Ex Parte Sakai et al

Patent Trial and Appeal Board

Apr 7, 2017

11523803 (P.T.A.B. Apr. 7, 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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/523,803 09/20/2006 Kazuo Sakai 50680-002001 5350
21559 7590
CLARK & ELBING LLP
101 FEDERAL STREET
BOSTON, MA 02110
EXAMINER
PRYOR, ALTON NATHANIEL
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
04/11/2017 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):
patentadministrator@clarkelbing.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KAZUO SAKAI, JOHN IENI,
and RAYMOND PRATT
Appeal 2014-008172
Application 11/523,803
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
for treating major depression. The Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
‘“Depression (or depressive state)’ is classified as a mood disorder
and is the most common mental disease” (Spec. 1:16—17). “‘Depression’ . . .
is classified as ‘296. xx: major depressive disorders’ and ‘minor depressive
disorders” (Spec. 8: 4—5). “The major depressive disorders are further
1 Appellants identify the Real Party in Interest as Eisai R&D Management
Co., Ltd. (see App. Br. 2).
Appeal 2014-008172
Application 11/523,803
classified as ‘single episode’ which is a major depressive episode for the
first time (single) and ‘recurrent episode’ which is experiences of two or
more major depressive episodes in the past” (Spec. 8:4—10).
“[I]t has been unexpectedly discovered that when a cholinesterase
inhibitor is combined with a selective serotonin reuptake inhibitor,
milnacipran, or duloxetine, it is possible to treat depression, in particular
refractory depression” (Spec. 4:24 to 5:2).
The Claims
Claims 1, 3—7, 12, 13, 19, 20, 31, 33, and 34 are on appeal.
Independent claim 1 is representative and reads as follows:
1. A method for treating major depression in a patient in
need thereof comprising administering donepezil or a
pharmaceutically acceptable salt thereof, and (i) a selective
serotonin reuptake inhibitor, (ii) milnacipran, an enantiomer
thereof, a diastereomer thereof, a pharmaceutically acceptable
salt thereof, an enantiomer of a pharmaceutically acceptable salt
thereof, a diastereomer of a pharmaceutically acceptable salt
thereof, an active metabolite thereof, or a prodrug thereof; or
(iii) duloxetine, an enantiomer thereof, a pharmaceutically
acceptable salt thereof, an enantiomer of a pharmaceutically
acceptable salt thereof, an active metabolite thereof, or a
prodrug thereof.
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The Issue
The Examiner rejected claims 1, 3—7, 12, 13, 19, 20, 31, 33, and 34
under 35 U.S.C. § 103(a) as obvious Nagy,2 Yoshimura,3 Schrag,4 Burt,5
Kemmerich,6 and Perlis7 (Ans. 2—5).
The Examiner finds Nagy teaches “Sertraline HC1, a selective
serotonin re-uptake inhibitor, can be used in the treatment of depressive
symptoms in elderly patients including those with [Alzheimer’s disease
(“AD”)] and “tests to determine drug-drug interaction in the co­
administration of donepezil HC1 and sertraline” (Ans. 3). The Examiner
finds Yoshimura teaches “paroxetine and donepezil are co-administered to a
patient with depressive pseudodementia” and Schrag teaches “with respect
to a patient with Parkinson’s disease donepezil is effective in treating
cognitive function and behavioural disorder; and with respect to depressive
symptoms a selective serotonin re-uptake inhibitor is effective” (id.). The
2 Nagy et al., Concurrent administration of donepezil HCI and sertraline
HCI in healthy volunteers: assessment of pharmacokinetic changes and
safety following single and multiple oral doses, 58 Br. J. Clinical
Pharmacology 25-33 (2004).
3 Yoshimura et al., A case of paroxetine having significant effect on
depressive pseudodementia, 22 Pharma Medica 134—136 (2004) (We rely
upon the English translation, numbered sequentially from the first page).
4 Schrag, A., Psychiatric aspects of Parkinson’s disease, 251 J. Neurol.
795-804 (2004).
5 Burt, T., Donepezil and Related Cholinesterase Inhibitors as Mood and
Behavioral Controlling Agents, 2 Curr. Psychiatry Rep. 473—478 (2000).
6 Kemmerich et al., Donepezil in therapy-refractory depression, 10
European Neuropsychopharmacology S264 (2000).
7 Perlis et al., The Effects of an Orally Administered Cholinergic
Agonist on REM Sleep in Major Depression, 51 Biol. Psychiatry 457—62
(2002).
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Application 11/523,803
Examiner finds Burt teaches “donepezil has an effect of improving
depression in a patient with Alzheimer Disease”; Kemmerich teaches
“donepezil is effective in treating refractory depression in a patient who does
not suffer from Alzheimer Disease”; and Perlis teaches “donepezil HC1 is
effective for a patient with major depression” (Ans. 4).
The Examiner finds it obvious to “coadminister paroxetine and
donepezil to treat all types on depressing since the prior art teaches that
donepezil individually and paroxetine individually can be used to treat
depression” (Ans. 5).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the prior art renders the claims
obvious?
Findings of Fact
1. Nagy teaches:
There is a high incidence of co-morbid depression in
patients with AD, and accumulating evidence shows that this
can have profound effects on both the long-term functioning of
AD patients and the wellbeing of their caregivers. . . .
Sertraline HC1 - a selective serotonin re-uptake inhibitor (SSRI)
- is indicated for the treatment of depression and anxiety
disorders.
(Nagy 26, col. 1—2).
2. Nagy teaches: “Donepezil HC1 is a potent and specific
piperidine-based inhibitor of acetylcholinesterase (AChE), and has been
demonstrated in placebo-controlled trials to significantly improve cognition”
(Nagy 26, col. 1).
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3. Nagy teaches the “concurrent administration of donepezil HC1
and sertraline HC1 was well tolerated, with no serious AEs reported during
this study. This observation is consistent with clinical data from AD patients
who received both donepezil HC1 and sertraline HC1” (Nagy 32, col. 1).
4. Yoshimura teaches a patient “was diagnosed as having
Alzheimer’s disease” (Yoshimura 2) and “[according to the diagnosis,
administration of 3 mg/day of donepezil was started . . . From the day she
visited us, administration of paroxetine 20 mg (once after supper) was
initiated” (Yoshimura 3).
5. Yoshimura teaches “paroxetine could be the first choice drug
for depressive state in aged persons” (Yoshimura 5).
6. Schrag teaches “[o]pen label trials have reported that selective
serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline,
citalopram, paroxetine or fluvoxamine are effective in treating depression in
PD [Parkinson’s disease] with only rare deterioration of parkinsonism”
(Schrag 797, col. 1).
7. Burt teaches in “a retrospective study in 86 AD [Alzheimer’s
disease] patients Mega et al. observed significant improvements from
baseline in delusions, agitation, anxiety, disinhibition, and irritability in
responders to donepezil” (Burt 475, col. 1).
8. Kemmerich teaches “[d]onepezil was administered to two
female patients (PI, P2), 67 and 64 years old respectively, diagnosed with
severe therapy-resistant depression (ICD-10 F32.3 (PI), F33.3 (P2))”
(Kemmerich S264, col. 1).
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9. Kemmerich teaches: “In both patients, we observed an
antidepressant effect accompanied by cognitive improvement after
administration of donepezil” (Kemmerich S264, col. 1).
10. Perlis teaches: “We have evaluated donepezil 10 mg (Aricept,
Pfizer-Eisai) to determine whether a single 10-mg dose alters REM timing
and whether this effect occurs preferentially in patients with MDD [major
depressive disorder]” (Persis 458, col. 1).
11. Perlis teaches “both of the orally active drugs, donepezil and
RS 86, induce REM sleep more quickly in depressed patients than in healthy
control subjects” (Perlis 460, col. 2).
12. The Specification teaches: “In accordance with ICD-10,
‘depression’ is classified and diagnosed as follows. F 32: Depressive
episode. In the three types of typical depressive episodes (light (F 32.30),
medium (F 32.1) or severe (F 32.2 and F 32.3), patients are usually bothered
by depressive mood” (Spec. 11:8—11).
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Principles of Law
“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.” In re
Kerkhoven, 626 F.2d 846, 850 (CCPA 1980). “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).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 2—5; FF 1—11) and agree that claim 1
would have been obvious to a person of ordinary skill in the art. We address
Appellants’ arguments below.
Appellants contend
a skilled artisan, reading the Perlis reference, which is the only
cited reference that mentions major depression, would not be
motivated to use donepezil to treat major depression, and thus
to co-administer donepezil and a previously known
antidepressant for treatment of major depression. As to the
other cited references, the Applicant reiterates that they do not
even mention major depression.
(App. Br. 5; underlining omitted). Appellants contend “Kemmerich is cited
for teaching that donepezil is effective for treating refractory depression.
However, as discussed at length in the Applicant’s prior replies, Kemmerich
does not teach that donepezil, by itself, has antidepressant activity. Further,
Kemmerich does not mention major depression” (Id. at 6).
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We do not find these arguments persuasive.8 Kemmerich specifically
teaches treatment of “severe therapy-resistant depression” with donepezil
(FF 8) and uses the same ICD-10 codes, F32.3 and F33.3, as the
Specification (FF 12). Thus, we agree with the Examiner that “Kemmerich
treats refractory depression which is a form of major depression” and that
“Appellants have not shown that the depression types differ” (Ans. 11).
That is, the evidence of record supports the Examiner’s position that when
Kemmerich refers to “severe therapy-resistant depression”, that condition is
a type of “major depression” within the scope of claim 1. Appellants
provide no evidence persuasively rebutting the position of the Examiner.
Nagy evidences that SSRIs and sertraline in particular, are useful for
treatment of depression (FF 1). Nagy also evidences that donepezil and
sertraline may be safely coadministered (FF 3), supporting the Examiner’s
reasonable expectation of success. The use of the combination of donepezil
and sertraline to treat depression (FF 1, 3, 8) is nothing “more than the
predictable use of prior art elements according to their established
functions.” KSR, 550 U.S. at 417.
Appellants address the Perlis reference, which also evidences that
donepezil may be safely administered to patients with major depression (FF
10), and contend “Perlis teaches away from using donepezil to treat major
depression” (App. Br. 3).
8 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).
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Although we need not rely on Perlis for the obviousness of claim 1
because we find Kemmerich and Nagy sufficient, we also find Appellants’
“teaching away” argument unpersuasive. “The prior art’s mere disclosure of
more than one alternative does not constitute a teaching away from any of
these alternatives because such disclosure does not criticize, discredit, or
otherwise discourage the solution claimed”. In re Fulton, 391 F.3d 1195,
1201 (Fed. Cir. 2004).
Appellants do not identify, and we do not find, any teaching in Perlis
that discourages, discredits or otherwise criticizes the use of donepezil for
treatment of major depression. We recognize that the REM latency of
patients with MDD changes (see Perlis 459, table 2), but that result has a
significance value of 0.06, which does not meet the threshold of 0.05 for
statistical significance.
Moreover, Perlis provides no direct evidence regarding the effect of
donepezil on symptoms of patients with major depression while Kemmerich
specifically teaches “we observed an antidepressant effect accompanied by
cognitive improvement after administration of donepezil” (FF 9).
Where the prior art contains “apparently conflicting” teachings
(i.e., where some references teach the combination and others
teach away from it) each reference must be considered “for its
power to suggest solutions to an artisan of ordinary skill. . . .
considering the degree to which one reference might accurately
discredit another.”
Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006).
Kemmerich provides a direct teaching of benefit of donepezil for patients
with severe depression (FF 8—9) while Perlis provides indirect teachings
regarding nonsignificant effects of donepezil on the REM movements of
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Application 11/523,803
patients with depression (FF 10—11). As we balance these conflicting
teachings, we find Kemmerich more persuasive regarding the expected
effects of donepezil on patients with major depression than Appellants’
interpretation of Perlis.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
prior art renders the claims obvious.
SUMMARY
In summary, we affirm the rejection of claim 1, under 35 U.S.C.
§ 103(a) as obvious Nagy, Yoshimura, Schrag, Burt, Kemmerich, and Perlis.
Claims 3—7, 12, 13, 19, 20, 31, 33, and 34 fall with claim 1.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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