Ex Parte Dunayevich et alDownload PDFPatent Trials and Appeals BoardMar 27, 201913991372 - (D) (P.T.A.B. Mar. 27, 2019) Copy Citation 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.) Appeal2017-007889 Application 13/991,372 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.).) 2 Appeal2017-007889 Application 13/991,372 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). 3 Appeal2017-007889 Application 13/991,372 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 4 Appeal2017-007889 Application 13/991,372 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. 5 Appeal2017-007889 Application 13/991,372 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 6 Appeal2017-007889 Application 13/991,372 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 ... 7 Appeal2017-007889 Application 13/991,372 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 8 Appeal2017-007889 Application 13/991,372 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.) 9 Appeal2017-007889 Application 13/991,372 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 10 Appeal2017-007889 Application 13/991,372 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 11 Appeal2017-007889 Application 13/991,372 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). 12 Appeal2017-007889 Application 13/991,372 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 13 Appeal2017-007889 Application 13/991,372 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 14 Appeal2017-007889 Application 13/991,372 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 15 Appeal2017-007889 Application 13/991,372 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. 16 Appeal2017-007889 Application 13/991,372 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).) 17 Appeal2017-007889 Application 13/991,372 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 18 Appeal2017-007889 Application 13/991,372 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. 19 Appeal2017-007889 Application 13/991,372 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- 20 Appeal2017-007889 Application 13/991,372 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. 21 Appeal2017-007889 Application 13/991,372 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. 22 Appeal2017-007889 Application 13/991,372 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- 23 Appeal2017-007889 Application 13/991,372 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 24 Appeal2017-007889 Application 13/991,372 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. 25 Appeal2017-007889 Application 13/991,372 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 Copy with citationCopy as parenthetical citation