Ex Parte Bolle et al

Patent Trial and Appeal Board

Sep 10, 2013

12149250 (P.T.A.B. Sep. 10, 2013)

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.
12/149,250 04/29/2008 Christina Bolle 26426UA 7006
34375 7590 09/11/2013
NATH, GOLDBERG & MEYER
112 South West Street
Alexandria, VA 22314
EXAMINER
DICKINSON, PAUL W
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
09/11/2013 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 CHRISTINA BOLLE and RUDOLF LINDER
__________

Appeal 2012-001746
Application 12/149,250
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
SUSAN L.C. MITCHELL, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal1 under 35 U.S.C. § 134 involves claims to processes of
treating patients suffering from airway disorders or arthritic disorders. The
Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 Appellants identify the real party in interest as NYCOMED GmbH (App.
Br. 3).
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Application 12/149,250

2
STATEMENT OF THE CASE
Claims 24-28 stand rejected and appealed (App. Br. 5). Appellants
have not argued the claims separately, so they stand or fall together. See 37
C.F.R. § 41.37(c)(1)(vii).
Claim 24, the only independent claim, is representative and reads as
follows:
24. A method for treating a patient suffering from an acute or
chronic airway disorder or disorder of the arthritic type comprising
administering to said patient in need thereof a therapeutically effective
amount of a topical pharmaceutical preparation comprising an active
pharmaceutical ingredient chosen from roflumilast, a salt of
roflumilast, the N-oxide of roflumilast and a salt thereof, wherein said
administration takes place by dermal administration.

The sole rejection before us for review is the Examiner’s rejection of
claims 24-28 under 35 U.S.C. § 103(a) as obvious over Amschler2 (Ans. 4-
5).
DISCUSSION
The Examiner cited Amschler as disclosing that compounds having a
generic formula encompassing roflumilast were useful for treating arthritic
as well as airway disorders (see Ans. 4). The Examiner noted Amschler’s
disclosure teaches that compositions containing the compounds “may be in
the form of an ointment, suspension, cream, gel, or paste (col 13, lines 1-3).
Patches are also contemplated, which read on a transdermal therapeutic
system (col 12, line 43)” (id. at 5).
While the Examiner noted that roflumilast was among Amschler’s
exemplified compounds (see id. at 4-5), the Examiner conceded that

2 U.S. Patent No. 5,712,298 (issued Jan. 27, 1998).
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Amschler “fails to teach administering the specific compound roflumilast to
treat an airway disorder or a disorder of the arthritic type. In other words,
Amschler fails to teach the specific combination of treating airway disorders
or orders of the arthritic type with compound 5, roflumilast” (id. at 5).
The Examiner reasoned, nonetheless, that an ordinary artisan would
have considered it obvious to administer roflumilast to treat an airway or
arthritic disorder in the manner claimed “as Amschler teaches that the
exemplified compounds may be used to treat disorders of the airway or
disorders of the arthritic type. The expectation of success is high, as
roflumilast (compound 5) is an exemplified compound of the invention”
(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 conclusion of obviousness as to
claim 24.
Claim 24 recites a process of treating an acute or chronic airway
disorder, or an arthritic type disorder, by administering a therapeutically
effective amount of a topical pharmaceutical preparation that contains
roflumilast, a salt of roflumilast, the N-oxide of roflumilast, or a salt of the
N-oxide. Claim 24 also requires the administration to occur by dermal
administration.
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Appellants’ Specification explains that dermal administration is
“application of the topical pharmaceutical preparations of the invention to
the skin or mucous membranes” (Spec. 15). The Specification also notes
that transdermal drug delivery systems were known in the prior art (see id. at
5).
Amschler discloses a number of compounds, roflumilast undisputedly
among them (see Amschler, col. 9, ll. 40-41 (compound 5)), which are
“suitable on the one hand as bronchial therapeutics . . ., but on the other hand
especially for the treatment of disorders, in particular of an inflammatory
nature, e.g. of the airways (asthma prophylaxis), of the skin, of the intestine,
of the eyes and of the joints” (id. at col. 11, ll. 35-42).
More specifically, Amschler discloses that treatable disorders include
“acute and chronic (in particular inflammatory and allergen-induced) airway
disorders . . .; dermatoses (especially of proliferative, inflammatory and
allergic type), such as psoriasis (vulgaris),” as well as “disorders of the
arthritis type” (id. at col. 11, l. 56, through col 12, l. 1).
Amschler discloses that its compounds can be delivered using a
number of dosage forms, including “tablets, coated tablets, capsules,
suppositories, patches, emulsions, suspensions, [or] gels or solutions” (id. at
col. 12, ll. 42-44 (emphasis added)), as well as using ointment bases (id. at
col. 12, l. 49). Appellants do not dispute the Examiner’s finding (Ans. 5),
that an ordinary artisan would have understood the disclosure of patches to
include a transdermal drug delivery system.
More specifically, Amschler discloses that “[f]or the treatment of
disorders of the respiratory tract, the compounds according to the invention
are preferably also administered by inhalation” (id. at col. 12, ll. 53-55). As
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Appellants note (see App. Br. 13), Example 2 of Amschler also describes the
effect of oral administration of one of the disclosed compounds on an animal
model of an allergy-based airway disorder (see Amschler, col. 14, l. 15,
through col. 15, l. 23).
Amschler further discloses that when treating dermatoses, such as
psoriasis or eczema, “the compounds according to the invention are in
particular administered in the form of those medicaments which are suitable
for topical application” such as “powders, emulsions, suspensions, sprays,
oils, ointments, fatty ointments, creams, pastes, gels or solutions” (id. at col.
12, l. 61, through col. 13, ll. 3).
Thus, given Amschler’s express disclosure that its compounds were
useful for treating arthritic type disorders, as well as the disclosure that its
compounds were suitably administered not only topically, but also using a
patch that an ordinary artisan would understand to encompass a transdermal
delivery system, we agree with the Examiner that an ordinary artisan would
have been prompted to treat an arthritic disorder by dermally administering
roflumilast, as required by claim 24. While we note that Amschler prefers
inhalation as the mode of administration for treating airway disorders, and
that Amschler’s Example 2 used oral administration in treating an animal
model of such a disorder, claim 24 is not limited to treating airway disorders.
Appellants argue that, as discussed in their Specification, it was
known in the art that compounds having low water solubility, such as
roflumilast, were difficult if not impossible to administer topically (App. Br.
11). Therefore, Appellants contend, an ordinary artisan “would not
reasonably expect that administering roflumilast (which has a very low
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solubility) dermally would successfully treat an airway or arthritic disorder”
(id. at 11-12).
Appellants argue that Amschler “only teaches the dermal
administration in connection with the topical treatment of dermatoses, which
are not presently claimed” (id. at 13). Appellants urge, moreover, that as to
treating airway disorders, Amschler teaches that inhalation is the preferred
administration method, with oral administration being used in Amschler’s
Example 2 (see id.).
Appellants’ arguments do not persuade us of Examiner error.
Appellants’ primary evidence supporting the asserted absence of a
reasonable expectation of success is the statement in the Specification that a
skilled person was aware that “the provision of dosage forms for topical
application may prove to be extremely difficult or is impossible if the
intention is to administer an active ingredient which has a very low
solubility” (Spec. 1 (emphasis added)), combined with the fact that
roflumilast has a water solubility of 0.53 mg/L at 21°C (see id.).
We agree that the statement in the Specification suggests that, in
certain cases, an ordinary artisan may have expected extreme difficulty, or in
some cases impossibility, when attempting to prepare topical formulations
for insoluble therapeutic compounds. We are not persuaded, however, that
Appellants have adequately explained with any specificity how that
statement, by itself, demonstrates that ordinary artisans lacked a reasonable
expectation of success whenever preparing such formulations. As our
reviewing court has explained, “[o]bviousness does not require absolute
predictability of success. . . . For obviousness under § 103, all that is
required is a reasonable expectation of success.” In re O’Farrell, 853 F.2d
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894, 903-04 (Fed. Cir. 1988); accord, In re Kubin, 561 F.3d 1351, 1359-61
(Fed. Cir. 2009).
Indeed, as noted above, the inventors in Amschler, presumably aware
of the potential difficulty of producing topical formulations with low water
solubility compounds, nonetheless expressly state that their compounds can
be administered in a number of different dosage forms, including “patches”
(Amschler, col. 12, ll. 43), a delivery device that an ordinary artisan would
have understood to encompass a transdermal drug delivery system.
We acknowledge, as noted above, Amschler’s teaching that
dermatoses should be treated by topical administration of the compounds.
Unlike treating dermatoses and airway disorders, however, Amschler
provides no preference or directive as to any particular mode of
administration for treating arthritic disorders. Thus, given Amschler’s
express listing of a transdermal patch alongside other dosage forms
providing systemic administration, such as tablets, capsules, and
suppositories (see id. at col. 12, ll. 40-43), we are not persuaded that an
ordinary artisan lacked a reasonable expectation that a patch containing the
claimed therapeutic compounds would be effective in treating arthritic
disorders.
Accordingly, for the reasons discussed, Appellants’ arguments do not
persuade us that the preponderance of the evidence fails to support the
Examiner’s conclusion of prima facie obviousness as to claim 24.
As to unexpected results, we note, as Appellants argue, that
radioactively labeled roflumilast was topically administered to rats, and that
the drug was absorbed transdermally into the bloodstream to a degree similar
to that achieved by oral administration:
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After percutaneous administration of 1.7 mg/kg [14C]roflumilast
to rats, the total radioactivity is transported well through the
skin and reaches a maximum plasma level of 0.214 mg equiv./l
after 4 h, irrespective of the preparation employed. Based on
the total radioactivity, the AUCs and the excretions with the
urine after percutaneous administration are negligibly different
from those after oral administration.

(Spec. 11 (Example A); see also id. at 12 (Example B, similar results
presented).) We also note the statement in the Specification that Appellants
“[a]lso found, entirely surprisingly, besides the local effect, is an excellent
systemic effect which is comparable with that of an oral dosage form” (id. at
1).
The Examiner argues that the results presented in Examples A and B
of Appellants’ Specification are not unexpected because the measured
concentrations of the drug in the plasma resulting from topical
administration, as expected, are slightly less than the measured amount of
the drug resulting from oral administration:
In oral administration the drug passes through the stomach
directly into the blood stream whereas in topical administration
the drug must pass through the skin first. Therefore the
ordinary artisan may expect the AUC and Cmax to be slightly
less for topical compared to oral administration, and this is what
the results show[.]

(Ans. 7-8 (reproducing the Cmax and AUC data from Examples A and B).)
Upon careful consideration, we again find that the Examiner has the
better position.
As a dosage form suitable for administering its compounds, Amschler
expressly lists a “patch” alongside other dosage forms that would be
expected to provide a systemic effect, such as tablets, capsules, and
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suppositories (see id. at col. 12, ll. 40-43). Thus, while Appellants have
confirmed the systemic effect of using a dermal delivery system as
suggested in Amschler, we agree with the Examiner that an ordinary artisan
would not have viewed these results as unexpected, given Amschler’s
express teaching to use that dermal delivery mode. Compare, In re Baxter-
Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“Mere recognition of
latent properties in the prior art does not render nonobvious an otherwise
known invention.”); with In re Woodruff, 919 F.2d 1575, 1577-78 (Fed. Cir.
1990) (obviousness rejection affirmed where using claimed elements in the
manner suggested by the prior art necessarily resulted in claim-recited
effect).
Thus, as we are not persuaded that the Examiner failed to make out a
prima facie case of obviousness, and as we are also not persuaded that the
Examiner erred in finding that the evidence of unexpected results fails to
outweigh the evidence of prima facie obviousness, we affirm the Examiner’s
rejection of claim 24 over Amschler.
As they were not argued separately, claims 25-28 fall with claim 24.
See 37 C.F.R. § 41.37(c)(1)(vii).
SUMMARY
We affirm the Examiner’s rejection of claims 24-28 as obvious over
Amschler.

Appeal 2012-001746
Application 12/149,250

10
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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