Yoneoka, Takatomo

Patent Trials and Appeals Board

May 28, 2020

2019005152 (P.T.A.B. May. 28, 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.
14/342,889 03/05/2014 Takatomo Yoneoka 473207US40PCT 8123
22850 7590 05/28/2020
OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P.
1940 DUKE STREET
ALEXANDRIA, VA 22314
EXAMINER
MCMILLIAN, KARA RENITA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
05/28/2020 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):
OBLONPAT@OBLON.COM
iahmadi@oblon.com
patentdocket@oblon.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte TAKATOMO YONEOKA
__________

Appeal 2019-005152
Application1 14/342,889
Technology Center 1600
__________

Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating or suppression progress of amyotrophic lateral sclerosis, which
have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Amyotrophic lateral sclerosis (ALS) “is one type of motor neuron
disease.” (Spec. ¶ 2.) “[A]s symptoms progress, a systemic muscle group is
affected.” (Id.) Although “[t]he causal factor of ALS has not yet been

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 Mitsubishi
Tanabe Pharma Corporation. (Appeal Br. 1.)
Appeal 2019-005152
Application 14/342,889
2
sufficiently elucidated,” there are several “main causal factors” that have
been hypothesized, one of which is “oxidative stress disorders.” (Id.)
3-methyl-1-phenyl-2-pyrazolin-5-one is a known therapeutic agent for
treating ALS or symptoms caused by ALS, and/or for suppressing the
progress of ALS. (Id. at 4–5.) This compound, however, has not been
“approved” to treat ALS. (See id. at 3 and 8.) Appellant “has found” that
this compound “is particularly effective for a specific [sub]group of patients
with ALS.” (Id. at 10.)
Claims 14–37 are on appeal. Claim 14 is representative and reads as
follows:
14. A method for treating amyotrophic lateral sclerosis or
suppressing progress of amyotrophic lateral sclerosis,
comprising:
administering an effective amount of 3-methyl-1-phenyl-
2-pyrazolin-5-one or a physiologically acceptable salt thereof to
a patient who scores two or more points from each of all items
constituting ALSFRS-R in combination with %FVC of 80% or
more such that the patient is in need thereof,
wherein the administering comprises repeating a 14-day
administration period and a 14-day drug holiday period or
establishing an initial 14-day administration period and an
initial 14-day drug holiday period and then repeating an
administration period for 10 out of 14 days and a 14-day drug
holiday period.
(Supplemental2 Appeal Br. 3.)

2 The Supplemental Appeal Brief was filed January 11, 2019 in response to
a Notification of Non-Compliant Appeal Brief dated December 18, 2018.
Appeal 2019-005152
Application 14/342,889
3
The prior art relied upon by the Examiner is:
Name Reference Date
Ikeda US 6,933,310 B1 Aug. 23, 2005
Yoshino (Yoshino 2008) US 2008/0161378 A1 July 3, 2008
J. Cedarbaum et al., The ALSFRS-R: a revised ALS functional rating scale
that incorporates assessments of respiratory function, 169 Journal of the
Neurological Sciences, 13–21 (1999)
B. Traynor et al., Clinical Features of Amyotrophic Lateral Sclerosis
According to the El Escorial and Airlie House Diagnostic Criteria, 57
Arch. Neurol. 1171–76 (2000)
H. Yoshino and A. Kimura, Clinical trials for amyotrophic lateral
sclerosis with free radical scavenger edaravone, 20(5) Japanese J.
Neurotherapy, 557–84 (2003) (Yoshino 2003)3
H. Yoshino and A. Kimura, Investigation of the therapeutic effects of
edaravone, a free radical scavenger, on amyotrophic lateral sclerosis
(Phase II study), 7 Amyotrophic Lateral Sclerosis, 247–51 (2006)
(Yoshino 2006)

The following grounds of rejection by the Examiner are before us on
review:
Claims 14–37 on the ground of non-statutory obviousness-type double
patenting as being unpatentable over claims 1–5 of Ikeda, Yoshino 2006,
and Cedarbaum.
Claims 14–37 under 35 U.S.C. § 103(a) as unpatentable over Yoshino
2008, Yoshino 2003, and Cedarbaum.
Claims 14–37 under 35 U.S.C. § 103(a) as unpatentable over Yoshino
2006, Traynor, and Cedarbaum.

3 The Examiner relies on the English language translation provided by
Appellant, as do we.
Appeal 2019-005152
Application 14/342,889
4
DISCUSSION
Obviousness-Type Double Patenting Issue
The Examiner finds that the claims of Ikeda teach treating ALS with
edaravone, the common name of the chemical recited in the appealed from
claims. (Final Action 8.) The Examiner recognizes that the Ikeda claims do
not recite the treatment regimen in the appealed from claims but finds that it
would have been obvious to one having ordinary skill in the art to optimize
patient treatment with that regimen based on the teachings of Yoshino 2006
and Cedarbaum. (Id.) In particular, the Examiner explains that Yoshino
2006 teaches treating patients diagnosed with sporadic amyotrophic lateral
sclerosis (SALS) or familial amyotrophic lateral sclerosis (FALS) with
edaravone employing the regimen recited in the appealed from claims. (Id.)
The Examiner relies on Cedarbaum for the fact that “the ALS
functional pharmaceutical rating scale (ALSFRS) is a validated
questionnaire-based scale that measures physical function in carrying out
activities of daily living of patients with ALS.” (Id. at 9.) The Examiner
notes that the scale was revised and includes 12 categories, each of which is
assigned a score of 0–4 (and that “a maximum score would be 48 wherein
the patient exhibits no symptoms of ALS”), and that Cedarbaum “teaches
patients having a mean ALSFRS-R score of 38.0 points and having a mean
%FVC of 87.5.” (Id.) According to the Examiner, it would have been
obvious “to treat all patients with ALS [with edaravone] . . . such as those
taught in Cedarbaum et al. having a mean score of the ALSFRS-R of 38,
which renders obvious two or more points from all items of the ALSFRS-R,
and having a mean % FVC of 87.5.” (Id.)
We agree with the Examiner’s conclusion that the claims on appeal
are obvious from the claims of Ikeda, Yoshino 2006, and Cedarbaum.
Appeal 2019-005152
Application 14/342,889
5
However, we agree with Appellant that Cedarbaum’s teaching of a mean
value for ALSFRS-R “cannot be interpreted to equate with each of the
patients scoring two or more points from each of all the items of ALSFRS-
R.” (Appeal Br. 20; Reply Br. 4.) Nevertheless, the absence of such a
teaching does not overcome the prima facie case of obviousness of the
claims over Ikeda and Yoshino 2006.
Appellant’s arguments are focused only on independent claims 14 and
26. (Appeal Br. 13.) There is no dispute by Appellant that Ikeda’s claims
recite treating, with edaravone, a patient with a motor neuron disease, which
ALS is. (Id. at 4.) Nor does Appellant dispute that Yoshino 2006 teaches
administering edaravone to ALS patients with the same treatment regimen
that is recited in the claims on appeal. (See id. at 5–6 (“there is no
disclosure, suggestion or indication, express or implied, that patients having
the specific characteristics of the claimed subpopulation of ALS patients” in
Yoshino 2006); id. at 15). However, argues Appellant, Yoshino 2006 does
not teach efficacious treatment of the claimed subpopulation and “the
efficacy of edaravone could not have been evaluated effectively” because
the “clinical trials were not parallel-group, placebo-controlled” and even
“Yoshino 2006 states that a placebo effect cannot be ruled out in its clinical
trial” that was focused on safety of the drug in the “general ALS patient
population.” (Id. at 15–16.)
Appellant further argues, relying on two different declarations by Mr.
Takeshi Sakata dated September 1, 2016 (Sakata Declaration I) and dated
April 26, 2017 (Sakata Declaration II), that one of ordinary skill in the art
would not have expected efficacious treatment of the subpopulation claimed.
(Id. at 16–17.) In particular, Sakata Declaration II reports on a confirmatory
study conducted between May 2006 and May 2008 in which patients with
Appeal 2019-005152
Application 14/342,889
6
severity of ALS classification of 1 or 2 (a classification based on the
Japanese ALS severity classification4) were treated with edaravone, where
the results of “a difference between the ALSFRS-R scores before the
initiation of the first course and upon the termination of the sixth course was
measured” and were compared to a placebo group. (Sakata Declaration II ¶¶
4–9.) Sakata explains that the “the differences between the placebo group
and the drug administration group [patients rated as 1 or 2] are very small
and indistinguishable, and that the efficacy of edaravone for ALS treatment
of the patient populations in these earlier stages of ALS could not have been
confirmed.” (Id. ¶ 9.) Sakata Declaration II also identifies a similar result
of very small differences between the placebo group and drug administration
group when the evaluation was of patients who scored ALSFRS-R 41 or
greater or those with a score of less than 41. (Id. ¶¶ 10–12.) As to this
population study, Sakata concludes that the population analysis “did not
produce any meaningful guidance for formulating a specific patient sub-
population . . . for the purposes of evaluating the effect of an ALS drug with
patients in clinical trials.” (Id. ¶ 12.)
We do not find Appellant’s argument or evidence, when combined
with the Examiner’s evidence of obviousness, overcomes the prima facie
case of obviousness established by the teachings of the Ikeda claims and
Yoshino 2006.5 First, Ikeda provides evidence of a reasonable expectation

4 The group identified as “1” designates “patients capable of working or
performing housework,” and “2” designates “patients capable of
independent living but incapable of working.” (Sakata Declaration II ¶ 8.)
5 In affirming a multiple reference rejection under 35 U.S.C. § 103, the
Board may rely on fewer than all of the references relied on by the Examiner
in an obviousness rationale without designating it as a new ground of
rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
Appeal 2019-005152
Application 14/342,889
7
of success of treating, with edaravone, any patient having ALS, no matter
what stage. The claims of Ikeda do not provide one of ordinary skill in the
art with reason to doubt the therapeutic benefit of edaravone to any
particular ALS subpopulation. Furthermore, even though Yoshino 2006
indicates that “a placebo effect cannot be ruled out,” it nevertheless indicates
“the suggested efficacy of edaravone.” (Yoshino 2006 at 250.)
“Obviousness does not require absolute predictability of success . . . .
For obviousness under § 103, all that is required is a reasonable expectation
of success.” In re O’Farrell, 853 F.2d 894, 903–04 (Fed. Cir. 1988); Par
Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1198 (Fed. Cir. 2014).
Proof sufficient “to obtain approval” for a drug by a regulatory agency, such
as by a randomized, placebo-controlled, double-blinded design (Appeal Br.
5, 16; Spec. ¶ 8, Sakata Declaration II ¶¶ 14, 15) is not necessary to establish
obviousness. Hoffmann–La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331
(Fed. Cir. 2014) (“[c]onclusive proof of efficacy is not necessary to show
obviousness.”). “Scientific confirmation of what was already believed to be
true may be a valuable contribution, but it does not give rise to a patentable
invention.” PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342,
1363–64 (Fed. Cir. 2007).
Yoshino 2006 reports that “[i]n almost all patients in the 60 mg group,
the level of CSF 3NT, a marker of oxidative stress, was markedly reduced to
almost undetectable levels at the end of the sixth cycle of administration,”
and that this compound “appear[s] to reduce the rate of decline of ALSFRS-
R score during the six-month treatment period,” i.e., suppress disease
progress. (Id. at 249.) Thus, Yoshino 2006 supports a reasonable
expectation of success in achieving some measure of treatment for any ALS
Appeal 2019-005152
Application 14/342,889
8
patient through the administration of edaravone using the cycle of
administration taught therein.
We also do not find Appellant’s argument that Sakata Declaration I
establishes “a lack of efficacy” (Appeal Br. 16) to be persuasive. First and
foremost, Mr. Sakata does not even conclude there was a demonstrated “lack
of efficacy” of edaravone. Instead, as noted above, Sakata’s conclusion is
directed to whether the data evaluated supports categorizing patients into
subpopulations for the purposes of evaluating the effect of an ALS drug.
(Sakata Declaration I ¶ 14; accord Sakata Declaration II ¶¶ 10–12.) 6

6 We note that Sakata asserts that “results from the confirmatory study [, a
study conducted between May 2006 to September 2008 (see Sakata
Declaration II ¶ 4),] invalidate the earlier speculations found in the 2003
Yoshino article and the 2006 Yoshino article as to the efficacy of edaravone
for the patients in the earlier stages.” (Sakata Declaration II ¶ 16 (referring
to the results stated in ¶¶ 10 and 11, which is the same study and results
addressed in Sakata Declaration I (¶¶12 and 13)).) In arriving at this
conclusion, Sakata only considered the change in ALSFRS-R scores
compared to placebo, not CSF 3NT measurements. Thus, Sakata’s assertion
of invalidation of earlier speculations in Yoshino 2003 and 2006 is not in
conflict with our conclusion. And, even Yoshino 2006 indicates that “[t]o
support the suggested efficacy of edaravone, we therefore looked for
changes in oxidative stress in CSF of the treated patients, using 3NT as a
marker.” (Yoshino 2006 250.) And regarding CSF 3NT, Yoshino 2006
states “[i]n almost all subjects, 3NT levels measured at the end of the sixth
cycle of administration were markedly reduced, and were close to or below
the threshold of detection.” (Id.) In conclusion, Yoshino 2006 states:
Accordingly, the marked reduction of 3NT seen in the present
study suggests that the free radical scavenger edaravone almost
completely eliminated oxidative -stress in the spinal cord of
ALS patients.
(Id.)
Moreover, the conclusion in Yoshino 2003 that “the group having an
ALSFRS of 40 or more points which did not require intervention in daily life
tended to have a smaller decline in the score 6 months later” and which is an
Appeal 2019-005152
Application 14/342,889
9
Second, the data does not establish lack of efficacy of edaravone. The
reported data is simply the change in ALSFRS-R score from start of
edaravone administration until end of treatment compared to placebo. (Id.;
Sakata Declaration I ¶¶ 12–13.) The ALSFRS-R assesses behavioral or
functional activity on a scale of 0–4, which scores are subjective measures
unlike, for example, the measure of CSF-3NT before and after treatment.
However, even as to these subjective measures, the data reported
demonstrates that in groups with an ALSFRS score of 41 or more before
initiation there was a reduction in the rate of decline of ALSFRS-R score
during the six-month treatment period compared to placebo, albeit a
between-group difference of less than one. (Sakata Declaration I ¶ 12).
There was also a slight decrease in the subjective measures of the ALSFSR-
R score in patients with a score of less than 41 before initiation of treatment.
(Id. ¶ 13.) Consequently, even these subjective measures demonstrate
efficacy in suppressing disease progress, i.e., treatment.
In any event, although it is true that Yoshino 2006 does not teach,
expressly or inherently, that the ALS patients treated had the ALSFRS-R
scores recited in the claim or the forced vital capacity (FVC) claimed, there
is nothing in either Yoshino 2006 or Ikeda that would lead one of ordinary

observation in Yoshino 2003 made after suggesting that “administering this
drug at the initial phase of the disease when peroxynitrite is eliminated early
would make it possible to expect greater clinical validity” (Yoshino 2003 at
562) is not undermined by the “confirmatory study.” That is because the
“Between-group Difference” for “the sub-population of patients who scored
the total of 41 or more on ALSFRS-R” was 0.66 and for those “who scored
the total of less than 41” it was 0.28. (Sakata Declaration II ¶¶ 10–11.) This
confirmatory data, thus, is in accord with Yoshino 2003’s observation of a
smaller decline in groups having a higher ALSFRS score and not requiring
intervention in daily life.
Appeal 2019-005152
Application 14/342,889
10
skill in the art not to expect at least a reduction in the level of CSF 3NT,
which would indicate a reduction in oxidative stress of the patient population
having the claimed ALSFRS-R scores and FVC. That is because CSF 3NT
is a marker of oxidative stress (indicative of oxidative cellular damage) in
ALS no matter what stage of the disease. (See Yoshino 2006 247
(“oxidative stress has been considered to contribute to the pathogenesis of
ALS”).) And edaravone is a free radical scavenger that Appellant does not
argue would not have been reasonably expected to cause a decline in CSF
3NT regardless of the stage of ALS. In sum, Ikeda and Yoshino 2006
provide a reason to treat all patients with ALS with a reasonable expectation
of success of achieving a decline in CSF 3NT and thus result in a therapeutic
benefit to the patient, including those determined to fit within the population
identified in the claims on appeal.
“To be sure, [i]t is well-settled that a narrow species can be non-
obvious and patent eligible despite a patent on its genus.” Prometheus
Labs., Inc. v. Roxane Labs, Inc., 805 F.3d 1092, 1098 (Fed. Cir. 2015)
(citation omitted). “The genus-species distinction may have particular
relevance in the field of personalized medicine, where, for example, a
particular treatment may be effective with respect to one subset of patients
and ineffective (and even harmful) to another subset of patients.” Id.
(emphasis added). Such is not what is adduced by the evidence here. The
fact that Sakata concluded that one could not confirm efficacy of edaravone
on the sub-populations classified as 1 or 2 under the Japanese ALS severity
classification solely by analysis of differences between ALFSRS-R scores
before initiation of treatment and end of treatment when compared to
placebo does not address a lack of efficacy of the drug in treating ALS of
those patient populations, nor does it address whether CFS 3NT was reduced
Appeal 2019-005152
Application 14/342,889
11
in this population. (See, e.g., Sakata Declaration II ¶¶ 6–9.) And, that
Sakata concluded “no meaningful guidance” was provided in analyzing
ALSFRS-R differences between treated and placebo populations who began
treatment with either ALSFRS-R 41 and above or less than 41 “for purposes
of evaluating the effect of an ALS drug with patients in clinical trials” also
does not address a lack of efficacy of the drug in treating ALS of those
patient populations, nor does it address whether CFS 3NT was reduced in
this population. (Sakata Declaration I ¶ 14; Sakata Declaration II ¶ 12.)
Moreover, while evidence of unexpected treatment results would be
another way to demonstrate a conclusion of obviousness is inappropriate
with respect to the patient subset set forth in Appellant’s claims,
Prometheus, 805 F.3d at 1098; In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995)
(“One way for a patent applicant to rebut a prima facie case of obviousness
is to make a showing of ‘unexpected results,’ i.e., to show that the claimed
invention exhibits some superior property or advantage that a person of
ordinary skill in the relevant art would have found surprising or
unexpected.”), we conclude that Appellant has not provided sufficient
evidence. Indeed, we note in particular that Appellant’s expert does not
attest to any unexpected or surprising results. Moreover, the Specification
does not identify any results as to efficacy among various groups as being
surprising or unexpected, and particularly no mention is made as to
unexpected efficacy in view of the teaching that edaravone was known to
reduce CFS-3NT in almost all patients treated (Yoshino 2006 abstract).
The Specification provides population analysis of ALSFRS-R scores
pre-treatment and after-treatment compared to placebo using various criteria
to define subgroups of an ALS patient population. (Spec. ¶¶ 51–60.) The
Specification explains that “when patients with amyotrophic lateral sclerosis
Appeal 2019-005152
Application 14/342,889
12
were not specified . . . the between-group difference was 0.7.” (Id. ¶ 60.)
The Specification goes on to explain that in every subdivided grouping (1)–
(7) “all of the obtained values were greater than the aforementioned value
0.7” and that in these groups “the effects of [edaravone] were more clearly
exhibited.” (Id.) This includes groups in which the difference was as low as
1.2. (Id.) The Specification goes on to state:
It has been reported that a difference of 1 point in the ALSFRS-
R score would increase the risk of death or tracheostomy for
patients with amyotrophic lateral sclerosis by 7% . . .
Accordingly, in the case of specific patients in the present
invention, the risk of such death or tracheostomy can be
reduced by 3.5% or more, and thus, this is greatly advantageous
for patients with amyotrophic lateral sclerosis.
(Id.)
Appellant’s argument in the brief as to an asserted unexpected “large
increase” in the observed between-group difference in ALSFRS-R as to
subpopulation (5), which is the claimed population, compared to the
between-group difference in ALSFRS-R of the subpopulations (3) and (4),
each of which has a single recited characteristic of the claimed population,
(Appeal Br. 22) is not persuasive. Appellant asserts that the differences
between Groups (3) and (4), and Group (5) is unexpected. Appeal Br. 22.
Group 3 is “Two or more points from all items constituting ALSFRS-R;
Group 4 is “80% or more %FVC; and Group 5 is “Two or more points from
each of all items constituting ALSFRS-R and 80% or more %FVC.” Group
5 is the claimed subpopulation of ALS patients and constitutes patients with
characteristics from Groups 3 and 4. The differences between the treatment
and placebo group is 1.6 for group 3, 1.3 for group 4, and 2.5 for group 5.
The expectation of success is assessed from the perspective of a person of
ordinary skill in the art, at the time the invention was made. Life Techs. Inc.
Appeal 2019-005152
Application 14/342,889
13
v. Clontech Labs. Inc., 224 F.3d 1320, 1326 (Fed. Cir. 2000). In this case,
Appellant did not provide evidence that one of ordinary skill in the art would
have found this difference unexpected. The assertion of “unexpected
results” in the Appeal Brief is attorney argument. An argument made by
counsel in a brief does not substitute for evidence lacking in the record. In
re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). The Specification, where
these results are described, does not specifically characterize them as
unexpected. Spec. ¶ 60. As explained above, the cited prior art provided an
expectation of success that the recited drug would be an effective treatment
for ALS. Consequently, Appellant had the burden to show that the claimed
subgroup is “unexpectedly” different from the cited prior art, but Appellant
did not provide a statement by one of ordinary skill in the art to establish
such a finding on this record.
Claims 15–25 and 27–37 have not been argued separately and
therefore fall with claims 14 and 26. 37 C.F.R. § 41.37(c)(1)(iv).
In light of the foregoing, we affirm the Examiner’s rejection of claims
14–37 as being unpatentable for obviousness-type double patenting over the
claims of Ikeda, Yoshino 2006, and Cedarbaum.
II
Obviousness: Yoshino 2008, Yoshino 2003, Cedarbaum
The Examiner explains that Yoshino 2008 claims treating ALS
patients with edaravone including using the treatment regimen set forth in
Appellant’s claims. (Final Action 11.) The Examiner also notes that
Yoshino 2008 teaches determining the ALSFRS-R score of a patient prior to
treatment and during treatment. (Id. at 12.) The Examiner further notes that
Yoshino 2008 describes suppression in decrease in respiratory function in
Appeal 2019-005152
Application 14/342,889
14
ALS by the claimed method. (Id. at 11.) The Examiner explains that what
is not specifically taught in Yoshino 2008 is treating the specific patient
population claimed. (Id. at 12.) The Examiner finds that such would have
been obvious from Yoshino 2003 and Cedarbaum. (Id. at 12–13.)
In particular, the Examiner finds that Yoshino 2003, like Yoshino
2008, teaches treating ALS patients with edaravone including using the
treatment regimen set forth in Appellant’s claims. (Id. at 12.) The Examiner
finds that Yoshino 2003 also teaches “administration of edaravone at the
initial phase of the disease when peroxynitrite is eliminated early [and]
would make it possible to expect greater clinical validity (page 17 of
Translation).” (Id.) Yoshino 2003 also teaches that patients having
ALSFRS of 40 or more points and which “do not require intervention in
daily life tend to have a smaller decline in the score 6 months later (page 17
of Translation).” (Id. at 12–13.)
The Examiner relies on Cedarbaum in the same manner as relied upon
in the obviousness-type double patenting rejection. (Id. at 13.)
According to the Examiner, “a patient having a score of 40 or more or a
patient that does not require intervention in daily life is necessarily a patient
having a score of two or more points from all items of the ALSFRS-R since
Cedarbaum et al. teaches that scores of less than 2 would require
intervention in daily life.” (Id.) The Examiner concludes that
it would have been obvious to a person of ordinary skill in the
art to treat patients according to the teachings of Yoshino et al.
wherein the patient has 40 or more points on the ALSFRS and
do not require intervention in daily life since Yoshino 2003
teaches that said patients tend to have a smaller decline in the
score 6 months following treatment with edaravone.
(Id.)
Appeal 2019-005152
Application 14/342,889
15
We agree with the Examiner’s conclusion that Appellant’s claims on
appeal are obvious from Yoshino 2008, Yoshino 2003, and Cedarbaum.
Appellant’s arguments are again focused only on independent claims 14 and
26. (Appeal Br. 25.)
As with the obviousness-double patenting, we do not rely on
Cedarbaum. We also agree with Appellant that Yoshino 2008 does not
necessarily and inherently teach the claimed subpopulation being treated.
(Appeal Br. 26–27.) Nevertheless, as with Ikeda, we conclude that Yoshino
2008 provides evidence of a reasonable expectation of success of treating,
with edaravone, any patient having ALS, no matter what stage. Yoshino
2008 does not provide one of ordinary skill in the art with reason to doubt
the therapeutic benefit of edaravone to any particular ALS subpopulation.
Nor does Appellant provide sufficient evidence that would give rise to such
doubt.
Appellant argues that Yoshino 2003 states “that the efficacy of
edaravone was inconclusive from [its] clinical trial[] and suggested further
studies. See Yoshino 2003 at 562.” (Appeal Br. 27.) From this, Appellant
concludes that there is a lack of “any teaching or suggestion that any
specifically identified ALS subpopulation, let alone the claimed
subpopulation, is efficaciously treated.” (Id.) We do not find this argument
persuasive of non-obviousness for similar reasons that we did not find
Appellant’s argument with respect to Yoshino 2006 persuasive. In
particular, Yoshino 2003 teaches that the CSF 3NT declined significantly
relative to the placebo group and this “decline[] due to administration of the
edaravone itself is reason to expect that it has a motor neuron protection
action.” (Yoshino 2003 561 (“3NT declined due to administration of the
edaravone itself”); see also id. at 559–60.) Appellant does not argue that a
Appeal 2019-005152
Application 14/342,889
16
decline in the CSF 3NT would not reasonably be expected regardless of the
stage of the disease, even if “rehabilitation” is not validated. (Id. at 562.) In
other words, Yoshino 2003, like Yoshino 2006 supports a reasonable
expectation of success in achieving some measure of treatment for all types
ALS patients (reduction of CNF 3NT) through the administration of
edaravone using the cycle of administration taught in Yoshino 2008.
Moreover, we agree with the Examiner that Yoshino 2003 indicates
that smaller decline in score of ALSFRS in those who did not require
intervention in daily life after 6 months of treatment was observed. (Id.; see
also Id. at 558–559). Such patients would necessarily have a score of
between 2– 4 in most categories of ALSFRS. (See Cedarbaum Table 1.)
Thus, Yoshino 2003 provides a reasonable expectation of better success, in
terms of smaller decline in ALSFRS score, in patients in an earlier stage of
ALS, as would be the status of the subpopulation set forth in Appellant’s
claim. In sum, Yoshino 2008 and 2003 provide a reason to treat all patients
with ALS, including those determined to fit within the population identified
in the claims on appeal, with a reasonable expectation of success of
achieving a decline in CSF 3NT and a reasonable expectation of achieving
better results (from Yoshino 2003) in the patient population claimed which
the Examiner stated, and Appellant does not disagree, “is consistent with a
patient in the early stages of the disease” (see Appeal Br. 14). Such a
reasonable expectation of success is sufficient to establish prima facie
obviousness. In re O’Farrell, 853 F.2d at 903–04; Par Pharm., Inc., 773
F.3d at 1198.
And for the reasons discussed above in the obviousness-type double
patenting rejection, we do not find Appellant’s evidence concerning
unexpected results, when considered along with the Examiner’s evidence of
Appeal 2019-005152
Application 14/342,889
17
obviousness, is sufficient to rebut the Examiner’s determination of
obviousness.
Consequently, we affirm the Examiner’s rejection of claims 14–37 as
being unpatentable for obviousness over Yoshino 2008, Yoshino 2003, and
Cedarbaum.

Obviousness: Yoshino 2006, Traynor, Cedarbaum
In this rejection, the Examiner relies on Yoshino 2006 and Cedarbaum
as discussed above in the obviousness-type double patenting rejection. The
Examiner relies on Traynor for its teaching of established diagnostic criteria
in 1997, and that ALS is a progressive degeneration disease and includes
“findings suggestive of ALS are accorded different levels of diagnostic
certainty.” (Final Action 15.) The Examiner finds that it would have been
obvious to one of ordinary skill in the art that the patients in Yoshino 2006
were diagnosed with well-known techniques such as disclosed in Traynor
and that the patient population to be treated is rendered obvious from
Cedarbaum. (Id. at 17.)
Appellant’s arguments concerning this rejection are the same as those
identified above for obviousness-double patenting and obviousness of the
claims over Yoshino 2008, Yoshino 2003, and Cedarbaum. (Appeal Br. 37–
45.) We do not find Appellant’s arguments persuasive regarding this
rejection for the same reasons discussed above, even though we agree with
Appellant that Yoshino 2006 does not necessarily and inherently teach the
claimed subpopulation being treated. (Appeal Br. 37.) As noted above
Yoshino 2006 provides a reason to treat all patients with ALS, including
those determined to fit within the population identified in the claims on
appeal, with a reasonable expectation of success of achieving a decline in
Appeal 2019-005152
Application 14/342,889
18
CSF 3NT in the patient population claimed. Such a reasonable expectation
of success is sufficient to establish prima facie obviousness. In re O’Farrell,
853 F.2d at 903–04; Par Pharm., Inc., 773 F.3d at 1198.
And for the reasons discussed above in the obviousness-type double
patenting rejection, we do not find Appellant’s evidence concerning
unexpected results, when considered along with the Examiner’s evidence of
obviousness, is sufficient to rebut the Examiner’s determination of
obviousness.
Consequently, we affirm the Examiner’s rejection of claims 14–37 as
being unpatentable for obviousness over Yoshino 2006, Traynor, and
Cedarbaum.
DECISION SUMMARY
In summary:
Claims
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed
14–37 Obviousness-Type
Double Patenting:
Ikeda, Yoshino 2006,
Cedarbaum
14–37
14–37 103 Yoshino 2008,
Yoshino 2003,
Cedarbaum
14–37
14–37 103 Yoshino 2006,
Traynor, Cedarbaum
14–37
Overall
Outcome
14–37

Appeal 2019-005152
Application 14/342,889
19
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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED