Ketan R. Patel

Patent Trials and Appeals Board

Jan 29, 2020

12451918 - (D) (P.T.A.B. Jan. 29, 2020)

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.
12/451,918 12/07/2009 Ketan R. Patel 98574.21500 4371
30734 7590 01/29/2020
BakerHostetler
Washington Square, Suite 1100
1050 Connecticut Ave. N.W.
Washington, DC 20036-5304
EXAMINER
RODRIGUEZ, RAYNA B
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
01/29/2020 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KETAN R. PATEL
Appeal 2018-006997
Application 12/451,918
Technology Center 1600
Before RICHARD M. LEBOVITZ, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.
HARDMAN, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–5, 18–21, 23, and 25–27. See Final
Act. 4. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM-IN-PART.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42. Appellant identifies the real party in interest as TROIKAA
PHARMACEUTICALS LTD. Appeal Br. 3.
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Application 12/451,918

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CLAIMED SUBJECT MATTER
The claims are directed to a non-aqueous topical solution of a
pharmaceutically acceptable salt of diclofenac. Claims 1 and 23, the two
independent claims on appeal, are reproduced below:
1. A novel composition consisting of:
an effective amount of a pharmaceutically acceptable salt
of diclofenac;
a penetration enhancer and solubilizer consisting of 10 to
30% v/v of a lower chain alcohol;
a solvent in an amount greater than or equal to 50% and
selected from propylene glycol, glycofurol or mixtures thereof;
and
an additional penetration enhancer selected from the group
consisting of
oleic acid,
N-methyl-pyrrolidone (NMP),
2-methyl-pyrrolidone, and
1-methyl-pyrrolidone;
wherein said composition is a non-aqueous topical
solution.
23. A novel composition comprising:
an effective amount of a pharmaceutically acceptable salt
of diclofenac in the range of 1.16% to 5% w/v;
a penetration enhancer and solubilizer in the range of 10
to 20% v/v of a lower chain alcohol;
a solvent in an amount greater than 75% and selected from
propylene glycol, glycofurol and mixtures thereof; and
an additional penetration enhancer in the range of 1 to 5%
w/v, and selected from the group consisting of
oleic acid,
N-methyl-pyrrolidone (NMP),
2-methyl-pyrrolidone, and
1-methyl-pyrrolidone;
wherein the composition is a non-aqueous topical solution.
Appeal Br. 10–12 (Claims Appendix).
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The Examiner indicated that the elected species under examination is
diethylamine diclofenac as the salt of diclofenac species, propylene glycol as
the solvent species, and ethanol as the lower chain alcohol species that is
identified as a “penetration enhancer and solubilizer” in claims 1 and 23.
Final Act. 2. Accordingly, as to the appealed rejection, we limit our analysis
to the patentability of this species, and take no position regarding the
patentability of the broader generic claims or the remaining species. See Ex
parte Ohsaka, 2 USPQ2d 1460, 1461 (BPAI 1987).
REFERENCES
The Examiner relies on the following prior art:
Name Reference Date
Samour US 5,976,566 Nov. 2, 1999
Zhang US 2007/0196453 A1 Aug. 23, 2007
H. Trommer & R.H.H. Neubert, Overcoming the Stratum Corneum: The
Modulation of Skin Penetration, 19(2) Skin Pharmacol Physiol. 106–21
(2006) (“Trommer”)
REJECTION
Claims 1–5, 18–21, 23, and 25–27 stand rejected under pre-AIA 35
U.S.C. § 103(a) as being unpatentable over Samour, Zhang, and Trommer.
Final Act. 4.
OPINION
Examiner’s Findings
The Examiner found that Samour teaches a composition consisting of
diclofenac diethylamine, a penetration enhancer, a solvent that is propylene
glycol, and ethanol, but “does not teach the penetration enhancer is one of
the additional penetration enhancers of claim 1.” Final Act. 5. The
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Examiner further found that Zhang “suggests a composition comprising a
pharmaceutically acceptable salt of diclofenac; ethanol; propylene glycol;
and . . . oleic acid,” while Trommer “establishes that propylene glycol in
combination with oleic acid function synergistically to improve penetration
of drugs through the skin.” Final Act. 6. The Examiner found that “it would
have been prima facie obvious for a person of ordinary skill in the art to
substitute one functional equivalence (any pharmaceutically penetration
enhancer) for another (oleic acid) with an expectation of success, since the
prior art establishes that both are suitable for topical compositions.” Final
Act. 6.
Regarding the amounts of ethanol (the elected species of lower chain
alcohol) and propylene glycol recited in claims 1 and 23, the Examiner
relied on Samour Figure 1, which is a ternary phase diagram showing the
miscibility of the penetration enhancer 2-n-nonyl-1,3-dioxolane at 10 and 2
wt% (squares and circles, respectively), in a vehicle consisting of varying
amounts of ethanol, propylene glycol, and water. Final Act. 7; see also
Samour 8:46–60, Fig. 1. The Examiner found that Samour Figure 1
demonstrates a formulation containing about 83% propylene glycol, 17%
ethanol, and 0% water. Final Act. 7. The Examiner found that this
formulation includes amounts of ethanol and propylene glycol that fall
within the ranges recited in claims 1 and 23. Final Act. 7. The Examiner
further found that
[i]t would have been prima facie obvious to one of ordinary skill
in the art to utilize the amount of ethanol and propylene glycol
taught by Samour as a starting point for optimizing []the amounts
of ethanol and propylene glycol in a composition consisting of
diclofenac diethylamine; propylene glycol, ethanol; and a
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penetration enhancer, wherein the penetration enhancer is oleic
acid.
Final Act. 7.
Regarding the amount of the additional penetration enhancer recited
in claim 23 (i.e., “1 to 5% w/v”), the Examiner found that “Samour
teaches[]2 to 15% of the skin penetration enhancer (col 4, line 62),” and
stated that “[i]t would have been prima facie obvious to one of ordinary skill
in the art to utilize the amount of penetration enhancer taught by Samour as
a starting point for optimizing the amount . . . of penetration enhancer, oleic
acid.” Final Act. 8.
Appellant’s Arguments
With respect to claim 1, Appellant argued that a person of ordinary
skill in the art would not have been motivated to change the penetration
enhancer in Samour, because Samour consistently describes its inventive
compositions as requiring a skin penetration enhancer selected from
dioxolane, dioxane, or acetal compounds. Appeal Br. 5–6. Appellant stated
that “[r]emoving or replacing these essential penetration enhancing
compounds from Samour et al.’s inventive formulations would render it
unsatisfactory for its intended purpose of substantially improving flux of
NSAIDS,” including as compared to a commercially available product that
Appellant asserted “includes medium chain triglycerides and
polyoxyethylene fatty acid esters that exhibit characteristics of penetration
enhancers.” Appeal Br. 6 (citations omitted); Reply Br. 2.
With respect to claim 23, Appellant made two arguments. First,
Appellant argued that Samour Figure 1 does not disclose a formulation
containing the recited amount of propylene glycol. Appeal Br. 7. That is,
Appellant argued that Figure 1 depicts the carrier only, and when factoring
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in even the minimum amount of active ingredient disclosed by Samour
(0.1%) and the penetration enhancer (10%), “the correct maximum amount
of propylene glycol . . . in a non-aqueous formulation is 74.62%.” Appeal
Br. 7. Accordingly, Appellant argued that Samour Figure 1 depicts a
formulation that includes less than the claimed amount (i.e., “an amount
greater than 75%”) of propylene glycol. Appeal Br. 8; see also Reply Br. 4.
Second, Appellant argued that Samour fails to teach the amount of
penetration enhancer recited in claim 23 (i.e., “1 to 5% w/v”). Specifically,
Appellant argued that despite Samour’s disclosure of an amount of
penetration enhancer that encompasses the claimed range (e.g., 2–15%, see
Samour 4:62), “the ternary phase diagram requires 10% penetration
enhancer to effectuate a non-aqueous formulation, with amounts less
resulting in an aqueous formulation.” Appeal Br. 8.
Analysis
Claim 1, and Claims that Depend Therefrom
We agree with and adopt the Examiner’s findings of fact on the
obviousness of claim 1, and determine that the Examiner has presented a
prima facie case of obviousness with respect to this claim.
We are not persuaded by Appellant’s argument that the Examiner has
failed to establish a motivation to modify Samour’s penetration enhancer.
Importantly, Appellant has not argued that substituting oleic acid for
Samour’s penetration enhancers would result in miscibility issues, or that
Samour Figure 1 is instructive only for formulations containing ethanol,
propylene glycol, and the enhancer 2-n-nonyl 1,3-dioxolane. In other words,
Appellant has not argued that the phase diagram in Samour Figure 1 is
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inapplicable to formulations containing a penetration enhancer other than 2-
n-nonyl 1,3-dioxolane.
Rather, with respect to claim 1, Appellant argues only that there was
no motivation to change Samour’s penetration enhancer because doing so
would render the formulation “unsatisfactory for its intended purpose of
substantially improving flux2 of NSAIDS.” Appeal Br. 6 (citing Samour
3:50–54); Reply Br. 2–4. We are not persuaded by this argument, because it
frames the “intended purpose” of Samour’s formulation in an overly narrow
way. Appellant cites only one of the disclosed benefits of Samour’s
formulations (i.e., “substantially improving flux of NSAIDS”). Appeal Br.
6. But elsewhere, Samour more broadly describes the intended purpose of
the invention, e.g., stating: “The present invention has as a principal object
to provide stable topical compositions effective for the transdermal
application of ibuprofen or other NSAID compounds by the application of
the composition to the skin.” Samour 3:62–65. Appellant has not
demonstrated that substituting Samour’s disclosed penetration enhancers
with oleic acid, based on its functional equivalence to the penetration
enhancers of Samour, would render the formulation inoperable for the
purpose of providing stable topical compositions effective for the
transdermal application of diclofenac.
Moreover, Appellant has not established that using oleic acid in place
of Samour’s penetration enhancers would have rendered the formulation
unsatisfactory even for the purpose of “substantially improving flux of
NSAIDS.” The comparison present in Samour referred to by Appellant is a

2 We understand flux in Samour to mean the percutaneous absorption rate of
active agent. See, e.g., Samour Example 1.
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comparison to commercially available formulations, one of which Appellant
contends includes materials that exhibit “characteristics of penetration
enhancers” (Appeal Br. 6; Reply Br. 2), but Appellant does not contend that
these formulations included oleic acid and propylene glycol. Trommer
teaches that propylene glycol and oleic acid function synergistically to
improve penetration of lipophilic drugs through the skin. Trommer 112–13.
Appellant has not addressed whether one of ordinary skill in the art would
have concluded the expected synergy taught by Trommer would not have
“substantially improv[ed] flux of NSAIDS.” Accordingly, on this record,
Appellant has not supported its contention that substituting oleic acid for
Samour’s penetration enhancers would render the formulations inoperable
for the purpose of “substantially improving flux.”
For the above reasons, Appellant’s arguments do not persuade us of
Examiner error, and thus we affirm the rejection of claim 1 as obvious over
Samour, Zhang, and Trommer. Claims 2–5, 18–21, and 26 directly or
indirectly depend from claim 1. See Appeal Br. 10–12 (Claims Appendix).
Appellant did not separately argue any of these dependent claims, and
instead relied on the arguments it made for claim 1. See Appeal Br. 8.
Accordingly, dependent claims 2–5, 18–21, and 26 fall with claim 1. See 37
C.F.R. § 41.37(c)(1)(iv) (2013).
Claim 23, and Claims that Depend Therefrom
With respect to claim 23, we are not persuaded by Appellant’s
argument that Samour fails to teach the limitation “a solvent in an amount
greater than 75%.” Appeal Br. 8. Appellant asserts that Samour’s ternary
phase diagram indicates that the non-aqueous formulation contains 74.62%
propylene glycol, which is less than the claimed amount of “greater than
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75%.” Id. at 7–8. However, it is well-settled that absent unexpected results,
“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). Thus, even
accepting Appellant’s argument that Samour teaches a formulation
containing 74.62% propylene glycol rather than “greater than 75%,” Samour
indicates that the amount of propylene glycol “may be varied to adjust the
initial flux of the NSAID through the skin.” Samour Abstract. Accordingly,
we agree with the Examiner that “[i]t would have been prima facie obvious
to one of ordinary skill in the art to utilize the amount of ethanol and
propylene glycol taught by Samour as a starting point for optimizing the
amount . . . of ethanol and propylene glycol,” particularly here, where
Samour discloses an embodiment having only slightly less propylene glycol
than is recited in claim 23. Final Act. 7.
We are persuaded, however, by Appellant’s argument that Samour
fails to teach the amount of “additional penetration enhancer” recited in the
“non-aqueous topical solution” of claim 23 (i.e., “1 to 5% w/v”). We agree
with Appellant that despite Samour’s general disclosure of using 2–15%
penetration enhancer (see Samour 4:62), “the ternary phase diagram requires
10% penetration enhancer to effectuate a non-aqueous formulation.” Appeal
Br. 8. Samour states that in the phase diagram, “the region below the lines
connecting the data points represent the proportions where the vehicle
components are immiscible.” Samour 8:54–60. The phase diagram shows a
single non-aqueous formulation, which contains 10% penetration enhancer;
formulations with less than 10% penetration enhancer (i.e., 2%) contain
water. See Samour Fig. 1. Therefore, an amount of penetration enhancer
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less than 10% would be immiscible with the other components and contrary
to the desired miscibility described by Samour. Samour 8:33–38.
Accordingly, in view of the teachings of Samour Figure 1, the Examiner has
not established that in optimizing the amount of penetration enhancer, a
skilled artisan would have been motivated to reduce the amount from 10%,
with a reasonable expectation of success of achieving the claimed range of
“1 to 5% w/v” penetration enhancer in a non-aqueous formulation. See, e.g.,
Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367
(Fed. Cir. 2016) (“The reasonable expectation of success requirement refers
to the likelihood of success in combining references to meet the limitations
of the claimed invention.”) (emphasis added).
For this reason, we determine that the Examiner has not established a
prima facie case of obviousness of claim 23, and thus we reverse the
rejection of claim 23 as obvious over Samour, Zhang, and Trommer. Claims
25 and 27 depend from claim 23. Appeal Br. 12 (Claims Appendix).
Appellant did not separately argue these dependent claims, and instead relied
on the arguments it made for claim 23. See Appeal Br. 8. Accordingly, for
the same reason discussed above with respect to claim 23, we reverse the
Examiner’s rejection of claims 25 and 27 as obvious over Samour, Zhang,
and Trommer. See 37 C.F.R. § 41.37(c)(1)(iv) (2013).
CONCLUSION
We affirm the rejection of claims 1–5, 18–21, and 26 under pre-AIA
35 U.S.C. § 103(a) as being unpatentable over Samour, Zhang, and
Trommer.
We reverse the rejection of claims 23, 25, and 27 under pre-AIA 35
U.S.C. § 103(a) as being unpatentable over Samour, Zhang, and Trommer
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Application 12/451,918

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DECISION SUMMARY
Claims
Rejected
35 U.S.C. § Reference(s)/Basis  Affirmed Reversed
1–5, 18–21,
23, 25–27
103(a) Samour, Zhang, and
Trommer
1–5, 18–
21, 26
23, 25, 27
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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED-IN-PART