UNIVERSITY OF CHICAGO

Patent Trials and Appeals Board

Jul 9, 2020

2019006053 (P.T.A.B. Jul. 9, 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.
14/773,088 09/04/2015 Sharon WAY ARCD.P0602US/1000348748 3598
32425 7590 07/09/2020
NORTON ROSE FULBRIGHT US LLP
98 SAN JACINTO BOULEVARD
SUITE 1100
AUSTIN, TX 78701-4255
EXAMINER
ULM, JOHN D
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
07/09/2020 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):
aoipdocket@nortonrosefulbright.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SHARON WAY, BENJAMIN CLAYTON, and
BRIAN POPKO
__________

Appeal 2019-006053
Application 14/773,088
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a
method of treating a demyelinating disorder. The Examiner rejected the
claims as failing to comply with the enablement and written description
requirements. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

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 The
University of Chicago (see App. Br. 1).
2 We have considered and refer to the Specification of Sept. 4, 2015
(“Spec.”); Final Action of June 18, 2018 (“Final Act.”); Appeal Brief of
Nov. 16, 2018 (“Appeal Br.”); and Examiner’s Answer of Feb. 19, 2019
(“Ans.”).
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Application 14/773,088

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Statement of the Case
Background
“A demyelinating disorder is a condition in which the myelin sheath
of a neuronal cell is damaged” (Spec. ¶ 3). “Multiple sclerosis (MS) is an
autoimmune disease affecting the brain and spinal cord, in which the body’s
own immune system attacks myelin or myelin producing cells” and “one of
the pathological hallmarks of MS is the presence of multiple demyelinated
plaques in the CNS” (id. ¶ 4).
The Claims
Claims 2, 7, 9, 11–13, 15, 27, 37, 38, 59, and 61–66 are on appeal.
Claim 2 is representative and reads as follows:
2. A method of treating a demyelinating disorder in a
subject in need thereof, comprising the step of administering to
the subject in need thereof an effective amount of a compound
of Formula I:

or a derivative or pharmaceutically acceptable salt thereof,
wherein R1, R2, R3, R4, and R5 are independently hydrogen,
deuterium, halogen, haloalkyl, alkyl, alkoxy, hydroxyl, aryl, or
aryloxy, thereby treating a demyelinating disorder in said
subject.

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The issues
The Examiner rejected claims 2, 7, 9, 11–13, 15, 27, 37, 38, 59, and
61–66 under 35 U.S.C. § 112(a) as failing to comply with the enablement
requirement (Ans. 3–8).
The Examiner rejected claims 2, 7, 9, 11–13, 15, 27, 37, 38, 59, and
61–66 under 35 U.S.C. § 112(a) as failing to comply with the written
description requirement (Ans. 8–10).

A. 35 U.S.C. § 112 (a), Enablement
The Examiner finds “one of ordinary skill in this art has no reasonable
expectation that a therapeutic protocol which has only been shown to be
effective in the treatment of a mouse EAE model system will be effective in
the treatment of MS, or in the treatment of all demyelinating diseases in
general, in humans” (Ans. 7–8). In other words, the Examiner contends that
Appellant has not enabled therapeutic efficacy using guanabenz in the
treatment of MS, or any other demyelinating diseases in humans by
demonstrating treating mice afflicted with EAE with guanabenz (Id.; see
also Final Action 3).
Appellant contends
the evidence shows that EAE mouse models are recognized by
persons of ordinary skill in the art as reasonably correlating to
MS. This is the most widely used model employed by the
scientific community to develop and test potential therapies for
MS. Appellants need not demonstrate that it has a greater than
50% success rate in order to support the conclusion of
reasonable correlation.
(Appeal Br. 12).
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We frame the enablement issue before us as follows: Has Appellant
demonstrated that the Examiner erred in finding it would require undue
experimentation to enable the treatment method required by claim 2?
The Examiner has the initial burden to establish a reasonable basis to
question the enablement provided for the claimed invention. See In re
Wright, 999 F.2d 1557, 1561–62 (Fed. Cir. 1993).
Factors to be considered in determining whether a disclosure
would require undue experimentation … include (1) the
quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence of
working examples, (4) the nature of the invention, (5) the state
of the prior art, (6) the relative skill of those in the art, (7) the
predictability or unpredictability of the art, and (8) the breadth
of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
As to the first and seventh Wands factors, the Examiner asserts a
“need for substantial further inventive contribution” (Ans. 3). The Examiner
cites Hart,3 Werkerle,4 Ransohoff,5 and Behan6 to support a finding that the
animal EAE model “was not considered a reliable predictor of the efficacy
of that protocol in the treatment of MS at the time of the instant invention,
and continues to be regarded as unreliable” (Ans. 3–7).

3 Hart et al., Modelling of multiple sclerosis: lessons learned in a non-human
primate, 3 Lancet Neurology 588–97 (2004).
4 Wekerle et al., Animal models of multiple sclerosis, 3 Drug Discovery
Today 359–67 (2006).
5 Ransohoff, Animal models of multiple sclerosis: the good, the bad and the
bottom line, 15 Nature Neuroscience 1074–7 (2012).
6 Behan et al., The sad plight of multiple sclerosis research (low on fact,
high on fiction): critical data to support it being a neurocristopathy, 18
Inflammopharmacol. 265–90 (2010).
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Appellant responds by relying on Steinman,7 and the Popko8 and
Reder9 Declarations to demonstrate “that the mouse EAE model is accepted
by those skilled in the art as reasonably correlating to multiple sclerosis”
(Appeal Br. 6).
We agree with Appellant because the evidence, reviewed as a whole,
demonstrates that the EAE model, even if flawed, is routinely used for
analysis of compounds associated with multiple sclerosis. Several of the
Examiner’s own cited references acknowledge this fact. Werkerle teaches
the “classic and most common model of MS is actively induced
experimental autoimmune encephalomyelitis (aEAE)” (Werkerle 360, col.
1). Werkerle teaches “[s]ome of the most successful therapies for MS now
applied in neurological clinics have originated in studies of the EAE model”
while also acknowledging that “[t]here have, however, also been spectacular
failures in the attempt to transport EAE therapies into MS treatment”
(Werkerle 365, col. 1).
Hart teaches that “many features of the MS immunepathogenesis have
been elegantly modelled in inbred strains of rats and mice” even if
“successful therapeutic interventions in these models have shown limited
predictive value for clinical success” (Hart 596, col. 2). Ransohoff teaches
that
EAE contributed enormously to our understanding of
autoimmunity, neuroinflammation, cytokine biology and

7 Steinman et al., Virtues and pitfalls of EAE for the development
of therapies for multiple sclerosis, 26 TRENDS in Immunol. 565–
71 (2005).
8 Declaration of Dr. Brian Popko, dated Jan. 3, 2017.
9 Declaration of Dr. Anthony Reder, dated Aug. 24, 2017.
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immunogenetics, and it surely changed the course of MS
research. One major MS treatment came directly, in a
mechanism-based fashion, from EAE research. Other
treatments, such as glatiramer acetate (a mixture of oligomeric
peptides), were first studied in EAE, but their application in
disease treatment has wandered fairly far from the initial
rationale for their development. For the most part, EAE has
proven poorly predictive of treatment success in MS.
(Ransohoff 1075, col. 2; citations omitted). Only Behan outright dismisses
EAE, finding it “cannot be accepted as a model for MS for a wide variety of
reasons” (Behan 283, col. 1).
In direct contrast to Behan, Steinman teaches “[d]espite its pitfalls,
EAE has been a useful model for predicting success with clinical trials in
multiple sclerosis (MS)” (Steinman 565, col. 1). Moreover, Dr. Popko states
Myself and many of the leaders in the field of neurobiology and
multiple sclerosis research not only feel that there is a
reasonable correlation between the mouse EAE model and the
human disease, multiple sclerosis, but also feel that the mouse
EAE model is a remarkably valuable model for drug discovery
and for understanding the underlying mechanisms of MS.
(Popko Decl. ¶ 4). Similarly, Dr. Reder states “[e]ven in the absence of
perfect correlation in multiple models of EAE, I and many of the leaders in
the field of neurobiology and multiple sclerosis research feel that the mouse
EAE model is a remarkably valuable model for drug discovery” (Reder
Decl. ¶ 6).
We therefore find that the first and seventh Wands factors support
enablement of the claims because the evidence, taken as a whole,
demonstrates that the EAE model is recognized as providing some guidance
as to whether a particular pharmaceutical would have been considered for
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further testing as a treatment of demyelinating disorders such as multiple
sclerosis.
As to the second Wands factor, the Specification provides substantial
guidance in selecting an appropriate patient population (see Spec. ¶¶ 73–95),
in disclosing screening assays for the efficacy of compounds of formula I
(id. at ¶¶ 96–98), and in selecting administration routes (id. at ¶¶ 143–162).
As to the third Wands factor, the Specification provides working cell
culture and animal model examples, using the EAE model (Spec. ¶¶ 184–
194). The EAE model examples demonstrate that guanabenz delays
symptom onset (id. ¶¶ 188, 194), reduces symptom severity (id. ¶¶ 189–
190), and reduces inflammatory immune responses (id. ¶ 193).
As to the fourth and eighth Wands factors, the claimed invention is
narrowly drawn to treatment of demyelinating disorders using a reasonably
small genus of compounds recited in Formula 1, including guanabenz (see
claims 2, 64).
As to the fifth Wands factor, the evidence of record, discussed above,
demonstrates that the EAE model is routinely used for screening compounds
for demyelinating disorders, as discussed above. The Examiner provides no
specific evidence demonstrating that guanabenz or the compounds of
Formula I, would not function in the treatment of human demyelinating
disorders.
As to the sixth Wands factor, the skill in the art is extremely high,
with the authors of these articles having doctoral degrees along with years of
experience in the relevant technical field of endeavor, as further evidenced
by the CV of Dr. Reder (see, e.g., Reder Decl. Exhibit A).
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Therefore, as we balance all of the evidence, we conclude that the
evidence does not support the Examiner’s position that the claims fail to
comply with the enablement requirement. The Examiner appears to confuse
the evidentiary basis needed to support enablement under the law for
obtaining a patent with the evidence of safety and efficacy necessary for
obtaining government approval to market a particular drug for a particular
treatment of humans. See Scott v. Finney, 34 F.3d 1058, 1063 (Fed. Cir.
1994) (“Testing for the full safety and effectiveness of a prosthetic device is
more properly left to the Food and Drug Administration (FDA). Title 35
does not demand that such human testing occur within the confines of Patent
and Trademark Office (PTO) proceedings.”) It is not necessary to “enable
one of ordinary skill in the art to make and use a perfected, commercially
viable embodiment absent a claim limitation to that effect.” CFMT, Inc. v.
Yieldup Int’l Corp., 349 F.3d 1333, 1338 (Fed. Cir. 2003). We conclude that
the record establishes that one of ordinary skill in the art would a have a
reasonable bases to conclude that the claimed compounds would have some
therapeutic efficacy in treating a demyelinating disease, even if further
research and development were need to obtain FDA approval of the drug for
such treatment. Cf. In re Brana, 51 F.3d 1560, 1568 (Fed. Cir. 1995) (
“[u]sefulness in patent law, and in particular in the context of
pharmaceutical inventions, necessarily includes the expectation of further
research and development. The stage at which an invention in this field
becomes useful is well before it is ready to be administered to humans.”)

B. 35 U.S.C. § 112 (a), Written Description
The Examiner finds:
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The claimed method of treating demyelinating disorders
in general, and MS in particular, is not adequately described in
the instant specification because there is no demonstrated
reasonable correlation between the results described in the
instant specification consequential to the administration of
guanabenz to EAE mice and the efficacy of a therapeutic
protocol in the of treatment demyelinating disorders in general,
and MS in particular.
(Ans. 8).
Appellant contends the “generic Formula I recited in claim 2 is
described in the specification” and the “specification further expressly
describes the use of the compounds within the genus of Formula I in
methods of treating a demyelinating disorder” (Appeal Br. 16). Appellant
further contends “the specification discloses experiments in which a species
within the genus of Formula I is effective in preventing loss of myelin and in
delaying onset of symptoms and reducing severity of symptoms in in vitro
and in vivo animal models of a demyelination” (id.). Appellant concludes
that the “structures of compounds within the scope of the claims are
sufficiently described in the specification and can be readily ascertained” (id.
at 17).
We agree with Appellant. The written description requirement can be
met by disclosing “complete or partial structure, other physical and/or
chemical properties, functional characteristics when coupled with a known
or disclosed correlation between function and structure, or some
combination of such characteristics.” Enzo Biochem, Inc. v. Gen-Probe Inc.,
323 F.3d 956, 964 (Fed. Cir. 2002). Claim 2 recites a reasonably small
genus of compounds with specific and complete structural limitations that
are correlated with the function of treating a demyelinating disorder. As
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Appellant points out, there is both extensive disclosure in the Specification
and working examples, as discussed above in the Wands factor analysis,
demonstrating possession of the invention.
To the extent that the Examiner is relying on inadequacies of the EAE
rodent model, we rely on our analysis above that demonstrates the rodent
model is recognized as a standard system for screening compounds for
treatment of demyelinating disorders. The model is fully described in the
prior art, as are the methods of using the model (see, e.g., Steinman 566,
figure 1). In addition, the Examiner has provided no evidence that the tested
guanabenz compound is not representative of the other, very similar,
compounds encompassed by formula I in claim 2 or that these compounds
would have different properties.
We therefore conclude that the claims satisfy the written description
requirement and do “not overreach the scope of the inventor’s contribution
to the field of art as described in the patent specification.” Ariad Pharm.,
Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010).

DECISION
In summary:

Claims
Rejected
35 U.S.C. § Basis/Reference(s) Affirmed Reversed
2, 7, 9, 11–13,
15, 27, 37, 38,
59, 61–66
112(a) Enablement 2, 7, 9, 11–13,
15, 27, 37, 38,
59, 61–66
2, 7, 9, 11–13,
15, 27, 37, 38,
59, 61–66
112(a) Written
Description
2, 7, 9, 11–13,
15, 27, 37, 38,
59, 61–66
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Claims
Rejected
35 U.S.C. § Basis/Reference(s) Affirmed Reversed
Overall
Outcome
2, 7, 9, 11–13,
15, 27, 37, 38,
59, 61–66

REVERSED