Ex Parte Lauterback et al

Patent Trial and Appeal Board

Apr 25, 2017

10139894 (P.T.A.B. Apr. 25, 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.
10/139,894 05/07/2002 Thomas Lauterback 6102-000065/US 5055
28997 7590 04/27/2017
HARNESS, DICKEY, & PIERCE, P.L.C
7700 Bonhomme, Suite 400
ST. LOUIS, MO 63105
EXAMINER
YOUNG, MICAH PAUL
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
04/27/2017 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):
stldocket@hdp.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte THOMAS LAUTERBACK, WALTER MULLER,
DIETRICH WILHELM SCHACHT, and HANS-MICHAEL WOLFF1
Appeal 2014-000890
Application 10/139,894
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and
ROBERT A. POLLOCK, Administrative Patent Judges.
PER CURIAM
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) from the
Examiner’s rejection of claims 15, 17—21, 27, 29—33, and 37-41. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The Specification is directed to “the use of a Transdermal Therapeutic
System (TTS) for delivering the dopamine receptor agonist rotigotine ... to
1 Appellants identify the Real Parties in Interest as LTS Lohmann Therapie-
Systeme AG and UCB Pharma GMBH (App. Br. 3).
Appeal 2014-000890
Application 10/139,894
provide therapeutically effective treatment or alleviation of symptoms of
Parkinson’s disease.” Spec. 1:11—15.
Claim 15, the only independent claim before us, recites:
15. A method for treating a subject suffering from Parkinson's
disease, comprising administering to the subject for an
administration period of at least 7 weeks a transdermal system
having an area of 10 to 40 cm2 3, comprising a matrix that
comprises at least one high tack and at least one medium silicone
pressure sensitive adhesive, said matrix having dispersed therein
0.1 to 3.15 mg/cm2 of rotigotine free base as an active ingredient,
in a daily dosage amount effective to provide a placebo
controlled improvement, as measured according to the Unified
Parkinson's Disease Rating Scale parts II and III, of at least about
2 units following administration.
The Board has previously issued decisions in Appeal Nos. 2013-
000345 and 2014-000987 in related applications 11/239,701 and 10/140,096,
respectively. See App. Br. 4.
STATEMENT OF THE REJECTION
The Examiner rejects claims 15, 17—21, 27, 29-33, and 37-41 under
35 U.S.C. § 103(a) as obvious in view of Muller2,3 and Pinter.4
2 Walter Muller et al., WO 99/49852 Al, published Oct. 7, 1999.
3 We cite herein to the English language equivalent of WO 99/49852 Al,
Walter Muller et al., US 6,884,434 BE issued Apr. 26, 2005.
4 Pinter et al., “Efficacy, safety, and tolerance of the non-ergoline dopamine
agonist pramipexole in the treatment of advanced Parkinson's disease: a
double blind, placebo controlled, randomised, multicentre study f 66 J.
Neurol. Neurosurg. Psychiatry 436-41 (1999).
2
Appeal 2014-000890
Application 10/139,894
ANALYSIS
We have reviewed Appellants’ contentions that the Examiner erred in
rejecting claims 15, 17—21, 27, 29-33, and 37—41 as obvious over the cited
art. App. Br. 6—16; Reply Br. 2—8. We disagree with Appellants’
contentions and adopt the findings concerning the scope and content of the
prior art set forth in the Examiner’s Answer and the Non-Final Rejection
dated December 19, 2012. For emphasis, we highlight and address the
following:
Findings of Fact
FF1. “Rotigotine is the International Non-Proprietary Name (INN) of
the compound (-)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]-amino]-
1-naphthalenol,” a “dopamine receptor agonist which has been used to treat
the symptoms of Parkinson's Disease.” Spec. 3:30-4:1.
FF2. Appellants’ Specification discloses that
[t]he silicone-based transdermal therapeutic system as used in the
present invention must contain at least one amine resistant
silicone compound as the main component. Usually, the silicone
compound will be a pressure sensitive adhesive or a mixture
thereof and will form a matrix in which the other components of
the TTS are embedded.
Spec. 7:10-15. Preferred adhesives are “BIO-PSA silicone pressure
sensitive adhesives manufactured by Dow Coming, particularly the Q7-4201
and Q7-4301 qualities.” Id. at 7:34—36. “A mixture of. . . Q7-4201
(medium tack) and Q7-4301 (high tack) amine resistant silicone pressure
sensitive adhesives in about equal amounts proved to be particularly useful
in the practice of this invention.” Id. at 8:12—16. Preferred solubilizers for
3
Appeal 2014-000890
Application 10/139,894
use in the TTS patch system include soluble polyvinylpyrrolidone, which is
commercially available as Kollidon®. Id. at 8:18—28.
FF3. According to the inventors,
it has been very surprising that a transdermal therapeutic system
containing rotigotine in free base form in a silicone matrix could
not only provide unexpectedly high plasma levels of rotigotine
but also a significant therapeutic progress in the transdermal
treatment of Parkinson's Disease. In particular, it has been
unexpected that a transdermal therapeutic system having a size
of as little as 10 or 20 cm2 could provide for an effective
treatment of Parkinson’s Disease in a placebo-controlled clinical
study, as indicated by an improvement in the Unified Parkinson's
Disease Rating Scale (UPDRS) of 2 or more compared to
placebo treatment.
Id. at 6:10-21.
FF4. Muller discloses a system for the administration of the free base
form of the D2 agonist, rotigotine, in particular a “transdermal therapeutic
system comprising a self-adhesive matrix layer containing the free base (-)-
5,6,7,8-tetrahydro-6-[propyl-l[2-(2-thienyl)ethyl]amino]-l-naphthalenol in
an amount effective for the treatment of the symptoms of Parkinson’s
syndrome, wherein the matrix is . . . [a] silicone-based polymer adhesive
system.” Muller, 2:5—6; Claim 1. D2 agonists “bind selectively to a
subgroup of the dopamine receptors, the D2 receptors.” Id. at 1:57—58.
“[I]n connection with silicone adhesives only the active substance base is
suitable.” Id. at 3:60-63; see also id. at 3:55—60 (noting that rotigotine salts
are “practically insoluble” in silicone adhesives).
FF5. Muller discloses that “[ajbout 1.5—5% (w/w) of
polyvinylpyrrolidone in an amine-resistant silicone adhesive increase the
solubility of [rotigotine] to about 10-15% (w/w).” Id. at 4:6—9. “This is
4
Appeal 2014-000890
Application 10/139,894
sufficient to dissolve 10 mg active substance in a 20 cm2 large patch having
a coat weight of the matrix of 50 g/m2.” Id. at 4:9-11. “[OJnly about 50%
of the active substance employed will be available during the period of
application . . . [and] given a daily dose in the range of 1—10 mg of the active
substance[,] a plaster size of between 2 and 40 cm2 can be expected ... to
achieve therapeutic plasma levels.” Id. at 4:11—17; see also id. at 5:14—18
(The disclosed systems “make it possible to administer the necessary daily
dose of the dopamine agonist. . . transdermally through the skin by means of
a patch having a size of approximately 20 cm2”).
FF6. Muller Example 2 discloses a silicone system in which 18
grams of rotigotine “dissolved in 40 g ethanol are added to 24 g of a 25%
solution of Kollidon 90F and the mass is homogenized ... 251 g of a
solution of an amine[-Jresistant silicone adhesive ... are added to this mass,
and the mass is homogenized.” Id. at 5:56—61. “[T]he mass is coated . . .
onto a polyester film ... [at a dry] coat weight of 50 g/m2.” Id. at 5:65—6:2.
“The concentration of [rotigotine] base in the patch matrix is 9%.” Muller,
6:7—9. “Suitable amine-resistant silicone adhesives are, for example, BIO-
PSA Q7-4301 and BIO-PSA Q7-4201.” Id. at 6:10-11.
FF7. Pinter discloses a double blind, placebo controlled trial
examining the efficacy, safety, and tolerance of the D2/D3 dopamine
receptor agonist, pramipexole, as an add-on drug in the treatment of
Parkinson’s disease. See Pinter, Abstract. “Daily doses of trial medication
were individually adjusted during a 7 week dose titration interval, with doses
being increased weekly from 0.2 mg up to 5.0 mg/day . . . followed by a 4
week maintenance period.” Id. at 437; see Abstract. Efficacy as compared
to placebo was measured on the “unified Parkinson’s disease rating scale
5
Appeal 2014-000890
Application 10/139,894
(UPDRS) including part I (mentation, behavior, and mood), Part II
(activities in daily living), Part III (motor examination) and part IV
(complications of therapy).” Id.', see, e.g., Tables 1, 2 and Figures 1, 2. “To
evaluate differences between the two treatment groups, the Wilcoxon-
MannWhitney test was applied to the UPDRS total score and subscores of
parts II, III, and IV.” Id.
Claim 15
The Examiner finds (and Appellants do not dispute)5 that Muller
discloses transdermal patches “identical to those of the instant claims.” Ans.
6. The Examiner further finds that
Pinter teaches a treatment method for for Parkinson's
disease characterized by a treatment, maintenance and titration
period where the dosage is optimized .... efficacy of the
treatment is measured on the Unified Parkinson's Disease Rating
Scale parts II and II... . results are tested against placebo [and]
.... administration is daily with the dosage being adjusted and
optimized during the titration period.
Id.
Accordingly, “[i]t would have been obvious to use the efficient
treatment protocol described in the Printer [sic] study to optimize and
develop a treatment regimen for the transdermal patches of Mueller [sic]”
“in order to produce a safe and effective method of treating Parkinson’s
disease.” Ans. 6.
5 We are somewhat confused, however, by Appellants’ assertion that “the
patches are not identical, e.g. the Pinter patch contained a different drug,” as
the Examiner does not assert, nor do we discern, that Pinter teaches patches.
App. Br. 9.
6
Appeal 2014-000890
Application 10/139,894
Appellants argue that one of ordinary skill in the art would have had
no reason to combine the teachings of Muller and Pinter because the
references relate to different drugs (rotigotine versus pramipexole) and
different routes of administration (transdermal patch versus oral). App. Br.
7—9; Reply Br. 2—5. We do not find Appellants’ arguments persuasive for
the reasons set forth in the Examiner’s Answer. See Ans. 7—8. In short,
Muller discloses a system for treating Parkinson’s disease by administering
the D2 receptor agonist rotigotine, whereas Pinter discloses a method for
treating the same condition with a similarly functioning compound, in this
case, a D2/D3 receptor agonist. See FFs 4, 7. “As Muller and Pinter are
solving the same problem, specifically treatment of Parkinson’s disease with
similarly functioning active ingredients (dopamine agonists) it would have
been obvious to apply the treatment protocol of [] Pinter to the patch of
Muller.” Ans. 7. That the two references employ different routes of
administration does not obviate the reason to combine because both routes
are intended to deliver the active ingredient to the brain via the bloodstream.
To the extent Appellants argue a lack of support for the Examiner’s
finding that aspects of Pinter’s protocol were “common in the art,”
Appellants neither provide persuasive countervailing evidence for this
assertion, nor convince us that one of ordinary skill in the art would not have
otherwise looked to the Pinter study in designing a treatment protocol for
Parkinson’s disease. See Ans. 6, 7; App. Br. 7; Reply Br. 10. See KSR Int’l
Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). (“[I]f a technique has been
used to improve one device, and a person of ordinary skill in the art would
recognize that it would improve similar devices in the same way, using the
7
Appeal 2014-000890
Application 10/139,894
technique is obvious unless its actual application is beyond his or her
skill.”).
We are also not persuaded by Appellants’ argument that the rejection
is in error because the claimed UPDRS improvement is not an inherent
property of the Muller patch. See App. Br. 9; Reply Br. 5—6. Muller teaches
a rotigotine patch identical to that set forth in claim 15. Appellants nowhere
argue that this patch is incapable of providing the claimed “placebo-
controlled improvement, as measured according to the Unified Parkinson's
Disease Rating Scale parts II and III, of at least about 2 units following
administration.” See, e.g.,In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir.
1997) (prior art may satisfy the claim limitations if it is merely capable of
performing the intended use); In re Spada, 911 F.2d 705, 709 (Fed. Cir.
1990) (“Products of identical chemical composition can not have mutually
exclusive properties.”). More to the point, we agree with the Examiner’s
rejection that one of ordinary skill in the art would have been motivated to
apply Muller’s patch according to the schedule suggested by Pinter for the
treatment of Parkinson’s disease. See Ans. 8—9. We also find reasonable the
Examiner’s finding that one of ordinary skill in the art would understand that
Muller’s patch “when applied as prescribed by Pinter would provide a
sufficient daily dosage along with preferred continuous application time.”
See id. at 8.
Appellants also argue that transdermal administration of D2 receptor
agonists was unpredictable, such that the claimed method was unexpectedly
efficacious. App. Br. 10—14 (referencing the Declaration under 37 C.F.R.
§ 1.132 of Michael Wolff, filed Dec. 16, 2005); Reply Br. 2, 6—8.
Appellants’ arguments, however, are based on comparison to the prior art
8
Appeal 2014-000890
Application 10/139,894
patches of, e.g., Hsu6 and Bondi7 which, as previously discussed in Appeal
2014-000987, do not comprise the mixture of high and medium tack silicone
adhesives found in the Muller patch. See Appeal 2014-000987, 8—11; Ans. 7
(Appellants’ “arguments are not germane to the Muller patch, as the Hsu
patch is acrylic based and Muller is silicone based”); id. at 10—11.
Accordingly, we do not find Appellants’ evidence persuasive. Similarly, in
light of Appellants’ failure to focus on the closest prior art, we accord little
weight to Appellants’ evidence of unexpected results. See In re Baxter
TravenolLabs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected
results are used as evidence of nonobviousness, the results must be shown to
be unexpected compared with the closest prior art.”).
For the above reasons, and for the reasons set forth in the Examiner’s
Answer and Non-Final Rejection, we affirm the rejection of claim 15.
Appellants do not separately argue the merits of claims 17—21, 27,
31—33, and 41, and they fall with claim 15. See 37 C.F.R. § 41.37(c)(l)(iv).
Claims 29 and 30
Depending from claim 15, claims 29 and 30 further require that the
content of rotigotine hydrochloride impurities present is less than 2 wt %
(claim 29) or less than 1% (claim 30) based on the amount of rotigotine in
free base form. Appellants argue that the rejection is in error because the
Examiner has “advanced no basis in fact or technical reasoning” establishing
the obviousness of these claims. Ans. 14—15. To the contrary, the Examiner
finds that Muller’s “patch is free of hydrochloride impurities.” Ans. 5. The
6 Tsung-Min Hsu et al., WO 94/07468 Al, published April 14, 1994.
7 Joseph V. Bondi et al., US 4,942,037, issued July 17, 1990.
9
Appeal 2014-000890
Application 10/139,894
Examiner’s determination is adequately supported by Muller’s disclosure
that “in connection with silicone adhesives [e.g., those used in Muller
Example 2,] only the active substance base is suitable” because rotigotine
salts are “practically insoluble” in silicone adhesives. See FFs 4, 6.
Claims 37 and 38
Claims 37 and 38, respectively, recite that the transdermal system of
claim 15 is administered “not more than once daily” or “once daily” for the
administration period. Appellants contend that the Examiner’s rejection is in
error because “Pinter does not disclose a daily administration in its study of
pramipexole, but rather only a daily dosage with no further administration
guidelines.” App. Br. 15. We do not find Appellants’ argument persuasive,
and agree with the Examiner’s implicit finding that one of ordinary skill in
the art would understand that Pinter’s “daily doses of trial medication”
evidence or make obvious once daily administration. See Ans. 6; Pinter,
437.
Claim 39
Appellants further contend that the limitation of claim 39, “wherein
the administration period comprises a maintenance period preceded by a
dosage titration period of up to 4 weeks,” recites an additional limitation not
disclosed in Muller. App. Br. 16. We do not find this argument persuasive
in light of Pinter’s disclosure of a “7 week dose titration interval” followed
by a “4 week maintenance period” for the treatment of Parkinson’s disease
with a dopamine receptor agonist. See FF 7. Although Pinter discloses a
longer dose titration period than set forth in claim 39, “where 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
10
Appeal 2014-000890
Application 10/139,894
Aller, 220 F.2d 454, 456 (CCPA 1955). In the present case, Appellants do
not suggest that the shorter titration period as compared to Pinter results in
any unexpected benefit. See In re Antonie, 559 F.2d 618, 620 (CCPA 1977)
(indicating that where “results of optimizing a variable” are “unexpectedly
good,” a patent may be obtainable for the claimed critical range).
Claim 40
Appellants further contend claim 40’s recitation, “during the titration
period the number or size of transdermal systems administered is increased
until an optimum maintenance dose for the subject is reached,” provides a
patentable limitation not taught or suggested by the prior art. See App. Br.
16. We do not agree. As noted by the Examiner, Pinter’s “administration is
daily with the dosage being adjusted and optimized during the titration
period” and “[i]t would have been obvious to apply these treatment protocols
[to] the administration of transdermal rotigotine patches.” Ans. 6. In the
present case, we agree with the Examiner’s implicit finding that increasing
the number or size of Muller’s transdermal systems would have been an
obvious method to titrate the daily dose to achieve optimum maintenance
levels.
SUMMARY
We affirm the rejection of claims 15, 17—21, 27, 29-33, and 37-41
under 35 U.S.C. § 103(a) as obvious in view of Muller and Pinter.
11
Appeal 2014-000890
Application 10/139,894
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
12