Ex Parte Loupenok

Patent Trial and Appeal Board

Dec 21, 2016

12711337 (P.T.A.B. Dec. 21, 2016)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/711,337 02/24/2010 Leon LOUPENOK PU63776T 1560
20462 7590 12/23/2016
GlaxoSmithKline
GLOBAL PATENTS -US, UW2220
P. O. BOX 1539
KING OF PRUSSIA, PA 19406-0939
EXAMINER
PIPIC, ALMA
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
12/23/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
US_cipkop @ gsk. com
arlene.e.cannon@gsk.com
laura.m.mccullen@gsk.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LEON LOUPENOK1
Appeal 2014-006162
Application 12/711,337
Technology Center 1600
Before TAWEN CHANG, RACHEL H. TOWNSEND, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to an oil-in-water
emulsion aerosol foam composition. The Examiner entered final rejections
for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
STATEMENT OF THE CASE
Background
According to the Specification,
1 Appellant identifies the Real Party in Interest as STIEFEL RESEARCH
AUSTRALIA. App. Br. 3
Appeal 2014-006162
Application 12/711,337
The present invention is directed to an oil in water emulsion
aerosol foam composition having an oil phase and a water
phase, said composition comprising a pharmaceutically active
agent, water, oil, an oil miscible organic solvent, a surfactant,
and a propellant. The present invention provides for a low oil
and a low surfactant content in an oil in water emulsion aerosol
foam composition.
Spec. 2:13-17.
The Claims
Claims 1, 16—18, 20, 23, 27, 29, 31, 35, 36, 41—54, and 56—60 are on
appeal. Claim 1 is illustrative and reads as follows:
1. An oil in water emulsion aerosol foam composition
comprising an oil phase and a water phase, said composition
comprising:
i) tazarotene,
ii) water in an amount from about 65% to about 90% by
weight,
iii) an oil present in an amount from about 1 % to about
9% by weight,
iv) an oil miscible organic solvent,
v) a surfactant component comprising a hydrophilic
ethoxylated fatty alcohol ether selected from the group
consisting of steareth-10, steareth-20, ceteareth-6, ceteareth-10,
ceteareth-12, ceteareth-15, ceteareth-20, ceteareth-21, ceteareth-
22, ceteareth-25, ceteareth-30, ceteareth-31, ceteareth-32,
ceteareth-33, laureth-5, laureth-9, laureth-10, laureth-12,
laureth-15, laureth-20, laureth-21, laureth-22, laureth-23,
nonoxynol-9, oleth-10, oleth-20, and mixtures thereof, in an
amount from about 1 % to about 8% by weight, and
vi) a propellant; and
wherein the tazarotene is solubilized in the oil phase of
the composition, wherein the particle size of the oil phase is
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Application 12/711,337
less than about 1000 nm, and wherein all percentages are based
on the total weight of the composition.
App. Br. Claims App’x. 35.
Grounds of Rejection
1. The Examiner rejected claims 1, 16—18, 20, 23, 27, 29, 31, 35, 36, 41—
43, 45—54, and 56—60 under 35 U.S.C. § 103(a) as obvious over Tamarkin,2
Larm,3 and Paspaleeva-kuhn.4 Ans. 2.
2. The Examiner rejected claim 44 under 35 U.S.C. § 103(a) as obvious
over Tamarkin, Larm, Paspaleeva-kuhn, and Popp.5 Ans. 6—7.
Rejection over Tamarkin, Larm and Paspaleeva-kuhn
The Examiner finds that Tamarkin teaches “a composition and a
therapeutic kit including an aerosol packaging assembly including a
container accommodating a pressurized product and an outlet capable of
releasing a foamable composition, including a retinoid as a foam” and
discloses percentage values of the composition components “on a weight
(w/w) basis.” Ans. 2. The Examiner finds “Example 1 (composition TZ-1)
is an oil-in-water foamable emulsion composition comprising: tazarotene [];
mineral oil 5.6% w/w []; isopropyl palmitate 5.6% w/w []; sorbitan stearate
2% w/w (surfactant); propellant 10% w/w []; preservative []; and water to
100 % w/w,” noting that “[sjince all of the components except for water
2 WO 2007/007198 A2, published Jan. 18, 2007 (“Tamarkin”)
3 US 2006/0057168 Al, published March 16, 2006 (“Larm”)
4 US 2004/0151793 Al, published Aug. 5, 2004 (“Paspaleeva-kuhn”)
5 US 2005/0095261 Al, published May 5, 2005 (“Popp”)
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Application 12/711,337
comprise 26.11 % w/w, water is necessarily present in an amount of 73.89%
w/w.” Id. at 2—3. The Examiner finds Tamarkin discloses use of the
emollients “isopropyl palmitate and diisopropyl adipate[,] among others.”
Id. at 3. The Examiner finds that one embodiment of Tamarkin discloses a
“surface active agent [that] has an HLB between about 9 to about 14, which
is the required HLB to stabilize an O/W [oil-in-water] emulsion” and that
“[e]xamples of surfactants include polyoxyethylene alkyl ethers.” Fin. Act.
4.6 The Examiner finds Tamarkin discloses “suitable propellants include
volatile hydrocarbons such as butane.” Thus, the Examiner concludes
Tamarkin teaches all limitations of claim 1 except that it does not identify
the particle size of the oil phase or name ceteareth-12 as a specific
polyoxyethylene alkyl ether surfactant. Id. at 4—5.
The Examiner finds Larm discloses “a method of formulating
microemulsions useful in therapeutic and cosmetic application in the field of
dermatology” and teaches that particle size is “critical to its ability to cross
the skin barrier and therefore its ability to deliver a pharmaceutically active
ingredient for the treatment of local or systemic medical condition” such that
smaller particles have increased potential efficacy because “the percentage
of exposed surface area of a particle in proportion to its volume is increased.
Id.
The Examiner finds Paspaleeva-kuhn discloses compositions in the
form of an emulsion, where “the [oil-in-water] emulsifier has an HLB value
6 Final Action, mailed August 8, 2013.
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Application 12/711,337
that is preferably 9—13,” and that ceteareth-12 is a suitable oil-in-water
emulsifier having an HLB of 13.0. Id. at 5.
The Examiner finds it obvious that, because “cetearth-12 has been
recognized as a suitable O/W emulsifier with an HLB of 13,”
it would have been prima facie obvious to a person of ordinary
skill in the art at the time of the invention to have modified the
oil-in-water emulsion TZ-1 of Tamarkin by replacing sorbitan
stearate (HLB=5) emulsifier with ceteareth-12 (HLB=13)
emulsifier in order to form a stable oil-in-water emulsion, with
a reasonable expectation of success because Tamarkin taught
that emulsifiers with an HLB value from about 9 to about 14
are required to form stable oil in water emulsions.
Id. The Examiner finds the skilled artisan “would have been motivated to
make this substitution in order to form a stable oil in water emulsion.” Id. at
5—6. The Examiner finds it obvious that “because Larm et al. taught that
emulsion particle size of 10-300 nm has enhanced transdermal delivery of
active ingredient” a “person of ordinary skill would have been motivated to
optimize the particle size of the emulsion in order to obtain a particle size
surface area that most efficiently delivers the active ingredient
transdermally.” Id. at 6. Finally, the Examiner concludes that because
“tazarotene is a hydrophobic compound, it would have been reasonable to
expect that it would be solubilized in the oil phase.” Id. at 7.
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that claim 1 is obvious over the
cited prior art?
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Application 12/711,337
Findings of Fact
1. Tamarkin teaches “[a] composition and therapeutic kit
including an aerosol packaging assembly including a container
accommodating a pressurized product and an outlet capable of releasing a
foamable composition, including a retinoid as a foam.” Tamarkin Abstract.
2. Tamarkin teaches an oil-in-water foamable emulsion
composition in Example 1 (TZ-1) that contains, among other things,
tazarotene, mineral oil 5.6% w/w, isopropyl palmitate 5.6% w/w, sorbitan
stearate 2% w/w, PPG15-stearyl ether 1% w/w, glyceryl monostearate
0.45% w/w, propellant 10% w/w, preservative, and water to 100 % w/w. Id.
1112. The Examiner finds that because “all of the components except for
water comprise 26.11 % w/w, water is necessarily present in an amount of
73.89% w/w). Id.', Ans. 3.
3. Tamarkin teaches:
According to one or more embodiments of the present
invention, the surface-active agent has a hydrophilic lipophilic
balance (HLB) between about 9 and about 14, which is the
required HLB (the HLB required to stabilize an O/W emulsion
of a given oil) of most oils and hydrophobic solvents. Thus, in
one or more embodiments, the composition contains a single
surface active agent having an HLB value between about 9 and
14, and in one or more embodiments, the composition contains
more than one surface active agent and the weighted average of
their HLB values is between about 9 and about 14. Yet, in
other embodiments, when a water in oil emulsion is desirable,
the composition contains one or more surface active agents,
having an HLB value between about 2 and about 9.
Id. at | 84.
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Application 12/711,337
4. Tamarkin discloses that:
The surface-active agent is selected from anionic, cationic,
nonionic, zwitterionic, amphoteric and ampholytic surfactants,
as well as mixtures of these surfactants . . . Nonlimiting
examples of possible surfactants include . . . poly(oxyethylene)
alkylyl ethers, such as poly(oxyethylene) cetyl ether,
poly(oxyethylene) palmityl ether, polyethylene oxide hexadecyl
ether, polyethylene glycol cetyl ether.
Id. at | 84.
5. Tamarkin teaches:
In one or more embodiments, the surface active agent includes
a mixture of at least one non-ionic surfactant and at least one
ionic surfactant in a ratio in the range of about 100:1 to 6:1. In
one or more embodiments, the non-ionic to ionic surfactant
ratio is greater than about 6:1, or greater than about 8:1; or
greater than about 14: 1, or greater than about 16: 1, or greater
than about 20: 1.
In one or more embodiments of the present invention, a
combination of a non-ionic surfactant and an ionic surfactant
(such as sodium lauryl sulphate and cocamidopropylbetaine) is
employed, at a ratio of between 1 :1 and 20:1, or at a ratio of
4:1 to 10:1. The resultant foam has a low specific gravity, e.g.,
less than O.lg/ml.
It has been surprisingly discovered that the stability of the
composition is especially pronounced when a combination of at
least one non-ionic surfactant having HLB of less than 9 and at
least one non-ionic surfactant having HLB of equal or more
than 9 is employed. The ratio between the at least one non-ionic
surfactant having HLB of less than 9 and the at least one non­
ionic surfactant having HLB of equal or more than 9, is
between 1 :8 and 8: 1, or at a ratio of 4: 1 to 1 :4. The resultant
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Appeal 2014-006162
Application 12/711,337
HLB of such a blend of at least two emulsifiers is between
about 9 and about 14.
Thus, in an exemplary embodiment, a combination of at least
one nonionic surfactant having HLB of less than 9 and at least
one non-ionic surfactant having HLB of equal or more than 9 is
employed, at a ratio of between 1 :8 and 8:1, or at a ratio of 4:1
to 1 :4, wherein the HLB of the combination of emulsifiers is
between about 9 and about 14.
Id. at ]Hf 87—90.
6. Tamarkin claims 18 and 19 recite:
18. The kit of claim 2, wherein the emulsion is a water in oil
emulsion and wherein the HLB of the surface active agent is
between about 9 and about 14.
19. The kit of claim 2, wherein the emulsion is a water in oil
emulsion and wherein the HLB of the surface active agent is
between about 2 and about 9.
Id. at 46.
7. Tamarkin discloses:
Solubility of the retinoid is an important factor in the
development of a stable foamable composition according to the
present invention. Thus, in one or more embodiments, the
retinoid is soluble in the aqueous phase of the emulsion; in
other embodiments, wherein the agent possesses hydrophobic
characteristics the agent is soluble in the oil phase of the
emulsion. Yet, in additional embodiments, the retinoid is
difficult to solubilize in either the aqueous phase of the water
phase and thus, it is suspended in the emulsion, which contains
suspension-stabilizing agents, i.e., the polymeric agents that are
listed herein. Thus, in certain embodiments of the present
invention, the composition and properties of the aqueous phase
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Appeal 2014-006162
Application 12/711,337
of the emulsion (e.g., pH, electrolyte concentration and
chelating agents) and/or the composition of the oil phase of the
emulsion are adjusted to attain a desirable solubility profile of
the active agent.
Id. at 140.
8. Tamarkin discloses:
The therapeutic foam of the present invention may further
optionally include a variety of formulation excipients, which
are added in order to fine-tune the consistency of the
formulation, protect the formulation components from
degradation and oxidation and modify their consistency. Such
excipients may be selected, for example, from stabilizing
agents, antioxidants, humectants preservatives, colorant and
odorant agents and other formulation components, used in the
art of formulation.
Id. at 1100 (emphasis added).
9. Larm teaches:
The size of a particle is critical to its ability to cross the skin
barrier and therefore its ability to deliver a pharmaceutically
active ingredient for the treatment of local or systemic medical
conditions of the patient concerned. As particles become smaller
(particularly below 100 nm), the percentage of exposed surface
area of a particle in proportion to its total volume when
compared to unrefined material is increased, and hence its
potential efficacy is increased.
Larm 13.
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Application 12/711,337
10. Larm teaches “[t]he characteristics of sub-micron particles in
their application to the delivery of pharmaceutically active ingredients across
the skin barrier may be summari[z]ed as follows:
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Id. at 112.
11. Paspaleeva-kuhn teaches “ a novel agent containing fat (oil). . .
[t]he agent is characterised in that the base thereof is based on oil, which
can be used to produce, for example, cream, lotion, fluid, massage, or balm
based products which contain fa[t] (oil).” Paspaleeva-kuhn Abstract.
12.Paspaleeva-kuhn teaches:
an object of the present invention [is] to provide a product
which has a highly compatible active ingredient and where said
ingredient is incorporated into an emulsion base, as a result of
which the skin will not dry out and moreover a positive, care, in
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Appeal 2014-006162
Application 12/711,337
particular elasticity-promoting, skincare effect can also be
achieved.
Id. at 121.
13. Paspaleeva-kuhn teaches that “[sjuitable O/W [oil-in-water]
emulsifiers are, in particular, those with a HLB value of 9-18, preferably 9—
15 and in particular 9-13” and include preferably ceteareth-12 with an HLB
value of 13. Id. at || 107—108.
14. Bee7 teaches “[t]he external oil/water emulsifier will normally
have an HLB of at least 8 and examples are polyoxyethylene sorbitan
esters.” Bee 2:67-3:1.
15. Evans8 discloses “[t]he more polar, hydrophilic, surfactants tend
to be more soluble in water and promote the formation of oil-in-water
emulsions, whereas the less polar, lipophilic, surfactants tend to be more
soluble in oil and promote water-in-oil emulsions.” Evans 6:31—35.
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int 7 Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Wrigley found a “strong case of obviousness based on the prior art
references of record. [The claim] recites a combination of elements that
7 Bee et al, US 4,985,250, issued Jan. 15, 1991
8 Evans et al, US 5,026,548, issued June 25, 1991
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Application 12/711,337
were all known in the prior art, and all that was required to obtain that
combination was to substitute one well-known ... agent for another.” Wm.
Wrigley Jr. Co. v. Cadbury Adams USALLC, 683 F.3d 1356, 1364 (Fed.
Cir. 2012).
Analysis
We adopt the Examiner’s findings regarding the scope and content of
the prior art (Final Act. 3—7; Answer 2—8, FF 1— 15) and agree that the
claimed composition would have been obvious over the combined teachings
of Tamarkin, Larm and Paspaleeva-kuhn. We address Appellant’s
arguments below.
Appellant argues that although Tamarkin mentions
“poly(oxyethylene) alkyl ethers” and “isoceteth-20” in paragraph [0085], it
does not teach that these particular surfactants are preferred, or
indeed, particularly suitable where the retinoid is tazarotene.
Moreover, these surfactants form part of a broad disclosure of
possible surfactants, and there is nothing in the reference that
would have motivated the artisan to select these particular
surfactants out of the very broad disclosure, while
simultaneously selecting tazarotene from the broad disclosure
of retinoids to arrive at the presently claimed tazarotene foam.
Accordingly, Tamarkin et al. provide no disclosure that would
have motivated the artisan to select the hydrophilic ethoxylated
fatty alcohol ether surfactants defined in independent claims 1
and 36, or ceteareth-12 recited in independent claims 53 and 60,
for use in an oil-in-water aerosol foam composition comprising
tazarotene.
App. Br. 20—21.
Appellant further argues Tamarkin teaches away from selection of a
hydrophilic ethoxylated fatty alcohol ether surfactant because the “most
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Application 12/711,337
relevant” example of Tamarkin, composition TZ-1 of Example 1, “describes
an oil-in-water emulsion foam comprising tazarotene and 5.6% mineral oil
. . . comprises three surfactant components . . . none [of which] are the
hydrophilic ethoxylated fatty alcohol ether surfactants defined in the present
independent claims . . . [and] the composition described in [the example]
does not comprise ceteareth-12 as required by [the claims].” App. Br. 21—
22.
Appellant argues that Tamarkin contains internal contradictions
regarding whether a high HLB is required to make a stable oil-in-water
composition. Compare FF 3 (stating HFB of 9—14 required to stabilize an
oil-in-water emulsion of a given oil) with FF 2 (TZ-1 composition, which
Appellant contends contains a low HFB) and FF 6 (claiming an oil-in-water
emulsion with an HFB between about 2 and about 9). Appellant argues he
submitted the Abram Declaration9 pursuant to a request by the Examiner “to
submit evidence that the choice of surfactant employed, by itself, would
have an impact on the stability of the resultant composition.” App. Br. 22—
23. The Abram Declaration reports the results of testing the composition of
TZ-1, made by Appellant according to Tamarkin (“Prior Art Foam”) in
comparison to the claimed composition (Inventive Foam”). Id. at 23.
Abram declares “[s]amples of each composition were subjected to an
elevated temperature storage study where samples were stored at 50-C for 0,
3.5 and 5.5 weeks.” Abram Deck 5. The samples were then tested for
physical stability by measuring persistence of foam expelled from the
9 Declaration of Albert Zorko Abram under 37 C.F.R. 1.132, dated April 29,
2013.
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Application 12/711,337
container for 5 minutes and chemical stability by measuring percent
persistence of tazarotene in composition following storage as measured by
conversion to tazarotene sulfoxide, a tazarotene degradant. Id. at 14. Abram
declares the Inventive Foam exhibited “superior chemical stability” because
100 percent of the tazarotene remains after 5.5 weeks storage while the Prior
Art Foam is “unstable with respect to the chemical stability of the
tazarotene” because 0.0035% w/w tazarotene sulfoxide is formed after 5.5
weeks storage. Id. Figure 3 from the Abram Declaration reflecting the
percentage loss in Tazarotene is reproduced below:
compositions after storage at SCTC for 0*3.5 and
BSwmks
99.0
1 98&
f
1
SS-Q
& j a «
* sr-c
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Based on the data in the Abram Declaration, Appellant argues a skilled
artisan would not have been motivated to depart from the explicit teachings
of Tamarkin because “by following the teachings of Example 1
(composition TZ— 1) of Tamarkin et al., a white foam is produced which
persists for greater than 5 minutes.” App. Br. 23.
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Application 12/711,337
Appellant references a study that was performed and is addressed by
the Houlden Declaration.10 Appellant claims the object of the study was to
reflect a comparison of “the stability of tazarotene foam compositions
prepared using ceteareth-12 (on the one hand) versus sorbitan monooleate,
sorbitan monostearate, sorbitan monolaurate or sorbitan monopalmitate (on
the other hand).” Id. Appellant argues Figure 1 shows the Inventive Foam
“appeared to display superior chemical stability of the tazarotene active
agent compared with all of the Comparative Foams which comprise a
mixture of a sorbitan ester and PEG-40 hydrogenated castor oil/ PEG-60
hydrogenated castor oil as the surfactant.” Houlden Dec. 1 8. Figure 1 is
reproduced below.
Figure 1
10 Declaration of Robert James Houlden under 37 C.F.R. § 1.132, dated
August. 26, 2013.
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Application 12/711,337
Appellant further cites the Houlden Declaration as evidence that
“variation in the chemical stability of the compositions may only be
attributed to the nature of the surfactants used in the compositions”
and that — “all variables being equal, the choice of surfactant is a
critical factor influencing the chemical stability of the tazarotene
active agent within the aerosol foam compositions of the present
invention.” Rep. Br. 7; App. Br. 26. Appellant argues that the Abram
and Houlden Declarations evidence “the Inventive Foams have
superior chemical stability to those of Tamarkin.” App. Br. 24.
The Examiner responds to Appellant’s arguments with several points.
Examiner states in an Advisory Action 211 that one would have been
motivated to modify the composition by substituting the low HLB surfactant
with a high HLB surfactant in order to obtain a more stable emulsion.
Tamarkin’s emulsion in example TZ-1, when dispensed from the container,
might have resulted in a physically stable foam, but that is not the same as
having a stable emulsion. The instantly claimed composition is an obvious
improvement of Tamarkin’s modified composition TZ-1. Tamarkin
exemplified a composition (TZ-1) and provided guidance in the general
teachings on how to improve it, by making it more stable. A person of
ordinary skill would have been motivated to improve TZ-1 in order to obtain
a composition that has better characteristics such as improved emulsion
stability. The Examiner finds “Tamarkin provides motivation to replace the
low HLB surfactants in the o/w emulsion TZ-1 with a high HLB surfactant
11 Advisory Action, mailed Sept. 9, 2013, at 2.
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[because it] teaches that a high HLB surfactant is required to form a stable
o/w emulsion [] and this teaching in Tamarkin is consistent with the general
teachings in the art regarding the selection of a surfactant for o/w
emulsions.” Ans. 8. The Examiner provides evidence of general knowledge
regarding the selection of surfactants for o/w emulsions from additional
prior art patents Bee and Evans (FF 13—14) and finds:
[a] person of ordinary skill would have been aware of the
general knowledge in the art and would have able to rely upon
it to clarity the ambiguity that is present in Tamarkin. It is well
known in the art that surfactants with low HLB (lipophilic)
values are used for making water in oil emulsions and that
surfactants with high HLB (hydrophilic) value are used for
making oil in water emulsions, and a person of ordinary skill
would have been aware of this general knowledge.
Ans. 8—9.
Furthermore, the Examiner finds:
[]a person of ordinary skill in the art would have been capable
of determining the HLB values of [the] surfactants [disclosed in
Tamarkin] and would have recognized that polyoxyethylene
alkyl ethers such as isoceteth-20 are surfactants with a high
HLB value . . . and have been capable of selecting an
appropriate high HLB surfactant that is considered suitable for
making a stable o/w emulsion and utilizing it [in] Tamarkin's
emulsion TZ-1.
Ans. 9.
In Reply, Appellant states the “Examiner does not provide evidence in
support of [the] statement” that the general knowledge of the art suggests
that stable oil-in-water emulsions should be made with surfactants having a
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Application 12/711,337
high HLB value and argues Appellant had “provided unrefuted evidence that
TZ-1 is a stable emulsion,” citing the Abram Declaration as evidence that
TZ-1 is a stable composition for its intended purpose and that one of skill in
the art would not be motivated as described by the Examiner to make a
different composition where TZ-1 of Tamarkin is already stable. Reply Br.
5-6.
Appellant’s arguments do not persuade us that the Examiner erred in
finding that a preponderance of the evidence suggests Tamarkin, Larm, and
Paspaleeva-kuhn render claim 1 obvious. Tamarkin teaches a composition
for use as a pressurized foamable product including retinoids. Tamarkin
discloses composition TZ-1, which Appellant acknowledges is “most
relevant,” and which contains all components of the claimed invention
(tazarotene, water, oil, oil-miscible solvent, polyoxyethylene alkyl ether
surfactant and propellant) other than the specific polyoxyethylene alkyl
ether(s) claimed. App. Br. 21; FF 1—2. Tamarkin teaches that a surface-
active agent with an HLB of between about 9 and about 14 is “required” to
stabilize an oil-in-water emulsion of a given oil. FF 3. Larm teaches the
importance of small particle size to the ability to cross the skin barrier and
discloses emulsions containing particles in the range of less than 1000 nin.
FF 9-10. Paspaleeve-kuhn discloses a highly active ingredient for
incorporation into an emulsion base for use in a skin product, and that
suitable oil-in-water emulsifiers for this purpose preferably include
ceteareth-12 with an HLB of 13. FF 10—12.
With regard to Appellant’s argument that Tamarkin discloses
composition TZ-1 and claims 18 and 19 with HLB ranges in apparent
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Application 12/711,337
contradiction to Tamarkin’s teachings in paragraph 84 regarding the need for
surfactants having a high HLB, i.e., of between about 9 and about 14, to
obtain a stable oil-in-water emulsion (App. Br., 22), we find these alleged
contradictory disclosures are not dispositive in light of Tamarkin’s teachings
as a whole.
Tamarkin teaches combinations of surfactants including non-ionic and
ionic surfactants or multiple non-ionic surfactants. FF 5. Tamarkin also
teaches that using a combination of surfactants provides “pronounced”
stability of an oil-in-water emulsion:
It has been surprisingly discovered that the stability of the
composition is especially pronounced when a combination of at
least one non-ionic surfactant having HLB of less than 9 and at
least one non-ionic surfactant having HLB of equal or more
than 9 is employed. The ratio between the at least one non­
ionic surfactant having HLB of less than 9 and the at least one
non-ionic surfactant having HLB of equal or more than 9, is
between 1 :8 and 8: 1, or at a ratio of 4: 1 to 1 :4. The resultant
HLB of such a blend of at least two emulsifiers is between
about 9 and about 14.
Id. Using such combinations, Tamarkin provides that where a non-ionic
surfactant with an HLB greater than 9 is combined with a second surfactant
“having HLB of less than 9,” the ratio of the combination is broadly between
1:8 and 8:1, resulting in a HLB between about 9 and 14. FF 5, emphasis
added. Accordingly, Tamarkin teaches that surfactants having a HLB of less
than 9 can be used to make a composition that provides a stabilizing HLB of
about 9 to 14.
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We further note that Example TZ-1 contains isopropyl palmitate,
which is a known nonionic emulsifier,12 at 5.6%. Tamarkin lists isopropyl
palmitate as a “solvent” with “emollient” capacity. Tamarkin at | 64. Thus,
the composition of TZ-1 contains four emulsifying agents: sorbitan stearate
(HLB= 5) emulsifier at 2%, PPG 15-stearyl ether at 1%, glyceryl
monostearate at 0.45%, and isopropyl palmitate (HLB=11.5) at 5.6%. Given
the ratios and respective HLB values of these emulsifiers and the fact that
the amount of isopropyl palmitate is present in nearly twice the amount of
the low HLB emulsifiers, Appellant has not established that the HLB value
of the composition is in fact less than “about 9 to 14.” further, claim 19,
reciting “wherein the HLB of the surface active agent is between about 2 and
about 9,” does not exclude the total HLB of the composition from being
“about 9 to 14,” only that it has a surface active agent as part of the foamable
composition that is between about 2 and about 9.13
12 See, e.g., PUBCHEM OPEN CHEMISTRY DATABASE, entry for
isopropyl palmitate, https://pubch.em.ncbi.nhn.nih.gov/compound/8907 (at
9.3 “BELIEVED TO BE USED ALMOST EXCLUSIVELY AS AN
EMOLLIENT & EMULSIFIER (1976)”, at 11.2.1: “Isopropyl palmitate's
production and use as an emollient and emulsifier in cosmetics and personal
care products...” and 11.2.2 “Isopropyl palmitate's production and use as an
emollient and emulsifier in cosmetics and personal care products may result
in its release to the environment through various waste streams.”
13 Claim 1, from which claim 19 ultimately depends, recites the transitional
phrase “including” which is synonymous with the transitional term
“comprising.” See e.g., MPEP 2111.03. Thus, there can be more than one
surface-active agent in the foamable composition, which is consistent with
the description in the Tamarkin specification. FF 5.
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Tamarkin teaches making adjustments to the components of an oil-in­
water emulsion to adjust the solubility of a retinoid active component to
form a stable foamable composition:
Solubility of the retinoid is an important factor in the
development of a stable foamable composition according to the
present invention. Thus, in one or more embodiments, the
retinoid is soluble in the aqueous phase of the emulsion; in
other embodiments, wherein the agent possesses hydrophobic
characteristics the agent is soluble in the oil phase of the
emulsion. Yet, in additional embodiments, the retinoid is
difficult to solubilize in either the aqueous phase of the water
phase and thus, it is suspended in the emulsion, which contains
suspension-stabilizing agents, i.e., the polymeric agents that are
listed herein. Thus, in certain embodiments of the present
invention, the composition and properties of the aqueous phase
of the emulsion (e.g., pH, electrolyte concentration and
chelating agents) and/or the composition of the oil phase of the
emulsion are adjusted to attain a desirable solubility profde of
the active agent.
FF 7 (emphasis added). Additionally, as discussed above, Tamarkin
teaches that a combination of surfactants provides a particularly stable
solution. FF 5. Thus, notwithstanding the disclosures cited by
Appellant — which we have explained are not dispositive on the issue
of HLB value — one of skill in the art could look to the teachings of
Tamarkin and understand that the surfactants disclosed could be
substituted with the goal of obtaining a high HLB based on
Tamarkin’s teachings regarding stable oil-in-water compositions, and
following Tamarkin’s specific methods for improving retinoid
solubility, and thereby emulsion stability, when desired. See FF 3, 7,
and 8. The Examiner’s stated motivation for creating a “more stable
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composition” is consistent with these teachings of Tamarkin (FF 3, 7,
8), Paspaleeva-kuhn (FF 13) as well as additional art cited by the
Examiner, Bee (FF 14) and Evans (FF 15). The Examiner has
sufficiently demonstrated that any confusion felt by one of skill in the
art in reading the teachings of Tamarkin and identified by Appellant
could be readily resolved by reviewing the remainder of Tamarkin and
by consulting these other references.
We agree with the Examiner’s reasoning that one of skill in the art
would be motivated by the goal of achieving a stable emulsion for storage of
the composition, rather than simply achieving a foam that is physically
stable after expulsion from the container, as demonstrated by Appellant’s
testing. Appellant’s own Specification describes the emulsions of the
present invention as “chemically and physically stable.” FF 1. Thus, as
physical stability alone is not a complete measurement of stability for
purposes of characterizing the prior art, we are not persuaded by Appellant’s
argument that the physical stability of the expelled TZ-1 composition alone
would dissuade further investigation by a skilled artisan interested in also
achieving chemical stability of the emulsion.
Turning to the storage stability tests disclosed by the Abram and
Houlden Declarations, we likewise are not persuaded that the modest
changes in storage stability disclosed by the Inventive Foams are sufficient
to overcome a finding of prima facie obviousness. See, e.g., Abram Dec. 14.
The slight changes in storage stability noted in the Abram and Houlden
Declarations were not identified as unexpected by the Specification or even
in the declarations themselves, but were submitted as unexpected by post-
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hoc argument of Appellant’s counsel in an attempt to overcome prior art.
“Attorney’s argument in a brief cannot take the place of evidence.” In re
Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Also, the values in Figure 1 of
Houlden and Figure 3 of Abram do not significantly differ. We agree with
the Examiner that the difference “does not represent a ‘difference in kind’
that is required to show unexpected results.” In re Harris, 409 F.3d 1339,
1344 (Fed. Cir. 2005) (citing In re Huang, 100 F.3d 135, 139 (Fed. Cir.
1996). Rather, the modest difference, which Appellant does not even
contend or establish is statistically different, is simply a difference in degree.
Accordingly, we do not find Appellant’s argument that the results of Figures
1 and 3 display superior chemical stability persuasive in light of our findings
of fact (FF 2—15) regarding the teachings of the prior art or in light of the
data itself.
Appellant’s final arguments are similar to each other: Appellant
argues that although Tamarkin teaches improvements in foamable
compositions, it fails to “direct the skilled person to the precise
improvements required to arrive at the instant invention.” App. Br. 24.
Likewise, Appellant argues Larm does not “remedy the deficiencies of
Tamarkin et al. because the reference fails to teach the use of the hydrophilic
ethoxylated fatty alcohol ether surfactants recited in the present independent
claims within a low oil, low surfactant aerosol foam composition comprising
tazarotene” (App. Br. 29) and “Paspaleeva-kuhn does not remedy the
deficiencies of Tamarkin et al. because [] one of skill in the art would not
have had reason to depart from the teachings regarding TZ-1, which
Appellant argues produced a physically stable foam product.” Id. These
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arguments are not persuasive because each fails to address the combined
teachings of Tamarkin, Larm, and Paspaleeva-kuhn. Nonobviousness
cannot be established by attacking the references individually when the
rejection is predicated upon a combination of prior art disclosures. In re
Merck & Co. Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986); see also In re
Keller, 642 F.2d 413, 426 (CCPA 1981) (finding “one cannot show
nonobviousness by attacking references individually where, as here, the
rejections are based on combinations of references” (citations omitted)).
The Examiner reasonably explains that a skilled artisan would have been
motivated to modify the oil-in-water emulsion TZ-1 of Tamarkin by
replacing the non-ionic emulsifier sorbitan stearate (HLB=5) with the non­
ionic emulsifier ceteareth-12 (HLB=13) in order to form a stable oil-in-water
emulsion, with a reasonable expectation of success, and that the artisan
would have been motivated to optimize the particle size of the emulsion
based on the teachings of Larm to obtain a particle size surface area that
most efficiently delivers the active ingredient transdermally. Ans. 5—6.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that claim
1 is obvious over the cited prior art.
Claims 16-18, 20, 23, 27, 29, 31, 35, 36, 41^13, 45-54, and 56-60
have not been argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
Rejection over Tamarkin, Larm, Paspaleeva-kuhn and Popp
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Appellant’s claim 44 depends from claim 1 and adds the additional
limitation that the composition comprises the preservatives sorbic acid and a
salt thereof. App. Br. Claims App’x. 40.
The Examiner finds Tamarkin, Larm, and Paspaleeva-kuhn do not
teach a combination of preservatives sorbic acid and a salt thereof. Ans. 7.
The Examiner finds Popp teaches topical compositions that can
include “oil in water type.” Id. The Examiner finds the compositions of
Popp “contain preservatives, wherein the useful preservatives include sorbic
acid, potassium sorbate among others, and mixtures thereof.” Id.
The Examiner concludes that because Popp teaches preservatives
including “sorbic acid, potassium sorbate and mixtures thereof’ that are
“known preservatives [] utilized in formulations intended for use on skin,” it
would have been obvious to have selected the preservatives of Popp for
inclusion in Tamarkin’s composition with a reasonable expectation of
success.” Id. at 7—8.
Findings of Fact
16. Popp teaches “[mjethods of treating rosacea using a storage-
stable topical composition comprising a mixture of an antimicrobial active
ingredient, sufficient amounts of at least one pH modifier to provide the
topical composition with an overall pH of about 3.0 to about 8.0, and a
pharmaceutically acceptable carrier.” Popp Abstract.
17. Popp teaches:
Non-limiting examples of specific preservatives useful in the
present topical compositions include methylparaben,
benzalkonium chloride, propylparaben, benzoic acid, EDTA,
phenolic acid, sorbic acid, benzyl alcohol, isopropyl alcohol,
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benzethonium chloride, bronopol, butylparaben, cetrimide,
chlorhexidine, chlorobutanol, chlorocresol, cresol,
ethylparaben, glycerol, imidurea, phenol, phenoxyethanol,
phenylethyl alcohol, potassium sorbate, propylene glycol,
sodium benzoate, sodium propionate, sorbic acid, thimerosol,
and mixtures thereof. A particularly preferred preservative in
this regard is methylparaben.
Popp 1137.
We adopt the Examiner’s findings regarding the scope and content of
the prior art (Final Act. 7—9; Answer 2—8, FF 1— 15) and agree that the
claimed composition would have been obvious over the teachings of
Tamarkin, Farm, Paspaleeva-kuhn, and Popp. We address Appellant’s
arguments below.
Appellant incorporates his prior arguments regarding references
Tamarkin, Farm, and Paspaleeva-kuhn, as set forth above. App. Br. 32—33.
Appellant further argues Popp does not remedy the deficiencies in these
references because “Popp et al. fail to describe or teach the use of a
hydrophilic ethoxylated fatty alcohol ether surfactant within an oil in water
emulsion aerosol foam composition comprising tazarotene, as claimed in the
present application.” Id. at 33.
We are not persuaded by this argument. We have addressed
references Tamarkin, Farm, and Paspaleeva-kuhn above, and note that the
alleged deficiencies of Popp are not dispositive to the sufficiency of the
rationale underlying the rejection because the rejection is based upon a
combination of Tamarkin, Farm, Paspaleeva-kuhn, and Popp. In re Merck
& Co. Inc., 800 at 1097. Popp establishes that sorbic acid and mixtures
thereof (e.g., a salt thereof) is a suitable preservative in topical compositions.
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FF 16—17. We are not persuaded that the Examiner’s finding that one of
skill in the art would have been motivated to add sorbic acid and its salt to
the composition described above is reversible error. Rather, use of sorbic
acid is merely a “predictable use of prior art elements according to [its]
established function[].” KSR, 550 U.S. at 417.
SUMMARY
In summary, we affirm the rejection of claims 1, 16—18, 20, 23, 27,
29, 31, 35, 36, 41—43, 45—54, and 56—60 under 35 U.S.C. § 103(a) as
obvious over Tamarkin, Larm, and Paspaleeva-kuhn, and the rejection of
claim 44 as obvious over Tamarkin, Larm, and Paspaleeva-kuhn and Popp
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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