Carmel -Haifa University Economic Corporation Ltd.

Patent Trials and Appeals Board

Jun 1, 2020

2019005415 (P.T.A.B. Jun. 1, 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.
14/345,695 03/19/2014 Yoram Yovell 58539 5522
67801 7590 06/01/2020
MARTIN D. MOYNIHAN d/b/a PRTSI, INC.
c/o Purrfect Patents LLC
11213 Piedmont Drive
Fredericksburg, VA 22407
EXAMINER
SOROUSH, LAYLA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
06/01/2020 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):
usptomail@ipatent.co.il
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte YORAM YOVELL
__________

Appeal 2019-005415
Application1 14/345,695
Technology Center 1600
__________

Before FRANCISCO C. PRATS, RACHEL H. TOWNSEND, and
JAMIE T. WISZ, 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
of treating acute suicidality, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm-in-part.
STATEMENT OF THE CASE
Appellant’s Specification states that “[s]uicide is a major cause of
death worldwide” and that “[a]s of now, there are no effective
pharmacological treatments for acute suicidality.” (Spec. 1.) Appellant’s

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 Carmel -
Haifa University Economic Corporation Ltd. (Appeal Br. 2.)
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Specification further states that “[d]espite their established antidepressant
effect, it is doubtful whether antidepressant medications exhibit a direct anti-
suicidal effect.” (Id.) The Specification indicates that “[s]everal lines of
evidence have recently suggested that suicidality, while being one of the
symptoms of depression, is at least partially independent of depression, and
may respond differently to treatment.” (Id.) Appellant’s claims on appeal
are directed to a method of treating acute suicidality with the mixed opioid
agonist-antagonist buprenorphine, a compound “used in narcotic
detoxification and in maintenance programs for people with opioid
dependence.” (Id. at 2–3.)
Claims 54–65, 75, and 76 are on appeal. Claims 54 and 75 are
representative and reads as follows:
54. A method of treating acute suicidality in a subject in
need thereof, the method being effected by administering to a
subject determined as having acute suicidality a therapeutically
effective amount of buprenorphine, or a pharmaceutically
acceptable salt thereof, thereby treating said acute suicidality in
a subject in need thereof, wherein said subject is not afflicted by
a depressive disorder.
75. A method of treating acute suicidality in a subject in
need thereof, the method comprising:
determining a presence of acute suicidality in a subject;
and administering to a subject determined as having acute
suicidality a first therapeutically effective amount of
buprenorphine, or a pharmaceutically acceptable salt thereof,
during a first time period, said first therapeutically effective
amount being in a range of from 0.05 to 0.12 mg per day,
thereby treating said acute suicidality in a subject in need
thereof.
(Appeal Br. 23, 25.)

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The prior art relied upon by the Examiner is:
Name Reference Date
ClinicalTrials.gov. National Library of Medicine, A Double-Blind Study
of Buprenorphine Treatment of Acute Suicidality, Identifier
NCT00863291 (2009), retrieved from
https://clinicaltrials.gov/ct2/show/NCT00863291 (“Yovell”)
R. Sittl et al., Analgesic Efficacy and Tolerability of Transdermal
Buprenorphine in Patients with Inadequately Controlled Chronic Pain
Related to Cancer and Other Disorders: A Multicenter, Randomized,
Double-Blind, Placebo-Controlled Trial, 25.1 Clinical Therapeutics 150–
68 (2003)

The following grounds of rejection by the Examiner are before us on
review:
Claims 54–62, 64, 65, 75, and 76 under 35 U.S.C. § 103(a) as
unpatentable over Yovell.
Claim 63 under 35 U.S.C. § 103(a) as unpatentable over Yovell and
Sittl.
DISCUSSION
The Examiner finds that Yovell “teaches administration of
buprenorphine showed reduction in acute suicidality” and that “[t]he
buprenorphine dosage ranged from 0.2-1.6 mg/day but with a starting dose
of 0.2 mg/day.” (Final Action 7.) The Examiner concludes that
[i]t would have been obvious to one of ordinary skill in the art
at the time of the invention to treat patients exhibiting acute
suicidality without depression. The motivation comes from the
teaching of Yovel[l] et al. that acute suicidality was treated with
buprenorphine.
(Id.) The Examiner also explains that:
The claimed subject matter would have been obvious because
the skilled artisan would have appreciated that certain factors
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would influence the dosage regimen required to effectively treat
the subject for the purpose taught by the references, including,
but not limited to the severity of the disease or disorder,
previous treatments, the weight, general health and/or age of the
subject and the presence of other diseases.
(Id. at 8.)
A. Claim 54
Appellant argues that the Examiner’s rejection of claim 54 is in error
because, inter alia, it “is an error of fact to allege that Yovell teaches that
successful treatment of suicidality with buprenorphine occurred.” (Appeal
Br. 7.) Appellant argues that “Yovel[l] merely describes a clinical trial
based upon a mere hypothesis without presenting positive results, and thus
would not suggest to a skilled person that the tested drug is effective against
the indicated condition” and provided the Declaration of Yovell, dated June
13, 2017, in support of the foregoing. (Appeal Br. 7–9.) According to
Appellant, withdrawing the allegation of fact, necessarily obviates the
Examiner’s grounds for rejection. (Id. at 9.)
Appellant also argues that the Examiner has not established that “it
would have been obvious to modify the teachings of Yovel[l] to treat acute
suicidality in patients not afflicted by a depressive disorder” where (1)
Yovell “relates to a clinical trial performed only on depressed patients” and
(2) “the only potential mechanism of action suggested [in Yovell] is that
buprenorphine is a reported antidepressant.” (Appeal Br. 10.) According to
Appellant “there is no apparent rationale for expecting success in treating
[condition X] without [condition Y] with an agent, merely because of a prior
art treatment of [condition X] with [condition Y] with the agent.” (Id. at 11.)
We conclude that the Examiner has not established a prima facie case
of obviousness of claim 54, which requires the treatment of acute suicidality
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be of a subject that is not afflicted by a depressive disorder. “An Examiner
bears the initial burden of presenting a prima facie case of obviousness.
Once the examiner establishes a prima facie case of obviousness, the burden
shifts to the applicant to rebut that case.” In re Huai-Hung Kao, 639 F.3d
1057, 1066 (Fed. Cir. 2011) (citations omitted).
We agree with Appellant, that Yovell cannot be deemed to describe a
clinical trial that was carried out and demonstrated effective treatment of
acute suicidality. Indeed, in a Declaration by Professor Yovell dated June
13, 2017, submitted by Appellant, Professor Yovell explains that the mere
fact that this reference states the drug was being studied for its efficacy to
treat acute suicidality, does not mean “that experimental evidence existed
showing efficacy of buprenorphine against acute suicidality.” (Yovell
Declaration 2.) However, such does not establish error in the Examiner’s
rejection of claim 54 for obviousness.
“Where claimed subject matter has been rejected as obvious . . . , a
proper analysis under § 103 requires, inter alia, consideration of two factors:
(1) whether the prior art would have suggested to those of ordinary skill in
the art that they should . . . carry out the claimed process; and (2) whether
the prior art would also have revealed that in so . . . carrying out, those of
ordinary skill would have had a reasonable expectation of success.” In re
Vaeck, 947 F.2d 488, 493 (Fed. Cir. 1991); In re Dow Chemical Co., 837
F.2d 469, 473 (Fed. Cir. 1988) (“The consistent criterion for determination
of obviousness is whether the prior art would have suggested to one of
ordinary skill in the art that this process should be carried out and would
have a reasonable likelihood of success, viewed in the light of the prior
art.”).
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It cannot reasonably be disputed that Yovell would have suggested to
one of ordinary skill in the art to carry out a process of treating a subject
with acute suicidal depression with buprenorphine: it is after-all a clinical
trial designed for just that purpose. (See Yovell 1 (“A Double-Blind Study of
Buprenorphine Treatment of Acute Suicidality”); see also Ans. 7 (noting
Yovell states: “The proposed double-blind study will examine the effect of
buprenorphine on acutely suicidal inpatients.”).) As the Examiner explains:
It is clear that the prior art intends to use buprenorphine for the
treatment of acute suicidality, therefore, rendering obvious the
use of buprenorphine for the treatment of acute suicidality.
(Ans. 7.)
We next turn to the question of a reasonable expectation of success.
We acknowledge that Professor Yovell states in his June 2017 declaration
that “[o]ne of ordinary skill in the art would not have presumed - based on
the teachings of Yovell - that buprenorphine has efficacy against acute
suicidality.” (Yovell Declaration 2.) However, we understand this
statement in context of the Declaration—directed at establishing that no
clinical trials for using this drug to treat acute suicidality had been carried
out and thus no “experimental evidence existed showing” such efficacy is
provided by Yovell (id.)—to mean that no absolute predictability that
buprenorphine has efficacy in treating acute suicidality could be presumed
from Yovell. We arrive at that interpretation of Yovell’s Declaration
because Yovell itself hypothesizes in a document that was used to obtain
permission from a regulatory agency to carry out the clinical study that the
depressed and acutely suicidal patient will “show rapid improvements in
objective and subjective measures of suicidality and depression” which is a
conclusion premised in part on “[a]necdotal evidence and several clinical
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studies [that] found the mixed opioid agonist-antagonist buprenorphine to be
an effective antidepressant with a rapid onset of action.” (Yovell 1
(Purpose).)
That there would not be an absolute predictability of success, is not
the standard by which obviousness is measured; there only need be a
reasonable expectation of success. In re O’Farrell, 853 F.2d 894, 903–04
(Fed. Cir. 1988) (“Obviousness does not require absolute predictability of
success. Indeed, for many inventions that seem quite obvious, there is no
absolute predictability of success until the invention is reduced to
practice.”). “That the inventors were ultimately successful is irrelevant to
whether one of ordinary skill in the art, at the time the invention was made,
would have reasonably expected success.” Life Techs. Inc. v. Clontech
Labs. Inc., 224 F.3d 1320, 1326 (Fed. Cir. 2000). We determine Yovell
provides a reasonable expectation of success at least with respect to treating
patients who have depression and acute suicidality.
However, as we noted above, claim 54 is directed at a patient
population that does not have depression. We agree with Appellant that the
Examiner has not established a suggestion to treat a patient with acute
suicidality that “is not afflicted by a depressive disorder” as required by
claim 54 with a reasonable expectation of achieving treatment of the acute
suicidality. The Examiner has not provided evidence that it was known
generally that drug treatments that are used to treat depression are known to
be effective as treatments of acute suicidality in non-depressed patients, nor
has the Examiner provided evidence that the same chemical imbalance or
biological trigger leads to both depression and acute suicidality such that it
would have been expected that a drug that treats the imbalance or addresses
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the trigger would be expected to treat both conditions independently, i.e.,
without the other condition being present. Moreover, Yovell itself would
have suggested the contrary as to drugs with anti-depressant activity. In
particular, the “purpose” section of Yovell states that anti-depressant
medication administered to many suicidal patients, “despite the[] established
antidepressant effect” has “not shown a clear anti-suicidal benefit.” (Yovell
1 (“Purpose”).)
The Yovell June 2017 Declaration explains that the phase III study
was not based on prior clinical or preclinical data establishing the efficacy of
buprenorphine for treating acute suicidality.2
Thus, for this reason only, we conclude that the Examiner has not
established obviousness of the claimed method of treatment set forth in
claim 54 based on Yovell alone.
Accordingly, we do not affirm the Examiner’s rejection of claims 54–
62, 64, and 65.

B. Claim 63
Regarding the rejection of claim 63, the Examiner’s reliance on Sittl,
directed to the use of buprenorphine as an analgesic, does not cure the

2 We note that the patient population to be treated in Yovell is identified as
“Depressed Inpatients.” (Yovell 1 (“Purpose: Official Title”).) That Yovell
states that the compound “may” treat “acute suicidality, especially in the
context of depression” (Ans. 8) does not establish that the patient population
will necessarily include a patient that does not have depression. Rather, we
understand this to mean, given the identified patient population to be treated,
one would reasonably expect treatment of acute suicidality in those patients
who have depression.
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deficiency noted above regarding Yovell. That is because Sittl, which
describes that “[b]uprenorphine is a potent opioid analgesic” (Sittl 150
(Abstract)), that “has high analgesic potency relative to morphine” and that
is “partial agonist at μ-opioid receptors and an antagonist at the kappa-
receptor” (id. at 151), does not address the effects of buprenorphine on acute
suicidality, nor does it provide evidence of a link between drugs that treat
pain and those that treat acute suicidality, or evidence that the biological
activity that buprenorphine is directed to agonizing or antagonizing in the
treatment of pain is an activity that is also an activity that is a cause of or
involved in acute suicidality. Accordingly, we do not affirm the Examiner’s
rejection of claim 63 as being obvious over Yovell and Sittl.

C. Claims 75 and 76
Unlike claim 54, claim 75 does not exclude treatment of patients that
have both acute suicidality and a depressive disorder. For the reasons
discussed above, we conclude that the Examiner, even considering the
Yovell Declaration (Appeal Br. 15), has provided a prima facie case of
obviousness of claim 75 based on Yovell.
As to the specific dosage range recited in the claim, the Examiner
contends that a prima facie case exists from the teachings of Yovell as the
recited range of 0.05 mg to 0.12 mg per day is close to the range of 0.2 to
1.6 mg per day recited in Yovell. (Final Action 4–5 (citing Titanium Metals
Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985).) We agree with the
Examiner. A claimed range overlaps with a prior art range if the two ranges
share a common endpoint. In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir.
1997). We agree with the Examiner that the end point of 0.12 mg per day of
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the claim is close to the 0.2 mg per day starting point of the range of Yovell
and one of ordinary skill in the art would have expected the therapeutic
effects to be similar. Thus, we do not find Appellant’s argument that the
Examiner’s rejection is in error because it relies on Titanium Metals to be
persuasive (Appeal Br. 18–19).
Appellant argues that the data in the Specification shows unexpected
superiority between a dose of 0.1 mg/day compared to 0.2 mg/day because
the side effect-related dropout rate was reduced considerably but “treatment
outcome was not compromised, with no observable reduction in therapeutic
effect.” (Appeal Br. 16–17.) According to Appellant, “it would be
completely illogical” “to take the position that 0.1 mg/day is expected to
have a similar therapeutic effect as 0.2 mg/day because the values are so
close, while simultaneously taking the position [that] the reduction in side
effect related dropout rate associated with 0.1 mg/day is expected because it
is considerably lower than 0.2 mg/day.” (Id. at 17.)
We do not find that the data Appellant relies on establishes
unexpected results. First, regarding the final BSI score analysis that
Appellant asserts demonstrates “no observable reduction in therapeutic
effect” (Appeal Br. 16 (referring to Spec. 71)), we note that this analysis
only mentions the starting dose and not the final dose. That is, although the
Specification indicates that the difference between final BSI score versus
baseline BSI score for those receiving a starting dose of 0.1 mg/day
compared to those receiving a starting dose greater than 0.1 mg/day, it does
not indicate what the dose at the end of the study period was for either
group. (Spec. 70–71.) It would appear from the study discussion that it was
not 0.1 mg/day in either case. In particular, it is noted that:
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The starting dose [being 0.1 mg per day] was gradually titrated
upwards to a maximal dose of 0.8 mg/day or less by the end of
the study period (except for the 3 subjects mentioned above, of
whom 1 received buprenorphine and 2 received placebo, at a
final dose of 1.6 mg/day). . . . Of the 25 patients who received
buprenorphine, 12 received a maximal dose of 0.2 mg/day,
another 8 patients received a maximal dose of 0.4 mg/day, 2
received a maximal dose of 0.6 mg/day, 2 received a maximal
dose of 0.8 mg/day, and 1 received a maximal dose of 1.6
mg/day.
(Spec. 68.) Thus, the data Appellant relies on does not establish the same
efficacy for a patient administered a therapeutically effective amount of 0.1
mg/day as compared to a patient administered a therapeutically effective
amount of 0.2 mg/day.3
Furthermore, we agree with the Examiner that “it would [have] be[en]
obvious that lower concentrations of the same drug would have less adverse
side effects than a high[er] concentration of the same drug.” (Ans. 9.)
Appellant does not respond to the Examiner’s position.
For the foregoing reasons, we affirm the Examiner’s rejection of
claims 75 and 76 as being obvious over Yovell.

3 We note that Appellant also relies on a Declaration of Professor Yovell
dated May 23, 2016 (Yovell May Declaration), which it asserts “further
corroborate[s]” the Appellant’s argument. (Appeal Br. 17.) However, we
find that this May 2016 Declaration relies on the same data at page 71 of
Appellant’s Specification to assert “the therapeutic effect of the
buprenorphine” was not compromised (Yovell May Declaration ¶ 2) and is,
therefore, similarly unpersuasive.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
54–62, 64,
65, 75, 76
103(a) Yovell 75, 76 54–62, 64,
65,
63 103(a) Yovell, Sittl 63
Overall
Outcome
75, 76 54–65

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-IN-PART