Ex Parte Gallyas et al

Patent Trial and Appeal Board

Apr 12, 2017

13002074 (P.T.A.B. Apr. 12, 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.
13/002,074 01/05/2011 Ferenc Gallyas DAN-058 (108400) 6893
12495 7590 04/12/2017
Jason D. Voight
5100A MacArthur Boulevard, NW
Second Floor
Washington, DC 20016
EXAMINER
CRUZ, KATHRIEN ANN
ART UNIT PAPER NUMBER
1621
MAIL DATE DELIVERY MODE
04/12/2017 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 FERENC GALLYAS, BALAZS SUMEGI, SARA VETO,
PETER ACS, and SAMUEL KOMOLY
__________

Appeal 2015-008258
Application 13/002,074
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
JOHN E. SCHNEIDER, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
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STATEMENT OF CASE
According to the Specification,
Poly ADP ribose polymerase (PARP), a nuclear enzyme
occuring in a high copy number is activated by oxidative stress-
induced DNA-breaks. Upon activation, PARP cleaves nicotinamide
group from NAD+ and ADP-ribosylates nuclear proteins. PARP
activation affects numerous nuclear processes such as DNA repair and
control of transcription. Among 30 others, expression of NFKB-
regulated genes during inflammatory processes needs PARP activation,
which is proven by the fact that expression of these genes is greatly
damaged in PARP-1 - mice (mice missing PARP-1). PARP1 - mice
proved resistant to inflammatory processes and septic shock while no
serious changes were found in these animals.

Spec. 2.
The invention is based on the recognition that use of PARP
inhibitors and Akt kinase activating compounds (for example estrogens
and stilbenes) in combination resulted in an unexpected protection in
relevant animal models of neurodegenerative diseases. It is very
surprising that the positive effects measured during the combined use
are higher than the sum of the positive effects of the individual
components, i.e. synergy is occurred in the combined use of the two
above active agents.

Spec. 4.

The following claim is representative.
1. A method for treating pathological conditions related to PARP
activation where the pathological condition related to PARP
activation is a neurodegenerative disease, said method comprising
administering to an animal or human, as active agents, in
combination, a PARP inhibitor selected from the group consisting
of tetracycline compounds, 4-hydroxyquinazoline and its
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derivatives and carboxamino-benzimidazole and its derivatives, and
an Akt kinase activating compound selected from the group
consisting of estrogen compounds and stilbene structured
compounds.

18. The method of claim 1, where the pathological condition related
to PARP activation is selected from the group consisting of multiple
sclerosis, encephalomyelitis, Parkinson's disease, Alzheimer's disease
and Huntington's disease.

Grounds of Rejection
1. Claims 1-4, 6-7, 9-11, 14, 16-18 and 21 is rejected under 35 U.S.C.
§103(a) as being unpatentable over Duncan and Voskuhl.
2. Claims 1, 3, 5, 9-10, 12, 14, 17-19 and 21 is rejected under 35
U.S.C. §103(a) as being unpatentable over Duncan and Toppo.

FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Final Action at
pages 2-9.

Cited References
Voskuhl WO 2007/038636 A2 pub. April 5, 2007
Duncan WO 02/20022 A1 pub. March 14, 2002
Toppo WO 2008/013764 A2 pub. January 31, 2008

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PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
As stated in In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980):
“It is prima facie obvious to combine two compositions each of which is
taught by the prior art to be useful for the same purpose, in order to form a
third composition which is to be used for the very same purpose.”

Rejection 1 – Obviousness Duncan and Voskuhl
The Examiner relies on Duncan for teaching
a method for treating certain neurological diseases by
administering to a patient and effective amount of tetracycline
compound (abstract). Duncan teaches that the neurological diseases
are Alzheimer's disease, Guillain Barre syndrome, parkinson's disease
and amyotrophic lateral sclerosis (claim 1). Duncan teaches that the
tetracycline compound is doxycycline (claim 7). Duncan teaches that
the tetracycline compound (e.g. doxycycline) effective amount is 0.1
mg/kg/day to about 45 mg/kg/day (claim 14). Duncan teaches that the
tetracycline compound in a suitable pharmaceutical carrier (vehicle)
or excipient as understood by practitioners in the art (page 5, lines 18-
21).
Duncan does not expressly teach estriol or estrogen.

Ans. 3.

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The Examiner relies on Voskuhl for teaching that estriol may be used
for the treatment of neurodegenerative disorders, and that the “estriol is
nyestriol, estriol succinate or estriol sulfamate or estriol dihexanate.” Ans. 4.
Voshkuhl describes estriol for the treatment of neurodegenerative disorders
including Alzheimer's disease, Parkinson's disease, multiple sclerosis,
stroke, amyotrophic lateral sclerosis, frontotemporal dementia, prion disease,
Huntington's Disease. Ans. 4. The Examiner concludes it would have been
obvious to one of ordinary skill in the art at the time of the invention to
administer both a PARP activator and an estrogen compound in combination
because they are both known in the art to treat neurodegenerative disorders.
Ans. 4-5.
Appellants contend that they provide evidence of unexpected results
in the Specification and in the Declaration of Dr. Gallyas, dated April 11,
2014. Br. 3-5.

ANALYSIS
The pending claims are subject to an election of species requirement.
Appellant has elected doxycycline as the PARP inhibitor and estriol as the
estrogen compound. When the examiner has required the applicant to elect
single chemical species for examination, the issue on appeal is the
patentability of the single elected species, it is appropriate to limit discussion
to that single issue and take no position respecting the patentability of the
broader generic claims, including the remaining, non-elected species. See
Ex parte Ohsaka, 2 USPQ2d 1461 (Bd. Pat. App. Int. 1987).
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Appellants do not argue the claims separately in the Brief, therefore
we select claim 1 as representative claim. The same evidence of unexpected
results is relied on in support of all claims by Appellants.
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellants’ arguments as set forth in the Answer. We find
that the Examiner has provided evidence to support a prima facie case of
obviousness. We provide the following additional comment to the
Examiner’s argument set forth in the Final Rejection and Answer.
We agree with the Examiner and are unpersuaded by Appellants’
evidence of unexpected results and Declaration evidence. We further agree
with the Examiner that, “appellants have not demonstrated in any data or
examples that the combination of doxycycline and estriol to [sic] treat any
neurodegenerative disease. Furthermore, Appellants’ instant claims all
neurodegenerative diseases, whereas the data results are not drawn to any
particular disorder other than hydrocephalus.” Ans. 8.
The Examiner specifically finds that
While it appears true that in the treatment of hydrocephalus the
combination of estriol and doxycycline demonstrates unexpected
results … [h]owever, this one showing is narrow in comparison to the
scope of the claims. Further, the treatment of hydrocephalus is not the
same as the treatment of neurodegenerative diseases (e.g. Alzheimer's,
Huntington's or Multiple Sclerosis).

Ans. 8. With respect to demyelination, Appellants do not provide evidence
that the combination of the elected species shows unexpected results. Ans.
8.

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Nor have Appellants provided evidence of unexpected results to
support the full scope of the claims. “Establishing that one (or a small
number of) species gives unexpected results is inadequate proof, for ‘it is the
view of this court that objective evidence of non-obviousness must be
commensurate in scope with the claims which the evidence is offered to
support.” In re Greenfield, 571 F.2d 1185, 1189 (CCPA 1978). See also In
re Grasselli, 713 F.2d 731, 743 (Fed. Cir. 1983). Appellants do not provide
evidence of unexpected results for the treatment of neurodegenerative
disorders or the specific scope of disorders delineated in claim 18 and
encompassed by claim 1, and the elected species.
Rejection 1 is affirmed for the reasons of record.

Rejection 2 – Obviousness Duncan and Toppo
Rejection 2 essentially presents the same issues as Rejection 1. The
reliance on Duncan is for the same reasons set forth in rejection 1. Toppo is
relied upon for the disclosure of the use of trans-resveratrol for the treatment
of Alzheimer’s disease. Ans. 6.
Appellants again rely on their evidence of unexpected results. For the
reasons indicated in the record, and herein with respect to rejection 1, we do
not find Appellants’ evidence of unexpected results to be persuasive.
Rejection 2 is affirmed for the reasons of record.

CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejections,
which are affirmed for the reasons of record. All pending, rejected claims
fall. We limit our decision to the elected species.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED