GEORGETOWN UNIVERSITY et al.

Patent Trials and Appeals Board

Dec 21, 2020

2020002235 (P.T.A.B. Dec. 21, 2020)

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.
15/022,654 03/17/2016 Mihael Polymeropoulos VAND-0166-US 1013
23550 7590 12/21/2020
HOFFMAN WARNICK LLC
540 Broadway
4th Floor
Albany, NY 12207
EXAMINER
JEAN-LOUIS, SAMIRA JM
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
12/21/2020 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):
PTOCommunications@hoffmanwarnick.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MIHAEL POLYMEROPOULOS, HOWARD J. FEDEROFF, and
XIAOMIN SU
__________

Appeal 2020-002235
Application115/022,654
Technology Center 1600
__________

Before RICHARD M. LEBOVITZ, RACHEL H. TOWNSEND, and
MICHAEL A. VALEK, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating a subject diagnosed with a neurodegenerative disease,
which have been rejected as obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.
STATEMENT OF THE CASE
Appellant’s Specification states “[g]enerally . . . the underlying
mechanisms causing [neurodegenerative diseases] are not well understood

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as Georgetown
University and Vanda Pharmaceuticals Inc. (Appeal Br. 1.)
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and few effective treatment options are available for preventing or treating
neurodegenerative diseases.” (Spec. 1.) Appellant’s invention is directed to
a method of treating a neurodegenerative disease by administering an
effective amount of fenofibrate. (Id.)
Claims 13–15, 17–22, and 26–28 are on appeal. Claim 13 is
representative and read as follows:
13. A method of treating a subject diagnosed with a
neurodegenerative disease who has been determined to exhibit a
reduced level of PGC-1α expression as compared to the
expression level expected in a subject lacking the
neurodegenerative disease, the method comprising:
administering to the subject an amount of fenofibrate
effective to increase a level of PGC-1α expression and treat the
neurodegenerative disease.
(Appeal Br. 7–8.)
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The prior art relied upon by the Examiner is:
Name Reference Date
Bartl et al. US 2007/0225326 A1 Sept. 27, 2007
A. Kreisler et al., Lipid-lowering drugs in the MPTP mouse model of
Parkinson’s disease: Fenofibrate has a neuroprotective effect, whereas
bezfibrate and HMG-CoA reductase inhibitors do not, 1135 Brain
Research 77–84 (2007)
J. St.Pierre et al., Suppression of Reactive Oxygen Species and
Neurodegeneration by the PGC-1 Transcriptional Coactivators, 127 Cell
397–408 (2006)
S. Austin and J. St.Pierre, PGC1α and mitochondrial metabolism –
emerging concepts and relevance in ageing and neurodegenerative
disorders, 125 J. Cell Science, 4963–71 (2012)

The following grounds of rejection by the Examiner are before us on
review:
Claims 13–15, 17–20, and 26–28 under 35 U.S.C. § 103(a) as
unpatentable over Kreisler, St. Pierre, and Austin.2
Claims 21 and 22 under 35 U.S.C. § 103(a) as unpatentable over
Kreisler, St. Pierre, Austin, and Bartl.

DISCUSSION
Obviousness of Claims 13–15, 17–22, and 26–28
Appellant argues the claims as a group. Thus, claims 14, 15, 17–22,
and 26–28 stand or fall with claim 13. 37 C.F.R. § 41.37(c)(1)(iv).
We address the rejection as it relates to representative claim 13. The
Examiner finds that Kreisler teaches testing of fenofibrate in the MPTP

2 The Examiner refers to this reference as St. Pierre Journal of Cell Science.
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mouse model of Parkinson’s disease (PD), “a classical experimental model
of PD” reproducing “some of its biochemical and pathological hallmarks.”
(Non-Final Action3 14.) The fenofibrate was administered orally and
prevented the MPTP-induced dopaminergic cell death and attenuated the
loss of tyrosine hydroxylase immunoreactivity. (Id.)
The Examiner finds that Kreisler teaches that “recent evidence
suggests that the PPARα agonist, fenofibrate, has neuroprotective effects in
an experimental mouse model of brain ischemia that encompasses
inflammatory response and oxidative stress (see page 78, last paragraph).”
(Id. at 13.) In addition, the Examiner finds that Kreisler teaches that “there
is some evidence to suggest that PPAR-α is involved in the suppression of
apoptosis.” (Id.) The Examiner also finds that Kreisler further teaches that
“the data suggest that PPAR-alpha activation by fenofibrate could have a
neuroprotective effect in PD through inhibition of inflammation, oxidative
stress, and/or apoptosis (see pg. 80 left col.).” (Id. at 14.)
The Examiner recognizes that Kreisler “does not specifically teach a
method of treating Parkinson disease wherein the subject has been
determined to exhibit a reduced level of PGC-1 alpha expression as
compared to the expression level expected in a subject lacking the
neurodegenerative disease.” (Id.) Nor does Kreisler teach that fenofibrate
induces PGC-1α expression in neural cells. (Id. at 14–15.)
The Examiner finds, however, that it would have been obvious to one
of ordinary skill in the art to have used fenofibrate to treat PD patients with
reduced PGC-1α expression with a reasonable expectation of treating PD

3 The Non-Final Action is dated Feb. 5, 2019.
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and preventing dopaminergic cell loss in view of the teachings of St. Pierre
and Austin. (Id. at 16–17.) The Examiner finds this to be so because
St. Pierre teaches PGC-1α, which is a PPAR gamma co-activator, is a
modulator of reactive oxygen species (ROS), “is required for the induction
of many ROS-detoxifying enzymes,” “and that increasing PGC-1α
dramatically protects neural cells in culture from oxidative-stressor mediated
death.” (Id. at 15.) In addition, the Examiner finds that St. Pierre teaches
“PGC-1α expression caused a powerful increase in the survival of neuronal
cells and had a protective effect in neuroblastoma cells (see pg. 404, left
col.).” (Id. at 15.) And the Examiner finds that Austin teaches PGC-1α is a
“powerful regulator of ROS removal,” thus minimizing the impact of ROS
on cell physiology and “is a transcriptional co-activator that is a central
inducer of mitochondrial biogenesis (see abstract).” (Id. at 16.) And, Austin
teaches “PGC-1α was found to protect against neuronal loss in cell culture
models of PD and PD mouse model (see pg. 4969, right col., top
paragraph).” (Id.) “In sum, [Austin] et al. teach that increased PGC-1α
levels appear to improve the various neurodegenerative diseases by either
improving mitochondrial functions and/or ROS detoxification (see pg. 4969,
right col., last paragraph).” (Id. at 17.)
The Examiner concludes:
one skilled in the art would have indeed found it obvious [to]
target subjects afflicted with neurodegenerative diseases with
low or reduced PGC-1α expression level and administer
fenofibrate given that St. Pierre stated that such subjects with
low or no PGC-1α expression tend to display neurodegenerative
lesions and increased ROS and given that Kreisler
demonstrated that administration of fenofibrate results in
decreased brain lesions and decreased ROS species.
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(Ans. 14.) The Examiner further concludes that one skilled in the art would
have found it obvious that administration of fenofibrate would lead to an
increased level of PGC-1α expression in neural cells “given that the prior art
teaches that such neuroprotective effect is conferred by PGC-1α wherein
reduced levels lead to neurodegeneration.” (Id. at 18.)
We agree with the Examiner’s conclusion of obviousness.
Kreisler teaches a study performed “to determine whether or not
fenofibrate, bezafibrate and two HMG-CoA reductase inhibitors
(atorvastatin and simvastatin) have neuroprotective effects on dopaminergic
cell loss in an acute MPTP mouse model of Parkinson’s disease.” (Kreisler
78.) The study involved administering “a diet containing 0.2% fenofibrate”
and determined that such a dosage amount was able to “prevent the MPTP-
induced loss of TH4-positive neurons in the substantia nigra pars compacta,”
a particular region of the midbrain, and “MPTP-induced loss of TH-
immunoreactivity-containing neurons in the striatum.” (Id. at abstract, 78–
79.)
Irrespective of whether Kreisler identified that fenofibrate increased
the level of PGC-1α expression (Appeal Br. 5), we agree with the Examiner
that Kreisler’s study provides motivation to one of ordinary skill in the art to
treat one suffering from a neurodegenerative disease, such as PD, with
fenofibrate. Indeed, as discussed above, Kreisler established in a mouse
model of PD that administration of fenofibrate provided a therapeutic
benefit.

4 TH stands for tyrosine hydroxylase
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We turn now to the patient population that the claims require to be
treated, namely a subject diagnosed with a neurodegenerative disease who
has been determined to exhibit a reduced level of PGC-1α expression as
compared to the expression level expected in a subject lacking the
neurodegenerative disease. (See, e.g., Claim 13.) St. Pierre and Austin
indicate that PGC-1α presence plays a role in improving neurodegenerative
diseases, and its absence can result in neurodegenerative lesions in the brain.
St. Pierre indicates that in animal models that were created to not have
PGC-1α, i.e., PGC-1α knockout mice, such mice “displayed
neurodegenerative lesions in the brain, particularly in the striatum, and also
showed behavioral abnormalities.” (St. Pierre 398.) St. Pierre also
explained that “[t]he absence of PGC-1α again renders the brain more
sensitive to neurodegeneration, with apoptotic cell death and increased
oxidative damage.” (St. Pierre 405.) St Pierre further states that “PGC-1α is
a highly inducible factor in most tissues” and “induc[ing] PGC-1α in the
brain . . . could represent a new mode of therapy.” (Id. at 406.)
In addition, Austin indicates that several studies support “a protective
role for PGC1α in Parkinson’s disease,” which is “characterised by the loss
of dopaminergic neurons in the substantia nigra,” and that “[t]he expression
of numerous PGC1α target genes, such as those of the respiratory chain, is
decreased in PD patients.” (Austin 4969.)
Austin further teaches, that PGC1α is reduced in numerous
neurodegenerative disease. In particular Austin, indicates that expression of
PGC1α is “reduced” in Huntington’s disease patients and Alzheimer’s
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patients. (Austin 4969.) Austin further teaches that the expression of
PGC1α is “repressed” in PD. (Id. (citing Shin5).)
Appellant admits that there are neurodegenerative diseases that are
“typified by reduced PGC-1α expression.” (Appeal Br. 5.) We conclude
that in light of this admission and the teachings discussed above of St. Pierre
and Austin that Kreisler’s suggestion of administering fenofibrate to PD
patients would include administering it to patients that would necessarily
have reduced levels of PGC1α.6
Although we disagree with the Examiner that one of ordinary skill in
the art would have expected from the prior art that a mechanism of action of
fenofibrate treatment is through an increase in PGC1α expression (Ans. 8–
10, 13–14; Non-Final Action 15–17), we nevertheless, agree with the
Examiner that, in view of the broad range of effective amounts disclosed in
the Specification, that it would have been reasonably expected that,
following the guidance of Kreisler, an increased level of PGC-1α expression

5 J. Shin et al., PARIS (ZNF746) Repression of PGC-1α Contributes to
Neurodegeneration in Parkinson’s Disease, 144 Cell 689–702 (2011) (copy
included with this decision); see Shin 696 (“We find that PGC-1α and NRF-
1 mRNA are downregulated in PD SN [(substania nigra)] and striatum
compared to control SN and striatum (Figure 6A and Figure S5A).”)
6 We also agree with the Examiner that it would have been obvious to one
of ordinary skill in the art to target patients having PD with a reduced level
of PGC-1α in light of the teachings of St. Pierre and Austin. (Ans. 15.) That
is because Austin indicates “PGC1α protects against neuronal loss in cell
culture models of PD” and that “increased PGC1α levels appear to improve
the phenotype of various murine models of [ageing and neurodegenerative
disorder] conditions.” (Austin 4969.) However, we disagree with the
Examiner that one of ordinary skill in the art would reasonably have
deduced from the cited prior art that at least one of the mechanisms of action
of fenofibrate in treating PD was the increase of PGC-1α expression.
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would result upon fenofibrate administration to human PD patients. (Non-
Final Action 17.) Specifically, Appellant’s Specification teaches that an
effective amount would be between 1–1000 mg daily. (See Spec. 7–8.)
And, we do not find persuasive Appellant’s argument, unsupported by data
or declaration evidence, that
The fact that fenofibrate was found to provide neuroprotective
effects in patients with a neurodegenerative disease that is
typified by reduced PGC-lα expression does not necessarily
mean that fenofibrate resulted in increased PGC-1α expression.
(Appeal Br. 5.) “[W]here the Patent Office has reason to believe that a
functional limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent characteristic of the prior
art, it possesses the authority to require the applicant to prove that the
subject matter shown to be in the prior art does not possess the characteristic
relied on.” In re Best, 562 F.2d 1252, 1254–55 (CCPA 1977). Given the
broad range of effective amounts disclosed in the Specification, and the lack
of evidence of the criticality of the effective amount, it would have been
reasonably expected that following the dosage guidance in Kreisler
increased PGC-1α expression would necessarily and inevitably result.7

7 Appellant argues further that the prior art does not conclude that an
increase in PGC-1α expression would provide neuroprotection. (Appeal Br.
4.) We do not find this argument persuasive. First, the claims do not require
treatment with fenofibrate to provide neuroprotection. The claims just
require an increase in the level of PGC-1α expression. Whether the prior art
recognizes that such a result was achieved is simply of no relevance here.
“[W]hen considering a prior art method, the anticipation doctrine examines
the natural and inherent results in that method without regard to the full
recognition of those benefits or characteristics within the art field at the time
of the prior art disclosure.” Perricone v. Medicis Pharm. Corp., 432 F.3d
1368, 1378 (Fed. Cir. 2005).
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Because our reasoning that the prior art renders claim 13 obvious
differs in significant respect from the Examiner’s, we designate our
affirmance as a new ground of rejection pursuant to 37 C.F.R. § 41.50(b).
Appellant does not separately address the Examiner’s rejection of
claims 21 and 22 under 35 U.S.C. § 103(a) except to say that Bartl does not
cure the defects of Kreisler, St. Pierre, and Austin. (Appeal Br. 6.) Because
we do not agree that there is a defect in the Examiner’s conclusion that claim
13 is not patentable over Kreisler, St. Pierre, and Austin, we affirm the
Examiner’s rejection of claims 21 and 22.

DECISION SUMMARY
In summary:
Claims
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed New
Ground
13–15,
17–20,
26–28
103 Kreisler, St. Pierre,
Austin
13–15,
17–20,
26–28
13–15,
17–20,
26–28
21, 22 103 Kreisler, St. Pierre,
Austin, Bartl
21, 22
Overall
Outcome
13–15,
17–22,
26–28
13–15,
17–20,
26–28

TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.”
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37 C.F.R. § 41.50(b) also provides that 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. . . .
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. . . .
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.

AFFIRMED; 37 C.F.R. 41.50(b)