Ex Parte Schollmayer

Patent Trial and Appeal Board

Dec 1, 2016

10429283 (P.T.A.B. Dec. 1, 2016)

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.
10/429,283 05/02/2003 Erwin Schollmayer 6102-000072/US 8910
28997 7590 12/05/2016
HARNESS, DICKEY, & PIERCE, P.L.C
7700 Bonhomme, Suite 400
ST. LOUIS, MO 63105
EXAMINER
FISHER, ABIGAIL L
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
12/05/2016 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 ERWIN SCHOLLMAYER1
Appeal 2014-004849
Application 10/429,283
Technology Center 1600
Before CHRISTOPHER G. PAULRAJ, JACQUELINE T. HARLOW, and
DAVID COTTA, Administrative Patent Judges.
HARLOW, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for the treatment of restless leg syndrome. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM.
1 According to Appellant, the Real Party in Interest is UCB Pharma GmbH
(App. Br. 3).
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Application 10/429,283
STATEMENT OF THE CASE
The “invention relates to the use of rotigotine for the effective
treatment of Restless Leg Syndrome (RLS).” Abstract.
Claims 1, 3, 27, 29, 35, and 37-45 are on appeal. Claim 1 is
illustrative and reads as follows:
1. A method of long-term dopamine agonist therapy for a subject
suffering from Restless Leg Syndrome (RLS), the method
comprising transepicutaneously administering to the subject
rotigotine in a daily dosage amount of 0.5 to 10 mg effective to
provide in at least 8 days an improvement of about 2 or more
units on the International Restless Leg Syndrome Study Group
(IRLSSG) scale, as compared to a placebo treatment.
The claims stand rejected as follows:
Claims 1, 3, 27, 29, 35, and 37-44 stand rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Rimpler2 and Muller.3
Claim 45 stands rejected under 35 U.S.C. § 103(a) as being
unpatentable over Rimpler, Muller, Brecht,4 and Horowski.5
I.
The Examiner has rejected claims 1, 3, 27, 29, 35, and 37-44 under
35 U.S.C. § 103(a) as being unpatentable over Rimpler and Muller. We
focus our discussion on claim 1, which is representative. We also address
claims 37 and 41—44, as these claims are separately argued.
The Examiner finds that Rimpler discloses rotigotine as “a potent and
selective D2 agonist that plays a significant role in the treatment of
2 Rimpler et al., US 2003/0166709 Al, published Sep. 4, 2003.
3 Muller et al., WO 99/49852, published Oct. 7, 1999. Citations to English
equivalent, US 6,884,434 Bl, issued Apr. 26, 2005.
4 Brecht, US 2001/0053777 Al, published Dec. 20, 2001.
5 Horowski et al., US 2004/0028723 Al, published Feb. 12, 2004.
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dopamine-related disorders such as Parkinson’s disease and Restless Leg.”
Ans. 2. The Examiner also finds that Rimpler discloses that transdermal
systems have been developed for the delivery of rotigotine to a patient. Id.
The Examiner finds that Rimpler teaches that rotigotine treatment may be
administered in the form of monotherapy, or in combination with other
antiparkisonian agents. Id.
The Examiner acknowledges that Rimpler does not specifically
identify the ingredients of transdermal rotigotine treatment systems, but
finds that Muller cures this deficiency. Id. at 3. In particular, the Examiner
finds that Muller discloses transdermal administration of 10 mg of rotigotine
in a 20 cm2 patch, which corresponds to 0.5 mg/cm2. Id. The Examiner
further finds that Muller teaches a daily dosage range of 1—20 mg, and a
plaster size range of 2 40 cm2, and that the matrix of the transdermal system
can be an acrylate-based or silicone-based polymer adhesive system. Id.
The Examiner finds that an ordinarily skilled artisan would have
“been motivated to utilize the transdermal patch system of Muller et al. in
the treatment of Restless Leg Syndrome because Rimpler et al. teach that
N-0923 (rotigotine) is known to treat Parkinson's Disease and Restless Leg
and that this compound has been formulated into transdermal patch form.”
Id. at 3^4.
We agree with the Examiner that the combination of Rimpler and
Muller renders obvious claims 1, 37, and 41—44, and adopt the Examiner’s
findings concerning the scope and content of the prior art. We address
Appellants’ arguments below.
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Claim 1
We do not find persuasive Appellants’ contention, set forth in the
Appeal Brief, that an ordinarily skilled artisan in possession of Rimpler and
Muller would not have had reason to use a rotigotine patch to treat RLS
because those references “fail to teach or suggest the claimed Rotigotine
Administration Route, [and] the entire field of RLS treatment fails to
motivate one of ordinary skill in the art to utilize a patch system to treat
RLS” (App. Br. 8).
As an initial matter, we note that during oral argument Appellants
clarified that they do not dispute that the combination of Rimpler and Muller
discloses the treatment of RLS with a rotigotine patch. Hearing Trans. 6:3—7
(“JUDGE HARLOW: .... So you're not disputing that the combination of
Rimpler and Muller would disclose the treatment of RLS with a rotigotine
patch. Is that correct? MS. KORAL: I'm not disputing it based on what our
current claim language is.”). For completeness, we additionally observe that
Rimpler discloses that rotigotine “is a potent and selective dopamine D2
agonist playing a signification role in the treatment of all diseases associated
with a dopamine-related metabolic disorder such as . . . Restless Leg”
(Rimpler 14), and explains that “transdermal systems” for rotigotine
administration have been developed in an attempt to address the
shortcomings of oral delivery (Rimpler || 9—10). Indeed, Rimpler identifies
Muller as a known transdermal patch for rotigotine administration. Id. ^ 9.
Accordingly, we agree with the Examiner that an ordinarily skilled artisan in
possession of Rimpler and Muller would have had reason to use the
rotigotine patch of Muller to treat RLS. Ans. 3^4.
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Appellants’ contention that the cited combination fails to disclose the
claimed “dosage window” (App. Br. 8—9) is similarly unavailing. The daily
dosage range of 0.5—10 mg recited in claim 1 is prima facie obvious in view
of Muller’s disclosure of administering 1—10 mg of rotigotine daily (Muller
4:9-17). See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“In
cases involving overlapping ranges, we and our predecessor court have
consistently held that even a slight overlap in range establishes a prima facie
case of obviousness.”); In re Alter, 220 F.2d 454, 456 (CCPA 1955) (“[I]it is
not inventive to discover the optimum or workable ranges by routine
experimentation.”).
Furthermore, we agree with the Examiner that because Muller teaches
the composition, dosage form, and dosage required by the claimed invention,
in the absence of any contrary showing by Appellants, there is a reasonable
basis to conclude that the properties of the claimed invention are inherent in
the composition of Muller. Ans. 11; see also PAR Pharm., Inc. v. TWI
Pharm., Inc., 773 F.3d 1186, 1196 (Fed. Cir. 2014) (explaining that in an
obviousness analysis inherency is appropriately relied upon to establish the
existence of a claim limitation where the limitation at issue is necessarily
present, “or the natural result of the combination of elements explicitly
disclosed by the prior art”); In re Papesch, 315 F.2d 381, 391 (CCPA 1963)
(a chemical compound and its properties are inseparable); In re Spada, 911
F.2d 705, 708 (Fed. Cir. 1990) (“when the PTO shows sound basis for
believing that the products of the applicant and the prior art are the same, the
applicant has the burden of showing that they are not.”).
Appellants’ reliance on the Federal Circuit’s decisions in Allergan
Inc. v. SandozInc., 726 F.3d 1286 (Fed. Cir. 2013), and Pozen Inc. v. PAR
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Pharm., Inc., 696 F.3d. 1151, 1165 (Fed. Cir. 2012) (App. Br. 9—10), does
not dictate a different result. Neither Allergan nor Pozen involved a
situation where the claimed composition was expressly disclosed by the
prior art; nor did the court in those cases address a dispute as to whether a
claimed benefit of a disclosed compound was an inherent property of the
compound. Allergan Inc., 726 F.3d at 1290; Pozen Inc., 696 F.3d. at 1161—
1165. Indeed, in Allergan, no allegation was made that the disputed
limitation was inherent to the composition claimed (726 F.3d at 1294), and
the portion of Pozen relied upon by Appellants does not concern inherency,
but rather, existence of a motivation to combine two prior art compounds
(696 F.3d. at 1165).
We are also unpersuaded by Appellants’ contention that an ordinarily
skilled artisan would not have had a reasonable expectation of success in
performing the claimed method (see App. Br. 10-13). As explained above,
Rimpler teaches the use of rotigotine to treat RLS, and identifies Muller as a
known prior art patch for transdermal rotigotine administration. Rimpler
4, 9. The patch disclosed by Muller is described as providing a daily dose
of 1—10 mg of rotigotine. Muller, 4:9—17. We thus agree with the Examiner
that “[sjince a patch known to transepicutaneously deliver rotigotine delivers
the drug in the same amount as instantly claimed, the active method steps
are suggested by the prior art.” Ans. 14. See KSRInt’l v. Teleflex Inc., 550
U.S. 398, 418 (2007) (“If a person of ordinary skill can implement a
predictable variation, § 103 likely bars its patentability.”); see also id. at 420
(“[A]ny need or problem known in the field of endeavor at the time of
invention and addressed by the patent can provide a reason for combining
the elements in the manner claimed.”); In re Baxter-Travenol Labs., 952
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F.2d 388,392 (Fed. Cir. 1991) (“Mere recognition of latent properties in the
prior art does not render nonobvious an otherwise known invention.”).
We recognize Appellants’ contention that it would not have been
obvious to try various dopamine agonists in order to arrive at the claimed
invention. App. Br. 12—13. We note, however, that this argument is moot in
view of the explicit disclosures of Rimpler and Muller.
Turning to Appellants assertion that the relevant art is unpredictable,
and the claimed method yields unexpected results, we observe that neither
Table 1 of the Appeal Brief, which compiles the results of studies assessing
the augmentation profiles observed with various dopamine agonists, nor the
Schollmayer Declaration, which includes data similar to Table 1, as well as
clinical trial results comparing the claimed RLS treatment to placebo,
establishes that the art is unpredictable, or that the results obtained from
performing the claimed method are unexpected.
As an initial matter, as the Examiner observes, Appellants do not
present a side-by-side comparison of RLS treatment results obtained via the
claimed method and the closest prior art. Ans. 14—15. For example, Table 1
of the Appeal Brief compares results obtained from rotigotine patch
treatment with those obtained from peroral treatment with other dopamine
agonists. Notably, Table 1 aggregates data from different sources, collected
using different protocols, and does not represent a true side-by-side
comparison of experimental results. In addition, Appellants do not provide
data from treatment with prior art dopamine agonist patches, such as lisuride
patches, or prior art rotigotine dosage forms, such as the depot dosage form
disclosed by Rimpler (Rimpler 126). Thus, neither Table 1 nor the
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Schollmayer Declaration can be said to represent a comparison of the
claimed invention with the closest prior art.
Furthermore, Appellants do not establish that the allegedly improved
results observed with a rotigotine patch as compared to oral forms of
pramipexole and ropinerole are unexpected. Rather, we agree with the
Examiner that an ordinarily skilled artisan would have expected increased
bioavailability and reduced side effects from transdermal administration of
dopamine agonists, as compared to peroral administration. Ans. 15. In this
regard, we observe that Rimpler discloses that peroral administration of
rotigotine is therapeutically ineffective due to poor bioavailability, and
observes that other dosage forms, including transdermal patches, have been
developed to overcome the shortcomings of peroral administration (Rimpler
Tflf4, 8, 9). We also agree with the Examiner that Horowski, which is prior
art to the claimed invention (and cited in the rejection of claim 45),
evidences that an ordinarily skilled would have expected improved RLS
treatment outcomes from transdermal dopamine agonist dosage forms as
compared to peroral administration. Ans. 14—15; see also Horowski H 1—6
(“Bioavailability is increased by the TTS as compared to peroral
administration, which typically reduces the overall dose required to achieve
the therapeutically desirable effect.”).
Claims 3 7 and 44
Claim 37 depends from claim 1 and further recites “wherein the
administration is in monotherapy.” Independent claim 44 recites “[a]
method of treating RLS, the method comprising transepicutaneously
administering to the subject rotigotine in a daily dosage amount of 0.5 to
5 mg, wherein the administration of rotigotine is in monotherapy.”
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Appellants argue that claims 37 and 44 are nonobvious because
Rimpler “fails to disclose the treatment of RLS by transepicutaneously
administering rotigotine in monotherapy” and “M[u]ller is directed to the
treatment of Parkinson's disease.” App. Br. 15, 18.
As explained above with regard to claim 1, an ordinarily skilled
artisan in possession of the cited references would have had reason to use the
transdermal patch of Muller to treat RLS, as taught by Rimpler.
Furthermore, Rimpler expressly discloses the use of rotigotine monotherapy
to treat RLS (Rimpler 120). In addition, for the reasons discussed above
with regard to claim 1, we determine that the daily dosage range of 0.5—5 mg
recited in claim 44 is prima facie obvious in view of Muller’s disclosure of
administering 1—20 mg of rotigotine daily (Muller 4:9—17). See In re
Peterson, 315 F.3d at 1329; In re Aller, 220 F.2d at 456. Accordingly, we
agree with the Examiner that claims 37 and 44 are prima facie obvious in
view of Rimpler and Muller. See In re Merck & Co., Inc., 800 F.2d 1091,
1097 (Fed. Cir. 1986) (“Non-obviousness cannot be established by attacking
references individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole.”).
We further agree with the Examiner, contrary to Appellants’
intimation (App. Br. 16, 18—19), that Brecht, which is not relied upon in the
rejection of claim 37 or claim 44, does not teach away from rotigotine
monotherapy. Ans. 15. See In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994)
(“A known or obvious composition does not become patentable simply
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because it has been described as somewhat inferior to some other product for
the same use.”).
Claims 41 and 42
Claim 41 depends from claim 1, and further recites “wherein the
subject is augmentation-prone, but wherein augmentation during said long­
term therapy is suppressed.” Independent claim 42 recites:
42. In a method using a dopamine agonist for long-term
therapy for a subject suffering from RLS, said subject being
augmentation-prone under long-term dopamine agonist therapy,
the improvement comprising
transepicutaneously administering rotigotine to the subject
in a daily dosage amount of 0.5 to 10 mg effective to provide in
at least 8 days an improvement of about 2 or more units on the
IRLSSG scale, as compared to a placebo treatment.
Appellants assert that because “[a] patient who is augmentation prone
is even more likely to experience augmentation,” “rotigotine’s reduction of
the [augmentationj-profile for such patient population is even further
unpredictable to one of ordinary skill in the art.” App. Br. 17.
We do not agree. As explained above with regard to claim 1,
Appellants have not established either that the relevant art was
unpredictable, or that the results obtained in performing the claimed method
were unexpected. Furthermore, we agree with the Examiner that it would
have been obvious to an ordinarily skilled artisan, based on Rimpler’s
disclosures concerning the usefulness of rotigotine to treat RLS, to
administer rotigotine to RLS patients who previously suffered from
augmentation. Ans. 15—16.
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Claim 43
Independent claim 43 recites:
43. A method of treating RLS in a subject at least 40 years old,
the method comprising
transepicutaneously administering to the subject rotigotine
in a daily dosage amount of 0.5 to 10 mg effective to provide in
at least 8 days an improvement of about 2 or more units on the
IRLSSG scale, as compared to a placebo treatment.
Claim 43 closely mirrors claim 1, but additionally recites that the
subject treated is at least 40 years old. Appellants acknowledge that Muller
discloses that Parkinson’s disease typically sets in between 58 and 62 years
of age, but contend that it would not have been obvious to treat RLS
sufferers of at least 40 years old according to the claimed method based on
the teachings of Rimpler and Muller. App. Br. 17—18.
We do not agree. As explained above, Rimpler and Muller render
obvious the treatment of RLS patients with the rotigotine patch of Muller,
including those of at least 40 years in age.
Conclusion
For the reasons set forth above, we conclude that a preponderance of
the evidence of record supports the Examiner’s conclusion that the
combination of Rimpler and Muller renders claims 1, 37, and 41—44
obvious. Claims 3, 27, 29, 35, and 38-40 have not been argued separately
and therefore fall with claim 1.
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II.
The Examiner has rejected claim 45 under 35 U.S.C. § 103(a) as
being unpatentable over Rimpler, Muller, Brecht, and Horowski.
Claim 45 recites:
45. A method of treating RLS in a patient who is experiencing
augmentation or who has experienced augmentation, the method
comprising
transepicutaneously administering to the subject rotigotine
in a daily dosage amount of 0.5 to 10 mg effective to provide in
at least 8 days an improvement of about 2 or more units on the
IRLSSG scale, as compared to a placebo treatment.
The Examiner reiterates the findings and conclusions set forth above
with regard to claim 1 concerning the combination of Rimpler and Muller.
The Examiner additionally finds that Brecht teaches transdermal
administration of dopamine agonists to treat RLS, and discloses that
“administration of L-DOPA led to typical augmentation during the day but
this augmentation disappeared when the patients switched to the dopamine
agonist.” Ans. 7.
The Examiner finds that Horowski describes a transdermal therapeutic
system for treating RLS. Id. The Examiner finds that Horowski discloses
that peroral dopaminergic therapies often lead to rebound and augmentation,
while transdermal therapies prevent these side effects. Id.
In addition to the reasons to combine Rimpler and Muller set forth
above with respect to claim 1, the Examiner finds that “[o]ne of ordinary
skill in the art would have been motivated to utilize [Muller’s] patch in a
patient who previously had augmentation as Brecht teaches that
administration of L-DOPA led to typical augmentation during the day but
this augmentation disappeared when the patients switched to the dopamine
agonist.” Id. at 8. The Examiner further concludes that “based on the
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teachings of Brecht and Horowski et al. one of ordinary skill in the art would
have a reasonable expectation that administration of N-0923 [rotigotine]
would additionally lead to disappearance of augmentation as compared to L-
DOPA administration when delivered via a transdermal patch.” Id. at 9.
We agree with the Examiner that the combination of Rimpler, Muller,
Brecht, and Horowski renders obvious claim 45, and adopt the Examiner’s
findings concerning the scope and content of the prior art. We address
Appellants’ arguments below.
Appellants contend that Brecht does not teach or suggest that
rotigotine doses resulting in a two-unit improvement on the IRLSSG scale
could also reduce the augmentation-profile for patients experiencing, or who
have experienced, augmentation. App. Br. 20. Appellants similarly assert
that an ordinarily skilled artisan would not have predicted, and that there is
no suggestion of an expectation of success, that transdermal administration
of rotigotine could reduce clinically-significant augmentation while
maintaining an improvement of at least two units on the IRLSSG scale. Id.
Appellants also argue that Brecht “seems to discourage only using DAs as a
treatment for RLS as evidenced by the undesirable side effects associated
with their use, especially if the dosage needs to be increased.” Id.
We are not persuaded. As an initial matter, we note that claim 45
requires only that a patient who is experiencing, or who has experienced
augmentation achieve an improvement of about two or more units on the
IRLSSG scale, relative to placebo, with transepicutaneous rotigotine
treatment. Claim 45 states no additional requirement that the recited method
produce a reduced augmentation-profile for patients; neither does claim 45
require monotherapy. Accordingly, we decline to read such limitations into
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that claim. See Bayer AG v. Biovail Corp., 279 F.3d 1340, 1348, (Fed. Cir.
2002) (“[A] court may not read into a claim a limitation from a preferred
embodiment, if that limitation is not present in the claim itself.”).
Moreover, we agree with the Examiner that one of ordinary skill in
the art would have had reason to combine Rimpler, Muller, Brecht, and
Horowski, and further, had a reasonable expectation of success that
transdermal rotigotine administration to patients experiencing, or who have
experienced augmentation, would result in a reduction in augmentation
relative to other therapies. Ans. 9. In particular, we agree with the
Examiner that
based on the teachings of Brecht it is known that administration
of L-DOPA can lead to augmentation, however, Brecht
additionally teaches that this augmentation disappeared when the
patient switched to a dopamine agonist. Horowski et al. teaches
that transdermal therapy affords many benefits over peroral
administration such that a continuous active ingredient flux is
established so that plasma concentrations can be set as defined
and variations can be controlled and decomposition in the plasma
is fast and controlled. This allows for prevention of the side
effects associated with peroral administration which includes
augmentation. Therefore, based on the teachings of Brecht and
Horowski et al. one of ordinary skill in the art would have a
reasonable expectation that administration of N-0923
[rotigotine] would additionally lead to disappearance of
augmentation as compared to L-DOPA administration when
delivered via a transdermal patch.
Id.
Turning to Appellants’ contention that the purportedly unexpected
results obtained from transdermal treatment of RLS patients with rotigotine
are sufficient to rebut the Examiner’s showing of prima facie obviousness,
as explained above with regard to claim 1, we determine that Appellants
have not established that alleged improvements observed with transdermal
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rotigotine treatment were in fact unexpected. We agree with the Examiner
that based on the teachings of Brecht, “one of ordinary skill in the art would
expect that when you switch from L-DOPA to another dopamine agonist you
would expect a decrease in the degree of augmentation,” and that “it is
reasonable to expect that there would be a difference in degree in the
reduction in the augmentation when switching from one dopamine agonist to
another.” Ans. 13. Moreover, as detailed above, the data Appellants present
is not a side-by-side comparison with the closest prior art.
Accordingly, for the reasons set forth above, we conclude that a
preponderance of the evidence of record supports the Examiner’s conclusion
that the combination of Rimpler, Muller, Brecht, and Horowski renders
claim 45 obvious.
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SUMMARY
We affirm the rejection of claims 1, 37, and 41—44 under 35 U.S.C.
§ 103(a) based on Rimpler and Muller. Claims 3, 27, 29, 35, and 38-40 fall
with claim 1.
We affirm the rejection of claim 45 under 35 U.S.C. § 103(a) based on
Rimpler, Muller, Brecht, and Horowski.
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)(l)(iv).
AFFIRMED
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