we determine that the information presented
in the Petition, notwithstanding the Preliminary Response, establishes that
there is a reasonable likelihood that Petitioner would prevail in
demonstrating unpatentability of claims 124. The Board has not yet made a
final determination of the patentability of any of claims 124 of the 657
patent.

IV.

ORDER
Accordingly, it is
ORDERED that pursuant to 35 U.S.C. 314, an inter partes review is

hereby instituted as to claims 124 of the 657 patent on the following

grounds:
References

Basis

Claims challenged

Austin and Freeman

103

Austin, Freeman, and Chaudhuri

Austin, Freeman, and Samour
Austin, Freeman, Friedman, and Atlas
Austin, Freeman, Friedman, and Samour
Austin, Freeman, and Shapiro

103
103
103
103
103

12, 45, 1016 and

1824
6
3, 7
8
9
17

FURTHER ORDERED that pursuant to 35 U.S.C. 314(c) and 37

C.F.R. 42.4, notice is hereby given of the institution of a trial commencing
on the entry date of this decision.

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Patent 7,767,657 B2
PETITIONER:
Jeffrey Blake
jblake@merchantgould.com
Kathleen Ott
kott@merchantgould.com

PATENT OWNER:
Andrea Reister
areister@cov.com
Enrique Longton
elongton@cov.com

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