Ex Parte Dunayevich et al

Patent Trials and Appeals Board

Mar 27, 2019

13991372 - (D) (P.T.A.B. Mar. 27, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/991,372 06/03/2013 Eduardo Dunayevich
48394 7590 03/29/2019
SERVILLA WHITNEY LLC
33 WOOD A VE SOUTH
SUITE 830
!SELIN, NJ 08830
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
NPP0015-00US 3528
EXAMINER
N ANOV A, SVETLANA M
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
03/29/2019 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):
docket@dsiplaw.com
lmurphy@dsiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte EDUARDO DUNA YEVICH, SUSAN MCELROY,
and RON LANDBLOOM 1
Appeal2017-007889
Application 13/991,3 72
Technology Center 1600
Before TA WEN CHANG, DEVON ZASTROW NEWMAN, and
DAVID COTTA, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating binge or compulsive eating, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
STATEMENT OF THE CASE
"Eating disorders include conditions which may be characterized by
abnormal eating habits" and include, for example, binge eating disorder.
(Spec. ,r 3.) "In general, a person having binge eating disorder is
1 Appellants identify the Real Party in Interest as Orexigen Therapeutics,
Inc. (Appeal Br. 3.)
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characterized by periodically being unable to exercise control over food
consumption," which "leads to eating of an unusually large amount of food
at one time." (Id. ,r 18.) "Binge eating disorder may also have similar
symptoms as compulsive overeating. Compulsive overeating ... is
characterized by an obsessive/compulsive relationship to food. A person
suffering from compulsive overeating disorder engages in frequent episodes
of uncontrolled or binge eating." (Id. ,r 22.) Unlike persons with binge
eating disorder, however, "compulsive overeaters obsess about food,"
including for example "spending excessive amounts of time and thought
devoted to food" or "secret[ly] planning or fantasizing about eating alone."
(Id.)
Claims 1-3, 5, 10-14, 16-18, 21, 23, 24, 28, 29, 31, and 32 are on
appeal. Claim 1 is illustrative and reproduced below:
1. A method for treating binge or compulsive eating,
compnsmg:
identifying a patient suffering from binge eating
disorder or compulsive eating disorder, wherein the
patient is not suffering from bulimia nervosa; and
administering to the patient a combination
consisting essentially of a therapeutically effective amount
ofbupropion or a pharmaceutically acceptable salt thereof,
and a therapeutically effective amount of naltrexone or a
pharmaceutically acceptable salt thereof.
(Appeal Br. 20 (Claims App.).)
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The Examiner rejects claims 1-3, 5, 10-14, 16-18, 21, 23, 24, 28, 29,
31, and 32 under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over
Adis, 2 NCT00624858, 3 Alger, 4 Kriiger, 5 Halford, 6 and Malhotra. 7 (Ans. 4.)
DISCUSSION
Issue
The Examiner finds that Adis discloses treating obesity with
Contrave®, a "fixed-dose combination of sustained release naltrexone and
bupropion ... in a single tablet" and further discloses that bupropion is an
antidepressant. (Ans. 5.)
The Examiner finds that "Adis does not explicitly disclose treatment
of binge or compulsive eating." (Id.) However, the Examiner finds that
Alger teaches that 25-30% of the obese population has been reported to
engage in binge eating and further teaches that naltrexone and imipramine,
an antidepressant, may be useful in treating binge eating. (Id. at 6.) The
2 Adis R&D Profile, Naltrexone/Bupropion: Contrave®; naltrexone
SR!Bupropion SR, 10 DRUGS IN R&D 25 (2010).
3 A Study of Naltrexone SR/Bupropion SR in Overweight or Obese Subjects
with Major Depression, https://clinicaltrials.gov/ct2/show/NCT00624858
(last visited Mar. 12, 2019).
4 Sharon A. Alger et al., Effect of a Tricyclic Antidepressant and Opiate
Antagonist on Binge-Eating Behavior in Normoweight Bulimic and Obese,
Binge-Eating Subjects, 53 AM. J. CLINICAL NUTRITION 865 (1991).
5 Stephanie Kruger and Sidney H. Kennedy, Psychopharmcotherapy of
Anorexia Nervosa, Bulimia Nervosa and Binge-Eating Disorder, 25 J.
PSYCHIATRY & NEUROSCIENCE 497 (2000).
6 Jason C. G. Halford et al., Pharmacological Management of Appetite
Expression in Obesity, 6 NATURE REV. ENDOCRINOLOGY 255 (2010).
7 Shishuka Malhotra and Susan L. McElroy, Medical Management of
Obesity Associated with Mental Disorders, 63 J. CLINICAL PSYCHIATRY 24
(2002).
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Examiner finds that Kruger teaches that bupropion in moderate doses
markedly decreased binge eating and purging in patients with bulimia
nervosa. (Id.) The Examiner also finds that Halford "review[ s] .. .
pharmacological management of appetite expression in obesity ... and
discloses assessment of behavioral traits with tools such as the Binge Eating
Scale." (Id.) The Examiner further finds that Malhotra teaches that both
buproprion and naltrexone are "recognized off-label drugs for treatment of
binge eating." (Id.)
The Examiner concludes that it would have been obvious to a skilled
artisan at the time of the invention to combine the teachings of the cited
prior art to arrive at the claimed invention, with a reasonable expectation of
success, because
Adis and Halford explicitly disclose Applicant's claimed
combination of naltrexone and bupropion for the treatment of
obesity, and Alger and [Kruger] further disclose that there is an
overlap between the binge eating population and the obese
population, and that each of the two drugs have been shown to
be useful in the treatment of binge eating. Moreover, in Alger a
combination of naltrexone with another antidepressant (i.e. [a]
drug of the same class [as] bupropion) was shown to be useful in
the treatment of binge eating. It would have been prima facie
obvious to one of ordinary skill in the art at the time the invention
was made to combine two compositions or treatments each of
which is taught by the prior art to be useful for the same purpose
in order to form a third composition to be used for the very same
purpose. . . . Even if naltrexone has been reported to show
inconsistent data in binge eating, the art nonetheless gives
guidance to try the combination ofbupropion and naltrexone ...
. [T]he combination of bupropion and naltrexone constitutes a
finite number of identified, predictable solutions, based on which
this particular combination stands as at least obvious to try for
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the treatment of binge eating as explicitly recognized as such by
the physician authors.
(Id. at 8-10.) With respect to the limitation "wherein the patient is not
suffering from bulimia nervosa," the Examiner finds that, "assuming,
arguendo, that there are issues of co-morbidity, i.e., assessment in some of
the above studies of binge eating in patients with bulimia nervosa, the art
still nonetheless discloses administering buproprion and/ or naltrexone for
binge eating alone." (Id. at 6; see also id. at 9.)
Appellants contend that,
although a combination of bupropion and naltrexone was
recognized for treating obesity, neither drug was a recognized
treatment for compulsive or binge eating disorder .... [O]ne of
skill in the art would understand that obesity, bulimia nervosa
and binge eating disorder are distinct disorders and that
treatments of one would not necessarily work as a treatment for
another, even when they share a common symptom - treatment
of psychiatric disorders is unpredictable. Thus, even if there
were a reason to combine two drugs from a list of potential
treatments of obesity to administer in combination, none of the
cited references provide a reasonable expectation of success that
this combination could treat binge or compulsive eating disorder.
(Appeal Br. 19. ( emphasis omitted))
Appellants do not separately argue the claims. We therefore limit our
analysis to claim 1 as representative. The issue with respect to this rejection
is whether the Examiner erred in concluding that a skilled artisan would
have had reason to administer a combination consisting essentially of
therapeutically effective amounts ofbupropion and naltrexone to non-
bulimic patients suffering from binge eating disorder or compulsive eating
disorder, with a reasonable expectation of success.
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Findings of Fact
1. Adis teaches a fixed-dose combination of naltrexone sustained
release (SR) and bupropion SR in a single tri-layer tablet, for the treatment
of obesity. (Adis 25, left column.)
2. Adis teaches that naltrexone is an opioid receptor antagonist,
bupropion is a dopamine and norepinephrine reuptake inhibitor prescribed as
an antidepressant, and, "[i]n combination, the agents are thought to stimulate
proopiomelanocortin (POMC) neutronal firing and modulate food cravings
through an effect on the reward pathways." (Id.; see also id. at 27, Table I.)
3. Adis teaches that a clinical trial assessing naltrexone
SR/bupropion SR (Contrave®) for treatment of obesity resulted in
"significant reduction in bodyweight, reductions in selected food craving
measures[,] and improvements in markers of cardiovascular risk." (Id. at 25,
right column; see also id. at 30, left column (stating that "patients receiving
naltrexone/bupropion had significant improvements in eating control ...
compared with placebo recipients").)
4. Adis teaches that, "[i]n obese mice, treatment with bupropion,
naltrexone or a combination of both agents resulted in food intake reductions
of 27%, 49% and 94%, respectively" and that "[a] separate study
demonstrated that administration of naltrexone plus bupropion to the ventral
tegmental area (VT A) was associated with a significant and synergistic
reduction of food intake." (Id. at 29, right column; see also id. at 27, Table
I.)
5. Alger teaches that "[a] subset of the obese population (25-30%)
has been reported to engage in binge eating at least twice weekly (bingers)
and to exhibit personality traits and food attitudes similar to those of
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nonnoweight bulimic women (bulimics)." (Alger Abstract; see also id. at
865, left column.)
6. Alger teaches that "injection of norepinephrine, opiates and
pancreatic polypeptides increases food intake, even in sated rats," that
"[ o Jpiates and norepinephrine both appear to be involved in the
compensatory hyperphagia that follows a period of food deprivation," and
that "[i]n laboratory rats, opiate blockers such as naloxone induce a marked
reduction in the time spent and rate of eating." (Id. at 865, left column and
bridging paragraph; see also id. at 868-869, bridging paragraph.)
7. Alger teaches that the above "animal observations may be
pertinent to the binge-starve cycle that commonly occurs in human subjects
who are normoweight bulimic (bulimics) or obese bingers." (Id. at 865,
right column.)
8. Alger teaches that "[i]mipramine, a tricylic antidepressant, is
believed to produce a satiety effect through the inhibition of central reuptake
of serotonin and norepinephrine." (Id. at 869, right column.)
9. Alger teaches that "[ t ]ricyclic antidepressants and opiate
antagonists effectively suppress binge eating in normoweight bulimics." (Id.
at Abstract; see also id. at 865, right column.)
10. Alger states that "[i]t seems possible that normoweight bulimics
and obese subjects who binge have comparable neurochemical aberrations,
and thus it is reasonable to speculate that this subset of obese individuals
might benefit from therapies known to control binging in bulimic subjects."
(Id. at 865, right column.)
11. Alger discloses a study of the effect of naltrexone and
imipramine on obese bingers as well as bulimics, wherein "[ n ]altrexone ...
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produced a significant reduction in binge duration in bulimics ... [ and]
imipramine significantly reduced binge duration in obese bingers," but "[a]
strong placebo effect was observed in obese bingers" such that, "although a
reduction in binge frequency occurred with both naltrexone and imipramine,
it was not significantly different from the effect in placebo control subjects."
(Id. at Abstract; see also id. at 867, left column, 867-868, bridging
paragraph, 868, left column, 869, bridging paragraph and right column.)
12. Alger also teaches that, in its study,
[ s ]everal naltrexone-treated subjects reported less severe
cravings for "forbidden foods" such as chocolate and ice cream,
foods that had typically triggered a binge episode before the
medication. The naltrexone subjects also reported improved
control in limiting the amount of any forbidden food consumed,
so that ingestion of a small amount no longer automatically
triggered the individual to consume huge quantities of that
particular food. These subjective changes in the control of food
binges were described by both normoweight bulimics and obese
bingers on their daily monitoring sheets, and the changes in food
cravings were documented by subjects during their twice-weekly
description of the type and quantity of foods ingested during a
binge.
(Id. at 869, left column.)
13. Alger concludes that "[ t ]he results of the present study lend
support to the hypothesis that obese bingers are a subgroup of obese
individuals who have behavioral and emotional similarities to normoweight
bulimic subjects." (Id. at 869, right column.)
14. Alger concludes that "naltrexone and imipramine may be useful
agents in the treatment of binge eating." (Id. at Abstract.)
15. Kruger teaches that " [ e ]vidence suggests that drug therapies
that have proven efficacious in the treatment of bulimia nervosa are also
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helpful in treating patients with binge-eating disorder." (Kruger 498, left
column.)
16. Kruger teaches that "bupropion in moderate doses markedly
decreased binge eating and purging and was generally well tolerated,"
although "the use of bupropion is not recommended for bulimia nervosa
unless it is combined with anticonvulsant medication" because treatment
with bupropion resulted in unexplained seizures in a number of patients. (Id.
at 503, bridging paragraph.)
1 7. Kruger explained that, while "Alger ... found no difference
between imipramine, naltrexone and placebo in reducing binge frequency"
in patients with binge eating disorder, "the placebo response rate in [the]
study was exceptionally high (70% median decrease in frequency of binges),
rendering the drug treatment results difficult to interpret." (Id. at 504, left
column.)
18. Kruger teaches that tricyclic antidepressants "may be somewhat
helpful in the short term in reducing binge-eating episodes." (Id. at 504,
right column.)
19. Kruger teaches that "[n]altrexone, an opiate antagonist, in
combination with fluoxetine or psychotherapy was shown to be somewhat
beneficial in reducing binge eating, suggesting that opiate blockade may be
considered in the clinical management of binge-eating disorder." (Id. at 505,
left column.)
20. Halford teaches that naltrexone reduces binge eating. (Halford
261, Table 4; see also id. at 263, right column (citing Alger).)
21. Halford teaches that bupropion is a dopamine and
noepinephrine reuptake inhibitor. (Id.)
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22. Malhotra teaches that "drugs reported effective in reducing
binge eating in open trials and/or case reports of bulimia nervosa or binge-
eating disorder include ... naltrexone." (Malhotra 27, left column.)
23. Malhotra teaches that, "[ f]or binge-eating disorder, ...
bupropion ( as long as there is no associated purging) might be considered."
(Id. at 28, left column; see also id., right column (suggesting that "bupropion
may be added when there are associated depressive or binge-eating
symptoms" in "an obese patient with a psychotic, mood, or eating
disorder"), Figure 1.)
24. Malhotra suggests a treatment algorithm for treating binge-
eating disorder comprising treatment with both bupropion and naltrexone.
(Id. at 29, Figure 2.)
25. Malhotra teaches that, in terms of effectiveness in treating binge
eating (in bulimia nervosa or binge eating disorder), reviewed literature
suggests that bupropion is "superior to placebo in at least 1 controlled study"
while there is "inconsistent data" for naltrexone. (Id. at 26, Table 1.)
26. Milano teaches that "there was a statistically significant
reduction in the number of binge-eating crises and purging episodes" in
bulimia patients treated with fluvoxamine as compared to placebo. (Milano
Abstract.)
27. Pearlstein teaches "[a] significant reduction in binge frequency,
Beck Depression Inventory scores and the eating concern, shape concern and
weight concern subscales of the Eating Disorder Examination were noted"
for binge eating disorder patients taking fluvoxamine as well as the placebo
group. (Pearlstein Abstract; see also id.at 149, left column.) Pearlstein
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teaches, however, that "[t]here were no significant differences between
fluvoxamine and placebo for any treatment outcome variable." (Id.)
28. Pearlstein teaches that the results of its study "contradict the
results of ... previously published [ double-blind placebo-controlled
(DBPC)] studies with [selective serotonin reuptake inhibitors (SSRis)],"
wherein "[ f]luvoxamine was superior to placebo in decreasing binge eating,
body weight and improving outcome as measured by the [Clinical Global
Impression (CGI)] scale" in patients with binge-eating disorder. (Id. at 150,
left column.)
29. Pearlstein teaches that "[i]t will be helpful in future studies to
include larger samples and a longer period of clinical treatment to decrease
the contribution of the high placebo response rates in [binge eating disorder
(BED)]." (Id. at 150, left column.)
Analysis
Unless otherwise noted, we adopt the Examiner's findings of fact and
reasoning regarding the scope and content of the prior art as they relate to
claim 1 (Final Act. 2-14; Ans. 4--23; FF1-FF29) and agree with the
Examiner that claim 1 is obvious over Adis, NCT00624858, Alger, Kruger,
Halford, and Malhotra. We address Appellants' arguments below. Only
those arguments timely made by Appellants in the briefs have been
considered; arguments not so presented are waived. See 37 C.F.R.
§ 4I.37(c)(l)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474
(BP AI 2010) (informative) ("Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived.").
Appellants first contend that, to the extent Adis teaches that the
combination of naltrexone and bupropion resulted in significant reduction in
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selected food craving measures, such "food cravings and binge or
compulsive eating are eating disorders characterized by different
symptoms." (Appeal Br. 6-7.) Appellants further contend that, even if food
cravings are part of binge eating disorder, a skilled artisan would understand
that, even if the same symptom ( e.g., food cravings) is present in two
different eating disorders (e.g., obesity and binge eating disorder), "this does
not mean that a treatment which reduces the symptom in the first eating
disorder will successfully reduce the symptom in the second eating
disorder." (Id. at 8.) Appellants thus contend that, even if food cravings
were a part of binge eating disorder and "even if Adis suggests that the
combination of naltrexone and bupropion may reduce cravings for certain
foods in obese patients, it would not be evidence that the combination would
modulate food cravings in patients suffering from binge or compulsive
eating disorders." (Id.)
While we agree with Appellants that Adis alone may not render the
claims obvious, 8 we are not persuaded by Appellants' arguments because the
8 Appellants dispute the Examiner's conclusion, based on Alger's teaching
that 25-30% of the obese population engages in binge eating, that "'[t]he
mere administration of the combination ofbupropion and naltrexone [in
Adis] to the 25-30% of the obese population who engage in binge eating,
and who are not bulimics, will necessarily result in treating binge or
compulsive eating."' (Appeal Br. 3-5.) To the extent the Examiner is
asserting that Adis inherently discloses treating a patient suffering from
binge or compulsive eating disorder with naltrexone and bupropion based on
Alger's teaching that 25-30% of the obese population engages in binge
eating, we disagree and do not adopt that portion of the Examiner's findings
of fact and reasoning. "Inherency may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient to establish inherency." Scaltech Inc. v.
Retec/Tetra L.L.C., 178 F.3d 1378, 1384 (Fed. Cir. 1999).
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Examiner's rejection is based on the combination of Adis and references
Alger, Kruger, Halford, and Malhotra. As discussed below, the cited
combination of prior art suggests that the combination of naltrexone and
bupropion would be useful in treating binge eating rather than simply reduce
food cravings per se.
We also agree with the Examiner that, while "a reduction in food
cravings is not per sea reduction in binge eating" (Spec. ,r 20), the prior art
suggests that the particular reduction of food cravings induced by naltrexone
and/or bupropion may also lead to reduced binge eating. For instance, Alger
teaches that both normoweight bulimics and obese bingers reported "less
severe cravings for ... foods that had typically triggered a binge episode
before the medication," as well as "improved control in limiting the amount
of any forbidden food consumed." (FF12.)
In the Reply Brief, Appellants contend that "[ t ]he fact that food
cravings might 'trigger' a binge eating episode ... is wholly consistent with
[Appellants'] assertions that 1) food cravings and binge or compulsive
eating are distinct eating disorders; and 2) the diagnostic criteria of binge
eating disorder do not require food cravings as a symptom." (Reply Br. 6.)
Appellants further contend that, "even if several subjects showed less severe
cravings, and this in tum reduced binge eating, the effect was not
significant" in Alger, because Alger reports that naltrexone did not
significantly reduce binge duration and frequency among obese bingers
when compared with obese placebo control subjects. (Id.)
However, the question is not whether food cravings and binge or
compulsive eating disorders are distinct disorders or whether the diagnostic
criteria of binge eating require food cravings as a symptom. Rather, the
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question is whether Adis' disclosure that naltrexone/bupropion reduced food
cravings in obese subjects and Alger's disclosure that several obese bingers
reported that naltrexone led to less severe cravings for foods that had
typically triggered a binge episode before medication and to improved
control in limiting amounts of such food consumed would have suggested to
a skilled artisan that naltrexone/bupropion may be useful in treating binge
eating disorder. We agree with the Examiner that these disclosures, together
with other cited prior art discussed below suggesting usefulness of
naltrexone and bupropion in treating binge eating, would have suggested to a
skilled artisan that naltrexone/bupropion may be useful in treating binge
eating disorder.
Appellants next contend that none of the other cited prior art suggests
that naltrexone or bupropion alone is useful for treating binge eating or
compulsive eating disorder. (Appeal Br. 9--13.) Appellants argue that,
because Alger discloses that administration of naltrexone to non-bulimic
obese bingers did not significantly reduce binge frequency or duration when
compared to placebo, a skilled artisan would conclude that Alger's statement
that "'naltrexone and imipramine may be useful agents in the treatment of
binge eating"' applies only to reducing binge duration in normoweight
bulimics. (Appeal Br. 10.)
We are not persuaded. Alger hypothesizes that obese bingers may
have "comparable neurochemical aberrations" to normoweight bulimics and
that they "might benefit from therapies known to control binging in bulimic
subjects." (FFlO.) Alger discloses that, in its study, naltrexone significantly
reduced binge duration in bulimics, imipramine significantly reduced binge
duration in obese bingers and, while the effect was not significant when
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compared to placebo control subjects due to a strong placebo effect, both
naltrexone and imipramine reduced binge frequency in obese bingers.
(FF 11.) Alger suggests that the results of its study "support ... the
hypothesis that obese bingers ... have behavioral and emotional similarities
to normoweight bulimic subjects," despite the fact that imipramine did not
significantly reduce binge frequency or duration in normoweight bulimics
and naltrexone did not significantly reduce binge frequency or duration in
obese bingers. (FF13.) Furthermore, although Alger was careful in
distinguishing between normoweight bulimics and obese bingers throughout
the paper where relevant, its suggestion that "naltrexone and imipramine
may be useful agents in the treatment of binge eating" was not limited to
either normoweight bulimics or obese bingers. (FF14.) Likewise, Halford
cites Alger as showing that naltrexone reduces binge eating, without limiting
the statement to a particular patient group. (FF20.) In light of the above,
and in the absence of persuasive evidence showing that skilled artisans in
fact read Alger as suggesting naltrexone may be useful only for
normoweight bulimics, we are not persuaded by Appellants' attorney
arguments that Alger should be so read. 9
9 Appellants contend in the Reply Brief that Alger does not suggest "the
combination of imipramine and naltrexone" and that, in any event, a skilled
artisan would not simply substitute one antidepressant (imipramine) for
another (bupropion), particularly because imipramine (a tricylic
antidepressant) and bupropion (a norepinephrine selective update inhibitor)
do no share a common mechanism. (Reply Br. 10.) To the extent the
Examiner suggests that claim 1 is obvious because Alger explicitly teaches
treating binge eating disorder with a combination of naltrexone and
imipramine and it would have been obvious to substitute imipramine with
bupropion, we do not adopt the findings of fact and reasoning with respect to
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Appellants next argue that Malhotra also does not support using
naltrexone for treating binge eating disorder. 10 (Appeal Br. 10-11; see also
Reply Br. 8-10.) Appellants contend that (1) in determining that there is
inconsistent data regarding whether naltrexone is effective in treating binge
eating, Malhotra reviewed literature relating to both bulimia and binge-
eating disorder and (2) Malhotra teaches that there is inconsistent data
regarding whether naltrexone is effective in treating binge eating. (Id.)
We are not persuaded. While Malhotra does teach that there is
inconsistent data as to whether naltrexone is effective in treating binge
eating, "[ o ]bviousness 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). Likewise, we are not persuaded by the argument that Malhotra does
not suggest naltrexone is effective in treating binge eating disorder because
Malhotra reviewed literature relating to both bulimia and binge-eating
disorder in coming to a conclusion regarding such effectiveness. As an
initial matter, the fact that Malhotra reviewed both sets of literature to
determine whether naltrexone is effective in treating binge eating suggests
that a skilled artisan considers literature relating to treatment of binge eating
that portion of the opinion and do not rely on this reasoning in our
obviousness analysis.
10 Appellants contend in the Reply Brief that the Examiner erroneously
asserts that Figure 2 of Malhotra "establishes the 'off-label use by physicians
of [Appellants'] claimed ingredients for treating binge eating."' (Reply Br.
6-7.) To the extent that the Examiner asserts that Figure 2 of Malhotra
establishes actual off-label use by physicians of naltrexone and bupropion
for treating binge eating disorder, we do not adopt the Examiner's findings
of fact and reasoning as to that portion of the rejection and do not rely on
such findings and reasoning in affirming the rejection.
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in bulimia to also be relevant to treatment of binge eating in patients with
binge eating disorder. More importantly, the fact that Malhotra reviewed
literature relating to treatment of binge eating in bulimic patients does not
take away from the fact that Malhotra also reviewed literature relating to
treatment of patients with binge eating disorder. 11
Finally, we note that, in addition to Alger and Malhotra, Kruger also
states that "[ n ]altrexone, an opiate antagonist, in combination with
11 In the Reply Brief, Appellants argue that "none of References 2-4, 6-10,
17-31 and 62-78 cited in Table 1 of Malhotra includes a single study related
to binge eating disorder." (Reply Br. 8.) Appellants also argue that, "with
respect to the conclusion that naltrexone alone has inconsistent data when
treating 'binge eating', one of skill in the art would understand that the
'inconsistent data' in Table 1 could potentially refer to 'binge eating' in
patients having bulimia nervosa or ... with binge eating disorder." (Id. at
8-9.) Appellants did not make these arguments in the Appeal Brief, thus
denying the Board the benefit of the Examiner's response, and no showing
of good cause was made by Appellants as to why the late arguments should
be considered by the Board. These arguments are thus waived. See 37
C.F.R. § 4I.41(b )(2); Cf Optivus Tech., Inc. v. Ion Beam Applications
S.A., 469 F.3d 978, 989 (Fed. Cir. 2006) (argument raised for the first time
in the Reply Brief that could have been raised in the opening brief
is waived). In any event, we are not persuaded by Appellants' argument.
Malhotra explicitly suggests using naltrexone to treat binge eating disorder.
(FF24.) To the extent Appellants' argument is that Malhotra does not
suggest using naltrexone alone in treating binge eating disorder (see, e.g.,
Reply Br. 9), we are not persuaded. As discussed further below, claim 1
does not require a composition containing only naltrexone and bupropion.
Appellants also contend that none of the other references cited in Malhotra
in the passage describing "the effects of psychotropics on binge eating"
teaches using "naltrexone alone for binge eating disorder" and that
Reference 104, Marrazzi, relates to "the use of naltrexone to attenuate
bulimia nervosa in controlled clinical trials." (Reply Br. 9.) Marrazzi,
however, is entitled, "Binge eating disorder: response to naltrexone."
(Malhotra 32 n. 104 (emphasis added).)
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fluoxetine or psychotherapy was shown to be somewhat beneficial in
reducing binge eating, suggesting that opiate blockade may be considered in
the clinical management of binge-eating disorder." (FF19.) Thus, we agree
with the Examiner that the combination of cited prior art suggests using
naltrexone to treat patients with binge eating disorder.
Neither are we persuaded by Appellants' arguments that the prior art
does not suggest using bupropion to treat binge or compulsive eating
disorder. Appellants first contend that "[t]he portion of [Kruger] cited by the
Examiner states: 'Home et al conducted the only multicentre placebo-
controlled trial of bupropion treatment of non-depressed patients with
bulimia nervosa." (Appeal Br. 12-13.) Appellants further argue that
Kruger had specific teachings regarding anorexia nervosa, bulimia nervosa,
and binge-eating disorder, suggesting that the teachings with respect to one
condition would not be applicable to the other conditions. (Id. at 13.)
We are not persuaded that a skilled artisan would have considered
data regarding treatment of binge eating in bulimic patients to be irrelevant
to whether the treatment would be useful in treating patients with binge
eating disorder. Indeed, Kruger teaches that "[ e ]vidence suggests that drug
therapies that have proven efficacious in the treatment of bulimia nervosa
are also helpful in treating patients with binge-eating disorder." (FF15.) In
addition, we note that Kruger must be read in combination with the other
cited prior art such as Malhotra, which also suggests that bupropion would
be useful in treating patients with binge eating disorder. (FF23-FF25.)
Appellants contend that Malhotra also "does not provide any
substantial evidence that bupropion alone is effective to treat binge eating
disorder." (Appeal Br. 13.) In particular, Appellants contend that
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Malhotra's rating ofbupropion as to its effectiveness in treating binge eating
is based on studies of both bulimia and binge eating disorder, and the two
references cited in support of the rating, References 95 and 96 of Malhotra
and Exhibit F and Exhibit G to the Appeal Brief, "disclose that the only
controlled clinical trials using bupropion are in bulimia nervosa, not
binge eating disorder." 12 (Id.) Appellants further contend that, "[w]hile
the authors of one [ of the] reference[ s] disclose anecdotal success using
bupropion for treating binge eating disorders," the authors offers no more
than "a tentative endorsement" of such an approach and emphasized the lack
of research data and their limited clinical experience. (Id.)
We are not persuaded for reasons similar to those already discussed
above. That is, based on the reviewed literature-whether such literature
related to treatment of binge eating in bulimia or binge eating disorder-
Malhotra suggested that bupropion may be considered for treating binge
eating disorder. (FF23, FF24.) We decline to substitute attorney arguments
regarding what the reviewed literature would have suggested to skilled
artisans for what such literature in fact suggested to Malhotra.
Appellants contend that even if two groups of patients with different
diseases (e.g., bulimia and binge eating disorder) "have 'behavioral and
emotional similarities[,]' there is no indication that the two diseases would
12 As discussed above, Appellants have waived the argument in the Reply
Brief that "none of References 2-4, 6-10, 17-31 and 62-78 cited in Table 1 of
Malhotra includes a single study related to binge eating disorder." (Reply
Br. 8; see also supra n.12.) In any event, we are not persuaded. As
discussed below, Malhotra explicitly suggested using bupropion to treat
binge eating disorder.
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have the same mechanism of action and therefore be responsive to the same
treatment." (Appeal Br. 11.)
We are not persuaded. Even if Appellants' statement is true as a
general matter, in this case the prior art explicitly suggests that treatment
effective for binge eating in bulimic patients may also be effective in
treating binge eating in patients with binge eating disorder. As discussed
above, Alger hypothesized that normoweight bulimics and obese bingers
may have comparable neurochemical aberrations and that obese bingers may
benefit from therapies known to control binging in bulimic subjects. (FFlO.)
Although Alger's study did not show the same treatment to have significant
effect for both bulimics and obese bingers, Alger nevertheless concluded
that the results of its study support the hypothesis that obese bingers have
behavioral and emotional similarities to bulimic subjects. (FFl 1, FF13.)
Likewise, Kruger teaches that "[ e ]vidence suggests that drug therapies that
have proven efficacious in the treatment of bulimia nervosa are also helpful
in treating patients with binge-eating disorder." (FF 15.)
Appellants cite Milano, Pearlstein, and Alger for the proposition that
"it is well-recognized by those of skill in the art that drugs that may be
effective for one eating disorder are not necessar[ily] effective for another."
(Appeal Br. 11-12.)
We are not persuaded. Milano teaches that fluvoxamine significantly
reduced binge-eating in bulimic patients while Pearlstein teaches that there
were no significant differences between fluvoxamine and placebo for any
treatment outcome variable for patients with binge eating disorder. (FF26,
FF27 .) In contrast to Appellants, however, Pearlstein did not conclude that
its study showed that fluvoxamine would not be effective to treat binge-
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eating disorder. Rather, it emphasized that there was a significant placebo
effect and that "[i]t will be helpful in future studies to include larger samples
and a longer period of clinical treatment to decrease the contribution of the
high placebo response rates in [binge eating disorder (BED)]." (FF29.)
Pearlstein further stated that the results of its study "contradict the results of
... previously published [double-blind placebo-controlled (DBPC)] studies
with [selective serotonin reuptake inhibitors (SSRis)]," wherein
"[f]luvoxamine was superior to placebo in decreasing binge eating, body
weight and improving outcome as measured by the [Clinical Global
Impression (CGI)] scale" in patients with binge-eating disorder." (FF28.)
Likewise, while Alger teaches that imipramine significantly reduced
binge duration in obese bingers but not in normoweight bulimics (Appeal
Br. 12 ), Alger teaches that "[p ]revious studies showed a reduction of binge
behavior in normoweight bulimics treated with imipramine and
desipramine" (Alger 869, right column). Thus, Alger, Milano, and
Pearlstein are not evidence that a drug effective in treating bulimia would
not be effective in treating binge eating disorder; rather, they merely show
that the design and conduct of clinical trials may influence whether a drug is
found to have a significant effect on reducing binge eating in patients with
bulimia and/or binge eating disorder. 13
13 In the Reply Brief, Appellants also cite to Malhotra Fig. 2 to support their
contention that "comorbidity does not mean there is no distinction between
the diseases, or that treatment for one will work for the other." (Reply Br.
10.) This argument is waived because it was not timely raised in the Appeal
Brief. Furthermore, Malhotra Figure 2 in fact suggests very similar
treatments for binge eating disorder and bulimia nervosa. For instance,
Figure 2 suggests that both bulimia nervosa and binge-eating disorder may
be treated by venlafaxine, SSRis, topiramate, zonisamide, and naltrexone.
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Finally, Appellants contend that there is no reason to combine the
cited references to arrive at the claimed invention, nor a reasonable
expectation of success for doing so. (Appeal Br. 14--17; Reply Br. 9-10.)
Appellants further contend that the combination of references does not
support an "obvious to try" rationale. (Appeal Br. 17-19; Reply Br. 9-10.)
We are not persuaded. Appellants contend that, because the claim
uses the transitional phrase "consisting essentially of," obviousness requires
that "there ... be a motivation to treat binge eating disorder, exclusive of
bulimia nervosa, using a combination consisting ofbupropion and
naltrexone, exclusive of other active pharmaceutical ingredients." (Appeal
Br. 14.) Appellants contend that there is no motivation to combine the
references to arrive at such an invention because (1) "there is no evidence
that each of [naltrexone and bupropion] have been shown to be useful in the
treatment of binge eating" and "the Examiner is conflating binge eating, as a
symptom, with binge eating disorder," (2) "there is no evidence of record
that treatments for obesity are also effective for treatment of binge eating,
even if there is significant overlap in the population," 14 (3) Malhotra does
not provide a reason "to treat binge eating disorder with a composition
consisting essentially of bupropion and naltrexone," and (4) "Malhotra
(Malhotra 29, Figure 2.) The only drug suggested for treatment of one
disorder that is not suggested for the other is, in fact, bupropion, where
Malhotra Figure 2 suggested that bupropion should be considered for use in
treating binge-eating disorder but did not suggest bupropion for treating
bulimia nervosa. (Id.)
14 As discussed above, to the extent the Examiner asserts that Adis suggests
treating binge-eating disorder with naltrexone/bupropion because it teaches
treating obesity with the combination and a significant percentage of obese
patients engage in binge eating, we do not rely on such a rationale for
affirming the rejection. See supra n.8.
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indicates that treatment of binge eating disorder is unpredictable, and thus,
teaches that there would be no motivation to arrive at the claimed
invention." (Id. at 14--16; see also Reply Br. 6-7.)
We are not persuaded. As discussed above, we find that the cited
prior art suggests that naltrexone and bupropion would be useful in treating
patients with binge eating disorder and that therapies effective in treating
binge eating in bulimics may also be effective in treating patients with binge
eating disorder. (See, e.g., FFlO, FF13-FF15, FF19, FF20, FF22-FF25.)
As for Appellants' argument that the prior art does not provide a
reason to treat binge eating disorder with a composition consisting
essentially of bupropion and naltrexone, we are likewise not persuaded.
Contrary to Appellants' contention that use of the transitional phrase
"consisting essentially of' requires that "there ... be a motivation to treat
binge eating disorder ... using a combination consisting of bupropion and
naltrexone, exclusive of other active pharmaceutical ingredients" (Appeal
Br. 14), it is well settled that "consisting essentially of' signals a partially
open claim wherein the invention necessarily includes the listed ingredients
and is open to unlisted ingredients that do not materially affect the basic and
novel properties of the invention. PPG Industries v. Guardian Industries
Corp., 156 F.3d 1351, 1354 (Fed. Cir. 1998). In this case, Appellants have
neither identified the "basic and novel properties" of its invention, nor how
such properties would be materially affected by the other ingredients
suggested for use in the prior art with naltrexone and/ or bupropion.
Appellants argue that Malhotra teaches that there is no motivation to
arrive at the claimed invention because it "indicates that treatment of binge
eating disorder is unpredictable." (Appeal Br. 14--16; see also Reply Br. 6-
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7 .) Appellants similarly argue that there is no reasonable expectation of
success as to the claimed invention because "neither bupropion nor
naltrexone alone were known to successfully treat binge or compulsive
eating disorder." (Appeal Br. 17; see also Reply Br. 3.)
We are not persuaded. Malhotra explicitly suggest treating binge
eating disorder using both bupropion and naltrexone. (FF22-FF24.) As
discussed above, although Malhotra suggests using these two compounds in
combination with other drugs, claim 1 does not preclude inclusion of other
ingredients in the claimed composition so long as they do not materially
affect the basic and novel properties of the invention. PPG Industries, 156
F.3d at 1354. Similarly, while some amount of unpredictability may be
involved in treating binge eating disorder patients with naltrexone and
bupropion, "[ o ]bviousness 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 at 903---04.
Finally, Appellants contend that it would not have been "obvious to
try" a combination of naltrexone and bupropion to treat binge or compulsive
eating disorder in a manner that would support a finding of obviousness. In
particular, Appellants contend that none of the references suggests "a
combination consisting essentially ofbupropion and naltrexone" and that
any solutions identified in the prior art relating to treatment of binge eating
disorder using bupropion and naltrexone are not predicable. (Appeal Br. 18;
Reply Br. 9-10.)
We are not persuaded. As discussed above, claim 1 does not preclude
inclusion of additional ingredients in the claimed composition, so long as
they do not materially affect the "basic and novel" properties of the
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composition. Likewise, obviousness does not require absolute predictability
of success. In this regard, we find O 'Farrell to be instructive. 0 'Farrell
explains that there are primarily two types of "obvious to try" inventions that
are, nevertheless, nonobvious: (1) cases in which what would have been
"obvious to try" is to "vary all parameters or try each of numerous possible
choices until one possibly arrived at a successful result, where the prior art
gave either no indication of which parameters were critical or no direction as
to which of many possible choices is likely to be successful"; and (2) cases
in which what would have been "obvious to try" is to "explore a new
technology or general approach that seemed to be a promising field of
experimentation, where the prior art gave only general guidance as to the
particular form of the claimed invention or how to achieve it." 0 'Farrell,
853 F.2d at 903. This case falls within neither of these categories. The prior
art explicitly suggests using naltrexone and/or bupropion to treat binge
eating disorder, thus providing direction as to the possible choices of
treatments that are likely to be successful as well as providing particularized
guidance as to the form of the claimed invention.
Accordingly, we affirm the Examiner's rejection of claim 1. Claims
2, 3, 5, 10-14, 16-18, 21, 23, 24, 28, 29, 31, and 32, which are not
separately argued, fall with claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
For the reasons above, we affirm the Examiner's decision rejecting
claims 1-3, 5, 10-14, 16-18, 21, 23, 24, 28, 29, 31, and 32.
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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).
AFFIRMED
26