Ex Parte Mantelle et al

Board of Patent Appeals and Interferences

Jan 24, 2011

11812198 (B.P.A.I. Jan. 24, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/812,198 06/15/2007 Juan Mantelle 041457-0849 9558
22428 7590 01/25/2011
FOLEY AND LARDNER LLP
SUITE 500
3000 K STREET NW
WASHINGTON, DC 20007
EXAMINER
ARNOLD, ERNST V
ART UNIT PAPER NUMBER
1613
MAIL DATE DELIVERY MODE
01/25/2011 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 JUAN MANTELLE and TERESE A. DIXON
__________

Appeal 2010-000114
Application 11/812,198
Technology Center 1600
__________

Before ERIC GRIMES, MELANIE L. McCOLLUM, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to products
and methods for topical administration of methylphenidate. The Examiner

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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has rejected the claims as obvious based on the prior art. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The Specification discloses that methylphenidate is known in the art
for treating attention deficit disorder (ADD) and attention deficit/
hyperactivity disorder (ADHD) (Spec. 2, ¶¶ 3-4). The Specification
discloses “a composition for topical administration of methylphenidate . . .
in a flexible, finite system” (id. at 6, ¶ 16). The Specification defines a
“flexible, finite system” as “a solid form capable of conforming to [a]
surface with which it comes into contact” and maintaining contact without
adverse physiological response or decomposition by aqueous contact (id. at
13, ¶ 33).
Claims 39-54 are on appeal. The claims have not been argued
separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii).
Claims 39 and 51 are representative and read as follows:
39. A composition for topical application of methylphenidate,
comprising methylphenidate in a flexible finite, system, wherein the
methylphenidate is present in an amount effective to deliver from 3.96 mg to
10.56 mg methylphenidate per 10 cm2 of said flexible finite, system within
the first 10 hours of delivery.

51. A method of treating attention deficit disorder or attention
deficit/hyperactivity disorder comprising topically administering
methylphenidate in a flexible, finite system, wherein the methylphenidate is
present in an amount effective to deliver from 3.96 mg to 10.56 mg
methylphenidate per 10 cm2 of said flexible finite, system within the first 10
hours of delivery.
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The claims stand rejected as follows:2
• Claims 39-54 based on Kinoshita,3 Baker,4 and Mantelle5 (Answer
3);
• Claims 39-44 and 46-54 based on Miranda6 and Baker (Answer 11);
and
• Claims 39-54 based on Mantelle and Baker (Answer 16).
Issue
The Examiner has rejected all of the claims on appeal as obvious
based on one or more of Kinoshita, Mantelle, and Miranda, in combination
with Baker. Because Appellants present the same arguments in response to
each of the rejections, we will address them together.
The Examiner finds that each of Kinoshita, Mantelle, and Miranda
discloses a tape or patch for delivering a drug to a patient, and each
reference also suggests using its device to administer methylphenidate
(Answer 4-7, 11, 17). The Examiner finds that Baker discloses treating
ADHD with methylphenidate (Answer 7). The Examiner concludes that,

2 In addition to the rejections based on § 103, the Examiner’s Answer
includes two rejections based on obviousness-type double patenting (Answer
23-24). However, as Appellants note (Reply Br. 2), they have filed a
terminal disclaimer to address the double-patenting rejections. The
Examiner has not stated on the record any reason for concluding that the
terminal disclaimer is deficient. If prosecution of this application is
resumed, the Examiner should clarify on the record whether the terminal
disclaimer overcomes the double-patenting rejections.
3 Kinoshita et al., JP 02255611, published Oct. 16, 1990. Our citations are
to the official translation made of record May 12, 2009.
4 Baker et al., US 5,874,090, Feb. 23, 1999
5 Mantelle, US 5,446,070, Aug. 29, 1995
6 Miranda et al., US 5,656,286, Aug. 12, 1997
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although none of the cited references expressly teaches delivering the
amounts of methylphenidate recited in the claims, those limitations would
have been obvious to a person of ordinary skill in the art, who would
routinely optimize the dosage rates and amounts delivered by the products
and methods that are made obvious by the prior art (Answer 8, 14, 18).
Appellants contend that Baker is non-analogous art because it only
describes oral dosage forms of methylphenidate (Appeal Br. 12). Appellants
also contend that the Examiner’s reliance on “routine optimization” is
misplaced because the “selection of suitable pharmaceutical dosages
implicates much more complicated factors than the product yield and
reaction time discussed in Aller” and because the cited references do not
teach any amounts of methylphenidate that should be delivered
transdermally and therefore do not provide a starting point for optimization
(Appeal Br. 13-14).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the claimed products and
methods would have resulted from routine optimization and therefore would
have been obvious to a person of ordinary skill in the art?
Findings of Fact
1. Kinoshita discloses a “tape preparation for disease treatment . . .
[that] is constituted by laminating an adhesive film containing a drug . . . on
a flexible support” (Kinoshita 5-6).
2. Kinoshita discloses that examples of drugs that can be used in its
device (id. at 12) include “methyl phenidate” (id. at 13).
3. Kinoshita discloses that “[t]he amount of mixture of the drug may
be a pharmacologically effective amount” (id. at 16) and that including a
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drug in an amount corresponding to 1-20 times the mole amount of
functional groups in the adhesive provides an improved initial release
together with sustained release of the drug (id. at 16-17).
4. Mantelle discloses “a flexible, finite, bioadhesive composition for
topical application” of a pharmaceutically active agent (Mantelle, col. 4,
ll. 24-27).
5. Mantelle discloses that some embodiments of its composition
contain a combination of local anesthetics (id. at col. 4, l. 45 to col. 5, l. 2).
6. Mantelle discloses that “[t]he concentration as well as the quantity
of anesthetic per unit area, namely per square or cubic centimeter[,] can be
varied independently in order to achieve the desired effect” (id. at col. 9, ll.
15-18). Mantelle discloses that higher concentrations lead to faster onset of
activity while greater quantity per unit area (i.e., greater thickness) leads to
longer duration of activity (id. at col. 9, ll. 18-30).
7. Mantelle discloses that “[g]enerally, the concentration of
solubilized pharmaceutically active agent can range, on a weight basis,
between about 1 and about 50%, preferably between 2.5 and 40% and more
preferably between 5 and 30% of the total weight of the composition” (id. at
col. 10, ll. 59-63).
8. Mantelle suggests substituting any of a variety of drugs for the
anesthetic in its exemplary embodiments (id. at col. 23, ll. 24-35), including
methylphenidate (id. at col. 37, l. 30).
9. Miranda discloses that “[t]he use of a transdermal composition, for
example a pressure-sensitive adhesive containing a medicament . . . is well
known” (Miranda, col. 1, ll. 35-38).
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10. Miranda discloses that “[d]rug concentration in a monolithic
transdermal delivery system can vary widely depending on the drug and
polymers used. For example, certain drugs are effective in low doses and
therefore the transdermal formulation may involve low concentrations. . . .
Other drugs, such as nitroglycerin, require larger doses to be effective.” (Id.
at col. 1, ll. 45-51.)
11. Miranda discloses a transdermal drug delivery system comprising
a mix of polymers (id. at col. 2, ll. 51-53).
12. Miranda discloses that “[e]xemplary of drugs that can be
administered by the novel transdermal drug delivery system of this invention
include” (id. at col. 11, ll. 62-63) methylphenidate (id. at col. 28, l. 7).
13. Miranda discloses that that the active agent in its device is
preferably included at 0.1-50% by weight, and optimally at 0.3-30% by
weight (id. at col. 34, ll. 5-16).
14. Baker discloses that “[m]ethylphenidate is a known drug. It is
used primarily to treat hyperactive children.” (Baker, col. 1, ll. 9-10.)
15. Baker discloses that the prior art suggests “the optimum dosage of
methylphenidate for children is 0.5-0.7 mg/kg/day” (id. at col. 1, ll. 33-35).
16. Baker discloses an enantiomeric form of methylphenidate (id. at
col. 1, ll. 62-65) that can be used to treat children with ADD or ADHD (id.
at col. 2, ll. 8-11).
17. Baker discloses that its enantiomeric methylphenidate can be
administered in a “conventional sustained-release formulation, via any
suitable route of administration. Conventional dosing parameters may be
adopted, i.e. those which are known to or adapted to the practice of those
skilled in the art.” (Id. at col. 2, ll. 4-7.)
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18. Baker discloses that “[b]y controlling the nature of the
formulation, it is possible to control dissolution in vitro [sic, in vivo?]” (id.
at col. 2, ll. 25-26).
19. Baker discloses that “[t]he serum level can also be controlled so
that it remains high during the day, after taking a dosage in the morning, and
is reduced in the evening, before it can have any undesirable effect on
sleeping patterns” (id. at col. 2, ll. 34-37).
Analysis
Each of Kinoshita, Mantelle, and Miranda discloses a transdermal
drug delivery system (FFs 1, 4, 11) that corresponds to the claimed “flexible,
finite system,” and each of these references expressly suggests including
methylphenidate in its system (FFs 2, 8, 12). With regard to the method
claims, Baker teaches that methylphenidate is used to treat ADD and ADHD
(FF 16).
Each of the cited references also provides evidence that those of
ordinary skill in the art routinely optimized the dosages of pharmaceutical
agents. Kinoshita teaches that its device can include any pharmacologically
effective amount of a drug (FF 3). Mantelle teaches that its device can
include 1-50 weight percent of active agent (FF 7), that the amount of local
anesthetic can be varied to achieve a desired effect (FF 6), and that methyl-
phenidate can be substituted for the local anesthetic (FF 8). Miranda teaches
that different drugs require different dosages in transdermal formulations
(FF 10) and that the active agent is preferably used in amounts of 0.1-50
weight percent (FF 13).
Finally, Baker teaches that the optimum children’s dosage for
methylphenidate is 0.5 to 0.7 mg/kg/day (FF 15) and that “[c]onventional
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dosing parameters . . . are known to or adapted to the practice of those
skilled in the art” (FF 17).
We agree with the Examiner that, in view of these disclosures, a
person of ordinary skill in the art would have considered it obvious to
modify the prior art drug delivery systems to include methylphenidate, and
to optimize the dosage of methylphenidate delivered by the devices to
provide an effective treatment of ADD and ADHD. Appellants have pointed
to no evidence of record showing that the dosages recited in the claims are
outside the range that would have been expected to provide effective
treatment of ADD or ADHD when administered via one of the prior art
transdermal drug delivery systems.
Appellants argue that Baker is nonanalogous art because it only
teaches oral dosage forms or methylphenidate, not the claimed topical or
transdermal compositions (Appeal Br. 12). Appellants also argue that “there
is no evidence of record that the skilled artisan would turn to teachings of an
appropriate oral dose when determining a dose for transdermal drug
delivery” (Reply Br. 3).
These arguments are not persuasive. Both Baker and the claims on
appeal relate to therapeutic administration of methylphenidate. Since Baker
is from the same field of endeavor and pertinent to the problem addressed by
the claimed method, see In re Clay, 966 F.2d 656, 658-59 (Fed. Cir. 1992), it
is analogous art. In addition, those of ordinary skill in the art would
recognize that Baker’s disclosure of an appropriate dosage for oral
administration of methylphenidate represents a reasonable starting point for
administering methylphenidate by other routes, including transdermal
administration. Baker provides evidence that those skilled in the art were
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aware of “conventional dosing parameters” (FF 17) and how to manipulate
dosages to achieve a desired effect (FFs 18, 19).
Appellants also argue that the Examiner’s reliance on “routine
optimization” is improper because the facts of the present case are much
different from those of In re Aller, 220 F.2d 454 (CCPA 1955) (Appeal Br.
13-14). Appellants argue that the cited references are silent on the amount
of methylphenidate that should be delivered transdermally within 10 hours
and therefore do not provide any starting point for “routine optimization”
(id. at 14-15).
These arguments are also unpersuasive. Kinoshita, Mantelle, and
Miranda disclose devices for administering an active agent transdermally,
which inherently provides sustained release of the active agent (see, e.g.,
Mantelle, col. 6, ll. 1-3). As the Examiner has pointed out (Answer 8), both
the amount of drug released and the rate of release are recognized in the art
as result-affecting variables in transdermal administration of an active agent
(FFs 3, 6, 7, 10, 13). “[T]he discovery of an optimum value of a variable in
a known process is normally obvious,” unless the results are unexpectedly
good or the variable was not recognized as one that affected the results. In
re Antonie, 559 F.2d 618, 620 (CCPA 1977). Appellants have not shown
that either of these exceptions applies to the claims on appeal or that the
dosage parameters recited in the claims would not have been arrived at by a
worker of ordinary skill during the course of routine optimization.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
claimed products and methods would have resulted from routine
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optimization and therefore would have been obvious to a person of ordinary
skill in the art.
SUMMARY
We affirm the rejection of claims 39-54 as obvious based on
Kinoshita, Baker, and Mantelle; the rejection of claims 39-44 and 46-54 as
obvious based on Miranda and Baker; and the rejection of claims 39-54 as
obvious based on Mantelle and Baker.
TIME PERIOD FOR RESPONSE
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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