Ex Parte Geczy

Board of Patent Appeals and Interferences

Feb 16, 2010

10182718 (B.P.A.I. Feb. 16, 2010)

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.
10/182,718 10/02/2002 Jozsef-Michel Geczy 02138 7742
23338 7590 02/16/2010
DENNISON, SCHULTZ & MACDONALD
1727 KING STREET
SUITE 105
ALEXANDRIA, VA 22314
EXAMINER
EBRAHIM, NABILA G
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
02/16/2010 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 JOZSEF-MICHEL GECZY
__________

Appeal 2009-008542
Application 10/182,718
Technology Center 1600
__________

Decided: February 16, 2010
__________

Before MELANIE L. MCCOLLUM, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
sustained-release oral form of molsidomine. The Patent Examiner rejected
the claims on the ground of obviousness. We have jurisdiction under
35 U.S.C. § 6(b). We reverse.
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Application 10/182,718

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STATEMENT OF THE CASE
The drug molsidomine is said to be “particularly useful for the
preventive treatment of all forms of angina attack insofar as its action causes
a relaxation of the vascular smooth muscle fiber . . . .” (Spec. 1:8-10.)
According to the Specification, the claimed form of molsidomine has
advantages over the forms on the market because a single daily dose
improves patient comfort and compliance, and “maintenance of a high
maximum plasma concentration guarantees an optimum efficacy.” (Id. at
3:17-25.)
Claims 24-40, which are all the pending claims, are on appeal. Claim
24 is representative and reads as follows:
24. A sustained-release solid oral galenical form of molsidomine which
contains a sustained-release matrix containing a therapeutically effective
amount of molsidomine or one active metabolite of molsidomine selected
from the group consisting of SIN-1 and SIN-lA,
said matrix consisting essentially of:
-at least 40% by weight of a material selected from the
group consisting of:
a polymeric material having a high swelling capacity in contact
with water or aqueous liquids and gelling properties, and which is a high
molecular weight hydroxypropyl methyl cellulose; and
a mixture of a polymeric material having a high swelling
capacity in contact with water or aqueous liquids selected from the group
consisting of crosslinked sodium carboxymethylcellulose, a crosslinked
hydroxypropylcellulose, a high molecular weight
hydroxymethylpropylcellulose, a polymethylmethacrylate, a crosslinked
polyvinylpyrrolidone and a high molecular weight polyvinylalcohol, and a
gellable polymeric material selected from the group consisting of
methylcellulose, carboxymethylcellulose, a low molecular weight
hydroxypropylmethylcellulose, a low molecular weight polyvinylalcohol, a
polyethyleneglycol and a non-crosslinked polyvinylpyrrolidone;
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-between 12% and 25% by weight of a lipophilic substance selected
from the group consisting of glycerol behenate, an hydrogenated castor oil,
glyceryl palmitostearate and glyceryl monooleate; and
-at least 25% by weight of at least one adjuvant selected from the
group consisting of diluents, lubricants, granulating agents, flow improvers
and colorants;
said galenic form having an in vitro dissolution rate, measured
spectrophotometrically at 286 or 311 nm by the method described in the
European Pharmacopoeia, 3rd edition or by the method USP XXIV, at 50
rpm, in 500 ml of a 0.1 N HCl medium, at 37°C of:
- 15 to 25% of molsidomine released after 1 hour
- 20 to 35% of molsidomine released after 2 hours
- 50 to 65% of molsidomine released after 6 hours
- 75 to 95% of molsidomine released after 12 hours
- >85% of molsidomine released after 18 hours
- >90% of molsidomine released after 24 hours,
and providing a plasma concentration of at least 5 ng/ml of plasma,
over a period of about 24 hours,
the plasma peak of molsidomine obtained in vivo occurring 2.5 to 5
hours following the administration of said form, and having a value of
between 25 and 40 ng/ml of plasma.

The Examiner rejected claims 24-40 under 35 U.S.C. § 103(a) as
unpatentable over the combined teachings of Wunderlich,1 Wong,2 and
Saslawski.3 Claims 25-40 have not been argued separately and therefore
stand or fall with claim 24. 37 C.F.R. § 41.37(c)(1)(vii).

1 US 6,068,854, issued to Jens-Christian Wunderlich et al., May 30, 2000.
2 US 5,962,013, issued to Ooi Wong et al., Oct. 5, 1999.
3 US 6,426,087 B1, issued to Olivier Saslawski et al., Jul. 30, 2002.
Appeal 2009-008542
Application 10/182,718

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OBVIOUSNESS
The Issue
The Examiner’s position is that Wunderlich taught a matrix
medicament used for controlled release of drugs, and taught molsidomine as
one of the drugs whose release could be controlled. (Ans. 3.) According to
the Examiner, Wunderlich taught the same matrix materials recited in
Appellant’s claims, but did not teach the dose recited in the claims. (Id.)
The Examiner found “it is within the skills of a person of ordinary skill in
the art to provide the perfect dose to each patient according to the severity of
the disease. It is also within the ability of the artisan to adjust the amounts
of polymers included in the claims since its properties are known to achieve
the sustained-release needed.” (Id. at 3-4.)
The Examiner found that Wong suggested adding the optionally
claimed metabolite SIN-1. (Id.) The Examiner found that Saslawski
disclosed ingredients that “control the kinetics of release of the active
ingredient,” including glycerol behenate in an amount of 20%, and taught
how to control drug release by incorporating glycerol palmitostearate, a
hydrogenated castor oil, glycerol behenate, or stearic acid. (Id. at 4-5.)
Based on these findings, the Examiner concluded that it would have been
obvious “to achieve a galenic prolonged release allowing improved
absorption by the gastrointestinal tract of active ingredients and also to
control the kinetics of release of the active ingredient.” (Id. at 5, citations
omitted.)
Appellant contends that “none of the cited references discloses or
suggests the claimed release profile, in itself, or in combination with
molsidomine.” (App. Br. 9.) According to Appellant, Wunderlich gave “no
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reason . . . to provide molsidomine in a 24 hour dosage having the claimed
release profile,” and Wunderlich’s examples result in 95-100% release after
6 hours. (Id.) Appellant contends that (1) nothing in Wong would lead to a
24 hour molsidomine dosage (id.), (2) Saslawski’s release profile “is not
known, the graphs of Figs. 1-9 being limited to 8 hours” (id.), and (3) it is
not known how Saslawski’s “release profile would apply to molsidomine,
which is not discussed in Saslawski” (id. at 10). According to Appellant, the
Inventor’s Declaration under Rule 132 shows the claimed composition
provides safe, therapeutic levels of molsidomine over a period of up to 24
hours, in contrast to conventional formulations. (Id. at 10-12.) Further,
Appellant argues, the claimed formulation when administered as a once a
day 16 mg formulation “totally unexpectedly” reduced angina attacks in
comparison to a known 8 mg sustained release formulation administered
twice a day. (Id. at 6.)
The issue with respect to this appeal is whether Appellant rebutted the
Examiner’s conclusion of obviousness.

Findings of Fact
1. Wunderlich described an oral medicament composed of a gelatin
matrix, in which the release of the medicament “is variable in time
and may be adjusted according to the medicament.” (Wunderlich,
Abstract.)
2. Wunderlich taught that suitable pharmaceuticals for sustained release
included molsidomine. (Id. at 6:35-36.)
3. Wunderlich disclosed gelatin tablets having dissolution times from 55
to 627 minutes. (Id. at 10:20-66.)
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4. Wunderlich provided examples in which 100% of a drug were
released in 7 hours (Example 3) and 6 hours (Example 4),
respectively. (Id. at 11:35 – 12:32.)
5. Wong described a monolithic matrix formulation for transdermal
administration of molsidomine. (Wong, Abstract.)
6. Wong disclosed that molsidomine “can be metabolized to SIN-1,
which is readily converted into the active metabolite SIN-1A.” (Id. at
3:62-64.)
7. Saslawski described “orally administrable galenic forms comprising
one or more active ingredients.” (Saslawski, 1:11-12.)
8. Saslawski’s dosage forms “allow[] increased control of the rate of
release during the phase of prolonged release of the active ingredient.”
(Id. at 2:11-15.)
9. In Example 20, Saslawski reported that:
The matrix tablet form…and the semisolid gelatin
capsule form make it possible to maintain or even
increase the relative bioavailability of acamprosate, and
furthermore the levels observed … at 6 h and 24 h are
greater than those observed for the reference gelatin
capsule.

(Id. at 24:20-27.)
10. According to Appellants’ Specification:
a preliminary clinical study has shown, totally
unexpectedly, that patients whose condition is stabilized
by a twice daily treatment with molsidomine (sustained-
release tablets containing an 8 mg dose), accompanied by
the sublingual administration of organic nitro derivatives
during attacks, exhibit a significant reduction in angina
attacks, and consequently in the consumption of organic
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nitro derivatives, after treatment with a galenical form
according to the invention (containing e.g. a 16 mg dose).

(Spec. 3:31-4:2.)

Principles of Law
When determining whether a claim is obvious, an Examiner must
make “a searching comparison of the claimed invention – including all its
limitations – with the teaching of the prior art.” In re Ochiai, 71 F.3d 1565,
1572 (Fed. Cir. 1995). “Rejections on obviousness grounds cannot be
sustained by mere conclusory statements; instead, there must be some
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006),
cited with approval in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-18
(2007).
[E]ven though applicant’s modification results in great
improvement and utility over the prior art, it may still not be
patentable if the modification was within the capabilities of one
skilled in the art, unless the claimed ranges “produce a new and
unexpected result which is different in kind and not merely
degree from the results of the prior art.”

In re Huang, 100 F.3d 135, 139 (Fed. Cir. 1996) (citations omitted).

Analysis
The Examiner found that “the combination of Wunderlich, Wong, and
Saslawski should provide the said release profile since [the] same
composition should have the same properties and functions.” (Ans. 7.) The
problem with this argument is that claim 24 lists specific weight percentages
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of several components, but the cited prior art provided little if any guidance
toward those specific percentages in combination. Even if we were to agree
that adjustment of the prior art parameters to achieve the 24 hour drug
release taught by Saslawski, for any of the drugs Wunderlich listed, was
within the skill in the art, and would have resulted in a composition having
the components in the proportions of claim 24, that would not resolve the
question of obviousness in this case.
Appellant argues that the claimed dosage form had a “totally
unexpected[]” result. (App. Br. 6.) That is, even patients already being
treated with twice daily 8 mg sustained release molsidomine experienced a
significant reduction in angina attacks when given a single 16 mg sustained
release molsidomine of Appellant’s composition. We accept the disclosure
as a fact. (FF10.) The Examiner did not address this result that the
Specification reported. Instead, the Examiner found that “[t]he expected
result [of combining the prior art teachings] would be a galenic prolonged
release tablet . . . .” (See, e.g., Ans. 8.) While we agree that the expected
result of combining the prior art teachings would have been a prolonged
release tablet, the Examiner did not argue or provide evidence that patients
given Appellant’s formulation would have been expected to exhibit a
“significant reduction” in angina attacks over the same quantity of drug
administered in a different sustained release formulation. Based on the
uncontested Specification report, we conclude that Appellant has met the
Huang standard. See Huang, 100 F.3d at 139.

CONCLUSIONS OF LAW
Appellant rebutted the conclusion of obviousness.
Appeal 2009-008542
Application 10/182,718

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SUMMARY
We reverse the rejection of claims 24-40 under 35 U.S.C. § 103(a) as
unpatentable over the combined teachings of Wunderlich, Wong, and
Saslawski.

REVERSED

lp

DENNISON, SCHULTZ & MACDONALD
1727 KING STREET
SUITE 105
ALEXANDRIA VA 22314