Ex Parte Abel et al

Patent Trial and Appeal Board

Dec 17, 2012

10570986 (P.T.A.B. Dec. 17, 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.
10/570,986 03/28/2006 Florian Abel 27232U 7260
34375 7590 12/17/2012
NATH & ASSOCIATES PLLC
112 South West Street
Alexandria, VA 22314
EXAMINER
HUI, SAN MING R
ART UNIT PAPER NUMBER
1629
MAIL DATE DELIVERY MODE
12/17/2012 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 PATENT TRIAL AND APPEAL BOARD
__________

Ex parte FLORIAN ABEL,
ANTJE BRUECK, KLAUS DIETZEL, KLAUS EISTETTER,
RUEDIGER NAVE, STEFAN POSTIUS, and OLIVER VON RICHTER
__________

Appeal 2011-004441
Application 10/570,986
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a method of
treating inflammatory bowel disease. The Examiner rejected the claims as
obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 7-23 stand rejected and appealed (App. Br. 5). Appellants do
not argue the claims separately, so they stand or fall together. See 37 C.F.R.
§ 41.37(c)(1)(vii). Claim 13 is representative and reads as follows:
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13. A method of treatment of inflammatory bowel disease in a
patient comprising administering a therapeutically effective amount of
ciclesonide to the patient in need thereof.

The sole rejection before us for review is the Examiner’s rejection of
claims 7-23 under 35 U.S.C. § 103(a) as obvious over Calatayud,
1
Ulmius,
2

Friend,
3
and Wright
4
(Ans. 4-6).
DISCUSSION
The Examiner found that Calatayud taught ciclesonide, the compound
administered in the method of claim 13, “in the form of racemic mixtures or
epimers, as a glucoc[o]rticoid and as useful in treating inflammatory
condition[s]” (Ans. 4). The Examiner also found that Calatayud taught that
ciclesonide had “low systemic absorption” (id.).
As to claim 13, the Examiner conceded that Calatayud did not
“expressly teach ciclesonide as useful in treating inflammatory bowel
diseases such as ulcerative colitis” (id.).
To address that deficiency, the Examiner cited Ulmius as disclosing
that a “glucocorticoid[] (budesonide) composition for oral or rectal
administration (enema) can be effectively used to treat ulcerative colitis
because [of] its high local anti-inflammatory effect with minimal systemic
absorption” (id.). The Examiner also cited Friend as teaching “colonic
delivery systems useful for deliver[ing] actives for treating ulcerative colitis
to the colon. Such actives include glucocorticoids” (id.).

1
U.S. Patent No. 5,482,934 (issued January 9, 1996).
2
EP 0 502 092 B1 (published July 26, 1995).
3
U.S. Patent No. 5,811,388 (issued September 22, 1998).
4
U.S. Patent No. 5,178,866 (issued January 12, 1993).
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Based on these teachings, the Examiner concluded that an ordinary
artisan would have considered it obvious to “to incorporate ciclesonide into
the colonic delivery system of [Friend] for treating ulcerative colitis”
(Ans. 5). The Examiner reasoned that the artisan would have been
motivated to incorporate ciclesonide into Friend’s ulcerative colitis treating
composition “since ciclesonide possesses excellent anti-inflammatory
activity with low systemic absorption. Such characteristic is similar to that
of budesonide. Therefore, employing ciclesonide in a method of treating
ulcerative colitis would be reasonably expected to be similarly effective as
employing budesonide” (id.).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Appellants’ arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner’s prima facie case of obviousness.
We are also not persuaded that Appellants’ evidence of unexpected results is
sufficient to outweigh the evidence of prima facie obviousness advanced by
the Examiner.
Appellants argue that the Examiner failed to make out a prima face
case of obviousness because “there is absolutely no teaching to be found in
the cited references themselves which would motivate the skilled artisan to
combine the ciclesonide of the present application with the oral delivery
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system of [Friend] or the oral or rectal delivery system of the Ulmius et al.
reference” (App. Br. 12).
We are not persuaded. As the Examiner pointed out, Friend discloses
that its oral dosage forms’ delivery of drugs to the colon is particularly
valuable with respect to glucocorticoids (Friend, col. 2, l. 55, through col. 3,
l. 1). Friend thus discloses a number of glucocorticoids, budesonide among
the preferred ones, which can be delivered using its dosage forms in
inflammatory bowel disease treatments (see id. at col. 8, ll. 13-56).
Ulmius also discloses treating inflammatory bowel diseases, including
ulcerative colitis and Crohn’s disease, with “certain glucocorticosteroids”
(Ulmius 3). As the Examiner pointed out, Ulmius discloses that budesonide
was considered a particularly advantageous glucocorticosteroid treatment for
inflammatory bowel disease because of its “high anti-inflammatory effect at
the place of application but a low degree of unwanted systemic
glucocorticoid side effect” (id. at 4).
As the Examiner also pointed out, Calatayud discloses that the
glucocorticoid compounds it discloses, which undisputedly include
ciclesonide, possess precisely the attributes described by Ulmius as being
desirable in its anti-inflammatory treatments (see, e.g. Calatayud, col. 1,
ll. 14-17 (“The purpose of the invention is to provide … certain
glucocorticoids which have a combination of high anti-inflammatory activity
at the application site and a low systemic glucocorticoid activity.”)).
Thus, an ordinary artisan would not only have recognized that
Calatayud’s ciclesonide was the same type of compound as that described in
Ulmius and Friend as being useful for treating inflammatory bowel diseases,
but also that ciclesonide possessed the desirable properties of having
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relatively low systemic side effects as compared to a relatively high activity
at the application site. We are therefore not persuaded that the Examiner
failed to advance adequate evidence that would have prompted an ordinary
artisan to treat an inflammatory bowel disorder with ciclesonide, as claim 13
requires. Rather, we find that a preponderance of the evidence supports the
Examiner’s prima facie case of obviousness.
As to the issue of unexpected results, as the Federal Circuit has noted,
“[m]ere improvement in properties does not always suffice to show
unexpected results. . . . [W]hen an applicant demonstrates substantially
improved results . . . and states that the results were unexpected, this should
suffice to establish unexpected results in the absence of evidence to the
contrary.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995).
In the instant case, as Appellants point out (App. Br. 13-17; see also
Reply Br. 4-8), the Specification presents data purporting to show that, in the
TNBS-induced rat model of inflammatory bowel disease, at all dosages
tested that produced the desirable topical effect, ciclesonide had a
significantly lower undesirable systemic effect as compared to budesonide,
with decrease in thymus weight and increase in adrenal gland weight being
the measures of the undesirable systemic side effects (see Spec. 10). The
Specification explains the import of the experimental data:
The results demonstrate the efficacy of ciclesonide, attenuating
the TNBS-increased colon width starting with 2,3 µmol/animal.
At the highest assessed dose of 6,9 µmol/animal, no additional
decrease of the TNBS-reduced thymus weight could be
detected. Instead, the TNBS-increased adrenal glands weight
was attenuated starting with 2,3 µmol/animal ciclesonide.

By contrast, budenoside [sic] seems to additionally reduce the
thymus weight starting with 2,3 µmol/animal and does not
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reverse the inhibitory effect of TNBS-treatment on the adrenal
glands weight in the assessed pharmacodynamic dose range.

(Spec. 11.)
The Examiner responds that, “when comparing the systemic effect --
thymus weight reduction, ciclesonide (compounds 8-9 in [Calatayud]) is
shown to have much less systemic effect than that of budesonide because
ciclesonide does not reduce the weight of thymus, whereas budesonide
reduces thymus weight (See col. 17-20, Table III)” (Ans. 7). Therefore, the
Examiner reasons, the low side effect profile of ciclesonide shown by
Appellants “would be seen as [an] expected effect” (id.).
Appellants reply that Table III of Calatayud “contains quantitative
values for topical and systemic activity, along with the therapeutic index for
the respective compounds. No qualitative conclusions appear in [Calatayud]
to serve as a basis for this conclusion” (Reply Br. 9).
We find that the Examiner has the better position here.
The data in Table III of Calatayud were derived from experiments in
which various compounds, undisputedly including ciclesonide, were tested
to assess their desirable topical anti-inflammatory effect as compared to their
undesirable systemic effect (see Calatayud, col. 15, l. 10, through col. 16,
l. 3).
As Calatayud explains, and as the Examiner found, the systemic effect
measurement included the same thymus and adrenal gland weight changes
measured by Appellants in their comparison (see id. at col. 16, ll. 5-10
(“Extraction and weighing of the thymus and adrenals were performed in all
animals and a fluorometric determination of the cortisol plasma levels was
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made. We consider the variation in these parameters indicative of the
systemic glucocorticoid activity of the products.”)).
Moreover, like Appellants, Calatayud compared the relative
topical/systemic effects of their compounds, which include ciclesonide, to
budesonide, and like Appellants, found that the ciclesonide had an overall
lower undesirable systemic side effect as compared to budesonide:
The products that are the object of the present invention
have shown in the pharmacologic studies performed a low
systemic effect in relation to the topical pharmacologic activity
found. The difference becomes even more evident when the
reference products, budesonide, flunisolide, and triamcinolone
acetonide are compared; effective local pharmacologic activity
and low systemic glucocorticoid response are demonstrated.

(Calatayud, col. 16, ll. 28-36.)
Thus, as seen in Table III, budesonide as a reference compound is
assigned an overall therapeutic index of “1” based on its relative measured
topical anti-inflammatory and systemic glucocorticoid activities (see id. at
cols. 19-20 (Table III)). In comparison, compounds 8 and 9, which
Appellants do not dispute as being ciclesonide, had significantly higher
therapeutic indices of 27.2 and 24.5 based on the same measurements (see
id. at cols. 17-18 (Table III)).
Therefore, while we acknowledge Appellants’ evidence that
ciclesonide exhibits lower systemic side effects than budesonide, given the
teachings of Calatayud discussed above, we agree with the Examiner that an
ordinary artisan would not have considered those properties of ciclesonide to
be unexpected. Thus, as we are not persuaded that the Examiner failed to
make out a prima facie case of obviousness as to claim 13, and as we are not
persuaded that Appellants have advanced adequate evidence of truly
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unexpected results, we affirm the Examiner’s rejection of claim 13 as
obvious over Calatayud, Ulmius, Friend, and Wright.
As they were not argued separately, the remaining claims fall with
claim 13. See 37 C.F.R. § 41.37(c)(1)(vii).
TIME PERIOD
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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