Ex Parte Tegeder et al

Patent Trials and Appeals Board

May 31, 2019

13881088 - (D) (P.T.A.B. May. 31, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/881,088 07/11/2013
23557 7590 06/04/2019
SALIW ANCHIK, LLOYD & EISENSCHENK
A PROFESSIONAL ASSOCIATION
PO Box 142950
GAINESVILLE, FL 32614
FIRST NAMED INVENTOR
Irmgard Tegeder
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.
BB.330 4626
EXAMINER
MATOS NEGRON, TAINA DELMAR
ART UNIT PAPER NUMBER
1621
NOTIFICATION DATE DELIVERY MODE
06/04/2019 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):
euspto@slepatents.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte IRMGARD TEGEDER and
GERD GEIS SLINGER 1
Appeal2018-008283
Application 13/881,088
Technology Center 1600
Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
ELIZABETH A. LA VIER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
The rejected claims in this Appeal are directed to a method of treating
multiple sclerosis. The Examiner rejected the claims under 35 U.S.C. § 103
as obvious. Pursuant to 35 U.S.C. § 134, Appellants appeal the Examiner's
determination that the claims are unpatentable. We have jurisdiction for the
Appeal under 35 U.S.C. § 6(b ).
The Examiner's decision is affirmed.
1 The Appeal Brief ("Br." entered Dec. 7, 2017) lists Fraunhofer-
Gesellschaft zur Forderung der angewandten Forschung e.V., as the real
party in interest. Br. 1.
Appeal2018-008283
Application 13/881,088
STATEMENT OF THE CASE
The claims stand finally rejected by the Examiner as follows:
1. Claims 1, 2, 4--10, and 14--21 underpre-AIA35 U.S.C. § I03(a) as
obvious in view of Klein et al. (WO 2008/036733 A2, published Mar. 27,
2008) ("Klein"), Geisslinger et al. (US 2009/0162421 Al, published June
25, 2009) ("Geisslinger"), and Kasper et al. (DENNIS L. KASPER & TINSLEY
RANDOLPH HARRISON, HARRISON'S PRINCIPLES OF INTERNAL MEDICINE
2463---64 (16th ed. 2005)) ("Kasper"). Final Office Action ("Final Act.") 3.
2. Claims 1, 2, 4--10, and 14--19 under pre-AIA 35 U.S.C. § I03(a) as
obvious in view of Cruz et al. (WO 2008/034244 Al, published Mar. 27,
2008) ("Cruz"), Geisslinger, and Kasper. Final Act. 6-7.
Claims 1 and 2 are representative and reproduced below:
1. A method for treating multiple sclerosis (MS) wherein said
method comprises administering, to a subject in need of such
treatment, an R-enantiomer of a compound according to the
following formula (I)
[(See Appeal Brief 10 (VIII. CLAIMS APPENDIX)
for complete formula (I))]
or a nitro-variant or pharmaceutically acceptable salt of said
compound,
and wherein said MS is relapsing-remitting MS or progressive
MS.
2. The method according to claim 1, wherein said R-
enantiomer is selected from R-Flurbiprofen (Tarenflurbil) and
Nitro-R-Flurbiprofen.
REJECTION BASED ON KLEIN
The Examiner found that Klein discloses treating and/ or delaying
multiple sclerosis ("MS") by administering R-flurbiprofen which is a species
of the genus of compounds recited in claim 1 and specifically recited in
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claim 2. Final Act. 3. The Examiner found that Klein does not disclose
treating relapsing-remitting MS or progressive MS as required by the claims,
but identified Kasper as providing evidence that relapsing-remitting MS
accounts for 85% of the MS cases at onset, and primary progressive MS
accounts for about 15% of cases. Id. at 4.
The Examiner also found that Geisslinger describes the use of
tarenflurbil (R-flurbiprofen) for the treatment of neuropathic pain associated
with multiple sclerosis. Final Act. 4. The Examiner found that Kasper
discloses that pain is a common symptom of MS, experienced by more than
50% of patients. Id.
Based on Klein's disclosure of treating MS with R-flurbiprofen, and
Geisslinger's of treating pain associated with MS with R-flurbiprofen, the
Examiner determined that the claimed method would been obvious to one of
ordinary skill in the art. Final Act. 4--5. The Examiner found that the skilled
worker would have understood that the treated patient populations in Klein
and Geisslinger are the same based on the disclosure in Kasper. Id. at 5.
The Examiner further determined that the amounts of administered R-
flurbiprofen recited in claims 4, 5, 9, and 14, would have been obvious to
one of ordinary skill in the art based on overlapping amounts in Klein and
Geisslinger and "because Klein et al. discloses that individual needs varied
determination of optimal ranges of effective amounts of each component and
Geisslinger et al. discloses that due to the low toxicity, the administered
daily dose can be adjusted widely to the individual situation of the patient."
Final Act. 6.
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Discussion
Appellants contend that the cited references do not provide motivation
for one of ordinary skill in the art to treat MS as claimed. Br. 4.
Appellants argue that Klein describes efforts to identify compounds
that might enhance vesicular transport, which is unrelated to the
pathogenesis of MS. Br. 4--5. As evidence of this, Appellants cite the
declaration by co-inventors Drs. Irmgard Tegader and Gerd Geisslinger
("the declarants") ( submitted November 12, 2015; hereinafter "the
Declaration"). The Declaration states that MS "results from an autoimmune
attack of the myelin sheaths and oligodendrocytes that causes degeneration
of axons and a potential final decline of axonal transport." Deel. ,r 6. The
Declaration further states that "[ w ]hen the degenerating neurons in an MS
patient encounter a deficit of axonal transport, the degeneration is likely
beyond a pharmacological repair." Deel. ,r 6. Furthermore, the declarants
state the Klein does not demonstrate that R-flurbiprofen enhances vesicular
transport. Deel. ,r 7. The declarants state that "in paragraph [0012] and
Figure 1, [Klein] reports that R-flurbiprofen inhibits secretion of invertase
from yeast cells, which indicates that R-flurbiprofen inhibits vesicular
transport." Deel. ,r 7. The declarants concluded that Klein "provides no
teaching whatsoever that would enable the person skilled in the art to treat
MS with R-flurbiprofen, or to even expect that such a treatment could be
possible." Deel. ,r 8.
We have considered the Declaration, but find that it does not provide
persuasive evidence that the Examiner erred in determining that the claims
are obvious in view of Klein, Geisslinger, and Kasper.
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Klein lists a number of neurological diseases which can be treated
with (R)-2-(2-fluoro-4-biphenyl)propionic acid, which is also known as R-
flurbiprofen. Klein ,r,r 7, 16, 19. The list includes MS. Id. ,r,r 7, 19. Klein
explains:
Multiple sclerosis or a sign or symptom thereof may also be
treated with compounds of the invention. Inflammation is the
cause of much neural damage in multiple sclerosis, resulting in
disruption of axonal transport ( Curr Opin Neural. 16:267,
2003). These observations indicate that the neurodegeneration
experienced by MS patients may be attenuated by agents that
enhance axonal transport.
Id. ,I 22.
The disclosure by Klein that inflammation is the cause of neural
damage in MS is consistent with the statement in the Declaration that MS is
an autoimmune disease (Deel. ,r 6) and the characterization of MS in the
Specification ("Spec.") that "MS is a chronic inflammatory demyelinating
disease" (Spec. 1) which is an autoimmune disease (Spec. 4). In other
words, one of ordinary skill in the art would recognize that inflammation is a
characteristic of an autoimmune disease.
While Klein includes MS in a list of "vesicle transport diseases"
(Klein ,r 19), it is evident from reading Klein in its entirely, including
paragraph 22 reproduced above, that Klein does not consider defects in
vesicle transport to be the primary defect in MS, but rather a consequence of
the disease. Klein teaches that "the phrase 'vesicle transport disease' means
a disease, disorder, or condition responsive to the modification of vesicle
transport, that is, a disease, disorder or condition amenable to treatment by
modulating vesicle transport." Id. ,r 18. Klein also teaches:
Vesicle transport diseases also include diseases such as
inflammatory myopathies or viral infections in which vesicle
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Id.
transport may be normal or functioning vesicle transport is
required but whose onset, symptoms, or progression can
nonetheless be alleviated by altering the movement of vesicles.
Thus, Appellants' contention that MS is not a vesicular transport
disease (Deel. ,r,r 2--4; Br. 4) overlooks the broader characterization in Klein
of this class of diseases as ones that can be treated by modulating vesicular
transport. The declarants did not address this broader disclosure in which
they dismissed Klein, stating there was no "sound basis" "to ascribe a
putative beneficial pharmacological effect in a broad array of very
heterogen[ e ]ous neurological diseases based on vesical transport." Deel.
,r 5. The declarants focused entirely on diseases in which the primary defect
is in the vesicle transport pathway (id. ,r,r 3--4) and did not recognize that
Klein's definition was broader. In sum, the evidence does not support
Appellants' contention that "a skilled artisan would not have looked to the
Klein reference for information relevant to treating MS." Br. 5.
The Declaration states that "[ w ]hen the degenerating neurons in an
MS patient encounter a deficit of axonal transport, the degeneration is likely
beyond a pharmacological repair." Deel. ,r 6. This statement is not
necessarily in conflict with Klein's teaching "that the neurodegeneration
experienced by MS patients may be attenuated by agents that enhance
axonal transport" because Klein does not indicate that the treatment is aimed
at neurons that have already degenerated. The declarants did not specifically
address this disclosure in Klein and explain how it was inconsistent with
Klein's treatment disclosure.
Appellants further argue that Klein would have discouraged one of
ordinary skill in the art from using R-flurbiprofen because Klein teaches that
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"the neurodegeneration experienced by MS patients may be attenuated by
agents that enhance axonal transport" (Klein ,r 22), but Klein discloses that
R-flurbiprofen "impairs" vesicular transport (Klein, Fig. 1, ,r,r 63 (Example
2), 64). Br. 6. We agree with Appellants that that these teachings appear to
be inconsistent with one another. However, we do not find that this apparent
inconsistency undermines the obviousness rejection.
First, Klein discloses generally that "the compound" R-flurbiprofen"
can be used to treat a "neurodegenerative diseases such as ... multiple
sclerosis" without reference to the mechanism of action. Klein ,r 7. Klein
also claims it, again, without reference to mechanism. Id. at 31, 32 ( claims
1, 5)
Second, Klein is not the only publication relied upon by the Examiner
to show the treatment of MS with R-flurbiprofen.
Geisslinger discloses describes that R-flurbiprofen ("tarenflurbil") can
be used to treat neuropathic pain caused by multiple sclerosis. Geisslinger
,r,r 22, 26. The claims do not exclude the treatment of neuropathic pain
caused by multiple sclerosis from their scope. The Specification
distinguishes Geisslinger on the basis that "the present invention relates to
the use of R-Flurbiprofen for the treatment of the neuroimmunological
pathology of multiple sclerosis and thereby for the prevention or progression
of a loss of motor functions and neurodegeneration which results from
immune-mediated demyelination." Spec. 3 (first full paragraph). However,
the term "treatment" which is recited in the claims is not defined in the
Specification to require "prevention or progression of a loss of motor
functions and neurodegeneration." But, rather the Specification discloses
that the "present treatments preferably do relate to a treatment that is
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different from the treatment of pain-associated neuropathy, i.e. preferably
does not involve the treatment of pain-associated neuropathy." Spec. 6, 11.
4--6. The statement of a "preference" for treatment of multiple sclerosis is
not an exclusion of unpreferred or undisclosed embodiments that fall within
the scope of treatment. Geisslinger provides an explicit reason to have used
R-flurbiprofen to treat MS, namely to treat pain associated with it, meeting
the limitations of claims 1 and 2.
Appellants also contend that the damed dosage is not obvious because
"a skilled artisan would have recognized that the cited references teach away
from using R-Flurbiprofen for treating MS. Therefore, the cited references
do not recognize the dosage of R-Flurbiprofen as a result effective variable
for treating MS." Br. 6. However, this argument only addresses the
disclosure in Klein. Geisslinger, as explained above, provides an express
reason to administer R-Flurbiprofen to patients with MS to treat neuropathic
pain caused by it. The Examiner made explicit findings regarding the
obviousness of adjusting the dosages disclosed in Geisslinger to treat MS.
Final Act. 4, 5-6. Appellants did not identify a defect in these findings or
the Examiner's reasoning as to why the dosages would have been obvious.
For the foregoing reasons and those of the Examiner, the rejection of
claims 1 and 2 are affirmed as obvious based on Klein, Geisslinger, and
Kasper. Claims 2, 4--10, and 14--21 fall with claim 1 because separate
arguments for these claims were not provided. 37 C.F.R. § 4I.37(c)(l)(iv).
REJECTION BASED ON CRUZ
The Examiner found Cruz describes treating multiple sclerosis with
cyclohexanehexol and an NSAID, where the NSAID can be R-flurbiprofen
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as required by the rejected claims. Final Act. 7. The Examiner also found
that the "composition can be administered in a therapeutically effective
amount according to factors such as the disease state, age, sex and weight of
the individual." Id. To meet the dosage limitations of the rejected claims,
the Examiner relied on Geisslinger as disclosing suitable dosages to
administer R-flurbiprofen. Id. at 8, 9.
Appellants argue the both R-flurbiprofen and multiple sclerosis are
among longer lists that would require "picking" and "choosing" to have
arrived at the claimed subject matter. Br. 7. Appellants also state that
"when R-Flurbiprofen is taught as a compound to be used in the methods
described by Cruz, Alzheimer's disease (AD) is always identified as the
disease to be treated." Id. Thus, Appellants argue that the "pattern of
preferences" would not have guided the skilled worker to treat multiple
sclerosis with R-Flurbiprofen. Id.
While it is correct that Alzheimer's disease is specifically mentioned
in Cruz in numerous places, so is "neurodegenerative diseases." See, e.g.,
Cruz (54) (Title), 1:6, 2:9, 4: 13, 5:2, 6:6. Multiple sclerosis is disclosed in a
short list of nine specifically named neurodegenerative diseases:
In certain selected aspects of the invention, the disease is a
neurodegenerative disease or neurodegenerative disorder
including such diseases and impairments as [ 1] Alzheimer's
disease, [2] dementia, [3] MCI, [4] Huntington's disease, [5]
multiple sclerosis, [ 6] Parkinson's disease, [7] amyotrophic
lateral sclerosis, [8] epilepsy, [9] Pick' s disease, and other
similar diseases and disorders disclosed herein.
Id. at 77: 1-5 (bracketed numbering added).
Cruz also discloses a short list of twelve R-NAIDS which include R-
flurbiprofen:
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In an aspect, a pharmaceutical composition is provided
comprising a scyllo-inositol compound and R-NSAID selected
from the group consisting of [ 1] R-flurbiprofen, [2] R-
ibuprofen, [3] R-ketoprofen, [4] R-ketorolac, [5] R-naproxen,
[6] R-tiaprofenic acid, [7] R-suprofen, [8] R-carprofen, [9] R-
pirprofen, [10] R-indoprofen, [11] R-etodolac and [12] R-
benoxaprofen.
Cruz 3:9--12 (bracketed numbering added).
This list is repeated at 3:24--26, 70:26-29, 8:18-20 in Cruz's
disclosure. While R- flurbiprofen is specifically mentioned as a treatment
for Alzheimer's disease as indicated by Appellants (e.g., 80: 11-20; 92:3---6),
there is no indication from Cruz that R-flurbiprofen is restricted to
Alzheimer's disease. Rather, as explained above, the list of twelve drugs
that includes R-flurbiprofen is described as generally applicable to
neurodegenerative diseases. Consistently, the claims in Cruz also indicate
that the same list of drugs (at page 120, claim 21) applies generally to
neurodegenerative diseases (at page 120, claim 15), and multiple sclerosis
(at page 120, claim 16 where MS is in a list of nine).
There are only 108 possible combinations of the list of nine specific
diseases (claim 16) and of twelve R-NSAIDS (claim 21). In our view,
because the number is small, and each combination could be immediately
envisaged, the combination of MS and R-flurbiprofen would have been
obvious to one of ordinary skill in the art. Indeed, in Wm. Wrigley Jr. Co. v.
Cadbury Adams USA LLC, 683 F.3d 1356, 1361---62 (Fed. Cir. 2012), claims
to a product comprising WS-23 (a coolant) and menthol (a flavoring agent)
were found to be anticipated by a prior art disclosure in which each of the
specific ingredients was recited in a longer list of alternative agents. The
choices to have arrived at the claimed invention does not necessitate vast
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picking and choosing, but rather only requires selecting from small, well-
defined groups. See also Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804,
807 (Fed. Cir. 1989) (The fact that a reference "discloses a multitude of
effective combinations does not render any particular formulation less
obvious."). Simply because Alzheimer's may preferred does not establish a
"pattern of preferences" that guide one of ordinary skill away from choosing
flurbiprofen and MS (Br. 7), when each appear a list of possible choices.
Appellants contend that Cruz would not have motivated one of
ordinary skill in the art "to treat relapsing-remitting or progressive MS or to
treat MS in a subject by administering to a subject a dosage of between 5
mg/kg/day and 15 mg/kg/day." Br. 8.
However, the Examiner additionally relied upon Geisslinger and
Kasper to reach these limitations in the claim. Final Act. 7-9. Appellants
did not identify a deficiency in the Examiner's findings or reasoning.
Appellants also argue that one of ordinary skill in the art would have
recognized that "clinical manifestations and symptoms of MS are different
from the clinical manifestations and symptoms of AD." Br. 8. Appellants
state that "while AD exhibits accumulation of amyloid B plaques and
resultant clinical manifestations; MS is an autoimmune attack of the myelin
sheaths and oligodendrocytes." Id. In view of these differences in the
pathology between AD and MS, Appellants contend "a person of ordinary
skill in the art would not have been motivated to use, and would not have
had a reasonable expectation of success in using, R-Flurbiprofen for the
treatment of relapsing-remitting MS or progressive MS or using the specific
dosage to treat MS." Id.
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This argument does not persuade us that the Examiner erred. While
Cruz describes the effect on the NSAID and cyclohexanehexol on AB levels
and amyloid (Cruz 3: 13--4:9), which Appellants state is related to
Alzheimer's disease, Cruz also has broader disclosure of treating other
neurodegenerative disease with the same compounds. For example, Cruz
discloses:
More specifically, the invention provides a composition for
treating and delaying the onset of neurodegenerative diseases.
A composition of the invention has one or more
cyclohexanehexol and one or more NSAID, in particular R-
NSAID, and optionally one or more pharmaceutically
acceptable carriers.
Cruz 2:8-11.
In an aspect, the invention provides a pharmaceutical
composition comprising an amount of a cyclohexanehexol and
an amount of a NSAID, in particular R-NSAID, wherein said
composition achieves a synergistic effect for treating a
neurodegenerative disease in a mammal in need thereof.
Id. at 5: 17-20.
For the foregoing reasons and those of the Examiner, the rejection of
claim 1 is affirmed. Claims 2, 4--10, and 14--19 fall with claim 1 because
separate arguments for these claims were not provided. 37 C.F.R.
§ 4I.37(c)(l)(iv).
DECISION
The rejection of claims 1, 2, 4--10, and 14--21 underpre-AIA 35
U.S.C. § 103(a) as obvious over Klein, Geisslinger, and Kasper is affirmed.
The rejection of claims 1, 2, 4--10, and 14--19 under pre-AIA 35
U.S.C. § 103(a) as obvious over Cruz, Geisslinger, and Kasper is affirmed.
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TIME PERIOD
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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