Philippe Perovitch et al.

Patent Trials and Appeals Board

Feb 11, 2020

12441762 - (D) (P.T.A.B. Feb. 11, 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.
12/441,762 03/18/2009 Philippe Perovitch 0603-1004 5164
466 7590 02/11/2020
YOUNG & THOMPSON
209 Madison Street
Suite 500
Alexandria, VA 22314
EXAMINER
PARAD, DENNIS J
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
02/11/2020 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
following e-mail address(es):
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PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte PHILIPPE PEROVITCH and MARC MAURY
__________

Appeal 2018-008666
Application 12/441,762
Technology Center 1600
__________

Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and
DEBORAH KATZ, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
galenical form for the administration by transmucous means of one active
ingredient. The Examiner rejected the claims as failing to further limit and
as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm in part.

Statement of the Case
Background
The Specification teaches that when active pharmaceutical agents are
administered by the digestive tract, the “active ingredients undergo the so-

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the joint inventors, Philippe Perovitch
and Marc Maury, as the real party in interest (see Appeal Br. 2).
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called first digestive pass effect, alterations and losses related to the stomach
environment or to variations of intestinal physiologies” (Spec. 1). Next, the
active ingredients “are then subjected to a so-called ‘first hepatic pass’
effect, which brings about their metabolization and/or their more or less
intense degradation” (id.). In addition to issues of loss of active agent, the
Specification teaches that “the beginning of the therapeutic effectiveness for
the patient takes place at the earliest 45 minutes after intake” (id. 2).
“A need therefore persists for a galenical formulation that makes it
possible to administer an immediately bioavailable quantity of active
ingredient so as to be able to treat painful symptoms or incapacitating
problems very promptly and effectively” (Spec. 3).
The Claims
Claims 1, 2, 11, 12, 15, and 31 are on appeal. Claim 1 is
representative and reads as follows:
1. A galenical form for the administration by transmucous
means of one active ingredient, said galenic form consisting of
one active ingredient and a hydroalcoholic solution based on
water and ethanol, said active ingredient being in a stable and
complete dissolved state in said hydroalcoholic solution such
that said active ingredient is in a molecular state in the
hydroalcoholic solution, wherein said galenic form is in a liquid
form, and said hydroalcoh[o]lic solution consists of at least
20% by mass of ethanol and 50% – 73% by volume of water
and 27% – 50% by volume of ethanol so as to allow rapid
absorption in less than 20 seconds of all of said active
ingredient through the gingival and/or jugal mucous membranes
of the buccal cavity, wherein the dose of said active ingredient
is less than 300 mg and the volume of said hydroalcoholic
solution is less than 5 ml.
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The Issues
A. The Examiner rejected claim 12 under 35 U.S.C. § 112, fourth
paragraph as failing to limit the subject matter of the claim upon which it
depends (Final Act. 3).
B. The Examiner rejected claims 1, 2, 11, 12, 15, and 31 under 35 U.S.C.
§ 103(a) as obvious over Dobrozsi,2 TWC,3 and Latini4 (Final Act. 4–6).

A. 35 U.S.C. § 112, fourth paragraph
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that claim 12 fails to further limit
claim 1?
Findings of Fact
1. Claim 12 reads as follows:
12. The galenical form according to claim 1, wherein the
volume for administration is less than 5 ml.
Principles of Law
A “violation of § 112, ¶ 4 renders a patent invalid . . . for failing to
add a limitation [in a dependent claim] to those recited in the independent
claim, as required by 35 U.S.C. § 112, ¶ 4.” Pfizer, Inc. v. Ranbaxy Labs.
Ltd., 457 F.3d 1284, 1292 (Fed. Cir. 2006).

2 Dobrozsi et al., US 2002/0086878 A1, published July 4, 2002.
3 TWC, Terry White Chemists Amiodarone Tablets 1–14 (2008).
4 Latini et al., Myocardial Disposition of Amiodarone in the Dog, 224 J.
Pharm. Exp. Therapeutics 603–8 (1983).
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Analysis
Appellant contends
the volume for administration is not equivalent to the volume
of the hydroalcoholic solution.
According to claim 1, the volume of the hydroalcoholic
solution is less than 5 ml, and the hydroalcoholic solution
consists of at least 20% by mass of ethanol and 50% - 73% by
volume of water and 27% - 50% by volume. Thus, the volume
of the hydroalcoholic solution of claim 1 excludes the active
ingredient.
Claim 12 refers to the volume for administration, which
is the combined volume of ethanol, water, and the active
ingredient, which is not defined in claim 1.

(Appeal Br. 4).
The Examiner responds
contrary to Appellant’s assertion, claim 1 explicitly requires
that the volume of hydroalcoholic solution consist of the active
ingredient, water, and ethanol because claim 1 requires the
active ingredient be dissolved in “said hydroalcoholic solution”
of water and ethanol. Therefore, the volume of the
hydroalcoholic solution and the galenic form are identical.
Since claim 12 merely recites the same volume parameters of
the same composition, claim 12 fails to further limit the subject
matter of claim 1 upon which it depends.
(Ans. 9–10).
We agree with the Examiner because the hydroalcoholic solution
recited in Claim 1 is the entire volume that is administered in Claim 1, and is
therefore identical to the volume for administration in Claim 12. That is,
Claim 1 states that the “galenical form for the administration” consists of an
active ingredient that is in a “complete dissolved state in said hydroalcoholic
solution.” Thus, the entire volume of the galenical form in claim 1 is limited
to the hydroalcoholic solution with the dissolved active ingredient. Claim 1
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then further recites that “said hydroalcoholic solution is less than 5 ml,” and
since “said hydroalcoholic solution” includes the dissolved active ingredient,
the volume of the hydroalcoholic solution in Claim 1 does not exclude the
active ingredient and does not differentiate from the “volume for
administration is less than 5 ml” limitation in Claim 12.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that claim
12 fails to further limit claim 1.

B. 35 U.S.C. § 103(a) over Dobrozsi, TWC, and Latini
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that Dobrozsi, TWC, and Latini
render the claims obvious?
Findings of Fact
2. Dobrozsi teaches a “preferred composition is in the form of an
anhydrous, hydrophilic liquids in a very stable enviro[n]ment for rapid
delivery of actives . . . [including] rapid transmucosal delivery” (Dobrozsi
¶ 11).
3. Dobrozsi teaches the composition “comprising
dextromethorphan [may] preferably comprise from about 0.1% to about
9.3% . . . and most preferably from about 1.16% to about 4.6%
dextromethorphan” (Dobrozsi ¶ 34).
4. Dobrozsi teaches the “solvent portion of compositions of the
present invention comprises from about 60% to about 99.975% . . . .
Solvents of the present invention are preferably selected from the group
consisting of . . . ethanol” (Dobrozsi ¶¶ 37–38).
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5. Dobrozsi teaches “the maximum level of water is about 10%,
preferably from about 1% to about 10% more preferably from 5% to about
10%” (Dobrozsi ¶ 40).
6. Dobrozsi teaches “[t]ypical dosage forms of the composition of
the present invention contain no more than about 3 ml” (Dobrozsi ¶ 59).
7. Dobrozsi teaches “a large increase in bioavailability with very
rapid absorption can be achieved when the subject compositions are placed
against any of the mucosal membranes of the mouth” (Dobrozsi ¶ 59).
8. Example IX of Dobrozsi is reproduced below:

Example IX shows a composition comprising 88.534% ethanol, 10% water
and 1.466 % Dextromethorphan base (see Dobrozsi ¶ 85). The Examiner
calculates that 1.466% Dextromethorphan base is equivalent to 27.05 mg.
9. Dobrozsi teaches “[s]urprisingly, adding water to a
composition, [particularly] one comprising low water-soluble actives
improves the active’s stability in such compositions” (Dobrozsi ¶ 8).
10. The Examiner does not identify a teaching in Dobrozsi
suggesting water volumes of 50–73% or ethanol volumes of 27–50% (see
Final Act. 4–6).
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11. TWC teaches “[a]miodarone hydrochloride is a white or almost
white, fine crystalline powder, very slightly soluble in water, freely soluble
in methylene chloride, soluble in methanol, sparingly soluble in alcohol”
(TWC 1).
12. Latini teaches “amiodarone was administered i.v. over 20 sec as
a dose of 5 mg/kg dissolved in 50% ethanol in water” (Latini 604, col. 1).
Principles of Law
A prima facie case for obviousness “requires a suggestion of all
limitations in a claim,” CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333,
1342 (Fed. Cir. 2003) and “a reason that would have prompted a person of
ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Analysis
We begin with claim interpretation, because before a claim is properly
interpreted, its scope cannot be compared to the prior art. Claim 1 recites a
“said galenic form consisting of one active ingredient and a hydroalcoholic
solution based on water and ethanol” where “said hydroalcohlic solution
consists of at least 20% by mass of ethanol and 50% - 73% by volume of
water and 27% - 50% by volume of ethanol.” We therefore interpret the
claims as limited to a three component solution of active ingredient, water,
and ethanol.
Appellant contends Dobrozsi does not teach “a hydroalcoholic
solution consisting of 50% - 73% by volume water and 27% - 50% by
volume ethanol as defined in instant claim 1” and “explicitly limits water to
a maximum of about 10% by weight, i.e. or about 10% by volume” (Appeal
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Br. 6). Appellant contends that Latini “does not disclose the 50% ethanol
mixture for trans-mucosal delivery of amiodarone” and “discloses (1) an
intravenous delivery system having the 50% ethanol mixture and (2) oral
delivery system in solid tablet form” (id. at 9). Appellant contends “the
skilled person would have had no reason to consider LATINI or TWC in
relation with a trans-mucosal administration, as there was no indication of an
expectation of success for a 50% ethanol mixture for trans-mucosal delivery
of amiodarone” (id.).
The Examiner cites In re Aller, 220 F.2d 454 (CCPA 1955), for the
proposition that optimization of result effective variables is obvious and that
Dobrozsi teaches “that the addition of water is a result-effective variable for
determining optimum or workable ranges by routine experimentation based
on the explicit teaching that ‘adding water to a composition, particularly one
comprising low water-soluble actives improves the active’s stability in such
compositions’ (para [0008])” (Ans. 12). The Examiner finds that
Latini et al and TWC were cited for teaching that amiodarone is
a low-soluble active that may be solubilized in a hydroalcoholic
solution consisting of 50% ethanol and water as set forth,
supra. Dobrozsi et al teach stable compositions using
hydroalcoholic solvents that solubilize low-water soluble
actives. Therefore, it would have been prima facie obvious to
one of ordinary skill in the art to substitute one low-soluble
active for another, both dissolvable in a hydroalcoholic solution
within the recited concentrations with a reasonable expectation
of success.
(Ans. 14).
We agree with Appellant because even if Dobrozsi teaches that the
amount of water is a “results-effective variable,” there is nothing in
Dobrozsi suggesting that five-fold increase from the maximum amount
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suggested in Dobrozsi’s disclosed range (FF 5, 9). This is different from the
situation in Brandt, for example, where the non-overlapping ranges were “so
mathematically close that the examiner properly rejected the claims as prima
facie obvious.” In re Brandt, 886 F.3d 1171, 1177 (Fed. Cir. 2018).
Instead, we find the instant situation with a five-fold increase in water
concentration to be more like Stepan, which found that “[a]bsent some
additional reasoning, the Board’s finding that a skilled artisan would have
arrived at the claimed invention through routine optimization is insufficient
to support a conclusion of obviousness.” In re Stepan Co., 868 F.3d 1342,
1346 (Fed. Cir. 2017). That is, while Dobrozsi may have reasonably been
understood to permit routine optimization of amounts of water greater than
the 10% maximum value in the disclosed ranges, the Examiner does not
persuasively explain why the artisan would optimize to generate a five-fold
increase from 10% to the claimed 50% of water because there is no evidence
that drugs with poor water solubility would have been expected to have
greater stability when the amount of water is increased five-fold.
We also agree with Appellant that Latini’s example of an intravenous
composition with 50% water/50% ethanol would not have been suggestive
of a transmucosal composition as recited in claim 1 because these modes of
administration differ significantly. We interpret the recitations in claim 1 of
“administration by transmucous means” and “to allow rapid absorption in
less than 20 seconds of all of said active ingredient through the gingival
and/or jugal mucous membranes of the buccal cavity” as functional
recitations that limit claim 1. These functional limitations require that the
final composition has rapid absorption through mucous membranes. Latini’s
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teaching of an intravenous composition provides no guidance suggesting the
benefit of rapid absorption through a mucous membrane (FF 12).
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Dobrozsi, TWC, and Latini render the claims obvious.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
12 112, fourth
paragraph
Improper Dependency 12
1, 2, 11, 12,
15, 31
103(a) Dobrozsi, TWC,
Latini
1, 2, 11, 12,
15, 31
Overall
Outcome
12 1, 2, 11, 15,
31

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 IN PART