Ex Parte Bracht

Board of Patent Appeals and Interferences

Sep 5, 2012

11091633 (B.P.A.I. Sep. 5, 2012)

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.
11/091,633 03/28/2005 Stefan Bracht 3239 5617
7590 09/05/2012
STRIKER, STRIKER & STENBY
103 EAST NECK ROAD
HUNTINGTON, NY 11743
EXAMINER
WEBB, WALTER E
ART UNIT PAPER NUMBER
1612
MAIL DATE DELIVERY MODE
09/05/2012 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte STEFAN BRACHT
__________

Appeal 2011-006365
Application 11/091,633
Technology Center 1600
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and
LORA M. GREEN, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the rejection of claims
27-46, directed to a transdermal pharmaceutical preparation of drospirenone.
The Examiner has rejected the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We reverse.

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STATEMENT OF THE CASE
Claims 27-46 are on appeal. Claim 27 is representative and reads as
follows:
27. A pharmaceutical preparation for transdermal administration of
drospirenone by applying the preparation to skin, said pharmaceutical
preparation consisting of:
drospirenone in an initial concentration of from 0.5 to 2.0% (m/m);
at least 60 % (m/m) of ethanol;
optionally at least one auxiliary substance that promotes super-
saturation of said drospirenone, which is selected from the group consisting
of isopropanol, propylene glycol, dipropylene glycol, 1,3-butandiol,
diethylene glycol monomethyl ether, diethylene glycol monoethyl ether,
propylene carbonate, isopropylidene glycerol, and monoterpene ingredients
of etheric oils;
optionally at least one of a lubricating agent and a crystallization
inhibitor;
optionally an estrogen compound;
optionally testosterone;
optionally water;
a gel former selected from the group consisting of hydroxymethyl
cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and polyacrylic
acids;
wherein said initial concentration of said drospirenone does not
exceed a saturation solubility of said drospirenone in an initial state of the
preparation prior to application to the skin, but when the preparation is
applied to the skin, the saturation solubility of the drospirenone is exceeded
by a factor of at least five while said preparation is applied to the skin
because of escape or discharge of the ethanol from the preparation.
The Examiner has rejected claims 27-46 under 35 U.S.C. § 103(a) as
obvious over van der Hoop

(US 2003/0027804 A1, February 6, 2003) and
Heil et al. (US 2002/0132801 A1, September 19, 2002).
1

1
The Examiner has withdrawn two obviousness rejections (Ans. 3) based in
whole or in part on the combined teachings of Laurent (US 6,177,416 B1,
January 23, 2001) and van der Hoop.
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FINDINGS OF FACT
1. van der Hoop teaches that “[s]ex hormone binding globulin is a
serum protein, and is known to bind to testosterone and estradiol, effecting
the biological activity of these hormones” (van der Hoop ¶ 85). van der
Hoop suggests that compounds that inhibit the synthesis of sex hormone
binding globulin (e.g., methyltestosterone and fluoxymesterone), when
administered with testosterone or estradiol, “provide a means of increasing
[free] hormone concentrations in the bloodsteam” and “produce a greater
therapeutic effect” (id. at ¶¶ 85, 86).
2. van der Hoop discloses “methods, combinations, and
compositions for treating, preventing, or reducing the risk of developing an
androgenic or estrogenic hormone deficiency, or a male or female
menopause disorder” (van der Hoop ¶ 69), comprising administering “a sex
hormone binding globulin synthesis inhibiting agent and one or more
steroids, including for example androgen and/or estrogen” (id.). “Sequential
or substantially simultaneous administration of each therapeutic agent can be
effected by any appropriate route including . . . oral routes, percutaneous
routes, intravenous routes, intramuscular routes, and direct absorption
through mucous membrane tissues” (id. at ¶ 72).
3. van der Hoop teaches that “[a] class of androgens useful in the
. . . compositions . . . include[s] steroids in the testosterone anabolic or
catabolic pathway” (van der Hoop ¶ 88), and provides an extensive list
which includes anabolic steroids and progesterone (id.). “Another class of
agents useful in the methods, combinaitons and compositions . . . include
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estrogenic hormones” (id. at ¶96), which “are currently available in various
formulations including . . . transdermal estrogen preparations” (id. at ¶ 97).
4. van der Hoop discloses ANDROGEL®, a transdermal gel
containing the following ingredients:

(van der Hoop ¶ 91, Table 6.)
5. Heil teaches that progesterone is typically administered in
combination with (i.e., in opposition to) an estrogen compound in estrogenic
hormone replacement therapy in order to protect the endometrium from
hyperplasia, a risk factor for endometrial cancer (Heil ¶¶ 16-18).
6. Heil teaches that “[t]he use of natural progesterone in
combination therapy is limited by the low bioavailability of natural
progesterone, even in micronized form” (Heil ¶ 19), but drospirenone “is a
synthetic progesterone that has a surprisingly similar physiological profile to
progesterone yet notably better bioavailability” (id.).
DISCUSSION
Claims 27 and 36, the only independent claims, are directed to a
transdermal formulation consisting of drospirenone (in an amount expressed
in finite and/or functional terms); at least 60% (m/m) ethanol; and a gel
former (e.g., polyacrylic acids). In addition, the formulation may contain a
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number of optional components, including an estrogen compound and/or
testosterone.
The Examiner finds that van der Hoop “teaches compositions for
treating or reducing . . . male or female menopause disorder” (Ans. 4),
including “a specific formulation of gel for transdermal delivery” (id.),
ANDROGEL®, which “consists of testosterone, carbopol 980 (polyacrylic
acid) . . . and 67% m/m ethanol” (id.). The Examiner further finds that van
der Hoop discloses “the use of progesterone in combinations and
compositions” (id.), but “does not teach drospirenone” (id.).
However, the Examiner finds that Heil “teaches that drospirenone is
synthetic progesterone, which is preferred over natural progesterone since
drospirenone has better bioavailability” (id.), and teaches that “„combination
therapy comprising the use of drospirenone as a progestagen, is remarkably
effective‟” (id. at 5).
The Examiner concludes that it would have been obvious “to have
used drospirenone as the progesterone in the composition of van der Hoop
since drospirenone has better bioavailability than natural progesterone and is
remarkably effective in androgen combination therapy, as taught by Heil”
(id.).
However, as noted by Appellant, “Heil refers specifically to the oral
bioavailablility of drospirenone, and not the transdermal bioavailability”
(App. Br. 19 (emphasis omitted)), and we agree that the oral availability of
drospirenone is of little or no relevance to transdermal bioavaialability.
In addition, Appellant contends that “the rejection does not provide
any motivation whatsoever for combining transdermally administered
drospirenone with transdermally administered testosterone” (id. at 17), nor
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has the Examiner identified any “condition or disorder that would be treated
by such a combination” (id.). We would have to agree with Appellant on
this point, as van der Hoop discloses combining progesterone with an
estrogen compound, but not an androgen like testosterone.
Assuming however, that the Examiner actually intended to express
that Heil “provides motivation for using the combination of estrogen and
drospirenone . . . for hormone replacement therapy” instead of estrogen and
progesterone (as clarified on page 5 of the Answer, in the Examiner‟s
Response to Argument), we agree. However, the Examiner has made no
factual findings regarding the compositions of any of the transdermal
estrogen preparations listed in paragraph 97 of van der Hoop. Nor has the
Examiner otherwise shown that it was known in the art to administer
estrogen and progesterone in a transdermal formulation with the same
ingredients (other than testosterone) as ANDROGEL®. Further, we agree
with Appellant that the Examiner has not adequately addressed the claim
limitations regarding the concentration and saturation solubility of
drospirenone.
In addition, we note that in addition to disclosing oral formulations,
Heil discloses that compositions for combination estrogen/drospirenone
therapy “may [also] be in the form of . . . transdermal formulation[s]” (id. at
¶¶ 87-88), prepared with “water or organic solvents” and “gelling agents”
including “polyacrylic acids” (id. at ¶ 88), or prepared according to one of
several conventional protocols (id.).
However, Appellant contends that Heil merely “provides reference to
general transdermal formulations, non[e] of which read on the formulation
recited in present claims 27 or 36” (App. Br. 20), and the Examiner has not
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disputed Appellant‟s contention, nor made any factual findings regarding the
components of any of the transdermal formulations discussed by Heil, much
less the concentration of the drospirenone or its saturation solubility in the
formulations.
Thus, the Examiner‟s initial burden of providing an adequate factual
basis and rationale for combining the references in the manner required by
the claims has not been met. On this record, we are constrained to reverse
the rejection of claims 27-46.
SUMMARY
We reverse the rejection of claims 27-46 under 35 U.S.C. § 103(a) as
unpatentable over van der Hoop and Heil.

REVERSED

cdc