DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Arguments
Applicant’s response from February 18, 2026 is acknowledged.
Claim Objections
In view of Applicant’s claim amendments, this objection is hereby withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s arguments have been carefully considered but have not been found to be persuasive.
First, with respect to Applicant’s new claim amendments, and Applicant’s arguments on p. 7-8, the Examiner notes the following. With respect the new claim limitation “but not suffering from bulimia nervosa” it is noted that this claim limitation was already addressed as a part of previously dependent, now cancelled, claims 53 and 61.
The limitation “wherein the patient exhibits weight loss relative to a baseline weight”, this limitation too was address in the Claim interpretation section, and in the Examiner’s prior responses to Applicant’s arguments.
Applicant’s claim 52 recites:
PNG
media_image1.png
216
702
media_image1.png
Greyscale
Support for this claim amendments appears to come from the following paragraphs of the specification:
[0053] As used herein, “mitigate” or “mitigation” of binge eating includes preventing or decreasing the amount of weight gain associated with binge eating or with the administration of another drug therapy for binge eating. In some embodiments, mitigation is measured relative to the amount of weight gain typically experienced when only one or neither of naltrexone or bupropion is administered. In some embodiments, mitigation is measured relative to the reduction in numbers of binge eating events. In some embodiments, mitigation is measured relative to the reduction in severity of binge eating events.
[0054] As used herein, “promotion” of weight loss includes causing weight loss relative to a baseline weight for a least a portion of the period of treatment. This includes an individual that initially gains some weight, but during the course of treatment loses weight relative to a baseline prior to beginning treatment, as well as individuals that regain a portion or all of the weight that is lost by the end of the treatment period. In a preferred embodiment, at the end of the treatment period, the individual has lost weight relative to a baseline. In a preferred embodiment, mitigation of weight gain or promotion of weight loss in a patient administered naltrexone and bupropion is greater than when neither or only one of naltrexone or bupropion is administered, and more preferably an at least additive, or better than additive, or synergistic, effect of administering the two compounds is achieved.
(emphasis added)
As can be seen from them, promoting weight loss is noted to be a function of mitigating binge eating. Applicant’s specification provides to this end that mitigating binge eating is measured relative to the amount of weight gain in a patient with weight loss.
Applicant’s claim 60 recites:
PNG
media_image2.png
217
723
media_image2.png
Greyscale
Support in the specification for “emotional eating” comes from paragraphs “[0005]-[0007].
[0005] Binge eating disorder appears common (>20% prevalence) in obese women. Obese women with binge eating disorder exhibit higher anxiety, depression, perceived stress and emotional and external eating scores than obese women without binge eating disorder. High levels of emotional eating and perceived stress can be used to predict binge eating disorder (Pinaquy et al., Obesity Research 2003). Although distinct from binge eating disorder, bulimia nervosa is also commonly associated with depressive symptoms and increased prevalence of depression.
[0006] Higher frequency of emotional eating (but not necessarily binge eating disorder) has also been associated with higher baseline BMI. Further, subjects who experience a decrease in emotional eating from an initially high level have been observed to experience greater weight loss than subjects who continued to report high levels of emotional eating (Blair et al., Appetite 1990).
[0007] Depression has also been linked to both emotional eating and obesity. For example, atypical depression is often associated with carbohydrate craving and weight gain. Higher BMI has also been associated with negative emotional states in the Diabetes Prevention Program. For example, higher BMI were found to correlate with feeling deprived, angry, or upset while dieting (Delahanty et al., Diabetes Care 2002).
As can be seen from para [0053], it has a specific reference that mitigating binge eating includes decreasing the amount of weight gain. This is not a reference to preventing alone, as Applicant has argued. As noted above, the language is “preventing or decreasing the amount of weight gain.” Decreasing the amount of weight gain means that there is causing weight loss relative to a baseline weight, per para [0054].
As can be seen from paragraphs [0005-7], Applicant’s specification provides no support for promoting weight loss in a patient with emotional eating per se, except by way of background, in which the term is mentioned 5 times. Based on this support, to the extent that the prior art teaches treating obesity and binge eating with Applicant’s drug combination, this will further correlate to promoting weight loss in a patient suffering from emotional eating in the obese and binge eating population.
Applicant has further argued:
PNG
media_image3.png
153
712
media_image3.png
Greyscale
PNG
media_image4.png
180
718
media_image4.png
Greyscale
(Response at 6-7).
In response, first, the transitional phrase is “comprising”, which is open-ended and does not preclude the addition of other active ingredients. Second, the Examiner has also shown that the pharmacological effect of both the individual ingredients, as well as of their specific combination.
Applicant has argued regarding Adis that it does not teach binge eating disorder, and that the Examiner has conflated promoting weight loss in obese individuals, reduction in food cravings and eating control with promoting weight loss in patients with binge eating disorder. (p. 7-8).
In response, Applicant’s response mischaracterizes the office action. Nowhere does it conflate any of the above. The office action solely reports what the disclosure of Adis provides. Specifically, it states exactly the following:
Adis discloses that Orexigen® Therapeutics is developing a proprietary fixed-dose combination of sustained release naltrexone and bupropion, known as Contrave® in a single tablet for the treatment of obesity. (p. 25). It discloses that bupropion is an antidepressant, which one of skill would know to encompass for treating major depressive disorder. Adis also discloses testing in clinical trials of naltrexone 32 mg/ bupropion 360 mg dosed daily (which is further the equivalent of 16mg/ 180 mg of each drug respectively twice daily) for 56 weeks in an obese population, and that the trials showed statistically significant results in reduction of body weight, and reduction in selected food craving measures. “Patients receiving naltrexone/bupropion also experienced reductions in the frequency and strength of food cravings and an increased ability to control their eating compared with placebo.” (p. 30, col. 1). One of skill would know such reduction in food cravings and an increased ability to control their eating to be indicative of treating of compulsive eating). A study with 16 mg/360 mg of the two drugs respectively is also disclosed. (p. 26). Of note, Adis discloses four already granted patents by the USPTO on Contrave®. (Id.). Adis discloses that three phase III trials of 32 mg naltrexone/ 360 mg bupropion (NB-301, NB-303 and NB-304) have met their co-primary endpoints. (p. 29). It reports vis-à-vis NB-304 that the patients experienced reductions in the frequency and strength of food cravings and an increased ability to control their eating compared with placebo. (p. 30). It also reports with respect to phase III NB-302 trial, wherein the naltrexone 32 mg/ buproprion 360 mg was dosed daily for 56 weeks that it met its co-primary and key secondary endpoints with a significant reduction in body weight and reductions in food craving measures, and with significant improvements in eating control. (p. 30).
The copy of Adis, which Applicant has made of record in the parent application 13/991,372, inexplicably, for what is a publicly available document1, has a portion of the first page either redacted out, or made almost impossible to read unless accessed independently.
PNG
media_image5.png
219
313
media_image5.png
Greyscale
This portion provides: “In January 2009, Orexigen reported that the trial had met its coprimary and key secondary endpoints, with a significant reduction in bodyweight, reductions in selected food craving measures and improvements in markers of cardiovascular risk. (p. 25, col. 2). (emphasis added). As was noted in the claim interpretation section above, Applicant’s specification provides that mitigating binge eating is measured relative to the amount of weight loss in a patient suffering from weight loss.
It is noted that the instant rejection is one of obviousness, and not of anticipation. Here and elsewhere, Applicant has continually attacked the references individually. As an initial matter the Examiner reminders Applicant that it is impermissible to attack references singly when the Examiner relies upon the combined teachings of the references, nor may they attack a reference for not teaching a limitation of the claim when the Examiner has explicitly relied upon another reference as teaching that limitation. See In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000)). To that end, the office action further very explicitly provides that: “Adis discloses reduction in the patients’ selected food cravings and bodyweight, an increased ability to control their eating, but does not explicitly disclose treatment of binge, or a patient suffering from binge eating, in ipsis verbis. This is remedied by the teachings of at least Alger, Kruger and Malhotra.”
Also as an initial matter, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
But even beyond that, as is noted further in the office action below, the art specifically discloses Applicant’s claimed drugs for treating binge eating. Thus, if the same combination is given to the same patient population, it will result in the same effect of promoting weight loss relating to a baseline in the binge eating population.
Applicant has further attacked Alger, Kruger, Malhotra and Halford on the following grounds.
Regarding Alger, Applicant has argued in relevant part:
PNG
media_image6.png
339
719
media_image6.png
Greyscale
In response, first, Applicant attacked Adis above for not teaching the use of the two claimed drugs individually for treating binge eating. Therefore, Alger, Kruger and Malhotra are all relevant prior art references, as they all three teach both drugs, although not in combination, as useful for treating binge eating, and more that, in clinical trials. As the office action provides:
Alger similarly discloses that a subset of the obese population (25-30%) has been reported to engage in binge eating. It discloses a placebo-controlled study of the effect of naltrexone and imipramine (an antidepressant), and reports that both may be useful agents in the treatment of binge eating. (Abstract).
Kruger is a review of agents used in the treatment of anorexia nervosa, bulimia nervosa and binge-eating disorder. It discloses a multicenter placebo-controlled trial of bupropion in patients with bulimia nervosa, with reference to Horne, in which bupropion in moderate doses is reported to have markedly decreased binge eating and purging. (p. 503).
Malhotra discloses that both buproprion and naltrexone, to include in combination, are recognized off-label drugs for treatment of binge eating. Table 1 assesses either effectiveness in binge eating or effectiveness in obesity of a number of drugs. It reports with respect to effectiveness in binge eating (in bulimia nervosa or binge eating disorder) that buproprion ranks as ++ (=superior to placebo in at least one controlled study), and that naltrexone ranks as +/- (=inconsistent data). (p. 26).
Therefore, Applicant has attacked the references individually, where the rejection was made based on the combination of references.
Regarding Applicant’s arguments pertaining to no weight reduction in Alger, the Examiner notes that Adis does teach weight reduction of the claimed drug combination, and Alger does teach naltrexone for treating binge eating. It is noted that the combination of naltrexone and imipramine did not show weight reduction in Alger, but this still needs to be reconciled with the showing of weight reduction in Adis, where the latter in fact is the more specific reference as it teaches the claimed drug combination.
Applicant has also attacked Kruger noting that it teaches bupropion for decreasing binge eating in patients with bulimia nervosa. (p. 9). In response, Malhotra teaches bupropion to be effective for binge eating in either bulimia nervosa or binge eating disorder. More than that, Malhotra discloses that both buproprion and naltrexone, to include in combination, are recognized off-label drugs for treatment of binge eating.
PNG
media_image7.png
596
761
media_image7.png
Greyscale
While Applicant has also attacked Kruger for not specifically teaching Applicant’s claimed combination of drugs for teaching binge eating, but rather a combination of naltrexone and another active ingredient, e.g. topiramate (p. 10), the Examiner notes in response that together with the remainder of the disclosure, Malhotra remains a very powerful reference, to include for the very reasons pointed by Applicant- that naltrexone, in combination with an anti-depressant (bupropion, SSRI), showed efficacy for treating binge eating.
But the relevance of Malhotra does not even stop here. As noted in the office action, Table 1 assesses either effectiveness in binge eating or effectiveness in obesity of a number of drugs. It reports with respect to effectiveness in binge eating (in bulimia nervosa or binge eating disorder) that buproprion ranks as ++ (=superior to placebo in at least one controlled study), and that naltrexone ranks as +/- (=inconsistent data). (p. 26). Again, there has been no conflating of any terms. The Examiner reported exactly what the references teach. While trying to seek differences on individual grounds, Applicant’s response is broadly and seemingly intentionally blindly sweeping over numerous guiding posts of similarities.
Further, that there is more than one particular combination of drugs that may be effective, per Malhotra, does not take away from the fact one of them is Applicant’s specifically claimed combination. “[I]n a section 103 inquiry, ‘the fact that a specific [embodiment] is taught to be preferred is not controlling, since all disclosures of the prior art, including unpreferred embodiments, must be considered.’” Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976)).
Applicant has also attacked Halford for not teaching other features of its claims, in yet another attack of a reference individually, where the rejection is based on a combination of references. (p. 11). Again, Halford was used for its teaching of the BES as known in the art. Specifically, Adis does not explicitly disclose use of the BES score, and the particular BES scores of Applicant’s claims. Halford is review of pharmacological management of appetite expression in obesity, to include with Contrave®. It discloses assessment of behavioral traits with tools such as BES. Thus, Halford not only teaches the BES score assessment, but it also adds to a list of references, which disclose that pharmacological management of appetite expression in obesity includes that with Contrave®. Moreover, the Examiner maintains that achieving a particular BES score is a function of the administration step.
Lastly, that Applicant has different notions on a motivation rationale does not take away from a strongly built record on motivation to combine the references. This motivation need not be express and may flow from the prior art references themselves, the knowledge of one of ordinary skill in the art, or from the nature of the problem to be solved. Brown & Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 1125 (Fed. Cir. 2000). See also In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992) ("As long as some motivation or suggestion to combine the references is provided by the prior art taken as a whole, the law does not require that the references be combined for the reasons contemplated by the inventor.").
For the foregoing reasons the rejection is maintained.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 52, 54-60 and 62-67 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Adis R&D Profile, Naltrexone/Bupropion Contrave®; Naltrexone SR/Bupropion SR, Drugs RD 2010: 10(1): 25-32 ("Adis", of record), further in view of Alger, Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects, Am J Clin Nutr. 1991 Apr;53(4):865-71 (“Alger”, of record), Kruger, Psychotherapy of anorexia nervosa, bulimia nervosa and binge-eating disorder, J. Psychiatry Neurosci 2000; 25(5): 497-508 (“Kruger”, of record), Malhotra et al., Medical Management of Obesity Associated with Mental Disorder, J. Clin. Psychiatry 2002; 63 [suppl 4]: 24-32 ("Malhotra", of record), NCT00624858, updated July 10, 2009, available at https://clinicaltrials.gov/study/NCT00624858?cond=NCT00624858&rank=1&tab=history&a=5 (“NCT00624858”, of record) and Halford et al., Pharmacological management of appetite expression in obesity, Nature Reviews Endocrinology, (May 2010) Vol. 6, No. 5, pp. 255-269 (“Halford”, of record).
Claim interpretation
Applicant’s claim 52 recites:
PNG
media_image1.png
216
702
media_image1.png
Greyscale
Support for this claim amendments appears to come from the following paragraphs of the specification:
[0053] As used herein, “mitigate” or “mitigation” of binge eating includes preventing or decreasing the amount of weight gain associated with binge eating or with the administration of another drug therapy for binge eating. In some embodiments, mitigation is measured relative to the amount of weight gain typically experienced when only one or neither of naltrexone or bupropion is administered. In some embodiments, mitigation is measured relative to the reduction in numbers of binge eating events. In some embodiments, mitigation is measured relative to the reduction in severity of binge eating events.
[0054] As used herein, “promotion” of weight loss includes causing weight loss relative to a baseline weight for a least a portion of the period of treatment. This includes an individual that initially gains some weight, but during the course of treatment loses weight relative to a baseline prior to beginning treatment, as well as individuals that regain a portion or all of the weight that is lost by the end of the treatment period. In a preferred embodiment, at the end of the treatment period, the individual has lost weight relative to a baseline. In a preferred embodiment, mitigation of weight gain or promotion of weight loss in a patient administered naltrexone and bupropion is greater than when neither or only one of naltrexone or bupropion is administered, and more preferably an at least additive, or better than additive, or synergistic, effect of administering the two compounds is achieved.
(emphasis added)
As can be seen from them, promoting weight loss is noted to be a function of mitigating binge eating. Applicant’s specification provides to this end that mitigating binge eating is measured relative to the amount of weight gain in a patient with weight loss.
Applicant’s claim 60 recites:
PNG
media_image2.png
217
723
media_image2.png
Greyscale
Support in the specification for “emotional eating” comes from paragraphs “[0005]-[0007].
[0005] Binge eating disorder appears common (>20% prevalence) in obese women. Obese women with binge eating disorder exhibit higher anxiety, depression, perceived stress and emotional and external eating scores than obese women without binge eating disorder. High levels of emotional eating and perceived stress can be used to predict binge eating disorder (Pinaquy et al., Obesity Research 2003). Although distinct from binge eating disorder, bulimia nervosa is also commonly associated with depressive symptoms and increased prevalence of depression.
[0006] Higher frequency of emotional eating (but not necessarily binge eating disorder) has also been associated with higher baseline BMI. Further, subjects who experience a decrease in emotional eating from an initially high level have been observed to experience greater weight loss than subjects who continued to report high levels of emotional eating (Blair et al., Appetite 1990).
[0007] Depression has also been linked to both emotional eating and obesity. For example, atypical depression is often associated with carbohydrate craving and weight gain. Higher BMI has also been associated with negative emotional states in the Diabetes Prevention Program. For example, higher BMI were found to correlate with feeling deprived, angry, or upset while dieting (Delahanty et al., Diabetes Care 2002).
As can be seen from para [0053], it has a specific reference that mitigating binge eating includes decreasing the amount of weight gain. This is not a reference to preventing alone, as Applicant has argued. As noted above, the language is “preventing or decreasing the amount of weight gain.” Decreasing the amount of weight gain means that there is causing weight loss relative to a baseline weight, per para [0054].
As can be seen from paragraphs [0005-7], Applicant’s specification provides no support for promoting weight loss in a patient with emotional eating per se, except by way of background, in which the term is mentioned 5 times. Based on this support, to the extent that the prior art teaches treating obesity and binge eating with Applicant’s drug combination, this will further correlate to promoting weight loss in a patient suffering from emotional eating in the obese and binge eating population.
With respect the new claim limitation “but not suffering from bulimia nervosa” it is noted that this claim limitation was already addressed as a part of previously dependent, now cancelled, claims 53 and 61.
Rejection
Adis discloses that Orexigen® Therapeutics2 is developing a proprietary fixed-dose combination of sustained release naltrexone and bupropion, known as Contrave® in a single tablet for the treatment of obesity. (p. 25). It discloses that bupropion is an antidepressant, which one of skill would know to encompass for treating major depressive disorder. Adis also discloses testing in clinical trials of naltrexone 32 mg/ bupropion 360 mg dosed daily (which is further the equivalent of 16mg/ 180 mg of each drug respectively twice daily) for 56 weeks in an obese population, and that the trials showed statistically significant results in reduction of body weight, and reduction in selected food craving measures. “Patients receiving naltrexone/bupropion also experienced reductions in the frequency and strength of food cravings and an increased ability to control their eating compared with placebo.” (p. 30, col. 1). One of skill would know such reduction in food cravings and an increased ability to control their eating to be indicative of treating of compulsive eating). A study with 16 mg/360 mg of the two drugs respectively is also disclosed. (p. 26). Of note, Adis discloses four already granted patents by the USPTO on Contrave®. (Id.). Adis discloses that three phase III trials of 32 mg naltrexone/ 360 mg bupropion (NB-301, NB-303 and NB-304) have met their co-primary endpoints. (p. 29). It reports vis-à-vis NB-304 that the patients experienced reductions in the frequency and strength of food cravings and an increased ability to control their eating compared with placebo. (p. 30). It also reports with respect to phase III NB-302 trial, wherein the naltrexone 32 mg/ buproprion 360 mg was dosed daily for 56 weeks that it met its co-primary and key secondary endpoints with a significant reduction in body weight and reductions in food craving measures, and with significant improvements in eating control. (p. 30).
The copy of Adis, which Applicant has made of record in the parent application 13/991,372, inexplicably, for what is a publicly available document3, has a portion of the first page, which is either redacted out, or made almost impossible to read unless accessed independently.
PNG
media_image5.png
219
313
media_image5.png
Greyscale
This portion provides: “In January 2009, Orexigen reported that the trial had met its coprimary and key secondary endpoints, with a significant reduction in bodyweight, reductions in selected food craving measures and improvements in markers of cardiovascular risk. (p. 25, col. 2). (emphasis added). As was noted in the claim interpretation section above, Applicant’s specification provides that mitigating binge eating is measured relative to the amount of weight loss in a patient suffering from weight loss. But even beyond that, as is noted further in the office action below, the art specifically discloses Applicant’s claimed drugs for treating binge eating. Thus, if the same combination is given to the same patient population, it will result in the same effect of promoting weight loss relating to a baseline in the binge eating population.
Adis discloses reduction in the patients’ selected food cravings and bodyweight, an increased ability to control their eating, but does not explicitly disclose treatment of binge, or a patient suffering from binge eating, in ipsis verbis. This is remedied by the teachings of at least Alger, Kruger and Malhotra.
Alger similarly discloses that a subset of the obese population (25-30%) has been reported to engage in binge eating. It discloses a placebo-controlled study of the effect of naltrexone and imipramine (an antidepressant), and reports that both may be useful agents in the treatment of binge eating. (Abstract).
Kruger is a review of agents used in the treatment of anorexia nervosa, bulimia nervosa and binge-eating disorder. It discloses a multicenter placebo-controlled trial of bupropion in patients with bulimia nervosa, with reference to Horne, in which bupropion in moderate doses is reported to have markedly decreased binge eating and purging. (p. 503).
Malhotra discloses that both buproprion and naltrexone, to include in combination, are recognized off-label drugs for treatment of binge eating. Table 1 assesses either effectiveness in binge eating or effectiveness in obesity of a number of drugs. It reports with respect to effectiveness in binge eating (in bulimia nervosa or binge eating disorder) that buproprion ranks as ++ (=superior to placebo in at least one controlled study), and that naltrexone ranks as +/- (=inconsistent data). (p. 26).
PNG
media_image8.png
785
403
media_image8.png
Greyscale
Of further significance, Figure 2 discloses a chart with a proposed treatment algorithm for comorbid eating disorder or binge eating. A separate column provides proposed treatment for bulimia nervosa, and another separate column provides proposed treatment for binge-eating disorder. In the column pertaining to treatment for binge-eating disorder bupropion is listed as an initial line of treatment, and naltrexone is listed as a subsequent line of treatment. Malhotra also provides that this is a disclosure of off-label use.
PNG
media_image7.png
596
761
media_image7.png
Greyscale
Again, as was noted in the claim interpretation section above, Applicant’s specification provides that mitigating binge eating is measured relative to the amount of weight loss in a patient suffering from weight loss.
Adis does not specifically disclose a titration scheme and BES score.
NCT00624858, titled “A Study of Naltrexone SR/ Bupropion SR in Overweight or Obese Subjects With Major Depression”, and conducted by Orexigen Therapeutics, Inc., discloses the patient population to be with a BMI of greater than or equal to 27 kg/m2 and less than or equal to 43kg/m2 and to have obesity with major depression. This disclosure further is per Applicant’s claim limitation related to a patient, who suffers from major depressive disorders. The age of the patients is from 18 years minimum age to 65 years maximum age. The primary outcome measures are: to assess the change in depressive symptoms as measured by Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks. The secondary outcome measures are: to assess the percentage change from baseline in total body weight at 12 and 24 weeks.
Although NCT00624858 does not disclose the very same titration scheme of Applicant’s claims as amended, it does disclose that as a part of the clinical trial a 4 week titration period up to the maintenance doses was conducted, at which point the maintenance dose was assessed for an additional 20 weeks. “Drug: naltrexone SR 32 mg/ bupropion SR 360 mg daily • All subjects are to complete a 4 week titration period at which time subjects will be titrated up to a maintenance level of study drug. Subjects will then take the maintenance dose of study drug for an additional 20 weeks.” NCT00624858 does not disclose that limitations were placed on the administration together with food.
Adis or NCT00624858 do not disclose the lower doses of Applicant’s claim 58. However, it does disclose that there was a titration over 4 weeks up to the maintenance doses, in view of which it would have been obvious to a person of skill in the art to optimize the titration regimen starting with lower than the maintenance doses of naltrexone 32 mg/ bupropion 360 mg. "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Adis does not explicitly disclose use of the BES score, and the particular BES scores of Applicant’s claims. Of note, a particular BES score and its reduction is a function of the administration step. In this respect, the office action addressed administering of Contrave®, to include in the obese population with food cravings, and Alger further specifically teaches that 25-30% of the obese population engage in binge eating. Thus, since the same drug is administered in the same patient population as in Adis, it will have the same effect of reducing binge eating. Further motivation to measure BES score so is in view of the additional references of record.
Halford is review of pharmacological management of appetite expression in obesity, to include with Contrave®. (p. 261). It discloses assessment of behavioral traits with tools such as the Binge Eating Scale (BES). (p. 258).
Applicant’s claims as amended during prosecution recite “wherein the patient is not administered another active ingredient for the treatment of binge or compulsive eating.” Applicant has argued in its responses that Table 2 of Malhotra discloses many different options and co-administration with other drugs. The Examiner has considered this argument, but on the totality of the record does not find it persuasive. “[T]he disclosure of “a multitude of effective combinations does not render any particular formulation any less obvious.” Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). “[P]icking and choosing may be entirely proper in the making of a 103, obviousness rejection.” In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Applicant provides no evidence of any secondary considerations to rebut the Examiner’s prima facie case of obviousness. On this particular record, first, there is disclosure of the just the combination of bupropion and naltrexone, as evidenced by Adis. The individual utility of the two agents in treating binge eating has also been assessed. Table 2 of Malhotra discloses off label use of the two drugs for treatment of binge eating disorder. Off label would designate that the formal study has not been done, and therefore is only a suggestion of possible combinations, plus it is in a comorbid situation, not just binge eating. Therefore, Table 2 of Malhotra does not preclude the assessment of bupropion and naltrexone in combination alone, and indeed, the disclosed possible options are very limited indeed.
Accordingly, it would have been obvious to a person of skill in the art at the time of the invention to combine the teachings of Adis, Alger, Kruger, Malhotra, NCT00624858 and Haltford with a reasonable expectation of success of practicing Applicant’s claimed invention. A person of skill in the art would have been motivated to do so because Adis and Halford explicitly discloses Applicant's claimed combination of naltrexone and bupropion for the treatment of obesity, to include by way of reduction selective food craving measures indicative of treatment of compulsive eating, 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. drug of the same class of 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. Further, Malhotra discloses that binge eating, to include in either a comorbid disorder or separately, can be treated with a combination of bupropion and naltrexone, and is in fact a known and prescribed off-label combination for this indication. As can be seen from Figure 2 of Malhotra above, the combination of bupropion and naltrexone constitutes a small and finite recognized medications for binge eating by practicing physicians. As was noted in the claim interpretation section above, Applicant’s specification provides that mitigating binge eating is measured relative to the amount of weight loss in a patient suffering from weight loss. As was further noted in the claim interpretation section above, and as can be seen from paragraphs [0005-7], Applicant’s specification provides no support for promoting weight loss in a patient with emotional eating per se, except by way of background, in which the term is mentioned 5 times. Based on this support, to the extent that the prior art teaches treating obesity and binge eating with Applicant’s drug combination, this will further correlate to promoting weight loss in a patient suffering from emotional eating in the obese and binge eating population.
The skilled artisan would have further been motivated to do so because NCT00624858 further discloses in an actual clinical trial, phase II, of Naltrexone SR/ Bupropion SR in overweight or obese subjects with major depression, and also conducted by Orexigen Therapeutics, Inc., and it discloses various other limitations of Applicant’s claims, as to specifics of the patient population. Although NCT00624858 does not disclose the very same titration scheme of Applicant’s claims as amended, it does not disclose that as a part of the clinical trial a 4 week titration period up to the maintenance doses was conducted, at which point the maintenance dose was assessed for an additional 20 weeks. “Drug: naltrexone SR 32 mg/ bupropion SR 360 mg daily • All subjects are to complete a 4 week titration period at which time subjects will be titrated up to a maintenance level of study drug. Subjects will then take the maintenance dose of study drug for an additional 20 weeks.”
Applicant’s claims 58 and 66 discloses specific titration dosing regimens. This reflects data in the specification on e.g. a 24-week study of SR naltrexone and SR buproprion for minimizing binge eating in subjects. (see, e.g., Example 1). As was noted above, the art, e.g. NCT00624858 discloses clinical trials with titration regimens of SR naltrexone and SR buproprion. Even though the art does not disclose the very specific timing, dose and frequency of administration of Applicant’s claims, it has been held as obvious to optimize dosing regimens of pharmaceutical drugs by routine experimentation when the general conditions of a claim are disclosed in the prior art. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) and MPEP §2144.05(11). The medical arts recognize that drug therapy may be optimized by designing regimens that account for the concentration of a drug, for example, to achieve a desired pharmacological response. Factors such as weight, age, gender, renal and hepatic status, inter alia, are always considered. Therefore, the determination of the optimum characterization of a particular dosing combination of buproprion and naltrexone would have been a matter well within the purview of one of ordinary skill in the art, at the time of the invention, through no more than routine experimentation.
Other Relevant Art and Judicial Proceedings
37 CFR 42.73(d)(3)(i) provides in relevant part.
42.73 Judgment.
(a) A judgment, except in the case of a termination, disposes of all issues that were, or by motion reasonably could have been, raised and decided.
(b) Request for adverse judgment. A party may request judgment against itself at any time during a proceeding. Actions construed to be a request for adverse judgment include:
(1) Disclaimer of the involved application or patent;
(2) Cancellation or disclaimer of a claim such that the party has no remaining claim in the trial;
(3) Concession of unpatentability or derivation of the contested subject matter; and
(4) Abandonment of the contest.
PNG
media_image9.png
18
19
media_image9.png
Greyscale
(c) Recommendation. The judgment may include a recommendation for further action by an examiner or by the Director.
(d) Estoppel.
(1) Petitioner other than in derivation proceeding. A petitioner, or the real party in interest or privy of the petitioner, is estopped in the Office from requesting or maintaining a proceeding with respect to a claim for which it has obtained a final written decision on patentability in an inter partes review, post-grant review, or a covered business method patent review, on any ground that the petitioner raised or reasonably could have raised during the trial, except that estoppel shall not apply to a petitioner, or to the real party in interest or privy of the petitioner who has settled under 35 U.S.C. 317 or 327.
(2) In a derivation, the losing party who could have properly moved for relief on an issue, but did not so move, may not take action in the Office after the judgment that is inconsistent with that party’s failure to move, except that a losing party shall not be estopped with respect to any contested subject matter for which that party was awarded a favorable judgment.
(3) Patent applicant or owner. A patent applicant or owner is precluded from taking action inconsistent with the adverse judgment, including obtaining in any patent:
(i) A claim that is not patentably distinct from a finally refused or canceled claim; or
(ii) An amendment of a specification or of a drawing that was denied during the trial proceeding, but this provision does not apply to an application or patent that has a different written description.
[Added, 77 FR 48612, Aug. 14, 2012, effective Sept. 16, 2012]
MPEP 2190 provides in relevant part:
II. RES JUDICATA
A patent owner or applicant may be precluded from seeking a claim that is not patentably distinct from a claim that was finally refused or canceled during an administrative trial or federal court proceeding under the doctrine of res judicata. Similarly, a patent owner may be precluded from seeking an amendment of a specification or drawing that was denied entry during a trial if the application or patent for which the amendment is sought has the same written description as the patent or application that was the subject of the administrative trial or federal court proceeding. See 37 CFR 42.73(d)(3).
PNG
media_image9.png
18
19
media_image9.png
Greyscale
A patent owner or applicant may be precluded from seeking a claim that is not patentably distinct from a claim that was previously rejected if the rejection was affirmed on appeal and the decision on appeal became final. A res judicata rejection should be applied only when the earlier decision was a decision of the Patent Trial and Appeal Board (or its predecessor Board) or any one of the reviewing courts and when there is no opportunity for further court review of the earlier decision. See In re Hitchings, 342 F.2d 80, 85, 144 USPQ 637, 641 (CCPA 1965) (holding that unappealed rejections from examiners cannot have a preclusive effect).
When making a rejection on res judicata, any prior art rejection under 35 U.S.C. 102 or 35 U.S.C. 103 should ordinarily be made on the basis of the same prior art, especially in continuing applications. In most situations, the same prior art which was relied upon in the earlier decision would again be applicable.
In the following cases, a rejection of a claim based on the ground of res judicata was sustained where it was based on a prior adjudication, against the inventor, on the same claim, a patentably nondistinct claim, or a claim involving the same issue.
Edgerton v. Kingsland, 168 F. 2d 121, 75 USPQ 307 (D.C. Cir. 1947).
In re Katz, 467 F.2d 939, 167 USPQ 487 (CCPA 1970) (prior decision by a district court).
In the following cases, res judicata rejections were reversed for various reasons.
In re Fried, 312 F.2d 930, 136 USPQ 429 (CCPA 1963) (res judicata not applicable based on the definition of a "final" Board decision found in an older version of the MPEP).
In re Hellbaum, 371 F.2d 1022, 152 USPQ 571 (CCPA 1967) (res judicata not applicable because the previously adjudicated and current claims were too different to satisfy the "identity of issues" element of res judicata).
In re Herr, 377 F.2d 610, 153 USPQ 548 (CCPA 1967) (res judicata not applicable despite similarities between previously adjudicated and current claims because applicant provided new evidence of patentability).
In re Kaghan, 387 F.2d 398, 156 USPQ 130 (CCPA 1967) (res judicata not applicable based on the definition of a "final" Board decision found in an older version of the MPEP).
In re Craig, 411 F.2d 1333, 162 USPQ 157 (CCPA 1969) (res judicata not applicable because the previously adjudicated and current claims were too different to satisfy the "identity of issues" element of res judicata).
In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) (res judicata not applicable because the previously adjudicated and current claims were too different to satisfy the "identity of issues" element of res judicata).
In re Russell, 439 F.2d 1228, 169 USPQ 426 (CCPA 1971) (res judicata not applicable despite similarities between previously adjudicated and current claims because applicant provided new evidence of patentability).
In re Ackermann, 444 F.2d 1172, 170 USPQ 340 (CCPA 1971) (res judicata not applicable because the previously adjudicated and current claims were too different to satisfy the "identity of issues" element of res judicata).
Plastic Contact Lens Co. v. Gottschalk, 484 F.2d 837, 179 USPQ 262 (D.C. Cir. 1973) (res judicata not applicable based on the definition of a "final" Board decision found in an older version of the MPEP).
Claim 1 was rejected under the doctrine of res judicata in the Non-final office action from 2/1/2023. While the rejection was withdrawn in view of Applicant’s claim amendments following Applicant’s claim amendments from 8/1/2023, the Examiner has moved it to this section for completeness of the record, and as the new claim amendments directed to particular titration dosing schemes render the claims obvious absent a showing of unexpected results.
PTAB already rendered a decision affirming the Examiner in the parent patent application 13/991,372, which has claims that a substantially similar, narrower and falling within the scope of instant claim 1. Since instant claim 1 is not patentably distinct, it is rejected under the doctrine of res judicata. Specifically, claim 1 of the ‘372 application recites:
PNG
media_image10.png
225
655
media_image10.png
Greyscale
Per MPEP 2190 and the applicable law of res judicata: “[a] patent owner or applicant may be precluded from seeking a claim that is not patentably distinct from a claim that was finally refused or canceled during an administrative trial or federal court proceeding under the doctrine of res judicata. Similarly, a patent owner may be precluded from seeking an amendment of a specification or drawing that was denied entry during a trial if the application or patent for which the amendment is sought has the same written description as the patent or application that was the subject of the administrative trial or federal court proceeding. See 37 CFR 42.73(d)(3).
A patent owner or applicant may be precluded from seeking a claim that is not patentably distinct from a claim that was previously rejected if the rejection was affirmed on appeal and the decision on appeal became final. A res judicata rejection should be applied only when the earlier decision was a decision of the Patent Trial and Appeal Board (or its predecessor Board) or any one of the reviewing courts and when there is no opportunity for further court review of the earlier decision. See In re Hitchings, 342 F.2d 80, 85, 144 USPQ 637, 641 (CCPA 1965) (holding that unappealed rejections from examiners cannot have a preclusive effect).”
The Examiner also further restates for the record the following cumulative prior art over which no rejections were made solely in view of its cumulative nature:
-US 20100166889
[0102] When treating binge eating the following active agents are particularly useful in combination with a methylphenidate prodrug or amphetamine prodrug: orlistat, bupropion, memantine, naltrexone, acamprosate, topiramate, zonisamide, sibutramine.
-US 20120115849
1. A method of treating an addiction that is an addiction to an addictive substance or that is the practice of an addictive or compulsive behavior associated with a primary impulse-control disorder or an obsessive-compulsive disorder, comprising: determining that a subject has or is at risk of developing an addiction; and administering to the subject an amount of an inhibitor of a phosphodiesterase 7 (PDE7) effective for the treatment or prevention of the addiction.
10. The method of claim 9, wherein the primary impulse-control disorder is selected from the group consisting of: binge eating, pathological gambling, pathological use of electronic devices, pathological use of electronic video games, pathological use of electronic communication devices, pathological use of cellular telephones, addiction to pornography, sex addiction, compulsive spending, anorexia, bulimia, intermittent explosive disorder, kleptomania, pyromania, trichotillomania, compulsive over-exercising, and compulsive overworking.
11. The method of claim 10, wherein the primary impulse-control disorder is binge eating.
19. The method of claim 1, further comprising administering an additional therapeutic agent with the PDE7 inhibitor, wherein each of the PDE7 inhibitor and the additional therapeutic agent contribute to the effective treatment or prevention of the addiction.
21. The method of claim 20, wherein the opioid antagonist is naltrexone or nalmefene.
22. The method of claim 20, wherein the antidepressant is fluoxetine, mirtazapine, or bupropion.
-US 20110021564
1. A method of treating binge eating disorder or obesity resulting from binge eating behavior, comprising diagnosing a patient as having a binge eating disorder or obesity resulting from binge eating behavior and providing an effective amount of amphetamine prodrug, methylphenidate prodrug, or methylphenidate analog to the patient, wherein the amphetamine prodrug, methylphenidate prodrug, or methylphenidate analog is provided as the only active agent or is provided together with one or more additional active agents.
5. The method of claim 1 wherein the amphetamine prodrug, methylphenidate prodrug, or methylphenidate analog is administered together with one or more other active agent(s).
11. The method of claim 5, wherein the one or more other active agent is an appetite suppressant, a weight loss drug, an anti-obesity agent, an anti-diabetes agent, a selective serotonin reuptake inhibitor, a serotonin 5HT receptor partial agonist or antagonist, a norepinephrine dopamine reuptake inhibitor, a serotonin norepinephrine dopamine reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a nicotinic acetylcholine receptor agonist or antagonist, an anti-convulsant a glutamate modulator, or a combination of the foregoing.
12. The method of claim 11, wherein the other active agent is orlistat, sibutramine, phentermine, riminobant, acamprosate, adinopectin, benzphetamine, butabinide, cetilistat, cholecystokinin, diethylpropion, d-cycloserine, lorcaserin, naltrexone, 6-beta-naltrexol, buprenorphine, octreotide, oleoyl-estrone, oxytocin, phenylylpropanolamine, phendimetrazine, phetermine, sodium oxybate, tesofensine, thyroxine, acarbose, acipimox, chlorpromide, diazoxide, exenatide, gliclazide, glimepiride, glipizide, glucagon, glyburide, liraglutide, metformin, miglitol, nateglinide, pioglitazone, pramlintide, repaglinide, rosiglitazone, saxagliptin, sitagliptin, tolazamide, vildagliptin, dapagliflozin, sergliflozin, clovoxamine, femoxetine, flesinoxan, citalopram, escitalopram, fluoxetine, fluvoxaminesertraline, duloxetine, desvenlafaxine, venlafaxine, atomoxetine, reboxetine, thionisoxetine, bupropion, mianserin, buspirone, amantadine, bromocriptine, cabergo line, lisuride, pergolide, pramipexole, ropinirole, vanoxerine, amisulpride, lamotrigine, levetiracetam, topiramate, zonisamide, modafinil, armodafinil, varenicline, galantamine, memantine, or pharmaceutically active salts or prodrugs thereof, or a combination of the foregoing.
-US 20100317572
1. A pharmaceutical composition comprising a therapeutically effective amount of (i) a compound of Formula I ##STR00003## wherein R.sup.a represents hydrogen or alkyl; R.sup.b represents a dihalophenyl group; any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and (ii) an anti-obesity compound; or a pharmaceutically acceptable salt thereof; together with one or more adjuvants, excipients, carriers and/or diluents.
5. The pharmaceutical composition of claim 1, wherein the anti-obesity compound is a cannabinoid CB1 receptor antagonist, a lipase inhibitor, a monoamine reuptake inhibitor, an anticonvulsant, a glucose sensitizer, a incretin mimetic, an amylin analog, a GLP-1 analog, a Y receptor peptide, a 5-HT2C serotonin receptor agonist, an opioid receptor antagonist, an appetite suppressant, an anorectic, a hormone; or a pharmaceutically acceptable salt thereof.
6. The pharmaceutical composition of claim 5, wherein the anti-obesity compound is selected from the group consisting of: rimonabant, surinabant, SLV-319, O-2093, orlistat, cetilistat, sibutramine, bupropion, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, milnacipran, mirtazapine, venlafaxine, desvenlafaxine, topiramate, zonisamide, metformin, exenatide, pramlintide, liraglutide, obinepitide, lorcaserin, naltrexone, phentermine, phendimetrazine, insulin, leptin, and pharmaceutically acceptable salts thereof.
13. A method of treatment, prevention or alleviation of obesity or an obesity associated disease of a living animal body, including a human, which method comprises the step of administering to such a living animal body in need thereof, a therapeutically effective amount of a combination of (i) a compound of Formula I ##STR00004## wherein R.sup.a represents hydrogen or alkyl; R.sup.b represents a dihalophenyl group; any of its stereoisomers or any mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof; and (ii) an anti-obesity compound; or a pharmaceutically acceptable salt thereof.
14. The method according to claim 13, wherein obesity or an obesity associated disease is a disorder or condition selected from the group consisting of obesity, over-eating disorders, bulimia nervosa, binge eating disorder (BED), compulsive over-eating, impaired appetite regulation, metabolic syndrome, type 2 diabetes, dyslipidemia, atherosclerosis.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SVETLANA M IVANOVA/Primary Examiner, Art Unit 1627
1 For completeness of the record, the reference, with the full text included, has been made of record, as accessed from a publicly available source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586099/pdf/40268_2012_Article_10010025.pdf
2 The instant application lists as assignee Nalpropion Pharmaceuticals LLC. The parent application 13/991372 lists Orexigen® Therapeutics as a former assignee.
3 For completeness of the record, the reference, with the full text included, has been made of record, as accessed from a publicly available source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586099/pdf/40268_2012_Article_10010025.pdf