Ex Parte Muller et al

Patent Trial and Appeal Board

Feb 12, 2019

10487393 (P.T.A.B. Feb. 12, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/487,393 02/20/2004
7590
William F Lawrence
Frommer Lawrence & Haug
745 Fifth Avenue
New York, NY 10151
02/12/2019
FIRST NAMED INVENTOR
Walter Muller
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
512100-2036 5045
EXAMINER
AHMED, HASAN SYED
ART UNIT PAPER NUMBER
1615
MAIL DATE DELIVERY MODE
02/12/2019 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 WALTER MULLER and THOMAS HILLE
Appeal2017-006238 1
Application 10/487 ,393
Technology Center 1600
Before FRANCISCO C. PRATS, DEBORAH KATZ, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to transdermal
therapeutic system (TTS) for administering fentanyl. The Examiner rejected
the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b ). We reverse.
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner's rejection of
claims 10-19 and 32-38 under 35 U.S.C. § 103(a), for obviousness over the
1 Appellants state that real party in interest is the assignee, L TS Lohmann
Therapie-Systeme AG. Appeal Br. 1.
Appeal2017-006238
Application 10/487 ,393
Poster Presentation, 2 the National Starch Letter, 3 Mueller, 4 and Houze. 5
Non-Final Act. 2---6 (entered May 18, 2016).
Claims 10 and 33 are the independent claims on appeal. Claim 1 is
illustrative and reads as follows:
Claim 10. A transdermal therapeutic system (TTS) consisting
of
A) an active compound-impermeable back layer;
B) one matrix layer based on polyacrylate and
comprising fentanyl; and
C) a protective film to be removed before use;
wherein said polyacrylate:
i) is self-adhesive;
ii) is free of carboxyl groups, but has at least one
hydroxyl group;
iii) is prepared from a monomer mixture consisting
of:
a) esters of acrylic and/ or methacrylic acid,
which are esters of alcohols having 1
to 8 carbon atoms;
b) vinyl acetate in amounts ofup to 50% by
weight; and
c) 2-hydroxyethyl acrylate or
2-hydroxyethyl methacrylate in
amounts of up to 20% by weight; and
iv) has a saturation solubility for fentanyl of
between 5 and 20 percent by weight; and
2 H.J. Yoon et al., TRANSDERMAL FENTANYL MATRIX PATCH SYSTEM
- Evaluation of a parallel binary matrix system-, Poster Presentation at
Millennial World Congress of Pharmaceutical Sciences (April 19, 2000)
("Poster Presentation").
3 Letter from Todd Manogold to Angela Nwaneri, dated April 28, 2004
("National Starch Letter").
4 US 6,436,433 B 1 (issued Aug. 20, 2002) ("Mueller").
5 US 2002/0058068 Al (published May 16, 2002) ("Houze").
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Application 10/487 ,393
wherein said one matrix layer contains at least 80 percent
by weight of the incorporated fentanyl in
molecularly disperse dissolved form.
Claim 33. A transdermal therapeutic system (TTS) consisting
of
A) an active compound-impermeable back layer;
B) at least one matrix layer based on polyacrylate and
comprising fentanyl; and
C) a protective film to be removed before use;
wherein said polyacrylate:
i) is self-adhesive;
ii) is free of carboxyl groups, but has hydroxyl
groups to effect crosslinking;
iii) is prepared from a monomer mixture consisting
of:.
a) esters of acrylic and/ or methacrylic acid,
which are esters of alcohols
having 1 to 8 carbon atoms;
b) vinyl acetate; and
c) 2-hydroxyethyl acrylate and/or
2-hydroxyethylmethacrylate;
wherein each monomer is present in
the monomer mixture; and
iv) has a saturation solubility for fentanyl of
between 5 and 20 percent by weight;
wherein said at least one matrix layer contains at least 80
percent by weight of the incorporated fentanyl in
molecularly disperse dissolved form;
wherein the amount of vinyl acetate is up to 50% by weight and
the amount of 2-hydroxyethyl acrylate and/ or 2-
hydroxyethylmethacrylate is up to 20% by weight; and
wherein said polyacrylate is crosslinked by polyvalent cations
that are selected from the group consisting of Al 3+ and
Ti4+.
Appeal Br. 19, 22-23 (emphasis added).
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Application 10/487 ,393
OBVIOUSNESS
The Examiner's Prima Facie Case
The Examiner cited the Poster Presentation as disclosing a
transdermal therapeutic system (TTS) composed of a combination of two
adhesive-containing matrices: (1) a matrix containing a fentanyl/silicone
adhesive mixture, and (2) a second matrix containing a fentanyl/polyacrylate
adhesive mixture. Non-Final Act. 3.
The Examiner determined that, because of the "consisting of'
language in the preamble of Appellants' independent claim 10, claim 10
does not encompass the silicone-containing TTS described in the Poster
Presentation. Id.
The Examiner found, however, that the "combination of fentanyl with
the acrylate as recited in iii) of applicants' claim 10 has already been
disclosed in Table 1 of the Poster Presentation. DURO-TAK 87-2287
contains only-OH groups and does not contain any -COOR functionality
(see National Starch letter, first page)." Id. at 3--4.
The Examiner found, in addition, that "the acrylate portion of the
disclosed parallel binary matrix system contains only acrylate polymer,
without any silicone (see e.g. slide entitled 'System Design')." Id. at 4.
Accordingly, the Examiner found Appellants' "claimed combination of a
fentanyl and the carboxyl free adhesive prepared from esters of acrylic
and/or methacrylic acid as a transdermal pressure sensitive adhesive has
already been disclosed." Id. at 4.
The Examiner found that the Poster Presentation's polyacrylate
adhesive inherently meets the saturation solubility feature of Appellants'
claim 1 0. Id.
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The Examiner found that the Poster Presentation's
polyacrylate/fentanyl matrix inherently meets claim 10 's limitation requiring
at least 80% of the fentanyl to be present in molecularly dispersed dissolved
form. Id. at 4--5. Alternatively, the Examiner found, "it would be obvious to
one of ordinary skill in the art to molecularly disperse/dissolve the fentanyl
in the DURO-TAK 87-2287 adhesive in order to prepare a transdermal
delivery device suitable for experimental and final use." Id. at 5.
The Examiner cited Houze and Mueller as evidence that features
recited in dependent claims 13, 15, 18, and 19 would have been obvious
elements of the polyacrylate/fentanyl matrix described in the Poster
Presentation. Id. at 5-6.
The Examiner found, as to the rejected claims' "impermeable backing
layer and adhesive release layer, these devices are commonly employed in
the field. It would be obvious to one of ordinary skill in the art to use these
layers to enable shelf stability and provide the commercial aspects suitable
for sale of the device to the consumer." Id. at 5.
Ultimately, the Examiner concluded:
It would have been obvious to a person of ordinary skill
in the art at the time the invention was made to make a
transdermal therapeutic system consisting of a matrix layer
based on polyacrylate comprising fentanyl, as taught by Poster
Presentation in view of Mueller further in view of Houze. One
of ordinary skill in the art at the time the invention was made
would have been motivated to combine these elements into a
single adhesive because of patient comfort and ease of use (see
Poster Presentation, slide entitled "OBJECTIVE").
Id. at 6.
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Analysis
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.
In KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), although the
Supreme Court emphasized "an expansive and flexible approach" when
analyzing the issue of obviousness, id. at 415, the Court also reaffirmed the
importance of determining "whether there was an apparent reason to
combine the known elements in the fashion claimed by the patent at issue."
Id. at 418.
Thus, even under the flexible analysis outlined in KSR, "[i]n
determining whether obviousness is established by combining the teachings
of the prior art, the test is what the combined teachings of the references
would have suggested to those of ordinary skill in the art." In re GPAC Inc.,
57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations omitted).
In other words, even post-KSR, "obviousness concerns whether a
skilled artisan not only could have made but would have been motivated to
make the combinations or modifications of prior art to arrive at the claimed
invention." Belden Inc. v. Berk-TekLLC, 805 F.3d 1064, 1073 (Fed. Cir.
2015).
In the present appeal, having carefully considered all of the arguments
and evidence advanced by Appellants and the Examiner, Appellants
persuade us that the preponderance of the evidence does not support the
Examiner's conclusion of obviousness. In particular, Appellants persuade us
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that the Examiner has not shown, by a preponderance of the evidence, that
the cited combination of references would have suggested preparing a
transdermal therapeutic system (TTS) containing only the components
recited in Appellants' independent claims 10 and 3 3.
Independent claims 10 and 33, as seen above, both recite a TTS
"consisting of' three components: ( 1) component A ( an active compound-
impermeable backing layer, (2) component B (a matrix layer composed of
polyacrylate and fentanyl) and (3) component C (a protective film to be
removed before use). Appeal Br. 19, 22-23.
As the Examiner acknowledges, "'closed' transition phrases such as
'consisting of are understood to exclude any elements, steps, or ingredients
not specified in the claim." AFG Indus., Inc. v. Cardinal JG Co., Inc., 239
F.3d 1239, 1245 (Fed. Cir. 2001).
Thus, claims 10 and 33 exclude TTSs that have components other
than components A, B, and C.
As the Examiner found, the Poster Presentation discloses a TTS that
includes a matrix layer composed of a combination of a silicone adhesive
and fentanyl, as well as an adjacent polyacrylate/fentanyl matrix layer. See
Poster Presentation 6 (showing TTS fabrication process and system design,
with Matrix I described as containing silicone adhesive, and
adjacent/attached Matrix II containing polyacrylate adhesive). 6 In particular,
6 In citing to the Poster Presentation, we cite to the first page as if it were
page 1, and the subsequent pages as if numbered sequentially. We note that
the document includes handwritten page numbers at the bottom left that are
consistent with that numbering scheme.
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we note that the Poster Presentation describes the fabrication process as
including a step of"[ c ]ombining two adhesive." Id.
As the Examiner found, the Poster Presentation discloses that the TTS
composed of the combined silicone/fentanyl matrix and
polyacrylate/fentanyl matrix is superior to a previously disclosed
commercial fentanyl-delivering TTS, known as Durogesic®:
The binary matrix of silicones and acrylates ... released higher
amount of fentanyl at initial stage (0-24hrs) and residual
fentanyl in system is relatively lower after 3 day application,
compared to Durogesic® reservoir system ....
It was expected that transdermal matrix system of better release
profile could be developed by combining two different types of
adhesives.
Id. at 15; see also id. at Attachment B "([B]y combining these two different
types of adhesive polymers, we could make a new transdermal matrix
system of fentanyl which has an improved release profile when compared
with Durogesic® reservoir system. Specifically, the binary matrix of
silicones and acrylates released higher amount of fentanyl at an initial stage
(0-24hrs ).").
As the Examiner found, because of the "consisting of' language in
independent claims 10 and 33, claims 10 and 33 do not encompass (i.e.
exclude), the TTS composed of the combined silicone/fentanyl and
polyacrylate/fentanyl matrices, taught by the Poster Presentation as
providing superior fentanyl delivery.
As the Examiner found, however, the Poster Presentation also
discloses the preparation of a matrix composed of only a polyacrylate
adhesive ("Durotak 2287") and fentanyl, for comparative purposes. See
Poster Presentation 7 (Table 1, disclosing solubility of fentanyl in Durotak
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Application 10/487 ,393
2287 as compared to other adhesive matrices including silicone-based
matrices, e.g. Bio-PSA 7-4102); id. at 9 (Table 2, showing permeation
characteristics of fentanyl through adhesive membranes as compared to
other matrices); id. at 10 (Figure 2, disclosing skin permeation profile from
various adhesive matrices, including Durotak 2287 and Bio-PSA 7-4202).
Although not stated expressly, the Examiner appears to have found
that the Durotak 2287 /fentanyl comparative matrix disclosed in the Poster
Presentation differs from the TTS recited in Appellants' claims 10 and 33 in
that the Durotak 2287 /fentanyl comparative matrix does not include the
claimed impermeable backing layer ( component A) or the protective film
( component C) recited in Appellants' claims. See Non-Final Act. 5.
As noted above, the Examiner's position is that the claimed backing
layer and protective film "are commonly employed in the field" and a skilled
artisan, therefore, would have considered it obvious "to use these layers to
enable shelf stability and provide the commercial aspects suitable for sale of
the device to the consumer." Id.; see also id. at 6 ("One of ordinary skill in
the art at the time the invention was made would have been motivated to
combine these elements into a single adhesive because of patient comfort
and ease of use (see Poster Presentation, slide entitled 'OBJECTIVE')).".
Thus, as we understand it, the Examiner's position is that a skilled
artisan would have been motivated to prepare a TTS composed of only the
components recited in Appellants' claims 10 and 33, despite the Poster
Presentation's disclosure that the TTS composed of both a silicone/fentanyl
matrix and a polyacrylate/fentanyl matrix provides superior fentanyl
delivery as compared to the commercial Durogesic® reservoir system. See
Ans. 4 ("In a situation where slow and sustained delivery of fentanyl is
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required, a person of ordinary skill in the art reading the Poster Presentation
would prefer the embodiment consisting of the acrylate adhesive alone over
the binary matrix system made of both silicone and acrylate adhesive
portions.").
We are not persuaded. We acknowledge the Poster Presentation's
disclosure that, in the experiments described therein, "acrylates showed [a]
... slow and sustained [fentanyl] release profile." Poster Presentation 15.
We acknowledge that even non-preferred embodiments may be
obvious. See In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) ("[A]
finding that the prior art as a whole suggests the desirability of a particular
combination need not be supported by a finding that the prior art suggests
that the combination claimed by the patent applicant is the preferred, or most
desirable, combination.").
In the present case, however, the Examiner does not identify any
specific evidence of record suggesting that a skilled artisan would have
considered it desirable, or even useful, to prepare a TTS having the fentanyl
release profile exhibited by the Durotak 2287 /fentanyl matrix disclosed in
the Poster Presentation. Thus, while the Examiner posits preparing a TTS
consisting only of the components recited in Appellants' claims 10 and 33
"[i]n a situation where slow and sustained delivery of fentanyl is required"
(Ans. 4), the Examiner does not identify in the record any specific situation
in the prior art in which the sustained/slow release profile of the Durotak
2287 /fentanyl matrix disclosed in the Poster Presentation would be required,
desirable, or useful.
Indeed, contrary to the Examiner's unsupported assertion that the
sustained/slow release profile of the Durotak 2287 /fentanyl matrix would be
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required in certain instances, the Poster Presentation discloses that it is the
TTS composed of both a silicone/fentanyl matrix and a polyacrylate/fentanyl
matrix that provides a desirable fentanyl release profile. See Poster
Presentation 1 O; see also id. at Attachment B.
Given the Poster Presentation's teaching that a desirable fentanyl
release profile was exhibited by a combination of both a silicone/fentanyl
matrix and a polyacrylate/fentanyl matrix, viewed alongside the absence of
any identified teachings suggesting that the fentanyl release profile exhibited
by the Durotak 2287 /fentanyl matrix would be useful or desirable, we are
not persuaded that the cited combination of references would have suggested
preparing a TTS having only the Durotak 2287 /fentanyl matrix, in the
absence of the silicone/fentanyl matrix. See Belden v. Berk-Tek, 805 F.3d at
1073 ("[O]bviousness concerns whether a skilled artisan not only could have
made but would have been motivated to make the combinations or
modifications of prior art to arrive at the claimed invention.").
In sum, for the reasons discussed, we are not persuaded that the
Examiner has advanced an adequate evidentiary basis for finding that a
skilled artisan would have been motivated to prepare a TTS consisting of the
Poster Presentation's polyacrylate/fentanyl matrix, in combination with the
impermeable backing layer and removable protective film, as recited in
Appellants' independent claims 10 and 33. Because the preponderance of
the evidence, therefore, does not support the Examiner's conclusion of
obviousness as to claims 10 and 33, we reverse the Examiner's rejection of
claims 10 and 33, and their dependent claims, over the cited references.
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SUMMARY
For the reasons discussed, we reverse the Examiner's rejection of
claims 10-19 and 32-38 under 35 U.S.C. § 103(a), for obviousness over the
Poster Presentation, the National Starch Letter, Mueller, and Houze.
REVERSED
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