Almirall, LLC

Patent Trials and Appeals Board

May 29, 2020

IPR2019-00207 (P.T.A.B. May. 29, 2020)

Trials@uspto.gov Paper 58
Tel.: 571.272.7822 Entered: May 29. 2020

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

AMNEAL PHARMACEUTICALS LLC, AMNEAL
PHARMACEUTICALS OF NEW YORK, LLC, and MYLAN
PHARMACEUTICALS INC.,
Petitioners,

v.

ALMIRALL, LLC,
Patent Owner.
____________

IPR2019-002071
Patent 9,517,219 B2
____________

Before SUSAN L. C. MITCHELL, CHRISTOPHER G. PAULRAJ,
and RYAN H. FLAX, Administrative Patent Judges.

FLAX, Administrative Patent Judge.

JUDGMENT
Final Written Decision
Determining All Challenged Claims Unpatentable
35 U.S.C. § 318(a)

1 Mylan Pharmaceuticals Inc., the petitioner in IPR2019-01095, has been
joined in this proceeding. When referring herein to “this case” or “this
proceeding” or “this Inter Partes Review,” or variants of these, we refer to
both IPR2019-00207 and IPR2019-01095.
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Patent 9,517,219 B2

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I. INTRODUCTION
Almirall, LLC (“Patent Owner”) is the owner of U.S. Patent
9,517,219 B2 (Ex. 1001, “the ’219 patent”). Amneal Pharmaceuticals LLC,
and Amneal Pharmaceuticals of New York, LLC (collectively, “Amneal” or
“Petitioner”) filed a Petition requesting inter partes review of claims 1–8 of
the ’219 patent. Paper 3 (“Pet.”). We instituted trial in this matter on May
10, 2019. Paper 13 (“Institution Decision”). On November 27, 2019,
IPR2019-01095 was instituted between Mylan Pharmaceuticals Inc.
(“Mylan”) and Almirall, LLC over the ’219 patent and Mylan joined this
proceeding. Paper 35 (“me-too” joinder). Unless otherwise stated, we
include Mylan when referring to Petitioner herein.
Following institution and joinder, Patent Owner filed a Response.
Paper 20 (“PO Resp.”). Petitioner filed a Reply to Patent Owner’s Response
and Patent Owner filed a Sur-Reply to Petitioner’s Reply. Paper 28 (“Pet.
Reply”); Paper 37 (“PO Sur-Reply”). A hearing was conducted on February
7, 2020, where the parties presented oral argument. Paper 55 (“Hr’g Tr.”).
We have jurisdiction under 35 U.S.C. § 6. After considering the
parties’ arguments and supporting evidence, we conclude that Petitioner has
proven by a preponderance of the evidence that claims 1–8 of the ’219
patent are unpatentable. 35 U.S.C. § 316(e) (2012).
Petitioner and Patent Owner each separately filed Motions to Exclude
regarding certain evidence of record. Paper 41 (“Pet. Mot. Exclude”); Paper
43 (“PO Mot. Exclude”). We deny Patent Owner’s motion and deny-in-part
and dismiss-in-part Petitioner’s motion.
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II. BACKGROUND
A. REAL PARTIES-IN-INTEREST
Amneal identifies the real parties-in-interest to be “Amneal
Pharmaceuticals LLC; Amneal Pharmaceuticals of New York, LLC.”
Pet. 64. Patent Owner identifies the real party-in-interest to be “Almirall,
LLC (‘Almirall’)” and states that “Almirall is a wholly-owned subsidiary of
Almirall, S.A.” Paper 5. Mylan identifies the real parties-in-interest to be
“Mylan Pharmaceuticals Inc., DPT Laboratories, Ltd., Mylan Inc., and
Mylan N.V.,” which “are subsidiaries of Mylan N.V.” Mylan Pharma. Inc.
v. Almirall, LLC, IPR2019-01095, Paper 1, 68 (PTAB June 7, 2019).
B. RELATED MATTERS
Petitioner has disclosed:
The following matters would affect, or be affected by, a
decision in this proceeding: (1) IPR2018-00608, challenging
claims of the related [U.S. Patent 9,161,926 (“the ’926 patent”)],
which are directed to the same topical dapsone compositions as
the ’219 patent; and (2) Almirall, LLC v. Taro Pharmaceutical
Industries Ltd., C.A[.] 1-17-cv-00663 (consolidated) (D.Del.)
. . . . Petitioners are not a party [to the district court case].
Pet. 64–65. In IPR2018-00608, the Board determined that the challenged
claims of the ’926 patent were not shown to be unpatentable. IPR2018-
00608, Paper 50. Patent Owner identifies the same related matters. See
Paper 5. In its petition, Mylan identifies these same related matters and
added IPR2019-00207, the current proceeding, which it sought to join.
Mylan Pharma. Inc. v Almirall, LLC, IPR2019-01095, Paper 1 at 68 (PTAB
June 7, 2019).
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C. THE ’219 PATENT
The ’219 patent issued December 13, 2016, from US Application
14/855,805, which was filed October 16, 2015. Ex. 1001, codes (45), (21),
(22). This application is identified as a divisional of US Application
14/082,955, filed November 18, 2013 (now US 9,161,926 B2). Id. at code
(62). The ’219 patent further asserts priority to provisional 61/728,403 filed
November 20, 2012, and provisional 61/770,768 filed February 28, 2013.
Id. at code (60). The parties each rely upon and do not dispute that the
earliest priority date, November 20, 2012, is the applicable date for
analyzing the patentability issues in this proceeding. See, e.g., Pet. 6, 7; PO
Resp. 2, 3.
The ’219 patent has eight claims, all of which are challenged and of
which claims 1 and 6 are independent claims. Independent claim 1 is
illustrative and is reproduced below:
1. A method for treating a dermatological condition
selected from the group consisting of acne vulgaris and rosacea
comprising administering to a subject having the dermatological
condition selected from the group consisting of acne vulgaris and
rosacea a topical pharmaceutical composition comprising:
about 7.5% w/w dapsone;
about 30% w/w to about 40% w/w diethylene glycol
monoethyl ether;
about 2% w/w to about 6% w/w of a polymeric viscosity
builder comprising acrylamide/sodium acryloyldimethyl taurate
copolymer; and
water;
wherein the topical pharmaceutical composition does not
comprise adapalene.
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Id. at 15:40–16:13. Claim 6 is very similar to claim 1. The only difference
between claims 1 and 6 is that claim 6 more specifically claims “about 30%
w/w diethylene glycol monoethyl ether” (“DGME”)2 and “about 4% w/w of
the viscosity building acrylamide/sodium acryloyldimethyl taurate
copolymer” (also identified by the commercial product name Sepineo and
referred to in this proceeding as “A/SA”––see Hr’g Tr. 37:1–5). Id. at
16:23–36. Claims 2–5 each depends directly from claim 1, and claims 7 and
8 each depends directly from claim 6. Ex. 1001, 16:14–22, 16:37–40.3
The ’219 patent’s abstract states:
Dapsone and dapsone/adapalene compositions can be useful for
treating a variety of dermatological conditions. The
compositions of this disclosure include dapsone and/or
adapalene in a polymeric viscosity builder. Subject
compositions can be adjusted to optimize the dermal delivery
profile of dapsone to effectively treat dermatological conditions
and improve the efficiency of pharmaceutical products applied
to the skin. Use of the polymeric viscosity builder provides
compositions with increased concentrations of diethylene glycol
monoethyl ether relative to compositions without the polymeric
viscosity builder.
Id. at Abstract. The Specification of the ’219 patent further states:

2 DGME is also called ethoxydiglycol and is known by the commercial
product name Transcutol. See Pet. 1; Ex. 1040, 17:23–21:20 (Dr. Osborne’s
(Patent Owner’s expert) deposition testimony discussing his published
patent application (Ex. 1007) and confirming that in 2006, a formulation of
7.5% dapsone and 30% Transcutol/DGME was created).
3 The claims that were considered in IPR2018-00608 recited a similar
composition to that included as part of the method of treatment claims of the
’219 patent, except that claim 1 of the ’926 patent recited about 2% w/w to
about 6% w/w of a polymeric viscosity builder “consisting of” (instead of
“comprising”) acrylamide/sodium acryloyldimethyl taurate copolymer. See
IPR2018-00608, Paper 50, 4–5.
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Dapsone, (4,4′-diaminodiphenyl sulfone) is a medicament
possessing several beneficial medicinal activities. Dapsone is
typically administered as one of the medicinal agents used in the
treatment of leprosy. Dapsone and its derivatives are also
effective for treatment of bacterial infections, protozoal
infections such as malaria, pneumocystis carinii, and plasmonic
infections such as toxoplasmosis.
Dapsone is also useful as an anti-inflammatory agent. It
has been used to treat skin diseases characterized by the
abnormal infiltration of neutrophils, such as Dermatitis herpetic-
formis, linear IgA dermatosis, pustular psoriasis, pyoderma
gangrenosum, acne vulgaris, and Sweet’s Syndrome.
Id. at 2:12–24.
Regarding the additional claimed components used in the claimed
acne/rosacea-treating method, the ’219 patent states “[d]iethylene glycol
monoethyl ether is a solubilizer for dapsone, thereby allowing compositions
to be prepared with increased solubilized concentrations of dapsone.” Id. at
2:48–50. The ’219 patent further states:
[U]se of a polymeric viscosity builder minimizes the intensity of
yellowing of the composition caused by the increased solubility
of dapsone in diethylene glycol monoethyl ether. In addition, the
polymeric viscosity builder influences dapsone crystallization.
This, in turn, results in compositions with improved aesthetics
(i.e., reduction in particle size which minimizes “gritty” feeling
upon application).
Id. at 2:54–61. Regarding this polymeric viscosity builder, the ’219 patent
further states, “[i]n some embodiments, the polymeric viscosity builder is an
acrylamide/sodium acryloyldimethyltaurate copolymer, and further includes
isohexadecane, sorbitan oleate, water, and Polysorbate 80.” Id. at 5:47–50.
The ’219 patent describes 62 different “embodiments” where various
amounts of these, and other, components are provided for an acne/rosacea-
treating composition. Id. at 6:58–12:40. The ’219 patent also describes
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eight different examples of formulations including these and other
components. Id. at 12:42–15:33.
D. PETITIONER’S ASSERTED GROUNDS FOR UNPATENTABILITY
Petitioner asserts two grounds for unpatentability, each under
35 U.S.C. § 103(a) for obviousness, as set forth below. Pet. 20–55.

Claims Challenged 35 U.S.C. § References/Basis
Ground 1 1–8 103(a) Garrett,4 Nadau-Fourcade5
Ground 2 1–8 103(a) Garrett, Bonacucina6

In support of these grounds for unpatentability, Petitioner submits, inter alia,
a Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.,7
and a Declaration of Elaine S. Gilmore, M.D., Ph.D.8
E. OVERVIEW OF THE PRIOR ART
Garrett
Garrett, entitled Topical Treatment with Dapsone in G6PD-Deficient
Patients, is the May 14, 2009, published version of international application
PCT/US/2007/023468, which was filed November 7, 2007. Ex. 1004, codes

4 WO 2009/061298 Al (published May 14, 2009) (Ex. 1004, “Garrett”).
5 WO 2010/072958 A2 (published July 1, 2010), English translation
(Ex. 1005, “Nadau-Fourcade”).
6 Giulia Bonacucina et al., Characterization and Stability of Emulsion Gels
Based on Acrylamide/Sodium Acryloyldimethyl Taurate Copolymer, 10(2)
AAPS PHARMSCITECH 368–75 (2009) (Ex. 1015, “Bonacucina”).
7 Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
(Ex. 1002, “Michniak-Kohn Declaration”).
8 Declaration of Elaine S. Gilmore, M.D., Ph.D. (Ex. 1018, “Gilmore
Declaration”).
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(21), (22), (54). Garrett is prior art with respect to the claims of the ’219
patent.
Garrett states:
The present invention provides a pharmaceutical carrier system
comprising a dermatological composition that is a semi-solid
aqueous gel, wherein dapsone is dissolved in the gel such that the
dapsone has the capacity to cross the stratum corneum layer of
the epidermis, and wherein the composition also contains
dapsone in a microparticulate state that does not readily cross the
stratum corneum of the epidermis. The present invention also
discloses the treatment of dermatological conditions in G6PD-
deficient patients with the composition, while avoiding adverse
hematologic effects.
Id. at Abstract.
In its Background section, Garrett states “[d]apsone is a sulfone with
both anti-inflammatory and antimicrobial properties” that has been used in
an oral formulation to treat a variety of disorders, including severe acne, but
notes that oral dapsone use presents issues relating to hemolysis and
hemolytic anemia, which causes oxidative damage to red blood cells in
association with the dapsone hydroxylamine metabolite. Id. at 2:7–18.9
Garrett identifies that individuals who are glucose-6-phosphate
dehydrogenase (G6PD) enzyme deficient (G6PD-deficient) are more prone
to such adverse reactions to dapsone, and that its invention seeks a method
of treating dermatological conditions in patients without the adverse
hematologic effects associated with oral dapsone administration. Id. at
2:18–3:6.

9 We note that, as submitted by Petitioner, Garrett (Ex. 1004) includes page
numbering at both the top and bottoms of the pages. We use the pagination
at the bottom of the exhibit’s pages, as has Petitioner.
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Furthermore, Garrett identifies that:
Aczone™ gel, 5%,[10] a topical formulation of dapsone, was
developed to deliver therapeutic concentrations of dapsone to the
skin. The United States Food and Drug Administration (US
FDA) approved Aczone™ gel, 5%, for the treatment of acne
vulgaris, but required certain language in the package insert due
to the US FDA’s concern that this drug carries a significant risk
of serious hematological adverse effects, including hemolysis, in
G6PD-deficient patients.
The US FDA required that the Aczone™ gel, 5%, label
state that all patients should be screened for G6PD deficiency
prior to initiation of Aczone™ treatment, with routine
monitoring of complete blood counts and reticulocyte counts
during treatment with Aczone™ in those patients identified as
having a history of anemia and predisposition to increased
hemolytic effect with dapsone (e.g., G6PD deficiency). While
previous clinical studies did not demonstrate evidence of
clinically significant anemia, an increased reticulocyte count and
a decreased hemoglobin level were noted to be associated in a
G6PD deficient patient treated with Aczone™ gel, 5% for acne
vulgaris.
Id. at 10:6–21. Garrett then noted that the results from its disclosed
invention demonstrate “that treatment of G6PD-deficient patients with the
Aczone gel, 5%, formulation does not result in adverse hematological
effects.” Id. at 10:22–25. Garrett also notes that previous clinical studies
showed that treatment with topical dapsone 5% gel (i.e., Aczone 5%) results
in ≤ 1% systemic exposure. Id. at 12:1–4.

10 Aczone (dapsone) Gel 5% (“Aczone 5%”) is Patent Owner’s first FDA-
approved (in 2005) topical dapsone product for treating acne. Hr’g Tr.
11:22–27; Ex. 2044; Ex. 2045; see also Ex. 1061 (Patent Owner’s second
FDA-approved dapsone acne treatment is Aczone (dapsone) Gel 7.5%).
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Further, Garrett states:
The present invention provides methods to treat glucose-
6-phosphate dehydrogenase-deficient patients with dapsone. In
one embodiment, the treatment is directed to dermatological
conditions and the treatment is provided by a topical dapsone
composition. The composition may include dissolved dapsone
and microparticulate dapsone. In certain embodiments, the
dermatological condition to be treated is inflammatory acne,
non-inflammatory acne or rosacea.
Id. at 3:9–15. Garrett states that “[i]n one preferred embodiment, the
composition includes about 0.5% to 4.0% carbomer [i.e., Carbopol11]; about
53.8% to 84.2% water; about 10% to 30% ethoxydiglycol [i.e., DGME];
about 0.2% methylparaben; about 5% to 10% dapsone in a microparticulate
and dissolved state; and about 0.1% to 2% sodium hydroxide solution.” Id.
at 4:2–5, 15:3–14. Of note, neither this preferred embodiment nor any other
formulation of Garrett is disclosed as including the pharmaceutical
adapalene. See generally id. Garrett states that “[i]n each of these
embodiments, the dapsone may exist as a microparticulate form, a dissolved
form, or both.” Id. at 4:29–31.
Further, Garret states that such compositions are used by
applying topically a dermatological gel composition that
includes a semisolid aqueous gel; dapsone dissolved in the gel,
wherein the dapsone has the capacity to cross the stratum
corneum layer of the epidermis and become available
systemically; and a microparticulate dapsone dispersed in the
gel, wherein the microparticulate dapsone does not cross the
stratum corneum of the epidermis in its microparticulate state.

11 Garrett identifies that the product Carbopol “is one of numerous cross-
linked acrylic acid polymers that are given the general adopted name
carbomer.” Ex. 1004, 13:17–18; see also Ex. 1005, 47:15–17 (Carbopol is a
carbomer gelling agent).
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The dermatological condition can include inflammatory acne,
non-inflammatory acne and/or rosacea.
Id. at 4:18–24.12 Garrett states that, “[t]ypically, for most persons affected
with acne, application [of its dapsone compositions] once or twice during a
day is sufficient” for treatment. Id. at 23:8–12.
Garrett’s formulations include a thickening agent. Garrett discloses
that:
Thickening agents include polymer thickeners. Polymer
thickeners that may be used include those known to one skilled
in the art, such as hydrophilic and hydroalcoholic gelling agents
frequently used in the cosmetic and pharmaceutical industries.
Preferably, the hydrophilic or hydroalcoholic gelling agent
comprises “CARBOPOL®” (B. F. Goodrich, Cleveland, Ohio),
“HYPAN®” (Kingston Technologies, Dayton, N.J.),
“NATROSOL®” (Aqualon, Wilmington, Del.), “KLUCEL®”
(Aqualon, Wilmington, Del.), or “STABILEZE®” (ISP
Technologies, Wayne, N.J.). Preferably, the gelling agent
comprises between about 0.2% to about 4% by weight of the
composition. More particularly, the preferred compositional
weight percent range for “CARBOPOL®” is between about
0.5% to about 2%, while the preferred weight percent range for
“NATROSOL®” and “KLUCEL®” is between about 0.5% to
about 4%. The preferred compositional weight percent range for

12 Garrett does not assert that topical dapsone formulations for treating acne
were new as of its disclosure, and it identifies and incorporates by reference
in its entirety, inter alia, U.S. Patent 5,863,560 to Osborne (Ex. 1016,
“Osborne ’560”). Ex. 1004, 11:28–33. David W. Osborne, the named
inventor of Osborne ’560, is Patent Owner’s expert witnesses in this
proceeding (see Ex. 2057; Hr’g Tr. 9:15–16) and Osborne ’560, similar to
Garrett, discloses a topical pharmaceutical for treating acne containing
0.5–10% by weight dapsone in dissolved and microparticulate states, and
also containing polymer thickeners (gelling agents) such as the carbomer
product CARBOPOL, methylparaben, DGME, and water. Ex. 1016,
Abstract, 4:7–6:6. Furthermore, like Garrett, no embodiment disclosed in
Osborne ’560 contains adapalene. See generally id.
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both “HYPAN®” and “STABILEZE®” is between about 0.5%
to about 4%.
Id. at 13:3–16.
Garrett indicates that its composition’s dapsone and DGME allow for
an optimized ratio of microparticulate drug to dissolved drug, which
determines the amount of drug delivered as compared to the amount of drug
retained in the formulation. Id. at 14:29–32. Garrett further states that:
The relative percentages for each of the reagents used in
the present invention may vary depending upon the desired
strength of the target formulation, gel viscosity, and the desired
ratio of microparticulate to dissolved dapsone. Unless otherwise
designated, all reagents listed [in Garrett] are commonly known
by one of ordinary skill in the art and are commercially available
from pharmaceutical or cosmetic excipient suppliers.
Id. at 18:17–22; see also id. at 23:4–7 (the carrier system can be adjusted to
optimize the delivery profile of the pharmacology of the active drug and the
nature of the disease state).
Garrett includes the following claim:
5. The method of claim 4,[13] comprising:
about 0.5% to 4.0% carbomer;
about 53.8% to 84.2% water;
about 10% to 30% ethoxydiglycol;
about 0.2% methylparaben;

13 Garrett’s independent claim 4, from which the quoted claim 5 depends, is
directed to “[a] method to treat a dermatological condition in a glucose-6-
phosphate dehydrogenase-deficient patient comprising applying topically a
dermatological gel composition including microparticulate pharmaceutical
and dissolved pharmaceutical.” Ex. 1004, 42:15–18. Garrett’s claim 8
recites that the dermatological condition of claim 4 can be inflammatory or
non-inflammatory acne or rosacea. Id. at 43:12–14.
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about 5% to 10% dapsone in a microparticulate and dissolved
state;
and about 0.1 to 2% sodium hydroxide solution.
Id. at 42:26–33.
Nadau-Fourcade
Nadau-Fourcade is the July 1, 2020, published version of international
application PCT/FR2009/052634, which was filed December 21, 2009, and
asserts priority to US provisional 61/193,793, filed December 23, 2008.
Ex. 1005, codes (43), (21), (22), (30). Nadau-Fourcade is prior art to the
claims of the ’219 patent.
Nadau-Fourcade states that that its
invention relates to a topical pharmaceutical composition
containing, as an active pharmaceutical ingredient, a water-
sensitive compound[14] in a dissolved form in a physiologically
acceptable medium, to a method for preparing same, and to the
use thereof in dermatology.
Id. at Abstract; see also id. at 40:21, 51:1–12 (a disclosed dermatological use
is “for treating acne” and for treating “acne rosacea”).15

14 Patent Owner identified dapsone as such a water-sensitive active
ingredient. Hr’g Tr. 50:7–12; see also Ex. 2057 ¶ 160 (Osborne
Declaration: “[W]hile dapsone is not mentioned in Nadau-Fourcade, a
POSA would have recognized this compound to be ‘water-sensitive.’”
(citing Ex. 1009, 3 (“Dapsone has negligible water solubility . . . .”))).
15 Nadau-Fourcade was published in French; however, Exhibit 1005 includes
both the French version and an English translation of the publication; the
English translation begins at page 37 of the exhibit. Page numbering is
provided at the bottom of each page of Exhibit 1005, which is how we cite
to the reference herein. See Ex. 1006 (certification of Nadau-Fourcade’s
translation from French to English).
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Nadau-Fourcade states:
Many active ingredients are difficult to use because they do not
dissolve easily in the commonly-used cosmetic or
pharmaceutical solvents, particularly water, and/or they are
sensitive to an aqueous, oxidizing environment. This water
sensitivity may lead to chemical instability of the active
ingredient and/or to crystallization of the initially-dissolved
active ingredient. This water sensitivity thus limits their
formulation in topically-applied cosmetic or dermatological
compositions.
Id. at 38:11–17. Nadau-Fourcade discloses that, to achieve a physically and
chemically stable composition with a water-sensitive active ingredient, such
a composition incudes:
- at least one water-sensitive active ingredient,
- a fatty phase containing at least one lipophilic phase that is a
solvent for the active ingredient,
- at least one polyol,
- at least 5% water,
characterized in that it is topical and that it includes at least one
surfactant from the sucroester or polyglycerol ester family.
Id. at 41:5–11; see also id. at 49:5–50:35 (describing topical composition of
oil-in-water emulsion type preferably containing a gelling agent). In
addition to these components, Nadau-Fourcade also teaches that “[i]n one
particularly preferred embodiment, the composition according to the
invention also contains one or more hydrophilic-phase gelling agents.” Id. at
47:11–12.
Nadau-Fourcade discloses several types and examples of gelling
agents, as well as a range of preferred concentrations (overlapping with
Garrett’s disclosure) that are suitable for its composition. Id. at 47:12–48:9.
Nadau-Fourcade states that “[p]referred gelling agents include carbomers,
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for instance Carbopol 980® or 981®, polyacrylamides, for instance Sepineo
P 600® or Simulgel 600 PHA®, and polysaccharides, for instance xanthan
gum” and that “[t]he gelling agent as described above may be used . . . more
preferentially ranging from 0.01% to 5%.” Id. at 48:5–9.
Nadau-Fourcade discloses several examples of water-sensitive active
composition formulations including gelling agents. Two such examples,
Examples 6 and 13, utilize similar components (e.g., sucrose laurate, sucrose
palmitate, demineralized water, glycerol, calcitriol, BHT, caprylic/capric
triglycerides, mineral oil, methyl paraben), but different gelling agents. For
comparison, we reproduce Nadau-Fourcade’s tables of components for these
two examples below:

Id. at 57, 62; see Hr’g Tr. 64:10–15 (Patent Owner directing the panel to
compare these examples at oral argument); see also Ex. 1002 ¶ 61
(Dr. Michniak-Kohn addressing Examples 5, 8, and 9). In the two examples
above, one formulation includes 0.10 % carbomer and the other formulation
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uses 0.20 % Simulgel 600 (A/SA).16 See Hr’g Tr. 72:1–23 (when asked
about these two examples from the reference and the similar amounts of
gelling agents, Patent Owner stated that “[n]umerically it’s not” a huge
difference and that in “evaluating[] [the examples,] does that difference
matter for the function of stabilizing dapsone . . . I don’t think so.”).
Bonacucina
Bonacucina is an article discussing research about Sepineo P 600,
published April 2, 2009. Ex. 1015, 368.17 Bonacucina is prior art with
respect to the claims of the ’219 patent.
Bonacucina states, “[i]n this work, the self-gelling properties of the
acrylamide/sodium acryloyldimethyl taurate copolymer (Sepineo P 600),
both alone and as dispersing phase for the preparation of o/w emulsion gels,
have been investigated by oscillatory rheological measurements and acoustic
spectroscopy.” Id. at 368–69.
Bonacucina states that:
Sepineo P 600, a concentrated dispersion of acrylamide/sodium
acryloyldimethyl taurate copolymer in isohexadecane, has self-
gelling and thickening properties and the ability to emulsify oily
phases, which make it easy to use in the formulation of gels and
o/w emulsion gels. In this paper, gels were prepared using a
Sepineo P 600 concentration between the 0.5% and 5% (w/w).
Id. at 368 (Abstract). Bonacucina further states that “the gel structure is
characterized by weak polymer–polymer interactions, an advantageous
characteristic for topical administration, as the sample is thus easier to rub

16 Simulgel 600 is an A/SA gelling agent, which we understand is also
referred to as Sepineo P 600. See Hr’g Tr. 65:17–66:2 (Patent Owner stating
that Simulgel and Sepineo are the same).
17 We use Bonacucina’s page numbering, original to the publication, herein.
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into the skin.” Id. Bonacucina’s Abstract concludes: “Sepineo P 600 gel
and emulsion gel are very effective systems for use in topical and other types
of applications.” Id.
Bonacucina disclosed that it combined Sepineo gels with “Sepicide
HB, an anti-microbial agent composed of a mixture of phenoxyethanol,
methylparaben, ethylparaben, propylparaben, and butylparaben,” and also
“almond oil . . . because it is widely used in pharmaceutical and cosmetic
applications for its practically inexistent toxicity and its high tolerability.”
Id. at 369.
Bonacucina concludes “that Sepineo P 600 thickens and gels well, a
property that depends strongly on polymer concentration. Concentration
increases from 0.5% (w/w) to 5% (w/w) modified the viscoelastic properties
of the Sepineo samples, changing the typical behavior of a concentrated non-
entangled solution to that of a ‘gel-like’ sample.” Id. at 374. Bonacucina
further concludes “Sepineo P 600 is a prime candidate for use in the
formulation of gels and emulsion gels with rheological properties suitable
for topical administration.” Id.
III. DISCUSSION
A. ORDINARY LEVEL OF SKILL IN THE ART
Petitioner asserts that
A POSA [(person of ordinary skill in the art)] relevant to
the ’219 patent would have the knowledge of both a formulator
of topical pharmaceutical compositions and clinician with
experience treating dermatological diseases.
The formulator POSA would possess a Ph.D. or equivalent
degree in pharmaceutics, chemistry or a related discipline such
as pharmacology, who also has practical experience (at least two
years) of formulating topical drug delivery products, or the
POSA could possess a Bachelors or Masters degree in one of the
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preceding disciplines with a greater level (at least four years) of
the same formulating experience. (AMN1002, ¶¶16-18).
The clinical POSA would possess an M.D. with a board
certification in dermatology with at least two years of experience
in dermatology, or otherwise treating skin conditions. It is also
possible that an M.D. without a certification in dermatology (i.e.,
a primary care physician, or a pediatrician) may qualify as a
clinical POSA, assuming that they have more than two years of
knowledge and experience treating skin conditions. (AMN1018,
¶¶19-21).
Pet. 6–7. Petitioner’s experts, Dr. Michniak-Kohn and Dr. Gilmore, echo
these definitions in their declarations. Ex. 1002 ¶¶ 17–18; Ex. 1018 ¶ 20.
Petitioner’s expert, Dr. Michniak-Kohn, adds:
[T]he person of ordinary skill would have knowledge and skill
relating to the use, function, and formulation of pharmaceutical
actives and excipients; knowledge and training regarding the
equipment, processes and techniques used to analyze and test
formulation materials; and an understanding of pharmacokinetic
principles and how they relate to drug development and use.
Ex. 1002 ¶ 18.
Patent Owner does not directly contest this combination, team-
oriented definition of the relevant “skilled artisans,” but states:
Patent [O]wner agrees with the examiner of what issued as the
ʼ219 patent, that “the level of skill in the art is high and is at least
that of a medical doctor with several years of experience in the
art.” Ex. 1017 at 54; Ex. 2055 ¶ 20.
To the extent that a skilled physician would have sought
assistance, they would likely have consulted a skilled drug
formulator. See Ex. 2055 ¶ [sic][.] The ordinary level of skill of
that such formulator would possess (i) a bachelor- or master-
level degree in chemistry, polymer science, pharmaceutics, or a
related discipline, plus at least three years of experience in drug
delivery, pharmaceutical formulations, or a related field; or (ii) a
doctoral degree in chemistry, polymer science, pharmaceutics, or
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a related discipline, plus some experience in drug delivery,
pharmaceutical formulations, or a related field. Ex. 2057 ¶ 86.
PO Resp. 27.
We see very little difference between Petitioner’s and Patent Owner’s
proposed definitions of the skilled artisan. Neither party argues that the
other side’s definition is incorrect. See, e.g., Hr’g Tr. 5:10–16. Neither
party asserts that selecting their definition over the other side’s definition is
determinative of any issues in this matter. See generally Pet.; PO Resp.
Each definition proposes a collaboration between a formulator and a
clinician/medical doctor, each having either a very advanced degree or a
lesser degree (e.g., in chemistry, polymer science, pharmaceutics, or a
related discipline) and proportional experience (2, 3, or 4, or “several” years)
where more experience compensates for less education.
We find that Petitioner’s definition is more specifically tailored to the
claimed subject matter of the ’219 patent as it states that a person of ordinary
skill in the art would have possessed the knowledge of both a formulator of
topical pharmaceutical compositions and clinician with experience treating
dermatological diseases, whereas Patent Owner’s definition more broadly
encompasses any medical doctor and drug formulator. Therefore, we accept
and use Petitioner’s definition of the skilled artisan, as set forth above, but
with the understanding that our conclusions would not change even under
Patent Owner’s definition. We have further taken into account the level of
skill in the art reflected in the prior art of record, which is consistent with
Petitioner’s definition. Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed.
Cir. 2001) (“[T]he prior art itself [may] reflect[] an appropriate level” as
evidence of the ordinary level of skill in the art. (quoting Litton Indus.
Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir. 1985))).
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When required below, our determinations and conclusions are from the
perspective of such a skilled artisan.
B. CLAIM CONSTRUCTION
Based on the filing date of the Petition (November 6, 2018), 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. § 42.100(b) (2018); Cuozzo Speed Techs., LLC v.
Lee, 136 S. Ct. 2131, 2142–46 (2016).18 Under that standard, and absent
any special definitions, we generally give claim terms their ordinary and
customary meaning, as would have been understood by one of ordinary skill
in the art in the context of the entire patent disclosure. In re Translogic
Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
Any special definitions for claim terms must be set forth in the
specification with reasonable clarity, deliberateness, and precision. See In re
Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). In the absence of such a
definition, limitations are not to be read from the specification into the
claims. See In re Van Geuns, 988 F.2d 1181, 1184 (Fed. Cir. 1993). “[W]e
need only construe terms ‘that are in controversy, and only to the extent
necessary to resolve the controversy . . . .’” Nidec Motor Corp. v.

18 On October 11, 2018, the USPTO revised its rules to harmonize the
Board’s claim construction standard for interpreting claims in trial
proceedings before the Patent Trial and Appeal Board with the standard used
in federal district court. Changes to the Claim Construction Standard for
Interpreting Claims in Trial Proceedings Before the Patent Trial and Appeal
Board, 83 Fed. Reg. 51,340 (Oct. 11, 2018) (codified at 37 C.F.R.
§ 42.100(b) (2019)). This rule change, however, applies to petitions filed on
or after November 13, 2018, and therefore, does not apply to this
proceeding, where the Petition was filed on November 6, 2018. Id.
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Zhongshan Broad Ocean Motor Co. Ltd., 868 F.3d 1013, 1017 (Fed. Cir.
2017) (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795,
803 (Fed. Cir. 1999)).
Petitioner states “[t]he broadest reasonable interpretation of the term
‘acne vulgaris,’ found in claims 1, 5, 6, and 8, means ‘acne consisting of
inflammatory or non-inflammatory lesions.’” Pet. 19–20 (citing Ex. 1018
¶¶ 22–26); see also (as further cited by Petitioner) Ex. 1001, 4:2–28;
Ex. 1004, 4:45–48, 25:8–9. Patent Owner argues “acne vulgaris” does not
require construction and is not in dispute. PO Resp. 28.
In view of the disputed issues in this proceeding, we find it
unnecessary to expressly construe “acne vulgaris” or any other claim terms.
C. APPLICABLE LEGAL STANDARDS FOR PATENTABILITY
“In an [inter partes review], the petitioner has the burden from the
onset to show with particularity why the patent it challenges is
unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed.
Cir. 2016) (citing 35 U.S.C. § 312(a)(3) (requiring inter partes review
petitions to identify “with particularity . . . the evidence that supports the
grounds for the challenge to each claim”)). This burden of persuasion never
shifts to Patent Owner. See Dynamic Drinkware, LLC v. Nat’l Graphics,
Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015) (discussing the burden of proof in
inter partes review).
Regarding obviousness, the Supreme Court in KSR International Co.
v. Teleflex Inc., 550 U.S. 398 (2007), reaffirmed the framework for
determining obviousness as set forth in Graham v. John Deere Co., 383 U.S.
1 (1966). The KSR Court summarized the four factual inquiries set forth in
Graham (383 U.S. at 17–18) that are applied in determining whether a claim
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is reasonably likely to be unpatentable as obvious under 35 U.S.C. § 103(a)
as: (1) determining the scope and content of the prior art; (2) ascertaining
the differences between the prior art and the claims at issue; (3) resolving the
level of ordinary skill in the pertinent art; and (4) considering objective
evidence indicating obviousness or non-obviousness. KSR, 550 U.S. at 406.
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
Id. at 416. “[W]hen the question is whether a patent claiming the
combination of elements of prior art is obvious,” the answer depends on
“whether the improvement is more than the predictable use of prior art
elements according to their established functions.” Id. at 417. It is generally
obvious to those skilled in the art to substitute one known equivalent for
another. See In re Omeprazole Patent Litigation, 483 F.3d 1364, 1374 (Fed.
Cir. 2007) (“[T]his court finds no . . . error in [the] conclusion that it would
have been obvious to one skilled in the art to substitute one ARC [alkaline
reactive compound] for another.”); see also Wm. Wrigley Jr. Co. v. Cadbury
Adams USA LLC, 683 F.3d 1356, 1364 (Fed. Cir. 2012) (the combination of
known elements and substitution of one well known agent for another is
obvious).
Concerning claims reciting a range for a given variable,
where there is a range disclosed in the prior art, and the claimed
invention falls within that range, there is a presumption of
obviousness. But the presumption will be rebutted if it can be
shown: (1) That the prior art taught away from the claimed
invention, In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997);
or (2) that there are new and unexpected results relative to the
prior art, In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990).
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Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir.
2004); see also Titanium Metals Corp. of Am. v. Banner, 778 F.2d 775, 783
(Fed.Cir.1985) (invention was obvious because it was close to prior art
range). “Selecting a narrow range from within a somewhat broader range
disclosed in a prior art reference is no less obvious than identifying a range
that simply overlaps a disclosed range.” In re Peterson, 315 F.3d 1325,
1329–30 (Fed. Cir. 2003). A claimed range overlaps with a prior art range if
the two ranges share a common endpoint (e.g., claim range of 50–100 Å
overlaps with prior art range of 100–600 Å). In re Geisler, 116 F.3d 1465,
1469 (Fed. Cir. 1997). In the context of an inter partes review, the Federal
Circuit has held that overlapping and abutting ranges found in the prior art
create a “presumption of obviousness,” which may be rebutted by a showing
of criticality of the claimed range, that the prior art taught away from the
claimed range, or that the parameter was not recognized as “result-
effective.” E.I. DuPont de Nemours & Company v. Synvina C.V., 904 F.3d
996, 1006 (Fed. Cir. 2018).
Relatedly, “the discovery of an optimum value of a variable in a
known process is normally obvious,” but exceptions to this rule include
(1) the results of optimizing a variable were unexpectedly good and (2) the
parameter optimized was not recognized in the prior art as one that would
affect the results. In re Antonie, 559 F.2d 618, 620 (CCPA 1977).
Expanding on the obviousness of optimization,
“where the general conditions of a claim are disclosed in the prior
art, it is not inventive to discover the optimum or workable
ranges by routine experimentation.” [In re] Aller, 220 F.2d
[454,] 456 [(CCPA 1955)]. [However,] [t]his rule is limited to
cases in which the optimized variable is a “result-effective
variable.” In re Antonie, 559 F.2d 618, 620 (CCPA 1977).
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In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012).
With these standards in mind, and in view of the definition of the
skilled artisan (supra Section III.A) discussed above, we address the parties’
positions and evidence of record below.
D. OBVIOUSNESS BASED ON GARRETT AND NADAU-FOURCADE (GROUND 1)
AND GARRETT AND BONACUCINA (GROUND 2)
Petitioner presents two separate obviousness challenges in this
proceeding, both of which rely upon the teachings of Garrett in combination
with other references. Under Ground 1 of the Petition, Petitioner asserts that
claims 1–8 would have been obvious under 35 U.S.C. § 103(a) over Garrett
and Nadau-Fourcade. Pet. 21–40. As an alternative to Ground 1, Petitioner
asserts that, under Ground 2, claims 1–8 would have been obvious over
Garrett and Bonacucina. Id. at 40–55. Patent Owner addresses Petitioner’s
Grounds 1 and 2 together, generally addressing claim 1, and does not present
separate arguments for any of the dependent claims. See PO Resp. 28–60.
Therefore, we address both grounds together. We focus our analysis
primarily on the parties’ contentions with regard to independent claims 1 and
6, and then separately address Petitioner’s proof for dependent claims 2–5,
7, and 8.
For the reasons discussed below, we conclude that Petitioner has
proven by a preponderance of the evidence that claims 1–8 are unpatentable
under 35 U.S.C. § 103(a) as obvious based on the combination of Garrett
and Nadau-Fourcade and separately based on the combination of Garrett and
Bonacucina.
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Claims 1 and 6
Independent claims 1 and 6 are substantially similar, as noted above at
Section II.C. Each is directed to a method for treating acne vulgaris (or
rosacea) by administering a topical pharmaceutical composition including:
(1) about 7.5% w/w dapsone,
(2) about 30–40% w/w DGME (for claim 1), or more
specifically about 30% w/w DGME (for claim 6),
(3) about 2–6% (for claim 1), or more specifically about 4% (for
claim 6), of a polymeric viscosity builder comprising A/SA
(e.g., Sepineo), and
(4) water,
(5) but not including adapalene.
Ex. 1001, 15:40–13, 15:23–36; see also Ex. 1017, 283 (the prosecution
history of the ’219 patent including an office action response dated Feb. 18,
2016, where the applicant identified the “formulation of the instant claims”
to “utilize[] as acrylamide/sodium acryloyldimethyl taurate copolymer . . .
‘Sepineo™ P 600’.”). Because claims 1 and 6 are similar, differing only in
the narrower concentration ranges for DGME and polymeric viscosity
builder recited in claim 6, Petitioner asserts the same evidence for each
claim and Patent Owner does not separately argue the claims. We address
the claims together as there is no material dispute over their differences.
Analysis of Ground 1 – Obviousness Based on Garret and
Nadau-Fourcade
Regarding Ground 1, Petitioner asserts claims 1 and 6 would have
been obvious over the combination of Garrett and Nadau-Fourcade. Pet. 21–
38. Petitioner provides a claim chart addressing each limitation of claims 1
and 6 as taught or suggested by the prior art (quoting disclosure therefrom),
which we reproduce below for claim 1:
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’219 Patent Claims Garret in view of Nadau-Fourcade
1. A method for
treating a
dermatological
condition selected
from the group
consisting of acne
vulgaris and rosacea
comprising
administering to a
subject having the
dermatological
condition selected
from the group
consisting of acne
vulgaris and rosacea
a topical
pharmaceutical
composition
comprising:

Garrett: “The present invention provides methods
to treat glucose-6-phosphate dehydrogenase-
deficient patients with dapsone. In one
embodiment, the treatment is directed to
dermatological conditions and the treatment is
provided by a topical dapsone composition. The
composition may include dissolved dapsone and
microparticulate dapsone. In certain
embodiments, the dermatological condition to be
treated is inflammatory acne, non-inflammatory
acne or rosacea.” (AMN1004, 3:9-15).

[a] about 7.5% w/w
dapsone;
Garrett: “In one preferred embodiment, the
composition includes about 0.5% to 4.0%
carbomer; about 53.8% to 84.2% water; about
10% to 30% ethoxydiglycol; about 0.2%
methylparaben; about 5% to 10% dapsone in a
microparticulate and dissolved state; and about
0.1% to 2% sodium hydroxide solution.”
(AMN1004, 4:2-5)

[b] about 30% w/w to
about 40% w/w
diethylene glycol
monoethyl ether;
Garrett: “In one preferred embodiment, the
composition includes about 0.5% to 4.0%
carbomer; about 53.8% to 84.2% water; about
10% to 30% ethoxydiglycol; about 0.2%
methylparaben; about 5% to 10% dapsone in a
microparticulate and dissolved state; and about
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0.1% to 2% sodium hydroxide solution.”
(AMN1004, 4:2-5)

[c] about 2% w/w to
about 6% w/w of a
polymeric viscosity
builder comprising
acrylamide/sodium
acryloyldimethyl
taurate copolymer;
Garrett: “Thickening agents include polymer
thickeners. Polymer thickeners that may be used
include those known to one skilled in the art, such
as hydrophilic and hydroalcoholic gelling agents
frequently used in the cosmetic and
pharmaceutical industries.” (AMN1004, 13:3-5)

“Preferably, the gelling agent comprises between
about 0.2% to about 4% by weight of the
composition.” (AMN1004, 13:10-11)

Nadau-Fourcade: “Preferred gelling agents
include carbomers, for instance Carbopol 980® or
981®, polyarylamides, for instance Sepineo P
600® or Simulgel 600 PHA®, and
polysaccharides, for instance xanthan gum.”
(AMN1005, 48:5-7).

[d] and water; Garrett: “The present invention provides a
pharmaceutical carrier system comprising a
dermatological composition that is a semi-solid
aqueous gel . . . .” (AMN1004, Abstract)

“In one preferred embodiment, the composition
includes about 0.5% to 4.0% carbomer; about
53.8% to 84.2% water; about 10% to 30%
ethoxydiglycol; about 0.2% methylparaben; about
5% to 10% dapsone in a microparticulate and
dissolved state; and about 0.1% to 2% sodium
hydroxide solution.” (AMN1004, 4:2-5)

[e] wherein the
[topical]
pharmaceutical
composition does not
comprise adapalene.
Garrett: “The present invention provides methods
to treat glucose-6-phosphate dehydrogenase-
deficient patients with dapsone.” (AMN1004, 3:9-
10)

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Pet. 21–24 (also citing Ex. 1002 ¶¶ 37–38, 48; Ex. 1018 ¶¶ 35–42).
Petitioner’s chart further asserts that the same evidence teaches or suggest
the respective limitations of claim 6. Id.
As can be ascertained from the chart above, Petitioner asserts that
Garrett discloses topical dapsone compositions for treating acne with each of
the components of claims 1 and 6, in the claimed amounts, with the only
exception being the use of a different thickening agent than the claimed
A/SA copolymer. Pet. 21–38 (citing Ex. 1002 ¶¶ 23, 25, 43, 49–54;
Ex. 1004, Abstract, 3:9–4:24, 12:1–4, 14:13–14, 14:20–15:18, 18:17–22,
18:27–29, 23:5–39:25 (Example 1)). Petitioner further asserts that Nadau-
Fourcade teaches utilizing an A/SA copolymer as a preferred thickening
agent for topical acne-treating compositions of water insoluble drugs, such
as dapsone, that it was a known alternative to Garrett’s preferred carbomer
thickening agent, and that using the A/SA copolymer instead of the
carbomer thickening agent would have been obvious and predictable. Pet.
31–35 (citing Ex. 1002 ¶¶ 56–57; Ex. 1005, Abstract, 38:5, 40:26–33, 41:1–
3, 47:12–32; 48:1–7).
Petitioner asserts that a skilled artisan would have recognized that
Sepineo (A/SA copolymer) and Carbopol (carbomer) were known
alternatives that were interchangeable with each other for functioning as a
gelling agent in a topical composition for a water-insoluble drug, and this
was exemplified by Nadau-Fourcade. Id. Petitioner also asserts that the
amounts of carbomer and A/SA used as thickening agents substantially
overlap between the two references, where Garrett discloses using about
0.2–4% of its preferred gelling agent and Nadau-Fourcade teaches using
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0.01–5% of its preferred gelling agent. Id. at 34 (citing Ex. 1004, 13:2–25;
Ex. 1005, 48:5–10; Ex. 1002 ¶ 58). Petitioner asserts such prior art ranges
also overlap with the claimed range of “about 2% to about 6%” recited in
claim 1 and encompass the narrower “about 4%” range recited in claim 6.
Id.; see also id. at 35–36 (addressing claim 6).
Petitioner asserts that the skilled artisan would have had a reasonable
expectation of successfully substituting the carbomer thickening agent of
Garrett with an A/SA copolymer based on their known interchangeability as
disclosed in Nadau-Fourcade. Pet. 33, 36–38 (citing Ex. 1002 ¶¶ 61–62;
Ex. 1004, 3:33–4:24, 13:3–5, 14:10–15:18; Ex. 1005, 39:10–24, 48:5–7,
64:10–65:5 (Example 16)). Petitioner asserts that the prior art informed the
skilled artisan that the claimed dapsone, water, DGME, and methyl paraben
were compatible components for a topical formulation, and that a
hydrophilic or hydroalcoholic thickening agent, such as carbomer, could also
be included. Id. at 37 (citing, inter alia, Ex. 1002 ¶¶ 61–62).
Petitioner further points out that the previously known FDA-approved
commercial product Aczone 5% included all the claimed components except
for the A/SA copolymer, thus confirming that those other components were
compatible with each other in a topical composition. Id. (citing Ex. 1010,
4). Petitioner asserts that, at the same time, A/SA copolymers, such as
Sepineo / Simulgel, were known thickening agents that Nadau-Fourcade
describes together in a small group with Carbopol as preferred hydrophilic
gelling agents for topical compositions including water-sensitive active
agents, like dapsone. Id.
We are persuaded by Petitioner’s positions regarding the teachings
and suggestions of Garrett and Nadau-Fourcade as set forth in Ground 1.
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Pet. 21–40. In particular, as explained below, we find that a person of
ordinary skill in the art would have found it obvious to substitute the A/SA
copolymer taught by Nadau-Fourcade for the carbomer gelling agent
disclosed in Garrett’s formulations to arrive at the claimed composition.
Garrett discloses a “method for treating . . . acne,” and that the
treatment “compris[es] administering to a subject having . . . acne vulgaris
. . . a topical pharmaceutical composition,” as recited in each of claims 1’s
and 6’s preambles.19 Ex. 1001, 15:40–16:4, 16:23–28. For example, Garrett
states, “[i]n one embodiment, the treatment is directed to dermatological
conditions and the treatment is provided by a topical dapsone
composition. . . . In certain embodiments, the dermatological condition to be
treated is inflammatory acne, non-inflammatory acne or rosacea.” Ex. 1004,
3:10–15. Nadau-Fourcade likewise teaches that the compositions disclosed
therein may be used for treating acne and rosacea. Ex. 1005. 3:21, 14:1–12.
We next consider how the prior art teaches or suggests the
formulation of the claims and its component’s concentrations, generally. As
with topical pharmaceutical composition of the challenged claims, Garrett
states that its composition is “a dermatological composition that is a semi-
solid aqueous gel, wherein dapsone is dissolved in the gel,” and that “[i]n
one preferred embodiment, the composition includes about 0.5% to 4.0%
carbomer; about 53.8% to 84.2% water; about 10% to 30% ethoxydiglycol
[DGME]; about 0.2% methylparaben; about 5% to 10% dapsone in a

19 “Generally, the preamble does not limit the claims.” Allen Eng’g Corp. v.
Bartell Indus., Inc., 299 F.3d 1336, 1346 (Fed. Cir. 2002)). Thus, we need
not decide the issue; regardless, Petitioner has shown that the recitations in
the preambles are satisfied by the prior art.
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microparticulate and dissolved state; and about 0.1% to 2% sodium
hydroxide solution.” Ex. 1003, 3:21–22, 4:2–5.
We find that this preferred embodiment of Garrett teaches the claimed
“about 7.5% w/w dapsone; about 30% w/w to about 40% [or about 30% of
claim 6] w/w diethylene glycol monoethyl ether; about 2% w/w to about 6%
[or about 4% of claim 6] w/w of a polymeric viscosity builder . . . ; and
water; wherein the topical pharmaceutical composition does not comprise
adapalene,” of claims 1 and 6. Ex. 1001, 16:5–13, 16:29–36; see also
Ex. 1002 ¶¶ 40–44, 48–55, 58–60. Garrett discloses a range for each of the
various components of the composition that either fully encompasses or
overlaps/abuts the ranges and amounts for those components recited in the
challenged claims, and this is sufficient to create a presumption of
obviousness as to the claimed amounts. See DuPont, 904 F.3d at 1006.
With respect to the requirement that the composition include about
7.5% dapsone, Garrett discloses formulations with dapsone in concentrations
of 5–10%. See Ex. 1004, 4:2–5, 14:1–7. Dr. Michniak-Kohn states that a
person of ordinary skill in the art would have understood from Garrett that
“each point in the range of 5–10%” dapsone, including the claimed 7.5%,
could have been used to make a topical dapsone composition. Ex. 1002
¶ 50. Dr. Michniak-Kohn further identifies other prior art, including patents
and publications by Patent Owner’s own experts,20 that taught topical

20 As of 2012, the use of topical dapsone (Aczone 5%) for acne treatment
was FDA-approved and had been a significant focus of those skilled in the
art, including Patent Owner’s expert witnesses, Dr. Osborne and Dr. Kircik.
See, e.g., US 2006/0204526 A1 (published Sept. 14, 2006) (Ex. 1007,
“Lathrop”); US 2010/0029781 A1 (published Feb. 4, 2010) (Ex. 1008);
David W. Osborne, Diethylene glycol monoethyl ether: an emerging solvent
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dapsone compositions for acne treatment wherein the amounts of 5% and
7.5% dapsone were “especially preferred.” Id.; see also Ex. 1007, Abstract,
¶¶ 14–15, 56 (teaching “Dapsone may range from about 0.005 percent to
about 30 percent . . . 5 and 7.5 being especially preferred,” “solvation
medium may range from about 0.5 percent to about 99 percent . . . most
preferably about 5 percent to about 30 percent,” and DGME as such a
solvent); Ex. 1040, 19:6–16 (Dr. Osborne agreeing that his own patent
application identified “that 7.5 percent dapsone concentration is an
especially preferred embodiment”).
In addition to the claimed amount of 7.5% dapsone being “squarely
within Garrett’s range” of about 5–10%, the evidence of record also supports
Petitioner’s contention that the skilled artisan would have been motivated to
increase amount of dapsone in the commercial Aczone 5% product
(Ex. 1010) to be at or above the claimed 7.5%. See Pet. 22, 25, 27; Pet.
Reply 13–15. First, as noted above, the prior art Lathrop reference
specifically stated that both 5% and 7.5% dapsone were especially preferred
for acne treatment. Ex. 1007 ¶ 47; see also Ex. 1016, Abstract, 4:62–5:4,
5:54–6:8 (prior art Osborne ’560 patent disclosing the use of dapsone up to

in topical dermatology products, J. COSMETIC DERM. 10:324-329 (2011)
(Ex. 1009); Physician’s Desk Reference, 65th ed., pp. 599-602 (2011)
(ACZONE Gel 5% Label) (Ex. 1010); U.S. Patent No. 5,863,560 to Osborne
(Ex. 1016, “Osborne ’560”); V.E. Gottfried Wozel, Innovative Use of
Dapsone, DERMATOL. CLIN. 28: 599–610 (2010) (Ex. 1022); Ex. 1039,
72:6–25 (Dr. Kircik agreeing that “[b]efore 2012 . . . [he] prescribe[ed]
Aczone 5% as either a maintenance therapy or as a monotherapy for the
treatment of acne” and “it was common before 2012 to use Aczone 5% to
treat acne in adult females, for example”); Ex. 1040, 72:15–20 (Dr. Osborne
agreeing that “by 2012, a POSA would have known that dapsone was
effective for treating acne vulgaris”).
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10% as an anti-inflammatory/antimicrobial agent in an acne treatment
formulation). From this evidence, we conclude that the higher end of
Garrett’s dapsone concentrations and the specific concentration of 7.5%
dapsone would have been considered by the skilled artisan to be an effective
amount.
Additionally, the evidence of record shows that the recognized safety
of dapsone and the desire to optimize the amount of drug delivered to
achieve once daily dosing would have served as a motivation to use the
claimed 7.5% dapsone concentration. Prior to 2012, Patent Owner’s FDA-
approved Aczone 5% product raised concerns regarding G6PD-deficient
patients and the potential for increased hemolytic effects with dapsone use.
Ex. 1004, 2:1–3:6, 10:4–25. The FDA required a warning on the product’s
labeling concerning this potential hazard. Id. at 10:13–21; Ex. 2044, 1;
Ex. 2045, 1; Ex. 1010, 3; Ex. 1018 ¶¶ 30–32, 35–40. As a counterpoint to
this evidence, however, Garrett teaches that 5% dapsone concentrations in
topical formulations were in fact not dangerous for G6PD-deficient patients,
or any other patient population, based on the results of a clinical study
disclosed therein. Ex. 1004, 12:1–4, 24:4–39:25 (Example 1 concluding that
“[d]ata from this study confirm that the safety profile for topical dapsone gel
treatment is excellent, and support that the risk of hemolytic anemia during
treatment with dapsone gel for acne vulgaris is remote for all patients,
including those with G6PD deficiency.”). Although the example in Garret
only studied a 5% dapsone topical formulation, we find that a POSA would
have nonetheless considered it relevant in determining whether higher
concentrations of the active agent within Garrett’s disclosed range of 5–10%
were also safe and effective based on Garrett’s teaching that 5% to 10%
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dapsone compositions “do[] not induce hemolytic anemia” or “adverse
hematologic events,” and Dr. Michniak-Kohn’s testimony that “this
information would have been of interest to a POSA.” Ex. 1043 ¶ 10 (citing
Ex. 1004, 4:2–5, 6:5–8, 42:25–32).
Once it was recognized that a (topical) 5% dapsone concentration was
not a health concern for G6PD-deficient patients (or any other acne
patients), as explained by Garrett, the skilled artisan would have understood
that the concentration of dapsone could be increased up to about 10%, as
also taught by Garrett. See Ex. 1043 ¶ 10 (stating “Garrett shows that one
preferred embodiment is a topical composition containing ‘about 5% to 10%
dapsone’”). In this regard, Garrett further states that “when an active agent
is used to treat acne, it is important to increase the level of drug that will
cross the intact stratum corneum lining the upper third of the pilosebaceous
unit.” Ex. 1004, 20:15–17. This statement in Garrett, in view of the
confirmed safety of topical dapsone by Garrett, and further in view of
Garrett’s express disclosure of preferred embodiments using more dapsone
(5–10%), suggests increasing the amount of dapsone in the Garrett
formulations above the amount included in the FDA-approved Aczone 5%
product in order to optimize the composition for once-daily dosing by
increasing the amount of drug reservoir available for sustained delivery. See
Ex. 1043 ¶¶ 19–26; see also Ex. 1018 ¶ 46 (person of ordinary skill would
have expected increasing dapsone strength would effectively treat patients
on a once-daily dosing schedule).
The increased drug concentration would have resulted in the benefit of
potentially decreasing the frequency of administration as compared to the
twice daily application approved by the FDA for Aczone 5%. Ex. 2044, 1
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(FDA Label for Aczone 5% indicating “[a]pply twice daily” under Dosing
and Administration). Garrett teaches that “[t]he dapsone dermatological
composition is typically applied to affected skin once or twice daily, but may
be applied more frequently, depending on the severity of the condition.”
Ex. 1004, 22:8–10. As explained by Petitioner’s medical expert,
Dr. Gilmore, the skilled artisan would have expected an increase in dapsone
concentration to allow for effective treatment in a once-per-day application.
Ex. 1018 ¶ 46 (“[A] POSA would have expected that an increased strength
dapsone product could effectively treat some, if not many, patients on a
once-daily dosing schedule.”); Ex. 1044 ¶¶ 31–32 (noting that “result of
shifting from twice-daily to once-daily dapsone administration was one
reason a POSA would have had to increase the concentration of dapsone
from 5% to 7.5% w/w,” and this was established by Garrett’s teaching that
the compositions described therein could be applied “once or twice daily”).
Thus, for the reasons above, we agree with Petitioner that it would
have been obvious to the person of ordinary skill in the art to use
formulations with dapsone above 5% and up to 10%, including the claimed
7.5%.
We next turn to how the prior art teaches or suggests the claimed
range of about 30% to about 40% DGME. We find that Garrett’s disclosed
range of DGME of about 10% to 30% also overlaps (or at least abuts) the
claimed about 30–40% range. The parties agree that use of the term “about”
in both Garrett and the ’219 patent claims to specify the amount of solvent
provides some overlap of their ranges. See Hr’g Tr. 7:26–8:2 (Petitioner
asserting an overlap in DGME ranges); id. at 42:3–13 and 89:9–10 (Patent
Owner agreeing that there is an overlapping range for DGME). Statements
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of Petitioner’s expert, Dr. Michniak-Kohn, further support such conclusions.
Ex. 1002 ¶¶ 41–43, 48–55.
As with the other claimed ranges, the overlap or abutment of Garrett’s
disclosed amount of DGME with the claimed range of about 30–40%
DGME is sufficient to support a presumption of obviousness under DuPont;
a presumption Patent Owner failed to rebut. 904 F.3d at 1006.
We next address the claim element requiring a polymeric viscosity
builder comprising A/SA in the amount of about 2–6%. Although Garrett
teaches that its acne-treating topical compositions preferably include a
gelling agent (a polymeric viscosity builder) at concentrations “between
about 0.2% to about 4% by weight of the composition,” which overlaps the
claimed range of about 2–6% recited in claim 1 and includes the about 4%
range recited in claim 6, Garrett does not disclose that its polymeric
viscosity builder comprises an A/SA copolymer.
Garrett discloses that its
[t]hickening agents include polymer thickeners. Polymer
thickeners that may be used include those known to one skilled
in the art, such as hydrophilic and hydroalcoholic gelling agents
frequently used in the cosmetic and pharmaceutical industries.
Preferably, the hydrophilic or hydroalcoholic gelling agent
comprises “CARBOPOL®” (B. F. Goodrich, Cleveland, Ohio),
“HYPAN®” (Kingston Technologies, Dayton, N.J.),
“NATROSOL®” (Aqualon, Wilmington, Del.), “KLUCEL®”
(Aqualon, Wilmington, Del.), or 10 “STABILEZE®” (ISP
Technologies, Wayne, N.J.). Preferably, the gelling agent
comprises between about 0.2% to about 4% by weight of the
composition.
Ex. 103, 13:3–11 (emphasis added). Garrett identifies five specific products
as preferred gelling agents: Carbopol, Hypan, Natrosol, Klucel, and
Stabileze. Id.
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The teachings of Nadau-Fourcade provide the missing claimed subject
matter relating to an A/SA polymeric viscosity builder, and we find that it
would have been obvious to the skilled artisan to substitute Nadau-
Fourcade’s Sepineo A/SA gelling agent for Garrett’s Carbopol gelling agent.
The general class of gelling agents, and even specific examples of products
disclosed in Garrett, significantly overlap with gelling agents taught by
Nadau-Fourcade for use in topical pharmaceutical compositions containing
water-sensitive active ingredients. Both Garrett and Nadau-Fourcade taught
the use of known gelling agents that were commonly used in pharmaceutical
formulations. See Ex. 1004, 12:3–6 (“Polymer thickener[s] that may be used
include those known to one skilled in the art, such as hydrophilic and
hydroalcoholic gelling agents frequently used in the cosmetic and
pharmaceutical industries.”) (emphasis added); Ex. 1005, 48:11–14
(discussing use of additives that are “commonly used in pharmaceuticals and
cosmetics to give [its] preparation specific properties” and noting that “[a]
person skilled in the art will adapt the choice of these additives in function
of the expected effect”) (emphasis added).
As noted above, Garrett discloses that its gelling agent is a hydrophilic
gelling agent, used for dapsone formulations. Ex. 1005, 12. Nadau-
Fourcade discloses gelling agents for formulations of similarly water-
insoluble drugs and, “[i]n one particularly preferred embodiment, the
composition according to the invention also contains one or more
hydrophilic-phase gelling agents.” Ex. 1005, 47:12–13. Nadau-Fourcade
identifies, as does Garrett, the specific example gelling agents Carbopol and
Natrosol, but also further expands this group to Sepineo and Simulgel, which
are A/SA copolymers. Ex. 1005, 47:12–24.
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Nadau-Fourcade specifically states “[p]referred gelling agents include
carbomers, for instance Carbopol 980® or 981®, polyacrylamides, for
instance Sepineo P 600® or Simulgel 600 PHA®, and polysaccharides, for
instance xanthan gum” and “at preferential concentrations . . . preferentially
ranging from 0.01% to 5%.” Id. at 48:5–9. Thus, we find that Nadau-
Fourcade and Garrett disclose the same classes, types, and specific gelling
agents in their topical pharmaceutical formulations for water-insoluble
drugs, in overlapping concentrations. See Ex. 1043 ¶ 48 (stating a POSA
would have been able to immediately appreciate that Carbopol and Sepineo
perform the same function and are interchangeable). Furthermore, Nadau-
Fourcade pairs Carbopol and Sepineo in a small set of especially preferred
gelling agents. Ex. 1005, 11:5–9.
Petitioner’s expert, Dr. Michniak-Kohn, identifies these overlapping
characteristics of Garrett’s gelling agents and Nadau-Fourcade’s gelling
agents as a reason the person of ordinary skill in the art would look to
Nadau-Fourcade for additional thickening agents for water-insoluble drugs
like dapsone. Ex. 1002 ¶ 56. Nadau-Fourcade teaches or suggests that
Sepineo and Carbopol are interchangeable alternatives for such uses because
they are included in a most preferred set of such agents, are indicated as used
in the same preferred concentration range (0.01–5%), and are shown in
examples to be used in very similar concentrations for similar formulations.
Id. ¶¶ 56–58; see also Ex. 1005, 52–67 (disclosing 13 formulation examples
with a gelling agent where 2 are carbomer and 11 are A/SA, where examples
6 and 13 utilize very similar amounts of carbomer and A/SA gelling agents
in similar formulations).
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Further, the evidence of record supports that the person of ordinary
skill in the art would have had a reasonable expectation of success in
substituting Nadau-Fourcade’s Sepineo (or Simulgel) for Garrett’s Carbopol.
Dr. Michniak-Kohn identifies that Garrett explicitly states that “[p]olymer
thickeners that may be used include those known to one skilled in the art,
such as hydrophilic and hydroalcoholic gelling agents frequently used in the
cosmetic and pharmaceutical industries.” Ex. 1002 ¶ 56 (citing Ex. 1004,
13:3–6). As noted above, Garrett identifies its Carbopol as fitting this
description and Nadau-Fourcade identifies its A/SA gelling agents as fitting
this description. Compare Ex. 1004, 12:3–6, with Ex. 1005, 47:12–48:14.
Dr. Michniak-Kohn concludes that “Garrett explicitly permitted such a
substitution” and states that “such a substitution was routine and predictable
because such thickening agents were known for use in topical compositions
with water insoluble drugs.” Ex. 1002 ¶ 57. As stated by Dr. Michniak-
Kohn, “a POSA would not have expected any incompatibilities in
substituting with acrylamide/sodium acryloyldimethyl taurate copolymer for
Carbopol® 980.” Id. ¶ 61.
Dr. Michniak-Kohn’s conclusion is supported by other evidence of
record. In particular, Petitioner cites the prior art reference Guo21 as
evidencing that it was known in the prior art that an A/SA polymeric
thickening agent was compatible and could be used specifically with
dapsone formulations. Pet. 37–38; Ex. 1013 ¶¶ 140, 172, 200–202
(disclosing dapsone as an active agent, among many, included over a
potential range of about 0.01 wt. % to about 15 wt. % based on disease or

21 US 2007/0190019 A1 (published Aug. 16, 2007) (Ex. 1013, “Guo”).
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condition to be treated, the patient, and other factors well understood by
those skilled in the art; disclosing sodium acrylate-sodium acryloyldimethyl
taurate copolymers as a polymeric thickening agent, among many, included
over a potential range of about 1 and about 10 wt. %); see also Ex. 1002
¶ 101 (Dr. Michniak-Kohn discussing Guo). Guo is directed to “vanishing
cream compositions suitable for topical application of an active agent to an
animal or plant comprising . . . a polymeric thickening agent,” where, among
many options, the active agent can be “[s]ulphones such as dapsone” and the
polymeric thickening agent can be “sodium acrylate-sodium
acryloyidimethyl taurate copolymers.” Ex. 1013, Abstract, ¶¶ 140, 200–202.
We find that Guo supports Petitioner’s position that A/SA and dapsone were
understood in the art to be compatible components, thus supporting the
interchangeability of Carbopol and Sepineo.
The evidence establishes that that Carbopol and Sepineo were
recognized to be interchangeable and equivalent gelling agents that could be
used in topical formulations containing dapsone, and they could be used in
the same concentration range of 0.01–5% (which overlaps the claimed
concentration range of about 2–6% of claim 1 and Garrett’s disclosed range
of 0.2–4%). Thus, we determine it would have been obvious to the person
of ordinary skill in the art to directly substitute Nadau-Fourcade’s Sepineo
(or Simulgel) for Garrett’s Carbopol gelling agent within the claimed
amounts. See, e.g., Ex. 1002 ¶¶ 56–60; see also In re Omeprazole, 483 F.3d
at 1374 (substituting known alternatives is obvious); Wm. Wrigley, 683 F.3d
at 1364 (replacing one well known agent with another is obvious); KSR, 550
U.S. at 416 (mere substitution of one element for another known in the field
must do more than yield predictable results). Because a person of ordinary
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skill “has good reasons to pursue the known options within his or her
technical grasp,” § 103 bars the patentability of such obvious variations, as
here. KSR, 550 U.S. at 417, 421.
Finally, we consider how the prior art teaches or suggest excluding
adapalene from the disclosed dapsone formulations, thereby satisfying the
negative limitation “wherein the pharmaceutical composition does not
comprise adapalene” recited in claims 1 and 6. Adapalene was another
active ingredient recognized in the prior art and the ’219 patent for treating
dermatological conditions, including acne. Ex. 1001, Abstract (noting that
“dapsone/adapalene compositions can be useful for treating a variety of
dermatological conditions”); Ex. 1032 (“A review of the use of adapalene
for the treatment of acne vulgaris.”). However, nowhere does Garrett
indicate that any of its formulations, each of which is an acne treatment
formulation, includes adapalene. See generally Ex. 1004.
It is not Garrett’s mere silence as to the presence of adapalene, but its
disclosure of complete dapsone formulations to treat acne in its absence that
suggests that adapalene is not included in Garrett’s formulations. Likewise,
the commercial Aczone 5% product referenced in Garrett did not include
adapalene, and was determined by the FDA to be safe and effective as a
monotherapy. Ex. 1018 ¶ 42; Ex. 1010; Ex. 2044. Thus, a skilled artisan
would have understood based on Garrett’s disclosure that no adapalene was
included or otherwise required for any of the dapsone formulations. See AC
Technologies S.A. v. Amazon.com, Inc., 912 F.3d 1358, 1367 (Fed. Cir.
2019) (“[A] reference need not state a feature’s absence in order to disclose
a negative limitation.”); Sud-Chemie, Inc. v. Multisorb Techs., Inc., 554 F.3d
1001, 1004–05 (Fed. Cir. 2009) (affirming finding that reference disclosed
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“uncoated” film where it did not describe the film as coated and did not
suggest necessity of coatings).
For the reasons above, we determine Petitioner’s evidence shows that
Garrett and Nadau-Fourcade teach or suggest each element of claims 1 and
6,22 within the claimed amounts, and that the person of ordinary skill in the
art would have had been motivated with a reasonable expectation of success
to incorporate Nadau-Fourcade’s A/SA gelling agent into Garrett’s dapsone
formulations for treating acne. We find this to be a situation where “[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.
Analysis of Ground 2 – Obviousness Based on Garret and Bonacucina
Having addressed Petitioner’s Ground 1 combination of Garrett and
Nadau-Fourcade in view of claims 1 and 6, we turn to Petitioner’s Ground 2
challenge based on the combination of Garrett and Bonacucina.
Petitioner’s Ground 2 is similar to Ground 1. For this ground,
Petitioner relies the same teachings of Garrett discussed above, but relies
upon Bonacucina’s teachings of an A/SA copolymer, i.e., Sepineo, instead
of Nadau-Fourcade’s similar teaching. Petitioner identifies additional
motivations for a person of ordinary skill in the art to combine the teachings
of Garrett and Bonacucina. In particular, Petitioner asserts that “[a] POSA
would have had a reason to use the claimed acrylamide copolymer [of
Bonacucina in Garrett’s formulations] because Bonacucina teaches that (1) it
is a ‘prime candidate’ for use in topical compositions (2) which did not
require neutralization with a harsh base to thicken.” Pet. 40. Petitioner also

22 There is no dispute that the prior art teaches including water, as claimed.
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asserts that mitigating the “grittiness” of dapsone compositions would be
another motivating factor to exchange Carbopol for Sepineo. Id.
Similar to Ground 1, Petitioner provides a claim chart identifying how
and where the cited prior art teaches the elements of claims 1 and 6. Id. at
41–43. We do not reproduce the entire claim chart as we did for Ground 1,
but note that Petitioner cites the same portions of Garrett and replaces the
portions citing Nadau-Fourcade with citations to Bonacucina. Id. Relative
to the claim limitations directed to the polymeric viscosity builder
comprising an A/SA copolymer, Petitioner’s chart identifies that Bonacucina
teaches:
“Sepineo® P 600, based on the concept of droplet hydroswelling,
is a concentrated droplet dispersion of acrylamide/sodium
acryloyldimethyl taurate (a viscous liquid at room temperature)
in isohexadecane as the oily dispersing phase.” (AMN1015, 2;
AMN1002, ¶70)
“Both techniques revealed that Sepineo® P 600 thickens and gels
well, a property that depends strongly on polymer concentration.
Concentration increases from 0.5% (w/w) to 5% (w/w) modified
the viscoelastic properties of the Sepineo® samples, changing
the typical behavior of a concentrated non-entangled solution to
that of a ‘gel-like’ sample.” (AMN1015, 7)
Id. (also citing Ex. 1002 ¶¶ 67–68, 72; Ex. 1018 ¶¶ 35–42). Thus, Petitioner
again accounts for each element of claims 1 and 6 in the prior art
combination, as it did for Ground 1.
Petitioner asserts that the person of ordinary skill in the art would
have been motivated to use Bonacucina’s Sepineo as a substitute for
Garrett’s Carbopol to reduce the potential grittiness of Garrett’s
composition. Id. at 47–48 (citing Ex. 1002 ¶¶ 80–81, 84). Petitioner’s
position is that, like the commercial Aczone 5% product, which has labeling
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indicating it is “gritty,” a person of ordinary skill in the art would have
understood that Garrett’s compositions including Carbopol would also be
gritty. See, e.g., Ex. 1010, 3 (“ACZONE Gel, 5%, is gritty with visible drug
substance particles.”); Ex. 2044, 2 (“ACZONE Gel, 5%, is gritty with visible
drug substance particles.”). Dr. Michniak-Kohn testified that a person of
ordinary skill in the art would have understood that the Carbopol thickening
agent used in the formulation was responsible for this grittiness. Ex. 1002
¶ 81.
Petitioner asserts that the person of ordinary skill in the art would
have selected Bonacucina’s Sepineo to replace Carbopol because
Bonacucina expressly calls it a “prime candidate” for use in topical
compositions. Pet. 48 (citing Ex. 1002 ¶ 84); see Ex. 1012, 7. Petitioner
asserts that Bonacucina teaches Sepineo is a “prime candidate” because it
“has self-gelling and thickening properties . . . which make[s] it easy to use
in the formulation of gels and [oil-in-water] emulsion gels.” Pet. 48
(quoting Ex. 1015, Abstract) (citing Ex. 1002 ¶¶ 28, 71, 84).
Petitioner also asserts that Carbopol requires a neutralization step
because it is an acidic coiled polymer that hydrates when dispersed in water
and a base must be added to convert the acidic molecules to a salt. Pet. 49
(citing Ex. 1002 ¶ 82; Ex. 1010, 4; Ex. 1020, 5–6 (“Carbopol® polymers
must be neutralized in order to achieve maximum viscosity. Once a
neutralizer is added to the dispersion, thickening gradually occurs.”), 11, 16,
19, 24–25). Petitioner argues one of ordinary skill in the art would have
chosen Sepineo instead because it does not require this additional step. Id.
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(citing Ex. 1002 ¶ 82); see also Ex. 1026, 1 (“Very easy to handle at room
temperature: No neutralization . . . .”).23
Petitioner asserts:
Next, the claimed “about 2% w/w to about 6% w/w” range
of the acrylamide copolymer [of claim 1] would have been an
obvious amount. (AMN1002, ¶¶85–86). A POSA would have
understood from Garrett that an amount between 0.2% to 4%
w/w [polymer thickener] was “prefer[red],” and would have
further understood from Bonacucina that concentrations from
0.5% to 5% w/w [of Sepineo gelling agent] were useful for
topical applications. (AMN1004, 13:3–25; AMN1015, 7).
Similarly, a POSA knew that amounts up to 5% w/w is useful.
(AMN1026, 2; AMN1034, 5). Because these prior art ranges
substantially overlap with the claimed range, the claimed amount
of copolymer would have been obvious. DuPont, [904 F.3d at
1006–1008]; Galderma[, L.P. v. Tolmar, Inc., 737 F.3d 731,
737–738 (Fed. Cir. 2013)]; In re Peterson, 315 F.3d at 1329; In
re Geisler, 116 F.3d at 1469; In re Woodruff, 919 F.2d at 1578.
Pet. 49–50. Petitioner further asserts, “[i]n any event, arriving at ‘about 2%
w/w to about 6% w/w’ [or about 4%] would have been the product of
routine optimization,” because the Sepineo thickening agent was well
understood and known to have a predictable effect on viscosity of a
composition. Id. at 50–52 (citing Ex. 1002 ¶¶ 85–89; Ex. 1007 ¶ 158;
Ex. 1004, 18:17–22; Ex. 1013 ¶ 323).
Petitioner asserts that the skilled artisan would have had a reasonable
expectation of successfully using Bonacucina’s Sepineo to replace Garrett’s

23 Ex. 1026 is a SEPPIC (2008) product information sheet for Sepineo P 600,
which at the relevant portion states “SEPINEO™ P 600 doses of use – gel
application => thickening power: up to 5%.” Ex. 1034 is a promotional
article from Pharma & Healthcare News about Sepineo, which states
“SEPINEO™ SE 68 standard dose of use is 5%” and “SEPINEO™ P 600
recommended dose of use is up to 5%.”
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Carbopol because, like Carbopol, Sepineo “was known for use in topical
compositions” and would be “used for its intended purpose and in its
intended amount.” Id. at 52 (citing Ex. ¶¶ 90–91). Petitioner asserts that
other prior art confirmed Sepineo was compatible with a variety of solvents,
a wide variety of pHs, and various temperatures, and that dapsone
compositions were compatible with about 1–10% w/w of acrylamide
copolymer. Id. at 53 (citing Ex. 1013 ¶¶ 140, 200–202; Ex. 1002 ¶¶ 90–91;
Ex 1026, 1–2; Ex. 1034, 4).
We are persuaded by Petitioner’s evidence and contentions regarding
the teachings of Garrett and Bonacucina. In particular, as discussed above,
we find that Garrett teaches each element of claims 1 and 6, except for the
use of an A/SA copolymer as a gelling agent, and further find that the person
of ordinary skill in the art would have been motivated to use Bonacucina’s
Sepineo as a substitute gelling agent for Garrett’s carbomer/Carbopol. We
agree that the person of ordinary skill in the art would have had a reasonable
expectation of successfully incorporating Bonacucina’s A/SA gelling agent
into Garrett’s dapsone formulations. We review the evidence of record on
this ground below.
As the same teachings and contentions related to Garrett discussed
under Ground 1 form the basis for the same claim limitations addressed
under Ground 2, we rely on our previous analysis of these teachings and
contentions. We only address here Petitioner’s contentions and evidence as
to combining the teachings of Garrett and Bonacucina with respect to the
requirement of an A/SA copolymer.
Regarding Bonacucina, the reference strongly suggests the use of
Sepineo as a gelling agent for topical pharmaceutical applications, like
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Garrett’s topical dapsone composition. See Ex. 1015, 368 (Abstract:
“Sepineo P 600 gel and emulsion gel are very effective systems for use in
topical and other types of applications”), 374 (“Sepineo P 600 is a prime
candidate for use in the formulation of gels and emulsion gels with
rheological properties suitable for topical administration.”). Dr. Michniak-
Kohn states that Garrett’s Carbopol “was known to have some drawbacks,”
for example, requiring neutralization to achieve maximum viscosity,
producing grittiness, and possible agglomeration if improperly added to
solvent. Ex. 1002 ¶¶ 81–82 (citations omitted). Such drawbacks made
replacing Garrett’s preferred gelling agent attractive, particularly with a
gelling agent with “self-gelling and thickening properties,” that is “pleasant
to the touch” and “perfectly spread[s] on the skin,” like Sepineo. See id.
¶¶ 84 (quoting Ex. 1015, Abstract; Ex. 1026, 2; Ex. 1034, 5).
Bonacucina teaches using Sepineo as a gelling agent at concentrations
of 0.5–5% (w/w), which overlaps the claimed “about 2% w/w to about 6%
w/w” of claim 1 and encompasses the “about 4% w/w” range of claim 6 (and
overlaps with Garrett’s range of 0.2–4.0%). Ex. 1015, 368 (Abstract), 374;
Ex. 1001, 16:8–10, 16:31–33. These overlapping ranges support the
conclusion that a person of ordinary skill in the art would have expected to
successfully replace Carbopol with equal amounts of Sepineo in Garrett’s
formulations. Furthermore, the increased efficiency in preparing
formulations with Sepineo, as compared to Carbopol, by omitting a
neutralization step would be another motivating factor to switch from
Carbopol to Sepineo in Garrett’s formulations. See Dystar Textilfarben
Gmbh & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1368
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(Fed. Cir. 2006) (recognizing that a motivation to improve efficiency is
technology-independent).
Petitioner asserts that “[a] POSA would have known that dapsone,
water, ethoxydiglycol, and methyl paraben were compatible when
formulated together.” Pet. 52 (citing, inter alia, Ex. 1002 ¶¶ 90–91;
Ex. 1004). Bonacucina’s disclosure teaches or suggests that Sepineo can
function as a gelling agent with similar components as Garrett’s dapsone
formulations. Bonacucina indicates that its Sepineo gelling agent can be
used with an anti-microbial agent (mixture of phenoxyethanol,
methylparaben, ethylparaben, propylparaben, and butylparaben), water, and
almond oil for pharmaceutical gel formulations. Ex. 1015, 369. Also, other
prior art indicated that A/SA gelling agents can be used at concentrations of
1–10% as optional additives with topical compositions including sulphones
such as dapsone. Ex. 1013 ¶¶ 140, 200–202; see also Ex. 1026 (describing
Sepineo’s advantages and gel doses up to 5%).
We conclude that replacing Garrett’s Carbopol with Bonacucina’s
Sepineo is an “alter[ation] by the mere substitution of one element for
another known in the field,” and each component of the Garrett-Bonacucina
combination, once Sepineo is substituted for Carbopol, is used for the same
function it is known to perform. KSR, 550 U.S. at 416. Petitioner’s asserted
motivating factors to make such a replacement are supported by the
evidence. We find that the skilled artisan would have had a reasonable
expectation of successfully replacing Garrett’s preferred gelling agents with
Bonacucina’s Sepineo, in the same amounts, to arrive at the composition
recited in the claims. As with Ground 1, here the person of ordinary skill
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would have had “good reasons to pursue the known options within his or her
technical grasp.” Id. at 417, 421.
Analysis of Patent Owner’s Positions
As Patent Owner argues the two Grounds together, we likewise
address Patent Owner’s arguments as to both grounds together below.
Patent Owner argues that, for several reasons, the skilled artisan
would not have pursued a dapsone formulation for acne treatment. Patent
Owner asserts that, at the relevant time, other active agents, for example
retinoids and benzoyl peroxide, were better “first-line” treatments for acne
and were known to be efficacious, which would make using dapsone
disfavored. PO Resp. 30. Patent Owner also argues that closer prior art than
Garrett, for example an FDA Review Package, indicated dapsone’s limited
efficacy. Id. at 41 (citing Ex. 2057 ¶ 111; Ex. 2055 ¶ 94; Ex. 2042, 4, 37).
This is not persuasive.
Immediately after making this argument in its Response, however,
Patent Owner identified that its own dapsone acne treatment product,
Aczone 5%, was FDA-approved, i.e., safe and effective, for acne treatment,
but called it a “second-line therapy.” Id. at 31. Whether dapsone would be a
first-line or later-tried therapy for acne is immaterial. The claims do not
require a first-line therapy. “[J]ust because better alternatives exist in the
prior art does not mean that an inferior combination is inapt for obviousness
purposes.” In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012).
Furthermore, during oral argument, Patent Owner stated that
“[d]apsone had long been known for a number of purposes and it had been
known to be effective for treating acne,” and Patent Owner’s expert testified
in agreement that “by 2012, a POSA would have known that dapsone was
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effective for treating acne vulgaris.” Hr’g Tr. 42:23–24; Ex. 1040, 72:15–
17; see also Ex. 2020, 1 (Dr. Kircik (2010): “Topical dapsone 5% gel offers
documented efficacy for the reduction of both inflammatory and non-
inflammatory acne lesions. . . . making topical dapsone 5% gel a worthwhile
anti-inflammatory treatment for many patients with mild-to-moderate acne
vulgaris.”). Thus, the evidence of record, and even Patent Owner’s own
alternative arguments, establish that dapsone formulations were known to be
effective for treating acne and would reasonably be considered for further
development by the person of ordinary skill in the art.
Patent Owner also asserts that potential antibiotic effects of dapsone
against other bio-flora would also be a disincentive to use it because of
concern in the field regarding antibiotic resistance. PO Resp. 32 (citing
Ex. 1004, 10:28–29; Ex. 1009, 4; Ex. 2055 ¶¶ 40, 41, 50, 54 n.2, 97;
Ex. 2062, 60:9–17, 67:9–69:3, 103:5–22; Ex. 2063, 200:11–20). Patent
Owner also asserts that dapsone’s “virtually insolub[ility] in water” makes it
“‘difficult to formulate’ as a topical.” Id. (citing Ex. 1009, 326; Ex. 2063,
85:7–10, 87:8–13; Ex. 1007 ¶ 33; Ex. 2057 ¶ 115). These are also not
persuasive points.
Dr. Kircik, Patent Owner’s expert, when asked whether people were
concerned about using dapsone due to its potential antimicrobial effect,
testified “I didn’t say people were concerned.” Ex. 1039, 68:11–15. It does
not appear from the evidence that antibiotic resistance was a significant issue
with dapsone, as may have been the case with classical antibiotic drugs such
as erythromycin or clindamycin. See Ex. 2055 ¶ 40; see also Ex. 2036
(discussing the potential drawbacks of traditional antibiotics such as
erythromycin and clindamycin, but not mentioning dapsone). As to the
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insolubility of dapsone, according to Garrett, solubility is not a concern
because “the dapsone may exist as microparticulate form, a dissolved form,
or both,” and Dr. Osborne’s published work prior to 2012 included
significant work with dapsone (and DGME), both utilizing greater than 5%
dapsone in formulations and illustrating dapsone’s predictable solubility in
DGME. Ex. 1004, 4:29–31; Ex. 1007, Abstract, ¶¶ 14–15, 47, 56; Ex. 1009,
3; Ex. 1016, Abstract, 4:62–6:9. Moreover, the evidence supports that the
solubility characteristics of dapsone in DGME solvent were well understood
as of 2012. See, e.g., Ex. 1009, 326–27 (Dr. Osborne discussing the
solubility of dapsone in DGME and providing a graph of the dapsone-
DGME solubility curve).
Patent Owner also asserts that the Petition does not identify any
reasonable motivation to develop a new dapsone formulation and
Petitioner’s suggestion that alleviating “grittiness” of the Aczone 5% FDA-
approved product was incorrect because, in 2012, grittiness was not a
concern. PO Resp. 33 (citing Ex. 2062 86:15–88:5, 90:16, 96:16–97:2;
Ex. 1009, 4; Ex. 2057 ¶¶ 42–43, 57, 154–155). Further, Patent Owner
asserts that the Petitioner’s allegation that the use of Carbopol was
disadvantageous because Carbopol requires neutralizing, where Nadau-
Fourcade’s Sepineo does not, is incorrect. Id. These are not persuasive
points.
As we have discussed above, there was ample rationale provided by
Petitioner and its expert, Dr. Michniak-Kohn, to develop dapsone acne
treatments because it was understood to be effective and safe. As to
grittiness of Aczone 5%, the product’s FDA-approved label itself plainly
indicates it is “gritty.” Ex. 1010, 3; Ex. 2055 ¶ 66 (Dr. Kircik confirms this
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labeling). Further, contrary to Patent Owner’s argument, Patent Owner’s
own expert, Dr. Kircik, testified that, “yes,” “patients [did] complain about
the grittiness” of Aczone 5%, and in his declaration Dr. Kircik states “[a]cne
patients are less likely to comply with prescribed use of topical medications
that feel gritty, as they are being asked to rub grit into sensitive skin on the
face.” Ex. 1039, 165:4–9; Ex. 2055 ¶ 55. Thus, it is clear that mitigating
grittiness would have provided a motivating factor to change from Carbopol
to Sepineo.
Finally, as to the need for neutralization of Carbopol versus Sepineo,
Sepineo requires no neutralization by a formulator because it is “pre-
neutralized” by the manufacturer. Ex. 1026, 1–2. Dr. Osborne confirmed
that Carbopol requires specific handling in use and requires neutralization by
the formulator prior to adding it to a formulation. Ex. 1040, 43:5–15; see
also id at 54:10–21 (Dr. Osborne asserting that it is “routine to neutralize”
Carbopol). Dr. Osborne may seek to minimize the apparent burden of
neutralizing Carbopol before its use, but nonetheless, it is an added step not
required of Sepineo. Increased efficiency, such as reducing steps by using
Sepineo instead of Carbopol, is a universally recognized, common-sense
based, motivating factor to modify the prior art. Dystar, 464 F.3d at 1368.
Patent Owner also argues that, by 2012, the dapsone formulation was
“optimized” such that it had a ratio of undissolved dapsone to dissolved
dapsone of 2:1.24 PO Resp. 37 (citing Ex. 1009, 327; Ex. 1004, 12:14-13:2,
Ex. 2057 ¶¶ 70, 133, 140, 147); see also PO Sur-Reply 5–7 (arguing Garrett

24 This argument appears to directly conflict with Patent Owner’s
immediately preceding argument that formulations with microparticulate
dapsone were disfavored.
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is limited to compositions with both dissolved and undissolved dapsone).
Patent Owner argues that the skilled artisan would not have strayed from this
optimized formula. PO Resp. 37. Patent Owner argues that increasing the
amount of dapsone in the formulation to 7.5%, as claimed, would require an
increased amount of solvent (DGME) to maintain the optimized ratio, which
would cause other components in the formulation to be reduced (i.e., water),
affecting the delivery and behavior of the formulation. Id. at 38; see also PO
Sur-Reply 8–9. Patent Owner asserts that this would mean the skilled
artisan would not have had a reasonable expectation of success in treating
dermatological conditions as effectively and safely as the commercial 5%
dapsone product (Aczone 5%). PO Resp. 38–39. Patent Owner also asserts
that a person of ordinary skill in the art would have been motivated to
decrease, rather than increase, the dapsone concentration. Id. at 43–45
(citing Ex. 1004, 14:20–26; Ex. 1007 ¶¶ 93, 100, 109, 111, 118, 127, 134,
142, 151; Ex. 1018 ¶¶ 46–47; Ex. 2062, 153:5–11, 154:17–155:2; Ex. 2055
¶ 101; Ex. 2053 ¶ 37).
Patent Owner also argues that Garrett teaches dapsone formulations
are not effective because Garrett limited its reported testing to the safety of
Aczone 5% and does not disclose any embodiment for treating rosacea or
effectiveness in treating non-inflammatory lesions, which is a symptom of
acne vulgaris. Id. at 39–41 (citing Ex. 2055 ¶¶ 80–82, 96; Ex. 2001, 35:16–
33; Ex. 2057 ¶¶ 126–135; Ex. 1004, 29:20–24; Ex. 1018, 10–12; Ex. 2028;
Ex. 2044); see also PO Sur-Reply 7–8 (arguing Garrett does not teach
dapsone is effective to treat acne). Patent Owner argues that the critical
conclusion a skilled artisan would draw from Garrett as of 2012 was that
Aczone 5% was indeed safe for G6PD-deficient patients, in spite of earlier
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concerns regarding oral formulations, but this was already known by 2009.
PO Resp. 40 (citing Ex. 2044 (revised Aczone 5% label)). These argument
are not persuasive.
It is difficult to reconcile Patent Owner’s arguments. Patent Owner at
once argues that there is an “optimized” dapsone acne treatment formulation
with a specific ratio of both dissolved and undissolved dapsone, but also
argues the skilled artisan would decrease the dapsone in formulations.
Patent Owner argues elsewhere in its Response that any undissolved
microparticulate dapsone was “undesirable” and to be avoided absent some
compelling reason to employ it and that, generally, dapsone was a disfavored
drug. See, e.g., PO Resp. 31, 33–34. Still elsewhere, Patent Owner argues
that, even though the dapsone formulations had (visible) microparticulate,
grittiness was not a problem. See, e.g., id. at 33. Patent Owner also argues
that, although it was FDA-approved to treat acne, the 5% dapsone
formulation had only limited efficacy. See, e.g., id. at 41. It is unclear how
an anti-acne formulation could be at once optimized and FDA-approved, but
also ineffective, or how such a formulation’s microparticles were at once
undesirable, but also required for optimization, or how such microparticles
were on the one hand disfavored, but on the other hand any grittiness of such
a formulation caused by such visible microparticles was a nonissue. These
arguments are incompatible and thus unpersuasive as whole.
Moreover, Patent Owner conceded that Garrett teaches the claimed
7.5% by weight of dapsone and the claimed 30–40% DGME. Hr’g Tr.
89:6–10 (Patent Owner: “If we walk through the elements besides being a
method for treatment, the preamble about 7.5 percent weight to weight
dapsone, that overlaps with Garrett. Yes, it does. Thirty to 40 percent it
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abuts, that overlaps with Garrett, yes, it does. Two to six percent of a
polymeric viscosity builder comprising A/SA, it does not overlap.”). Thus,
Patent Owner’s arguments are largely rendered moot by its own concession
at the hearing.
Even if Patent Owner’s arguments were not inconsistent with one
another and the point was not conceded at oral argument, we note that
Garrett teaches that in each of its embodiments “the dapsone may exist as a
microparticulate form, a dissolved form, or both,” which suggests that there
is no required optimized ratio of these components for a dapsone
formulation. Ex. 1004, 4:29–31; see also Ex. 1043 ¶ 8 (Dr. Michniak-Kohn
explaining that there was no specially optimized dapsone ratio). As we
discussed above, the skilled artisan would have been motivated, based on
Garrett’s disclosure, to increase the dapsone concentrations in acne
treatment formulations. Indeed, even Dr. Osborne confirms that well before
2012, 7.5% dapsone and 30% DGME acne treatment formulations were
disclosed and, in fact, created. See Ex. 1040, 17:23–21:20 (Dr. Osborne’s
deposition testimony discussing his published patent application (Ex. 1007)
and confirming that in 2006, a formulation of 7.5% dapsone and 30%
DGME was created). Thus, Garrett’s example, although not necessarily
establishing that 7.5% dapsone formulations were effective, is nonetheless
significant in Garrett’s disclosure by indicating that its 5–10% dapsone
formulations are safe for treating acne, where the acne is inflammatory, non-
inflammatory, or both. See, e.g., Ex. 1004, 3:2–31. Regarding whether or
not Garrett’s dapsone formulations were effective to treat rosacea, such
treatment is not required by the ’219 patent claims, which recite “treating a
dermatological condition selected from the group consisting of acne vulgaris
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and rosacea,” where either one of these two conditions may be treated.
Ex. 1001, 15:40–16:3, 16:23–25.
Patent Owner also argues that the claim limitation requiring that the
dapsone formulation have no adapalene is important because the prior art
taught that combinations of dapsone and adapalene were superior to
dapsone-only formulations. PO Resp. 45–47 (citing, e.g., Ex. 1009 ¶ 34;
Ex. 2008, 3:10–23, 7:5–26, Tables 2A–2B, Figs. 1–5; Ex. 2055 ¶¶ 44–45,
106–112; Ex. 2057 ¶ 58); see also PO Sur-Reply 9 (continuing this
argument). For example, Patent Owner identifies and asserts Ahluwalia,25 a
prior art international patent application publication, as evidencing a need
for adapalene in dapsone formulations. See PO Resp. 46–47. Further,
Patent Owner argues that “while Garrett does not mention adapalene, neither
does it exclude compositions with both dapsone and adapalene” and “[a]t no
point does Garrett suggest that dapsone must be used as the sole API [active
pharmaceutical ingredient].” PO Resp. 46. Therefore, Patent Owner argues
the negative limitation of the claims is not obvious in view of Garrett. Id.
This argument is not persuasive.
As discussed above, there is ample evidence of record supporting the
conclusion that Garrett’s dapsone formulations for treating acne neither
inherently included nor implicitly required adapalene. Dr. Gilmore states
that “[i]t would have been obvious to a [person of ordinary skill in the art] to
not include adapalene in a topical dapsone composition.” Ex. 1018 ¶ 41. As

25 WO 2011/014627 A1 (published Feb. 3, 2011) (Ex. 2008, “Ahluwalia”).
We note that Kevin S. Warner is a named inventor in Ahluwalia, who
appears to be the same Kevin S. Warner who is a named inventor in the ’219
patent. Compare Ex. 2008, codes (72), (75), with Ex. 1001, code (72).
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noted by Dr. Gilmore, “[i]ndeed, the prior art FDA-approved ACZONE Gel
5% is a dapsone monotherapy and had been determined by the FDA to be
safe and effective as a monotherapy.” Id. ¶ 42 (citing Ex. 1004; Ex. 1007;
Ex. 1010); see also Ex. 2020, 1 (Dr. Kircik (in 2010) describing dapsone 5%
gel as an effective treatment for acne vulgaris and describing its optional
pairing with other agents adapalene and benzoyl peroxide, but concluding “it
is notable that there was no statistically significant difference between
topical dapsone alone versus the combination regiments for inflammatory
lesions” and “[t]hese findings actually reveal that topical dapsone alone is a
very powerful agent against inflammatory lesions.” (emphasis added)).
Moreover, contrary to Patent Owner’s arguments, Ahluwalia does not
evidence that adapalene is a required component for dapsone formulations.
Rather, Ahluwalia evidences only that adapalene is an optional active agent
that may be advantageously added to a dapsone formulation, along with
several other alternative optional agents. Ex. 2008, 5:31–6:33 (“[s]uitable
compounds that can be combined with dapsone (2 – 10% w/w) include:”
benzoyl peroxide, other antimicrobial actives, salicylic acid, azelaic acid,
sulfacetamide-sulfur, other keratolytic agents, tretinoin, tazarotene,
adapalene, additional retinoids, erythromycin, clindamycin, and
tetracycline). This does not suggest that a person of ordinary skill in the art
would have viewed adapalene to be necessary in Garrett’s dapsone
formulations. See WAG Acquisition, LLC v. WebPower, Inc., 781 Fed.
Appx. 1007, 1012–13 (Fed. Cir. 2019) (although the prior art did not
expressly specify that a negatively claimed component was not used, nothing
in the record suggested that it must be used; therefore, the negative
limitation directed to omitting the component was met by the prior art). In
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view of the evidence of record, we find that Garrett’s dapsone formulations
excluded adapalene.
Patent Owner also asserts that Petitioner has not established a
reasonable motivation to modify Garrett’s formulations to include the
claimed polymeric viscosity builder comprising A/SA copolymer. Id. at 47–
58. We disagree. Whether the skilled artisan would have found motivation
based on the known interchangeability of Carbopol and Sepineo, as set forth
in Ground 1, or the mitigation of grittiness caused by Carbopol and the
elimination of a neutralization step by its replacement with Sepieno, as set
forth in Ground 2, we have addressed and, are persuaded by, Petitioner’s
evidence and arguments that motivation existed. See supra (discussion of
Petitioner’s challenges).
Regarding the “interchangeability” rationale of Ground 1, Patent
Owner contends that the Sepineo gelling agent of Nadau-Fourcade’s
formulations would not have been interchangeable with Carbopol gelling
agent of Garrett’s formulations. In particular, Patent Owner argues that
Nadau-Fourcade’s water-sensitive drug is intended to be completely
dissolved in its formulations, with no crystallization of the active ingredient.
PO Resp. 51 (citing Ex. 1005, 38:4–16, 39:16–25, 40:27–30, 41:12–14,
41:28–30; Ex. 2057 ¶¶ 99–105). Patent Owner argues that this contrasts
with Garrett’s formulations, where some dapsone is purposefully left
undissolved. Id. at 52; see also PO Sur-Reply 11–12 (arguing that the water-
sensitive dapsone of Garrett would not be completely dissolved as required
of such water-sensitive APIs by Nadau-Fourcade). Thus, argues Patent
Owner, Garrett and Nadau-Fourcade are incompatible and there would be no
motivation to combine the references because it was not expected for
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Sepineo to support Garrett’s undissolved drug. PO Resp. 52. This argument
is not persuasive.
Petitioner does not assert that Nadau-Fourcade’s teachings must be
combined, in their entirety, with those of Garrett, but only that Nadau-
Fourcade teaches that Sepineo is interchangeable with Carbopol as a gelling
agent in topical pharmaceutical formulations containing water-insoluble
drugs like dapsone. Pet. 3–4, 33–34. Indeed, in response to questioning at
the oral hearing about why it mattered if Nadau-Fourcade’s preferred
embodiments were formulations with fully dissolved API, Patent Owner
acknowledged “[w]ell, it may or it may not [matter].” Hr’g Tr. 59:18–60:1.
The challenged claims themselves do not specify whether the dapsone is
dissolved or undissolved in the composition. Further, Garrett discloses that
a partially dissolved and partially undissolved dapsone formulation may be
preferred, but it is not required. Ex. 1004, 4:29–31 (“In each of these
embodiments, the dapsone may exist as a microparticulate form, a dissolved
form, or both.”); see also Ex. 1040, 92:17–93:3 (Dr. Osborne confirming
such a teaching in Garrett). Thus, the issue of whether Sepineo might not
have been understood to adequately support undissolved dapsone in a gel is
not determinative of whether a person of ordinary skill in the art would have
found motivation to include it for the dissolved dapsone formulations that
are also taught by Garrett.
Furthermore, even for the embodiments of Garrett where some
dapsone is in microparticulate form, Dr. Michniak-Kohn states that
“thickening agents [like Sepineo] are meant to ‘improve suspending
capacity’ when added to a composition, that alone would have been
sufficient reason to use Sepineo,” and further stated that this would be the
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understanding in the field as exemplified by Bonacucina’s teaching that
Sepineo “is a novel polymer that instantly forms ‘stiff’ and ‘stable’
semisolid systems, making it a ‘prime candidate’ in topical formulations.”
Ex. 1043 ¶ 59 (citing Ex. 1015, 2, 7; Ex. 2001, 14:23-24). Moreover,
Dr. Michniak-Kohn explained that the skilled artisan would have understood
that replacing Carbopol with Sepineo would also “reduce the particle size or
particle shape” of, e.g., dapsone, to allow the skilled artisan not to disturb
“the amount of undissolved dapsone particles in the composition.” Id. ¶ 63.
Other evidence shows that that it was known that Sepineo could be used “to
thicken solvent-rich media,” like Garrett’s DGME-rich formulations and that
A/SA copolymer was a known, FDA-approved gelling agent component for
acne treatment gels. Ex. 1026, 1; Ex. 1012, 1, 6 (FDA-approved label from
2008 for Epiduo, an adapalene/benzoyl peroxide gel acne vulgaris treatment
containing an A/SA copolymer).
As we discussed above, the teachings of Guo (Ex. 1013) further
support the conclusion that A/SA copolymer would have been considered
compatible with dapsone formulations. Pet. 37–38; Ex. 1013 ¶¶ 140, 172,
200–202. Patent Owner argues that Petitioner’s citation to Guo as
evidencing the use of an A/SA copolymer with dapsone is misplaced
because Guo only used dapsone as an antimicrobial drug, but not
specifically as an anti-acne agent, and lists “hundreds” of other active
agents. PO Resp. 53–54 (citing Ex. 1013 ¶¶ 91–172, 200–202). Patent
Owner’s disparagement of Guo is not persuasive. Whether Guo expressly
discloses dapsone as an anti-acne treatment is not determinative because
dapsone is used as an active agent and A/SA is used as a gelling agent,
thereby confirming their compatibility with each other.
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Regarding the “grittiness” rationale of Ground 2, Patent Owner argues
that, although the Aczone 5%’s FDA-approved labeling indicates the
presence of grittiness, with visible drug particles, this really was not the case
and would not have motivated the skilled artisan to substitute Carbopol with
Sepineo. Id. at 49 (citing Ex. 1010, 3; Ex. 2044, 2; Ex. 2054, 1:11;
Ex. 1009, 4; Ex. 2057 ¶¶ 44, 154, 186–187; Ex. 2062, 86:15–88:5, 90:16–
21, 96:16–97:2). We find this argument is contradicted by the FDA-
approved labeling of the Aczone 5% product indicating grittiness (Ex. 1010,
3; Ex. 2044, 2) and also by statements by experts on both sides of this case
(Ex. 2055 ¶ 55, 66–67 (Dr. Kircik Declaration stating grittiness caused
compliance issues); Ex. 1039, 164:25–165:9 (Dr. Kircik deposition
testimony that Aczone 5% was gritty); Ex. 1002 ¶¶ 80–81 (Dr. Michniak-
Kohn Declaration stating mitigation of Aczone 5%’s grittiness was reason to
replace Carbopol with Sepineo)).
Regarding the “neutralization” rationale of Ground 2, Patent Owner
argues that the practitioner of the ’219 patent’s claimed method would be a
medical doctor, not a formulator, and thus would not care about a
neutralization step). PO Resp. 49–50 (citing Ex. 1017, 54; Ex. 2063 45:20–
46:18; Ex. 2062, 74:21–76:16). Patent Owner asserts that Sepineo, like
Carbopol, also requires a neutralization step, as evidence by the Sepineo
brochure, but it is performed at a different stage of manufacture, i.e., it is
pre-neutralized before the Sepineo product is sold. Id. at 50 (citing
Ex. 1026, 1). These arguments are not persuasive.
Contrary to Patent Owner’s argument, the parties agree that the skilled
artisan would “work as part a multi-disciplinary team” because both clinical
and formulation knowledge and experience would define the person of
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ordinary skill in the art. See supra Section III.A. Thus, we find that such a
person of ordinary skill in the art would consider whether one technique or
formulation was more efficient than another. A product that is pre-
neutralized is more efficiently used than one that must be neutralized by the
user before its use and would be attractive to the skilled artisan for this
reason. See Ex. 1002 ¶¶ 82–84; Dystar, 464 F.3d at 1368 (motivation to
improve efficiency is technology-independent).
Patent Owner also argues that Petitioner has failed to show the skilled
artisan would have had a reasonable expectation of success in substituting
the A/SA copolymer of Nadau-Fourcade in Garrett’s formulations.
PO Resp. 52–53 (citing Ex. 2057 ¶¶ 61, 63; Ex. 2063 172:19–173:8,
173:14–174:20). This is not a persuasive argument. The reasonable
expectation of success for using Sepineo as a gelling agent in Garrett’s
dapsone formulations stems from the fact that Sepineo was a well-known
gelling agent that had been successfully used for other similar topical
formulations. The evidence supporting this conclusion has been addressed
above.
Patent Owner also argues that formulating a topical dapsone
composition with an A/SA copolymer was unpredictable based on the
§ 1.132 Declaration filed by one of the inventors, Dr. Kevin Warner,
(“Warner Declaration”) during the prosecution of the ’219 patent, which
Patent Owner argues showed Sepineo and Carbopol were not
interchangeable in 7.5% dapsone formulations with high concentrations of
DGME. Id. at 59–60 (citing Ex. 1017, 290–291; Ex. 2057 ¶¶ 175–181).
Patent Owner relies upon the same Warner Declaration as evidence showing
unexpected results of the claimed compositions over the closest prior art. Id.
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at 60–64 (citing Ex. 1017, 59–63, 282–85, 289–93); see also PO Sur-Reply
23 (reiterating this argument). These are not persuasive points.
As discussed further below in addressing Petitioner’s Motion to
Exclude, Dr. Warner is not a witness in this proceeding, as he did not
provide a declaration specific to this proceeding nor was he subject to any
cross-examination regarding his prosecution declaration in this proceeding.26
Moreover, Patent Owner has expressly stated that it is not relying upon the
Warner Declaration for the truth of the matters asserted therein or as
evidence in its own right of unexpected results, but only for the limited
purpose of providing a basis for some of its expert’s (Dr. Osborne’s)
opinions. Paper 50, 6 (PO Opp. to Pet. Mot. Exclude: “Almirall, moreover,
is not relying on the Warner Declaration for its truth. Amirall is not relying
on it as proof of unexpected results.”); Hr’g Tr., 95:1–99:7 (discussing the
issue). Insofar as Patent Owner has disclaimed any reliance on the truth of
the matters stated in the Warner Declaration for purposes of this proceeding,
we do not consider the Warner Declaration as credible evidence of the
factual veracity of the statements made therein.
Nonetheless, because an expert witness may rely upon hearsay
evidence, we have considered Dr. Osborne’s expert opinions based upon the
Warner Declaration and have examined the Warner Declaration for the
limited purpose of assessing the basis for Dr. Osborne’s opinions. See, e.g.,
Daubert v. Merrill Dow Pharm., Inc., 509 U.S. 2786, 2797–98 (1993) (Rule

26 Dr. Warner was deposed in prior litigation and questioned about his
declaration, and that deposition testimony is evidence of record in this
proceeding. Ex. 1078. However, we need not and have not considered this
evidence in reaching our decision herein.
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703 provides that expert opinions based on otherwise inadmissible hearsay
are to be admitted if the facts or data are “of a type reasonably relied upon
by experts in the particular field in forming opinions or inferences upon the
subject.”). We conclude Dr. Osborne’s opinions in this regard are not
sufficiently supported by the evidence of record, and thus are not persuasive
to establish unexpected results or unpredictability in using Sepineo for
dapsone formulations. Dr. Osborne’s opinions largely parrot the statements
set forth in the Warner Declaration. Ex. 2057 ¶¶ 175–194. Based on his
reading of the Warner Declaration, Dr. Osborne expresses the opinion that
the claimed invention’s A/SA copolymer gelling agent (Sepineo) produced
the unexpected result of being compatible with 40% DGME whereas
Carbopol was incompatible with the same amount of DGME. Id. Dr.
Osborne also relies on the Warner Declaration as evidencing that this use of
Sepineo produced smaller dapsone particles sizes than using Carbopol,
which he equates to improved “Ostwald ripening” characteristics. Id.
¶¶ 177, 188.27

27 Dr. Osborne, describes Ostwald ripening in his declaration, as follows:
“Ostwald ripening is a phenomenon observed in liquid sols (a homogeneous
non-crystalline substance consisting of very small solid particles in a
continuous liquid medium). It is when an inhomogeneous structure over
time, i.e., small crystals or sol particles dissolve, and redeposit onto larger
crystals or sol particles.” Ex. 2057 ¶ 183. Dr. Osborne provided the
following figure intended to “depict[] the process of Ostwald Ripening”:

The figure above shows a large particle and a smaller particle, where, over
time (shown by an arrow) the smaller particle breaks down and its released
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Dr. Osborne acknowledged during his deposition that he himself did
not speak with Dr. Warner regarding the data set forth in the Warner
Declaration, that he did not independently verify the accuracy of the results,
and that he “would have found it beneficial to have more detail in the
Warner declaration.” Ex. 1040, 76:23–82:8, 107:9–108:15. As such, we
decline to give Dr. Osborne’s opinion based on the Warner Declaration
significant weight. See 37 CFR § 42.65 (“Expert testimony that does not
disclose the underlying facts or data on which the opinion is based is entitled
to little or no weight.”).
Moreover, even if the statements set forth in the Warner Declaration
were considered and assumed to be truthful, they do not demonstrate
unexpected results that are commensurate in scope with the claimed
invention. In particular, Dr. Osborne opines that “a POSA would have had
no reason to expect polymer aggregates in a 7.5% dapsone formulation using
Carbopol® 980 with 40% DGME, given that no such aggregates were seen
when Carbopol® 980 was used with 25% DGME.” Ex. 2057 ¶ 178.
However, there is nothing of record to suggest that the same polymer
aggregates reported in the Warner Declaration for 40% DGME formulations,
and considered unexpected by Dr. Osborne, would have been observed for
the full range of about 30–40% DGME recited in claim 1 or the 30% DGME
amount recited in claim 6. In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir.
2003) (A “showing of unexpected results must be commensurate in scope
with the claimed range.”). Indeed, the lower end of the claimed DGME

parts combine with the larger particle, which increases in size. Id. (citing
“Ostwald Ripening.” ENTEGRIS, Inc.,
http://pssnicomp.com/definitions/ostwald-ripening/, July 31, 2019).
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range (30%) is closer to the 25% DGME formulation for which no
unexpected aggregation was reportedly observed by Dr. Warner. This lower
30% DGME amount is also the point at which the claimed range
overlaps/abuts the 10–30% DGME range disclosed in Garrett. Petitioner’s
obviousness contentions in this proceeding are not based upon modifying
Garrett’s dapsone formulation to include higher amounts of DGME.
Additionally, we find the Warner Declaration itself says nothing about
its disclosed results or data relating to the invention being unexpected, and
thus does not support Dr. Osborne’s opinions. See Ex. 1017, 289–292. The
Warner Declaration indicates that Dr. Warner and his team expected both
Carbopol and Sepineo to be promising gelling agents, but when the DGME
concentrations were elevated to 40%, the Carbopol formulation exhibited
“undesired polymer aggregates” while the Sepineo formulations did not
show such aggregates. Id. at 290–291. That is, the expectation was that
both formulations would be compatible with dapsone formulations because
both Sepineo and Carbopol were identified as “promising gelling agents.”
Id. at 291; see also Ex. 1040 82:25–83:12 (Dr. Osborne agreeing that
Dr. Warner considered both Carbopol and Sepineo to be promising gelling
agents, but not knowing what type of preliminary evaluation Dr. Warner
conducted in making such an assessment). Thus, we find the Warner
Declaration to be an inadequate basis for Dr. Osborne’s opinion that the use
of Sepineo in the claimed composition was unpredictable and led to
unexpected results.
Patent Owner also asserts there is evidence of failures of others
supporting non-obviousness because there has been no success in the field in
treating rosacea with topical dapsone. PO Resp. 64 (citing Ex. 2057 ¶¶ 195–
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196). Regarding evidence of the failure of others, again, Patent Owner relies
on Dr. Osborne, who states only that:
I have been instructed by counsel that the prior failure of
others is another secondary consideration of non-obviousness. I
believe that others in the industry have previously failed to
effectively treat the condition rosacea with a topical dapsone
formulation, until the claimed invention of the ’219 Patent.
Garrett II (Ex. 2001) teaches that the use of Aczone 5% is
not effective in the treatment of patients with rosacea. The
results in Garrett show that patients treated with the control
vehicle experienced an average decrease of -8.3 lesions from
baseline. Garrett II (Ex. 2001) at 27: 30-32. While patients
treated with Aczone 5% experienced less of a decrease than the
control vehicle: Aczone 5% at twice a day had an average of -8.0
lesions from baseline; and Aczone 5% once a day experienced
an average of -5.3 lesions from baseline. Id. at 27:27-30. These
results show that Aczone 5% is not effective as a rosacea
treatment.
Ex. 2057 ¶¶ 195–196.
Petitioner responds that, to the extent Patent Owner presents any
evidence of what represents success in treating rosacea with dapsone,
Garrett II evidences such success rather than failure. Pet. Reply 27.
Dr. Michniak-Kohn states that Patent Owner and Dr. Osborne misstate the
results from Garrett II because Garrett discloses that Aczone 5% used twice
a day results in improvement in rosacea compared to a vehicle without the
active agent. Ex. 1043 ¶¶ 85–87 (citing Ex. 2001, 28:21–29:21, 30:26–
31:12, 36:1–22). Dr. Michniak-Kohn also states that Patent Owner’s other
expert, Dr. Kircik, agrees with this conclusion. Id. (citing Ex. 2055 ¶ 81
(“Garrett II reports that Aczone 5% twice-a-day did result in improvement as
compared to vehicle in the subgroup of papulopustular rosacea patients with
a high number of inflammatory lesions (≥20), but does not indicate any
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statistical significance. [Ex. 2001,] 28:21–29:21, 30:26–31:12, 36:1–22. The
lack of statistical analysis is glaring”)).
We are not persuaded by Patent Owner’s argument or evidence
concerning failure of others. We first note that rosacea is only one of two
alternative dermatological conditions to be treated according to the claimed
methods. Patent Owner does not present any evidence or arguments
concerning the failure of others in treating acne vulgaris, the other condition
recited in the claims. Accordingly, Patent Owner’s evidence, if credited, is
not commensurate with the scope of claims 1 and 6. See Polaris Indus, Inc.
v. Arctic Cat, Inc., 882 F.3d 1056, 1072 (Fed. Cir. 2018) (“objective
evidence of non-obviousness must be commensurate in scope with the
claims which the evidence is offered to support.”). Moreover, Dr. Kircik
acknowledged that at the time of the ’219 patent’s invention, “it was known
that Dapsone was used in some capacity for the treatment of rosacea.”
Ex. 1039, 152:9–18. Although Dr. Kircik testified that dapsone failed to
gain FDA approval for treating rosacea, he nonetheless opined that, in 2012,
it would have been reasonable to prescribe dapsone along with other
medications (e.g., Finacea, azelaic acid) to treat rosacea if one medication
was insufficient for treatment. Id. at 152:19–154:2, 157:9–158:9. This
evidence contradicts Patent Owner’s assertion that there was only failure in
rosacea treatments with dapsone prior to its invention.
Moreover, we cannot agree with Patent Owner’s position that
Garrett II is evidence of the failure of others to treat rosacea. The title of
Garrett II is “DAPSONE TO TREAT ROSACEA,” and the reference is
clearly directed to treating rosacea with topical formulations of dapsone.
Ex. 2001, code (54), Abstract. Garrett II discloses, “[t]he invention includes
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a method to treat rosacea by topically administering a pharmaceutical
composition of dapsone and a pharmaceutically acceptable carrier to a
patient.” Id. at 1:30–33. Even if Garrett II’s examples did not show
dramatic results, Garrett II repeatedly states, for example, that in comparing
dapsone rosacea treatments with other rosacea treatments, “[s]ubjects in all
treatment groups experience a mean decrease from baseline in inflammatory
lesion count” and “[a]ll study treatment groups experienced a mean percent
decrease from baseline in lesion counts.” Id. at 28:1–2, 28:10–11; see also
id. at 28:33–29:4, 29:11–12, 35:5–29. Garrett II indicated success in treating
rosacea with both the vehicle MetroGel alone and with dapsone in
combination with Metrogel, and even if the difference was insubstantial we
find this nonetheless evidences some success, not failure. Id. at 5:5–29.
Contrary to Patent Owner’s arguments, Garrett II states “[t]he success rate
for the combination treatment of dapsone + MetroGel® was higher than
MetroGel® alone (39.5% success rate compared with 32.5%).” Id. at
35:27–29. Therefore, we are not persuaded that evidence of the failure of
others evidences non-obviousness of the claimed methods.
Summary
For the reason above, having considered the parties’ arguments and
evidence, we find that Petitioner has proven by a preponderance of the
evidence that claims 1 and 6 would have been obvious under 35 U.S.C.
§ 103(a) over Garrett and Nadau-Fourcade and also over Garrett and
Bonacucina. Petitioner has proven by a preponderance of the evidence that
the prior art combinations teach or suggest each element/step of claims 1 and
6, that the person of ordinary skill in the art would have been motivated to
make the prior art combinations, and that the person of ordinary skill in the
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art would have had a reasonable expectation of successfully combining these
references to achieve the claimed invention. Patent Owner’s evidence of
unexpected results and failure of others have been considered as objective
indicia of non-obviousness, and accorded it appropriate weight along with
the other Graham factors, but is insufficient to demonstrate non-
obviousness. Thus, claims 1 and 6 are unpatentable in view of Grounds 1
and 2 set forth in the Petition.
Dependent Claims 2 and 3
Claim 2 depends from claim 1 and, like claim 6, further requires “the
diethylene glycol monoethyl ether is present at a concentration of about 30%
w/w.” Ex. 1001, 16:14–16, 16:30–33. Claim 3 depends from claim 1 and,
like claim 6, further requires “the polymeric viscosity builder is present at a
concentration of about 4% w/w.” Id. at 16:17–18, 16:30–33. We have
discussed these claim limitations above when analyzing Petitioner’s case
challenging claim 6, which as noted above, requires the claimed DGME to
be at a concentration of about 30% w/w and requires the claimed polymeric
viscosity builder to be at a concentration of about 4%, which are the claim
limitations that differentiate claim 6 from claim 1. Compare id. at 15:40–
16:18, with id. at 16:23–36
Petitioner asserts:
For the same reasons as for claim 1 and 6, claim 2 is obvious.
Compositions containing 7.5% w/w dapsone and about 30% w/w
ethoxydiglycol were explicitly taught in Garrett. (AMN1004,
3:33–4:24). A POSA would have understood that about 30%
w/w was an acceptable and well-known amount of
ethoxydiglycol to use in a dapsone composition. (AMN1002,
¶¶59, 63–64). Therefore, using about 30% w/w of
ethoxydiglycol in dapsone compositions would have been
obvious.
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Pet. 39, 54 (further citing Ex. 1002 ¶¶ 92–93). Further, regarding claim 3,
Petitioner asserts “[t]his same limitation is also found in claim 6. For the
same reasons that claims 1 and 6 would have been obvious, claim 3 would
have been obvious.” Id. at 39, 54 (further citing Ex. 1002 ¶¶ 63, 65, 92, 94).
Patent Owner presents no arguments specifically directed to claim 2
or claim 3. See generally PO Resp.; PO Sur-Reply.
We discussed above that Patent Owner conceded Garrett taught the
claim elements directed to “about 30%” DGME. See Hr’g Tr. 89:6–10.
Furthermore, we discussed above that each of Garrett, Nadau-Fourcade, and
Bonacucina teach a range of gelling agent encompassing the claimed “about
4%.” Thus, for the reasons above, we also conclude that Petitioner has
established by a preponderance of the evidence that claims 2 and 3 would
have been obvious over Garrett and Nadau-Fourcade and over Garrett and
Bonacucina. The claims are unpatentable.
Dependent Claim 4 and 7
Claim 4 depends from claim 1, claim 7 depends from claim 6, and
each further requires “the topical pharmaceutical composition further
comprises methyl paraben.” Ex. 1001, 16:19–20, 16:37–38.
Petitioner asserts:
The use of methyl paraben would have been obvious.
(AMN1002, ¶¶29, 66). Methyl paraben was a widely-known
preservative in topical compositions. (AMN1014, 4–5). The
presence of preservatives, such as methyl paraben, was known to
inhibit bacterial growth in the composition and maintain the
integrity of the composition, thereby increasing its shelf-life.
(AMN1028, 20). Topical dapsone compositions using methyl
paraben were explicitly taught in the art: (1) Garrett specifically
discloses dapsone compositions having methyl paraben and (2)
methyl paraben had been successfully employed in the prior art
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Aczone® Gel 5%. (AMN1002, ¶¶63, 66; AMN1010, 4;
AMN1004, 3:33–4:25, 14:20–15:18). Therefore, the addition of
methyl paraben to topical dapsone compositions would have
been obvious.
Pet. 39–40, 54–55 (further citing Ex. 1002 ¶ 95).
Patent Owner presents no arguments specifically directed to claim 4
or claim 7. See generally PO Resp.; PO Sur-Reply.
We find Petitioner has established that Garrett teaches including
methyl paraben in its formulations, as claimed. See Ex. 1004, 4:2–5, 13:26–
33; see also Ex. 1005, 48 (Nadau-Fourcade also teaches incorporating
methyl paraben); Ex. 1015, 369 (Bonacucina also teaches incorporating
methyl paraben). Thus, for the reasons above, we also conclude that
Petitioner has established by a preponderance of the evidence that claims 4
and 7 would have been obvious over Garrett and Nadau-Fourcade and over
Garrett and Bonacucina. The claims are unpatentable.
Dependent Claims 5 and 8
Claim 5 depends from claim 1, claim 8 depends from claim 6, and
each further requires “the dermatological condition is acne vulgaris.”
Ex. 1001, 16:21–22, 16:39–40.
Petitioner asserts “[c]laims 5 and 8 simply narrow the condition being
treated from ‘acne vulgaris and rosacea’ to ‘acne vulgaris.’ For the same
reasons described above, the use of the recited dapsone formulation to treat
acne vulgaris would have been obvious. (AMN1018, ¶¶35-40).” Pet. 40, 55
(further citing Ex. 1018 ¶¶ 52–42).
Patent Owner presents no arguments specifically directed to claim 5
or claim 8. See generally PO Resp.; PO Sur-Reply.
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Garrett is directed to treating inflammatory and non-inflammatory
acne. See generally Ex. 1004. Nadau-Fourcade discloses that acne is a
disorder treated by its formulations. Ex. 1005, 51:1–10. Bonacucina teaches
that Sepineo is suitable for topical applications, like Garrett’s gel. Ex. 1015,
374. We find Petitioner has established that the cited prior art combination
teaches treating acne vulgaris, as claimed. See Ex. 1004, 4:2–5, 13:26–33.
Thus, for the reasons discussed above, we also conclude that Petitioner has
established by a preponderance of the evidence that claims 5 and 8 would
have been obvious over Garrett and Nadau-Fourcade and over Garrett and
Bonacucina. The claims are unpatentable.
IV. MOTIONS TO EXCLUDE
Both parties have moved to exclude evidence in this proceeding.
A. PETITIONER’S MOTION TO EXCLUDE.
Petitioner moved to exclude Exhibits 2010, 2011, 2013, 2017, 2018,
2021, 2024, 2026, 2027, 2029, 2032, 2038, 2039, 2040, 2050, 2051, 2052;
and also pages 289–93 of Exhibit 1017 (the Warner Declaration); paragraphs
1–19, 21–22, 83–93, 95, 98–100, 102–105, and 113–114 of Exhibit 2055
(Dr. Kircik’s Declaration); and paragraphs 1–37, 87–88, 109, 173–174, 165,
175–181, 190, 192–194, and 197 of Exhibit 2057 (Dr. Osborne’s
Declaration), generally for relevancy under Fed. R. Evid. 401–403, as
improper expert testimony under Fed. R. Evid. 702 and 703, or as hearsay
under Fed. R. Evid. 801 and 802. Paper 41.
As to all but the Warner Declaration, and the portions of
Dr. Osborne’s declaration relying upon the Warner Declaration, our
conclusions in this Final Written Decision do not rely upon or consider any
of the evidence that Petitioner seeks to exclude. Accordingly, Petitioner’s
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Motion to Exclude is dismissed as moot as to the evidence not cited in this
decision. Regarding the Warner Declaration, we deny Petitioner’s Motion to
Exclude for the reasons below.
Petitioner contends that the Warner Declaration constitutes
inadmissible hearsay under Federal Rules of Evidence (FRE) 801 and 802
because it contains out-of-court statements from Dr. Warner about his
observations of dapsone compositions that were not under oath and were not
subject to cross-examination. Paper 41, 5. Petitioner notes that Patent
Owner did not offer Dr. Warner for deposition in the first instance and then
did not provide Dr. Warner for deposition before January 17, 2020. Id.; see
also Paper 39 (December 31, 2019 order granting Patent Owner’s motion for
additional discovery, including the deposition of Dr. Warner).
In its Opposition to Petitioner’s Motion to Exclude, Patent Owner
contends it “is not relying on the Warner Declaration for its truth,” and “not
relying on it as proof of unexpected results.” Paper 50, 6. Rather, according
to Patent Owner, the Warner Declaration is offered as evidence by Patent
Owner only as support for its expert’s opinion. Id. Patent Owner further
contends that the Warner Declaration falls within one of the exceptions to
the hearsay rule. Id. at 7–10.28

28 Patent Owner further argues that Petitioner failed to timely object to the
Warner Declaration under 37 C.F.R. § 42.64(b)(1) because it was Petitioner
who submitted and relied upon the Warner Declaration, as part of its
Petition. Id. at 6–7. We are not persuaded that Petitioner failed to timely
object to the Warner Declaration. 37 C.F.R. § 42.64(b)(1) provides that
“[a]ny objection to evidence submitted during a preliminary proceeding
must be filed within ten business days of the institution of the trial.”
Although it was Petitioner that initially cited and discussed the Warner
Declaration it its Petition, Petitioner itself did not rely upon the Warner
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We agree with Petitioner that the Warner Declaration constitutes
hearsay to the extent it is offered for the truth of the statements contained
therein. We are not persuaded that an exception to the hearsay rule applies.
In this regard, despite Patent Owner’s assertion in its Opposition to
Petitioner’s Motion to Exclude that the Warner Declaration was not offered
for its truth, Patent Owner’s counsel indicated during the hearing a desire for
the Board to rely upon the Warner Declaration for its truth in assessing its
contentions regarding unexpected results. See, e.g., Hr’g Tr., 95:11-12
(“Well, hopefully you’ll rely upon it for its truth, Your Honor.”); 97:12-13
(“Well, I think if you credit the evidence, then you are relying on it as if it’s
true.”). We recognize, however, that Patent Owner’s experts may
nonetheless rely upon Warner Declaration in forming their opinions even if
the declaration itself constitutes inadmissible hearsay. See Fed. R. Evid.
703; Monsanto Co. v. David, 516 F.3d 1009, 1015–16 (Fed. Cir. 2008)
(“[N]umerous courts have held that reliance on scientific test results
prepared by others may constitute the type of evidence that is reasonably
relied upon by experts for purposes of Rule of Evidence 703.”). As
discussed in our analysis above, we have considered the Warner Declaration
and Dr. Osborne’s opinions based on the Warner Declaration only in this
limited capacity.

Declaration for the truth of what was stated. Pet. 18, 28, 45, 50, 57–61. To
the contrary, Petitioner argued preemptively that the Warner Declaration
failed to establish unexpected results and thus we should institute inter
partes review notwithstanding the Examiner’s prior reliance on it. Id. We
do not interpret our Rule 42.64(b)(1) to require Petitioner to object to its
own citation of the Warner Declaration in the Petition within ten business
days of institution.
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For these reasons, Petitioner’s Motion to Exclude is denied-in-part
with respect to pages 289–93 of the Warner Declaration and dismissed-in-
part as to the remaining evidence to which Petitioner objects.
B. PATENT OWNER’S MOTION TO EXCLUDE
Patent Owner moves to exclude portions of Exhibits 1043 and 1044,
which are the second declarations of Dr. Michniak-Kohn and Dr. Gilmore,
because they are unreliable opinions based on the deposition testimony of
Patent Owner’s experts. Paper 43. Patent Owner’s motion is denied.
Federal Rule of Evidence 703 is explicit that “[a]n expert may base an
opinion on facts or data in the case that the expert has been made aware of or
personally observed.” “It has long been accepted that an expert witness may
voice an opinion based on facts concerning the events at issue in a particular
case even if the expert lacks first-hand knowledge of those facts.” Williams
v. Illinois, 567 U.S. 50, 67 (2012); see also Summit 6, LLC v. Samsung Elec.
Co., LTD., 802 F.3d 1283, 1298 (Fed. Cir. 2015) (expert witnesses may
testify as to hypothetical scenarios and may base opinion on information
from others, any flaws in data or factual assumptions go to the weight of the
evidence, not admissibility).
The fact that Petitioner’s experts gave opinions based on scenarios
described by Petitioner’s counsel rather than their own eye witness
observations is immaterial because a declarant may offer an opinion based
on a hypothetical. We find that Patent Owner’s arguments go to the weight
to be given these declarants’ statements and not to the admissibility of them.
For these reasons, we deny Patent Owner’s motion.
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V. CONCLUSION
Petitioner has demonstrated by a preponderance of the evidence that
claims 1–8 of the ’219 patent would have been obvious over (1) the Garrett
and Nadau-Fourcade prior art combination and (2) the Garrett and
Bonacucina prior art combination, as discussed above.
In summary, on Petitioner’s unpatentability challenges:29

ORDER
Accordingly, it is hereby:
ORDERED that Petitioner has demonstrated by a preponderance of
the evidence that claims 1–8 of the ’219 patent are unpatentable;
FURTHER ORDERED that, because this is a Final Written Decision,
any party to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2; and

29 Should Patent Owner wish to pursue amendment of the challenged claims
in a reissue or reexamination proceeding subsequent to the issuance of this
decision, see the April 2019 Notice Regarding Options for Amendments by
Patent Owner Through Reissue or Reexamination During a Pending AIA
Trial Proceeding. See 84 Fed. Reg. 16654 (Apr. 22, 2019). If Patent Owner
chooses to file a reissue application or a request for reexamination of the
challenged patent, Patent Owner has a continuing obligation to notify the
Board in updated mandatory notices. See 37 C.F.R. § 42.8(a)(3), (b)(2).
Claims 35 U.S.C. § References/Basis
Claims
Shown
Unpatentable
Claims
Not Shown
Unpatentable
1–8 103(a) Garrett, Nadau-Fourcade 1–8
1–8 103(a) Garrett, Bonacucina 1–8
Overall Outcome 1–8
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FURTHER ORDERED that Petitioner’s Motion to exclude is denied-
in-part and dismissed-in-part; and
FURTHER ORDERED that Patent Owner’s Motions to Exclude is
denied.
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For PETITIONER:

Representing Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of
New York, LLC:

Dennies Varughese
Adam LaRock
Tyler Liu
STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
dvarughe-ptab@skgf.com
alarock-ptab@skgf.com
tliu-ptab@skgf.com

Representing Mylan Pharmaceuticals Inc.:

Jitendra Malik
Alissa Pacchioli
Lance Soderstrom
Heike Radeke
KATTEN MUCHIN ROSENMAN LLP
jitty.malik@kattenlaw.com
alissa.pacchioli@kattenlaw.com
lance.soderstrom@kattenlaw.com
heike.radeke@kattenlaw.com

For PATENT OWNER:

James Trainor
Elizabeth Hagan
FENWICK & WEST LLP
jtrainor@fenwick.com
ehagan@fenwick.com