Ex Parte Mantelle et al

Patent Trial and Appeal Board

May 9, 2017

13962464 (P.T.A.B. May. 9, 2017)

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.
13/962,464 08/08/2013 Juan Mantelle 041457-1018 1715
22428 7590 05/11/2017
Foley & Lardner LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
EXAMINER
ARNOLD, ERNST V
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
05/11/2017 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ipdocketing @ foley. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JUAN MANTELLE, TERESE A. DIXON, and DAVID KANIOS
Appeal 2015-004605
Application 13/962,464
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
composition for topical application of methylphenidate. The Examiner
rejected the claims as failing to comply with the written description rejection
and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse
and enter a new ground of rejection.
Statement of the Case
Background
A “controlled release tablet of methylphenidate . . . which was
designed to eliminate the need for multiple administrations of a tablet during
1 Appellants identify the Real Party in Interest as Noven Pharmaceuticals,
Inc. (see App. Br. 3).
Appeal 2015-004605
Application 13/962,464
the school day for children and reduce dosing to either once or twice a day,
falls short of providing effective treatment for a significant portion of the
patient’s waking hours” (Spec. 1—2). “Topical application of drugs provides
many advantages over conventional oral administration” (Spec. 2).
A “new topical application system whereby delivery of the active
substance, herein methylphenidate, achieves substantially zero-order kinetics
over a time period of at least 10 hours has been developed” (Spec. 4).
The Claims
Claims 1—6 are on appeal. Independent claim 1 is representative and
reads as follows:
1. A composition for topical application of
methylphenidate comprising methylphenidate and a
pharmaceutically acceptable adhesive carrier in a flexible,
finite system,
wherein the methylphenidate is present in an amount
sufficient to achieve substantially zero order kinetics for
delivery to the skin or mucosa of a patient in need thereof
over a period of time at least 10 hours,
wherein the proportion of methylphenidate : silicone
adhesive : acrylic adhesive (wt % dry) is about 5-30 : 0-70 :
40-90, respectively, and wherein the composition is
substantially free of ritalinic acid at the time of manufacture.
The issues
A. The Examiner rejected claims 1—6 under 35 U.S.C. § 112 (a) as failing
to comply with the written description requirement (Final Act. 3—5).
B. The Examiner rejected claims 1—6 under 35 U.S.C. § 103(a) as
obvious over Mantelle ’2112 and Mantelle ’7053 (Final Act. 14—17).
2 Mantelle et al., US 6,348,211 Bl, issued Feb. 19, 2002.
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Application 13/962,464
C. The Examiner rejected claims 1—6 under 35 U.S.C. § 103(a) as
obvious over Quan,4 Prashad,5 and Dimas6 (Final Act. 7—12).
A. 35 U.S.C. § 112(a), written description
The Examiner finds “Claims 1 -3 introduce new matter as the claim
recites the limitation 40-90; 40-80 and 40-90, respectively, for the amount of
acrylic adhesive wt% dry. There is no support in the specification for this
limitation” (Final Act. 4). The Examiner contends “Applicant is attempting
to define a new range from a prior range and a data point from an example to
create a new subrange” (Id. at 4—5).
Appellants contend
the Examiner’s Answer recognizes at page 6 that the 40% and
90% end points of the range at issue are supported by different
examples! In view of this disclosure, and as set forth in the
Appeal Brief, the situation at hand is analogous to the claims at
issue in In re Wertheim that were found to satisfy the written
description requirement.
(Reply Br. 3).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the range of acrylic adhesive
from 40—90 wt% dry as required by claim 1 represents new matter?
3 Mantelle et al., US 6,210,705 Bl, issued Apr. 3, 2001.
4 Quan et al., US 5,601,839, issued Feb. 11, 1997.
5 Prashad et al., The First Enantioselective Synthesis of (2R,2R)-threo-(+)~
Methylphenidate Hydrochloride, 64 J. Organic Chem. 1750—53 (1999).
6 Dimas et al., Effect of Several Factors on the Mechanical Properties of
Pressure-Sensitive Adhesives Used in Transdermal Therapeutic Systems, 1
AAPS PharmsciTech (2000) (We number the pages sequentially 1—7).
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Appeal 2015-004605
Application 13/962,464
Findings of Fact
1. Original claim 1 recites “wherein the proportion of
methylphenidate : silicone adhesive : acrylic adhesive (wt % dry) is about 5-
30 : 0-70 : 0-90, respectively” (Spec. 19, claim 1).
2. Original claim 2 recites “wherein the proportion of
methylphenidate : silicone adhesive : acrylic adhesive (wt % dry) is about 5-
30 : 0-70 : 0-80, respectively” (Spec. 19, claim 2).
3. The Specification teaches the “weights percentages in the
examples are based on dry weight of the system” (Spec. 14).
4. The Specification teaches, in Example 2, that a “composition
was prepared from 30 Wt% methylphenidate base, 40wt% Duro-Tak 87-
2296 and 30wt% Bio-PSA X7-4403” where Duro-Tak 87-2296 is an acrylic
adhesive (Spec. 15).
5. The table on page 17 of the Specification is reproduced, in part,
below:
Example (%vv/w cm a
dry basis)
10 n 12 13 14 22
Duro-Tak
£7-4194
(Acrylic adhesive)
20
50
20 40
The table reports the amounts of components used in various topical delivery
systems (see Spec. 17).
Principles of Law
“[I]n light of the description of the invention as employing solids
contents within the range of 25-60% along with specific embodiments of
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Appeal 2015-004605
Application 13/962,464
36% and 50%, we are of the opinion that, as a factual matter, persons skilled
in the art would consider processes employing a 35-60% solids content
range to be part of appellants’ invention.” In re Wertheim, 541 F.2d 257,
265 (CCPA 1976).
Analysis
We find that Appellants have the better position. The Specification
teaches ranges for the acrylic adhesive, on a weight dry percentage basis,
between 0 and either 80 or 90 in the original claims (FF 1—2). The
Specification teaches three additional specific values for acrylic adhesive, on
a weight dry percentage basis (FF 3), including 20, 30, and 40 (FF 4—5). We
agree with Appellants that this tracks the Wertheim fact pattern and
reasonably provides support for the subgenus range of 40-90 recited in
claim 1.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the range of acrylic adhesive from 40-90 wt% dry as required by claim
1 represents new matter.
B. 35 U.S.C. § 103(a) over Mantelle ’211 andMantelle ’705
The Examiner states “Appellant correctly notes that this rejection
hinges upon the written description rejection because if the written
description rejection is reversed then this rejection must also be reversed
given the priority dates because the two Mantelle patents would no longer be
prior art” (Ans. 5). Therefore, because we reverse the written description
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Appeal 2015-004605
Application 13/962,464
rejection, we necessarily also reverse this obviousness rejection because the
Mantelle patents are not prior art.
C. 35 U.S.C. § 103(a) over Quan, Prashad, and Dimas
Appellants contend “a person of ordinary skill in the art would not
have expected methylphenidate and oxybutynin to exhibit similar
pharmacokinetic properties from similar adhesive carrier compositions, but
instead would have expected them to exhibit different properties” {Id.).
Appellants rely on the Nguyen Declaration I7 for a finding that:
a person working in the field of transdermal drug delivery at the
time of the 1997 priority date of the Application (or any time
since) would not have expected methylphenidate and
oxybutynin to exhibit similar flux properties from similar
adhesive carrier compositions, but instead would have expected
them to exhibit different flux properties.
(App. Br. 16; cf Nguyen Decl. 18).
The Examiner responds to the Nguyen Declarations by stating
there are at least three flaws. 1. It is unknown what
components are in Daytrana. 2. No other combinations of
acrylics and silicones have been provided to demonstrate that
all acrylics and silicones can achieve the results. 3. The claims
are not commensurate in scope with the unknown Daytrana
composition that has achieved the results.
(Ans. 4).
7 Declaration of Dr. Viet Nguyen, dated Jan. 22, 2014 (“Nguyen Decl. I”).
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Application 13/962,464
We find that Appellants have the better position because the Examiner
addresses the Nguyen Decls. I and II8 regarding unexpected results, but the
Declarations were not submitted for that reason. The Examiner does not
address or persuasively explain why Quan would have provided a reasonable
expectation of success in light of the Declaration concerns (cf Reply Br. 4
“the data at issue were not submitted to establish ‘unexpected results,’ but
rather to demonstrate the high level of unpredictability in the art”).
Therefore, the Examiner has not satisfied the burden of establishing a prima
facie case of obviousness. We therefore reverse this rejection.
D. New Ground of Rejection9
Under the provisions of 37 C.F.R. § 41.50(b), we enter the following
new ground of rejection.
Claims 1—6 are rejected under 35 U.S.C. § 103(a) as obvious over
Miranda,10 Baker,11 Prashad, and Quan.
Findings of Fact
6. Miranda teaches “a transdermal drug delivery system wherein a
blend of at least two polymers . . . permits increased loading of a drug and
8 Declaration of Dr. Viet Nguyen, dated Mar. 3, 2014 (“Nguyen Decl. II”).
9 “Should the Board have knowledge of any grounds not involved in the
appeal for rejecting any pending claim, it may include in its opinion a
statement to that effect.” 37 C.F.R. § 41.50(b). We note that the instant
application is related to Appeals 2010-000114 and 2013-008738 in which
the Board previously affirmed rejections based on Miranda and Baker.
10 Miranda et al, US 6,656,286, issued Aug. 12, 1997.
11 Baker et al., US 5,874,090, issued Feb. 23, 1999.
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Application 13/962,464
adjusts the solubility of a drug in the blend and thereby modulates the
delivery of the drug from the system and through the dermis” (Miranda
2:52-57).
7. Miranda teaches “the transdermal permeation rate of a drug
from the multiple polymer adhesive system can be selectively modulated by
adjusting the solubility of the drug in the device. As used herein, the term
‘transdermal permeation rate’ means the rate of passage of the drug through
the skin” (Miranda 7:14—19).
8. Miranda teaches the “transdermal permeation rate is also
controlled by varying the relative proportions of the polymers comprising
the multiple polymer adhesive system” (Miranda 9:8—10).
9. Miranda teaches that:
Those skilled in the art can readily determine the rate of
delivery of drugs from the multiple polymer adhesive system in
order to select suitable combinations of polymers and drug for a
particular application. Various techniques can be used to
determine the rate of delivery of the drug from the polymer.
Illustratively, the rate of delivery can be determined by
measuring the transfer of drug from one chamber to another
through cadaver skin over time, and calculating, from the
obtained data, the drug delivery or flux rate.
(Miranda 9:25—33).
10. Miranda teaches, in a “preferred embodiment of the invention,
the multiple polymer adhesive system comprises a pressure-sensitive
adhesive blend of an acrylic polymer, a silicone polymer ... the acrylic-
based polymer and silicone-based polymer are preferably in a ratio by
weight, respectively, from about 2:98 to about 96:4” (Miranda 34-42).
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Application 13/962,464
11. Miranda teaches: “Suitable acrylic adhesives are commercially
available and include the polyacrylate adhesives sold under the trademarks
Duro-Tak 80-1194, Duro-Tak 80-1196, and Duro-Tak 15-1197” (Miranda
11:13-16).
12. Miranda teaches: “Suitable silicone pressure-sensitive
adhesives are commercially available and include the silicone adhesives sold
under the trademarks BIO-PSA X7-3027, BIO-PSA X7-4503, BIO-PSA X7-
4603, BIO-PSA X7-4301, BIO-PSA X7-4303, BIO-PSA X7-4919, BIO-
PSA X7-2685, and BIO-PSA X7-3122” (Miranda 11:48-53).
13. Miranda teaches the “concentration by weight of the drug in the
transdermal drug delivery system is preferably about 0.1 to about 50
percent” (Miranda 10:14—16).
14. Miranda teaches the use of methylphenidate and claim 50 of
Miranda is reproduced below:
50. The transdermal drug delivery system of claim 49,
wherein the drug is nicotine, methylphenidate and tacrine.
(Miranda 64:10-11; cf. Miranda, 28:7).
15. Miranda teaches:
The amount of drug to be incorporated in the composition
varies depending on the particular drug, the desired therapeutic
effect, and the time span for which the device is to provide
therapy. For most drugs, the passage of the drugs through the
skin will be the rate-limiting step in delivery. Thus, the amount
of drug and the rate of release is typically adjusted so as to
provide transdermal delivery characterized by a zero order time
dependency for a prolonged period of time.
(Miranda 32:51—59).
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Appeal 2015-004605
Application 13/962,464
16. Figure 16 of Miranda is reproduced below:
FIG. 16
15-S
,F 'B-
£XAiSPL£4S
/
/__
AVEHASEaUX i /
i ugi /
EXAMPLE 44
/
—........ A——
UE; his ;
-A :
O EXAMPLE 44 □ EXX«?L£45 A EsSiadwm’*
“FIG. 16 shows the average flux of estradiol for two compositions of this
invention containing a soluble PVP” (Miranda, col. 6,11. 11—12).
17. Baker teaches that “[mjethylphenidate is a known drug . . . used
primarily to treat hyperactive children” (Baker, col. 1,11. 9—10).
18. Baker teaches “nominal dose levels of racemate: 1.5, 3, 4.5 or 6
mg base/kg body weight” (Baker, col. 3,11. 2—3).
19. Baker teaches that “a serum level of [methylphenidine] can be
attained that is at least 50% of Cmax, over a period of at least 8 hours, e.g. 8—
16, 8-12 or 8-10 hours” (Baker, col. 2,11. 28-31).
20. Prashad teaches “a novel and the first enantioselective synthesis
of (IR,2 7^-t/zreo-(+)-methylphenidate hydrochloride with > 99% optical
purity in a total of nine steps and 13.0% overall yield starting from
phenylacetic acid” (Prashad 1752, col. 1).
21. Prashad teaches “an enantioselective synthesis of
[methylphenidate] that is suitable for manufacturing of this drug substance
on a commercial scale” (Prashad 1750, col. 1).
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Appeal 2015-004605
Application 13/962,464
22. Quan teaches “to provide a composition and a method for
enhancing percutaneous delivery of a basic drug through the skin or
mucosa” (Quan 3:32—34).
23. Quan teaches a formulation comprising 60% adhesive acrylic
copolymer and 20% oxybutynin drug (Quan 9:64, Table 2).
24. Quan teaches the composition of Formulation 5-K, reproduced
below:
Formulation 5-K
Methy Ipheni d ate 0.1—1.0%
(Quan 12:55-58).
Principles of Law
“[W]here the general conditions of a claim are disclosed in the prior
art, it is not inventive to discover the optimum or workable ranges by routine
experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955).
“Obviousness does not require absolute predictability of success . . .
all that is required is a reasonable expectation of success. ” In re Kubin, 561
F.3d 1351, 1360 (Fed. Cir. 2009).
Analysis
Miranda teaches topical transdermal drug delivery compositions (FF
6). Miranda teaches transdermal compositions comprising methylphenidate
(FF 14) in an amount range of 0.1 to about 50 percent (FF 13) that fully
overlaps the claimed range of 5 to 30 percent. Miranda teaches the use of
two polymers, silicone adhesives and acrylic adhesives (FF 10-12) in
amount ranges of 2 to 96 percent for acrylic adhesives and 4 to 98 percent
Silicone Adhesive
Triacedn
94.0-97.4%
2.5-5.0%
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Appeal 2015-004605
Application 13/962,464
for silicone adhesives that fully overlap the 0 to 70 percent claimed range for
silicone adhesives and 40 to 90 percent claimed range for acrylic adhesives
(FF 10).
Miranda specifically teaches optimization, teaching that delivery rates
“can be selectively modulated by adjusting the solubility of the drug” (FF 7)
or “by varying the relative proportions of the polymers” (FF 8). Miranda
further suggests optimizing to obtain zero order kinetics, teaching that “the
amount of drug and the rate of release is typically adjusted so as to provide
transdermal delivery characterized by a zero order time dependency for a
prolonged period of time” (FF 15).
Miranda does not expressly teach delivery for 10 hours, that the
composition is free of ritalinic acid, or exemplify methylphenidate
transdermal compositions.
Baker teaches reasons to use methylphenidate and teaches that the
doses may be optimized based on parameters including body weight (FF 17—
18) and teaches optimization of delivery times in a range of 8—16 hours that
overlaps the claimed delivery period (FF 19).
Prashad evidences that methylphenidate may be 99% pure (FF 20) and
is “suitable for manufacturing of this drug substance on a commercial scale”
(FF 21).
Quan exemplifies a transdermal delivery system comprising
methylphenidate and silicone polymers (FF 24) and suggests the use of
acrylic adhesive polymers (FF 23).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the ordinary artisan would have found obvious a transdermal
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Application 13/962,464
patch composition comprising methylphenidate, an acrylic polymer, and a
silicone polymer because Miranda suggests each of these components in
amounts overlapping the claimed ranges as well as optimization of the
amounts in order to obtain zero order kinetics (FF 7—15). Moreover, Baker
teaches delivery time periods overlapping the claims (FF 19) while Prashad
teaches pure methylphenidate for use in manufactured products (FF 20-21).
Therefore, the combination of these components is merely a “predictable use
of prior art elements according to their established functions.” KSR, 550
U.S. at 417. Moreover, the broad ranges recited in claim 1 fall within the
ranges disclosed by Miranda, and “discovery of an optimum value of a result
effective variable in a known process is ordinarily within the skill of the art.”
In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
With regard to claim 2, Miranda’s range of 2 to 96 percent for acrylic
adhesives (FF 10) also overlaps the 40 to 80 percent range recited.
With regard to claim 3, Baker teaches dose levels within the deliver
rates recited in the claim (FF 19) and Miranda recognizes the optimizability
of dose levels (FF 9, 15).
With regard to claims 4—6, Miranda teaches a range of acrylic
adhesive polymers from 2 to 96 percent that overlaps the recited range (FF
10).
We note that Appellants provide no evidence of secondary
consideration, such as unexpected results, that would need to be weighed
with the prima facie case of obviousness.
We will address Appellants’ primary argument, that “there would
have been no reasonable expectation that the oxybutynin of Quan’s
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Application 13/962,464
examples could be replaced with methylphenidate to arrive at a
methylphenidate composition that achieves the pharmacokinetics recited in
the claims” (App. Br. 19).
We have considered the Nguyen Declarations I and II, as well as
Appellants’ arguments regarding a reasonable expectation of success, but do
not find these arguments persuasive relative to the teachings of Miranda,
Baker, Prashad, and Quan.
The Nguyen Decl. I states “that a drug flux that is therapeutically
effective for oxybutynin would not be expected to be therapeutically
effective for methylphenidate” (Nguyen Decl. 119). Similarly, the Nguyen
Decl. II states “a person of ordinary skill in the field would not have
expected to be able to simply replace oxybutynin with methylphenidate and
arrive at a therapeutically effective methylphenidate product” (Nguyen Decl.
I1112).
While the Nguyen Declarations may demonstrate that simple
substitution of methylphenidate for oxybutynin would not result in the
claimed pharmacokinetics, these declarations do not rebut Miranda’s
teaching that the pharmacokinetic delivery time is an optimizable variable,
specifically teaching that the “amount of drug to be incorporated in the
composition varies depending on . . . the time span for which the device is to
provide therapy” (FF 15). Miranda suggests zero order kinetics (FF 15).
Moreover, Figure 16 of Miranda demonstrates release of drug from a
transdermal delivery device over time periods exceeding 10 hours (FF 16).
Even when weighed against the Nguyen Declarations, these teachings
of Miranda, along with Miranda’s further teachings regarding routine
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Application 13/962,464
optimization of the drug and polymer components (FF 7—9) and Baker’s
teaching to deliver methylphenidate for up to 16 hours (FF 19), provide a
reasonable expectation of success in optimizing methylphenidate delivery
using acrylic and silicone polymers with zero order kinetics over 10 hours
(FF 6—24). Kubin stated that, “[responding to concerns about uncertainty in
the prior art influencing the purported success of the claimed combination,
this court [in O’Farrell] stated: ‘[o]bviousness does not require absolute
predictability of success ... all that is required is a reasonable expectation
of success.'’” In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re
O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)).
SUMMARY
In summary, we reverse the rejection of claims 1—6 under 35 U.S.C.
§ 112 (a) as failing to comply with the written description requirement.
We reverse the rejection of claims 1—6 under 35 U.S.C. § 103(a) as
obvious over Mantelle ’211 and Mantelle ’705.
We reverse the rejection of claims 1—6 under 35 U.S.C. § 103(a) as
obvious over Quan, Prashad, and Dimas.
We newly reject claims 1—6 under 35 U.S.C. § 103(a) as obvious over
Miranda, Baker, Prashad, and Quan.
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review.”
Section 41.50(b) also provides:
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Application 13/962,464
When the Board enters such a non-final decision, the
appellant, within two months from the date of the decision,
must exercise one of the following two options with respect to
the new ground of rejection to avoid termination of the appeal
as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the prosecution
will be remanded to the examiner. The new ground of rejection
is binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the
opinion of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.
REVERSED: 37 C.F.R, $ 41.50(b)
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