Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Status of claims
The amendment filed on Jan. 16, 2026 is acknowledged. Claims 1-20 have been canceled. Claims 21-40 are under examination in the instant office action.
Applicants' arguments, filed on Jan. 16, 2026, have been fully considered but they are moot in view of a new ground of rejections, which are necessitated by the amendments (adding new limitations). Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied in view of the amendments. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112 (a)
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention
New matter Rejection
Claims 21-40 are rejected 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 21 is amended to recite: “assessing whether the patient loses at least 4% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof; and continuing to administer about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof after 12 weeks only if the patient loses at least 4% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof”.
Also, Claim 31 is amended to recite: “further comprising assessing whether the patient loses at least 5% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof; and continuing to administer about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof after 12 weeks only if the patient loses at least 5% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof”.
While the specification discloses “the promotion of weight loss is measured by a percent change from a baseline body weight and the amount of weight loss can be at least 4% or 5%, the original disclosure does not support “continuing to administer the claimed combination only to a subset of patient population who loses at least 4% or 5% of initial body weight after 12 weeks of administering the claimed combination. Such newly recited conditional limitation was not disclosed in the original disclosure or the prior applications to which the instant application claims the benefit of priority. Therefore, it is considered as new matter.
New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 (a) to § 608.04(c).
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 31-40 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. All the dependent claims are included.
Claim 31 is amended to recite: “further comprising assessing whether the patient loses at least 5% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof; and continuing to administer about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof after 12 weeks only if the patient loses at least 5% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof”.
However, claim 21 from which claim 31 depends already recites “assessing whether the patient loses at least 4% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof; and continuing to administer about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof after 12 weeks only if the patient loses at least 4% of initial body weight after 12 weeks of administering about 32 mg per day of naltrexone or a pharmaceutically acceptable salt thereof and about 360 mg of bupropion or a pharmaceutically acceptable salt thereof”.
Since claim 31 incorporates all the limitation of claim 21, the method of claim 31 comprises both assessing steps: “assessing whether the patient loses at least 4% of initial body weight after 12 weeks….” and “assessing whether the patient loses at least 5% of initial body weight after 12 weeks….”. As such, the claim 31 inlcudes the broad recitation of “at least 4%” and then also recites “at least 5%”, which is the narrower statement of said “at least 4%”, in the same claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). It is unclear which assessing step is controlling and should be performed. As such, the scope of the claims is indefinite. Appropriate correction is required.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 21-29 and 31-39 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clinical Trial titled “A Study of Naltrexone SR/ Bupropion SR in Overweight or Obese Subjects With Major Depression” (Clinical trial.gov ID: NCT00624858, Version 3: 9/4/2008; hereafter, NCT00624858) in view of Hausenloy (“Contrave: novel treatment for obesity”, 2009, Clinical Lipidology, Vol. 4(3), pp. 279-285; cited in the IDS filed on 10/29/2021) in further view of Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002).
NCT00624858 discloses a study of naltrexone SR (sustained release)/ bupropion SR (sustained release) in overweight or obese subjects with major depression (Title and p1, Study Identification). NCT00624858 further discloses that the patients have body mass index (BMI) greater or equal to 27 and less than or to equal 43kg/m2 and meet criteria for major depression (p3, Eligibility). Thus, the patients are overweight or obese and have been identified to suffer from major depressive disorder as claimed.
NCT00624858 further discloses that naltrexone SR 32 mg/ bupropion SR 360 mg daily.
NCT00624858 also discloses that 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 and subjects will then take the maintenance dose of study drug for an additional 20 weeks (P2, Arms and Interventions). The 4-week titration period plus additional 20 week meets at least 24 weeks recited in claims 22 and 32.
In addition, NCT00624858 discloses that the change in depressive symptoms is measured by Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks (p2, Outcome Measures).
NCT00624858 does not specifically discloses specific escalating dosing schedule recited in claim 21. Also, it is silent about whether the naltrexone SR and bupropion SR is administered more than once per day (claims 27 and 37) and they are in a single oral dosage form (claims 28 and 38).
Hausenloy teaches CONTRAVE for the treatment of obesity. CONTRAVE is a fixed-dose combination of bupropion sustained release and naltrexone sustained release (single dosage form) (abstract). Hausenloy teaches that bupropion is a well-known anti-depressant used for the treatment of depression (including major depression) (the paragraph bridging pages 279-280). Hausenloy also teaches that bupropion and naltrexone are believed to act in a synergistic manner on the central neural pathways within the hypothalamic arcuate nucleus to reduce appetite and increase energy expenditure (page 280, right column, 1st sentence). Hausenloy discloses phase III clinical trials using CONTRAVE in two dosage formulations: bupropion SR 360 mg with naltrexone SR 32 mg, and bupropion SR 360 mg with naltrexone SR 16 mg wherein the dosage amounts are increased over the course of 4 weeks (page 283, right column, “Dosage & administration”).
As to the specific escalating dosing schedule and the dosing frequency (more than once per day), NCT00624858 teaches and suggests that 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 and subjects will then take the maintenance dose of study drug for an additional 20 weeks. Also, Hausenloy teaches that the dosage amounts are increased over the course of 4 weeks. Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to optimize titration schedule and dosing frequency to find out the optimum dosage regimen. Based on the overlapping dosages and the escalating dosing schedule taught by the prior art, it would have been prima facie obvious to a person of ordinary skill in the art to arrive at the claimed escalating dosing regimen by gradually increasing the dosage over the 4 weeks of the titration period to reach the maintenance dose (naltrexone SR 32 mg and bupropion SR 360 mg) taught by the prior art. Optimizing an appropriate dosing schedule during the titration period and dosing frequency could be determined by good medical practice, the clinical condition of the individual patient, and patient’s response to initial administration, without undue experimentation. Typically, a physician will determine the actual dosage which will be most suitable for an individual patient and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. In addition, it is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426. “[W]here 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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”)
As to the new limitation, while NCT00624858 already discloses assessing the percentage change from baseline in total body weight at 12 and 24 weeks (p3, Secondary Outcomes Measure), NCT00624858 is silent about “continuing to administer only if the patient loses at least 4% or 5% of initial body weight after 12 weeks”.
Jain et al. disclose a study evaluating the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults for 26 weeks (abstract). Jain et al. teach assessing mean change from baseline body weight (initial body weight) at week 12 and adjusting the dosage of bupropion if patients who lost <5% of baseline weight at week 12 (abstract). Jain et al. further teach that response on the Beck Depression Inventory (BDI-II) which is indicative of depressive symptoms (i.e., at least 50% decrease in the total score) in the overall sample was significantly related (p < 0.0001) to losing at least 5% of baseline body weight regardless of treatment and patients who lost at least 5% of baseline body weight were three times more likely to be BDI-II responders than patients who had not lost at least 5% of their baseline body weight (p1052, col 2, last para-p1053, col 1, para 1). Jain et al. teach that weight loss of ≥5% may improve mood in obese patients with depressive symptoms (abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to assess the percentage change from baseline in total body weight at 12 weeks and to continue administration of the combination for those who lost at least 5 % of initial body weight because of the following reasons. NCT00624858 already discloses assessing the percentage change from baseline in total body weight at 12 and 24 weeks (p3, Secondary Outcomes Measure). Also, NCT00624858 discloses the patient continues administration of naltrexone SR 32 mg/ bupropion SR 360 mg 12 weeks after assessing the percentage change from baseline in total body weight as stated above. In addition, it was well-known in the art that assessing percent change from baseline body weight (initial body weight) as efficacy measure is commonly performed at week 12 in weight loss therapy and the percent change from the initial weight at week 12 can be a basis for adjusting the treatment as evidenced by Jain et al. Jain et al. further teach that those who lost at least 5% of baseline body weight after the treatment with bupropion SR are more likely to improve depressive symptoms in obese patients with depressive symptoms. Thus, the skilled artisan would have recognized that patients who lost at least 5% of baseline body weight at week 12 would be similarly better responders to the combination in the treatment of obese patients with major depressive disorder, thus would be motivated to continue the treatment for maintaining the effects in those patients. This is what a person of ordinary skill in the corresponding art would do.
As to claims 28 and 38, a single oral dosage form comprising bupropion SR and naltrexone SR such as CONTRAVE was available as evidenced by Hausenloy, one of ordinary skill in the art would have been motivated to use such single oral dosage form for improving patients’ convenience and compliance.
Claims 30 and 40 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clinical Trial titled “A Study of Naltrexone SR/ Bupropion SR in Overweight or Obese Subjects With Major Depression” (Clinical trial.gov ID: NCT00624858, Version 3: 9/4/2008; hereafter, NCT00624858) in view of Hausenloy (“Contrave: novel treatment for obesity”, 2009, Clinical Lipidology, Vol. 4(3), pp. 279-285; cited in the IDS filed on 10/29/2021) in further view of Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002) as evidenced by US 2005/0282911.
The teachings of NCT00624858), Hausenloy and Jain et al. as applied supra are herein applied for the same teachings in their entirety.
The references do not specifically disclose “monitoring the patient for suicidal ideation” recited in claims 30 and 40.
NCT00624858 already discloses that the change in depressive symptoms is measured by Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks (p2, Outcome Measures). Also, it was well known in the art that suicidal ideation is a symptom of MDD and MADRS evaluates ten areas of depressive symptomatology: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts as evidenced by US 2005/0282911 (abstract and [0003] [0044]). Thus, NCT00624858 implicitly discloses monitoring the patient for suicidal thoughts (ideation) by measuring MADRS.
In the alternative, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to monitor suicidal ideation while providing weight loss therapy in a patient with major depressive disorder because suicidal ideation was known to be a critical symptom of depression and NCT00624858 already teach measuring depressive symptoms by MADRS, which includes suicidal ideations. A person of ordinary skill in the art, which is a healthcare provider, would have been motivated to do so since the patient also suffers from major depressive disorder. This is what a person of ordinary skill in the corresponding art would do.
Claims 21-29 and 31-39 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Plodkowski et al. (Expert Opin. Pharmacother., 10(6):1069-1081, published online: 13 Apr 2009; cited in the IDS filed on 10/29/2021) in view of Croft et al. (CLINICAL THERAPEUTICS, 24 (4): 662-672, 2002; cited in the IDS filed on 10/29/2021) in further view of Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002).
Plodkowski et al. disclose the efficacy of the combination comprising naltrexone and bupropion in sustained release formulation for promoting weight loss wherein naltrexone SR potentiates the effects of bupropion SR; thus, this synergistic combination has the potential for additional weight loss compared to monotherapy (abstract). Contrave® is a combination of the sustained-release forms of both naltrexone and bupropion (single oral dosage form), currently being studied in Phase III clinical trials (Table 1) (p1074, 5. Contrave). The treatment period is 24 weeks (p1078, Table 1).
The clinical study randomized 419 healthy, non-diabetic, obese (BMI > 30.0 kg/m2) subjects to either bupropion 200 mg BID, naltrexone 48 mg/day dose BID, bupropion 200 mg BID with naltrexone 16, 32, 48 mg/day dose (divided twice daily), or placebo (p1079, 5.4 Clinical studies) and the greatest weight-loss effects were observed in the naltrexone 16 mg/day combined with bupropion 200 mg BID group and in the group given naltrexone 32 mg/day combined with bupropion 200 mg BID (400 mg) (Table 1 and p1079, 5.4 Clinical studies).
While Plodkowski et al. disclose that a combination of the sustained-release forms of both naltrexone and bupropion such as Contrave® is effective for reducing weight in obese or overweight subjects, Plodkowski et al. do not specifically teach the use of the combination for a subpopulation who is obese or overweight and also suffers from major depressive disorder.
However, Plodkowski et al. disclose clinical studies that have shown effectiveness of bupropion SR (400 mg/day and 300 mg/day) in achieving weight loss (p1073-1074, 4.4 Clinical efficacy and p1077, Table 1). Plodkowski et al. also disclose a randomized, double-blind, placebo-controlled study which evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults at week 12 wherein depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression and further showed weight loss of ≥ 5% may improve mood in obese patients with depressive symptoms (p1073-1074, 4.4 Clinical efficacy).
In addition, Croft et al. disclose the long-term effects of bupropion SR (300 mg/d) in patients with major depression wherein weight loss increased with increasing baseline body weight were observed with long-term bupropion SR treatment (abstract). Croft et al. suggest that bupropion SR is an appropriate therapeutic option in normal weight or overweight patients with depression (abstract and conclusion).
Thus, it would have been obvious to one of ordinary skill in the art at the time the invention was made to use the combination of bupropion and naltrexone (e.g., CONTRAVE) for weight reduction disclosed in Plodkowski et al. for overweight or obese subjects who also suffer from major depressive disorder because bupropion has been available for several years for the treatment of depression and clinical studies show its effect on weight loss in obese or overweight adults with depression symptoms and major depressive disorder as evidenced by Plodkowski et al. and Croft et al. The skilled artisan would have been motivated to use the combination of bupropion and naltrexone for providing both weight loss therapy and the treatment of depressive symptoms in those subjects. The skilled artisan would have a reasonable expectation of success that the combination would be effective for reducing weight in overweight or obese people with major depressive disorder while treating depression.
As to the escalating dosing schedule recited in claim 21 and the dosing frequency (once per day) in claims 26 and 36, and the dosage amount of bupropion (360 mg per day), Plodkowski et al. disclose that oral naltrexone is administered at escalating doses from 10 mg/day to 150 mg/day over a 3-week period in the clinical trials evaluating the effects of naltrexone on food consumption and weight loss (p1071, 3.4 Clinical studies) and bupropion was started at 100 mg/day and gradually titrated to a maximum dose of 200 mg twice daily (400 mg) in a clinical study of bupropion involving 50 overweight and obese women (p1073, 4.4 Clinical studies). Plodkowski et al. further disclose that both 400 mg/day and 300 mg/day of bupropion SR are effective in achieving weight loss (p1073-1074, 4.4 Clinical efficacy and p1077, Table 1).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to optimize titration schedule and dosing frequency to find out the optimum dosage regimen. Based on the overlapping dosages and the escalating dosing schedule taught by Plodkowski et al., it would have been prima facie obvious to a person of ordinary skill in the art to arrive at the claimed escalating dosing regimen by gradually increasing the dosage over the 4 weeks of the titration period to reach the maintenance dose. Optimizing an appropriate dosing schedule during the titration period and dosing frequency could be determined by good medical practice, the clinical condition of the individual patient, and patient’s response to initial administration, without undue experimentation. Typically, a physician will determine the actual dosage which will be most suitable for an individual patient and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. Also, the prior art discloses overlapping dosage amounts. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). In addition, it is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426. “[W]here 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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”)
As to the new limitation, Plodkowski et al. disclose bupropion sustained-release (bupropion SR) alone improved depressive symptoms and showed weight loss of ≥ 5% in obese adults with a history of major depression as stated above. Also, Plodkowski et al. disclose naltrexone SR potentiates the effects of bupropion SR and the synergistic combination of naltrexone SR and bupropion SR has the potential for additional weight loss compared to monotherapy (abstract). Thus, one of ordinary skill in the art would have reasonably expected that administering bupropion SR in combination with naltrexone SR would result in weight loss of ≥ 5% and reduction in depressive symptom in obese adults with major depression because the combination was taught to provide synergistic effects in reducing the body weight while reducing symptoms of depression compared with bupropion SR alone.
However, Plodkowski et al. is silent about “continuing to administer only if the patient loses at least 4% or 5% of initial body weight after 12 weeks”.
Jain et al. disclose a study evaluating the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults for 26 weeks (abstract). Jain et al. teach assessing mean change from baseline body weight (initial body weight) at week 12 and adjusting the dosage of bupropion if patients who lost <5% of baseline weight at week 12 (abstract). Jain et al. further teach that response on the Beck Depression Inventory (BDI-II) which is indicative of depressive symptoms (i.e., at least 50% decrease in the total score) in the overall sample was significantly related (p < 0.0001) to losing at least 5% of baseline body weight regardless of treatment and patients who lost at least 5% of baseline body weight were three times more likely to be BDI-II responders than patients who had not lost at least 5% of their baseline body weight (p1052, col 2, last para-p1053, col 1, para 1). Jain et al. teach that weight loss of ≥5% may improve mood in obese patients with depressive symptoms (abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to assess the percentage change from baseline in total body weight at 12 weeks and to continue administration of the combination for those who lost at least 5 % of initial body weight because of the following reasons. Plodkowski et al. already discloses assessing the percentage change from baseline in total body weight at 12 weeks. In addition, it was well-known in the art that assessing percent change from baseline body weight (initial body weight) as efficacy measure is commonly performed at week 12 in weight loss therapy and the percent change from the initial weight at week 12 can be a basis for adjusting the treatment as evidenced by Jain et al. Jain et al. further teach that those who lost at least 5% of baseline body weight after the treatment with bupropion SR are more likely to improve depressive symptoms in obese patients with depressive symptoms. Thus, the skilled artisan would have recognized that patients who lost at least 5% of baseline body weight at week 12 would be similarly better responders to the combination in the treatment of obese patients with major depressive disorder and thus would be motivated to continue the treatment for maintaining the effects in those patients. This is what a person of ordinary skill in the corresponding art would do.
Claims 30 and 40 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Plodkowski et al. (Expert Opin. Pharmacother., 10(6):1069-1081, published online: 13 Apr 2009; cited in the IDS filed on 10/29/2021) in view of Croft et al. (CLINICAL THERAPEUTICS, 24 (4): 662-672, 2002; cited in the IDS filed on 10/29/2021) and Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002) in further view of US 2006/0150989.
The teachings of Plodkowski et al., Croft et al., and Jain et al. as applied supra are herein applied for the same teachings in their entirety.
The references do not specifically disclose “monitoring the patient for suicidal ideation” recited in claims 30 and 40.
It was well known in the art that suicidal ideation is a critical symptom of depressive disorders such as MDD and should be monitored in the treatment of MDD as evidenced by US 2006/0150989 (abstract, [0010], [0037], [0094]and claims 1, 3, and 28-29). Also, US 2006/0150989 teaches that similar methods can be used successfully for other conditions where depressive symptoms are often present as coexisting condition, such as overweight/weight control (abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to monitor suicidal ideation while providing weight loss therapy in a patient with major depressive disorder because suicidal ideation was known to be a critical symptom of depression and to be monitored for preventing it. A person of ordinary skill in the art, which is a healthcare provider, would have been motivated to do so since the patient also suffers from major depressive disorder. This is what a person of ordinary skill in the corresponding art would do.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9,248,123 in view of Clinical Trial titled “A Study of Naltrexone SR/ Bupropion SR in Overweight or Obese Subjects With Major Depression” (Clinical trial.gov ID: NCT00624858, Version 3: 9/4/2008; hereafter, NCT00624858) and Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a method of providing weight loss therapy to a patient who is suffering from major depressive disorder (MDD) and is also overweight or obese, comprising administration of naltrexone or a pharmaceutically acceptable salt thereof and bupropion or a pharmaceutically acceptable salt thereof in the same escalating dosing schedule as claimed.
As to the new limitation, the claims of the patent is silent about assessing whether the patient loses at least 4% or 5% of initial body weight after 12 weeks and “continuing to administer only if the patient loses at least 4% or 5% of initial body weight after 12 weeks”.
However, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to assess the percentage change from baseline in total body weight at 12 weeks and to continue administration of the combination for those who lost at least 5 % of initial body weight because of the following reasons. NCT00624858 already discloses assessing the percentage change from baseline in total body weight at 12 and 24 weeks (p3, Secondary Outcomes Measure). Also, NCT00624858 discloses the patient continues administration of naltrexone SR 32 mg/ bupropion SR 360 mg 12 weeks after assessing the percentage change from baseline in total body weight as stated above. In addition, it was well-known in the art that assessing percent change from baseline body weight (initial body weight) as efficacy measure is commonly performed at week 12 in weight loss therapy and the percent change from the initial weight at week 12 can be a basis for adjusting the treatment as evidenced by Jain et al. (abstract and p1052, col 2, last para-p1053, col 1, para 1). Jain et al. further teach that those who lost at least 5% of baseline body weight after the treatment with bupropion SR are more likely to improve depressive symptoms in obese patients with depressive symptoms (abstract and p1052, col 2, last para-p1053, col 1, para 1. Thus, the skilled artisan would have recognized that patients who lost at least 5% of baseline body weight at week 12 would be similarly better responders to the combination in the treatment of obese patients with major depressive disorder and thus would be motivated to continue the treatment for maintaining the effects in those patients. This is what a person of ordinary skill in the corresponding art would do.
Thus, the instant claims would have been obvious over the claims of the patent.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,322,121 in view of Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a method of administering naltrexone or a pharmaceutically acceptable salt thereof and bupropion or a pharmaceutically acceptable salt thereof in the same escalating dosing schedule to the same patient who is suffering from major depressive disorder (MDD) and is also overweight or obese wherein the reduction in symptoms of depression is measured using Montgomery-Åsberg Depression Rating Scale.
As to the new limitation, the claims of the patent is silent about assessing whether the patient loses at least 4% or 5% of initial body weight after 12 weeks and “continuing to administer only if the patient loses at least 4% or 5% of initial body weight after 12 weeks”.
However, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to assess the percentage change from baseline in total body weight at 12 weeks and to continue administration of the combination for those who lost at least 5 % of initial body weight because of the following reasons. The claims of the patent further recite the pharmaceutical composition is administered to the patient for a period of at least 12 weeks or at least 24 weeks. In addition, it was well-known in the art that assessing percent change from baseline body weight (initial body weight) as efficacy measure is commonly performed at week 12 in weight loss therapy and the percent change from the initial weight at week 12 can be a basis for adjusting the treatment as evidenced by Jain et al. (abstract and p1052, col 2, last para-p1053, col 1, para 1). Jain et al. further teach that those who lost at least 5% of baseline body weight after the treatment with bupropion SR are more likely to improve depressive symptoms in obese patients with depressive symptoms (abstract and p1052, col 2, last para-p1053, col 1, para 1. Thus, the skilled artisan would have recognized that patients who lost at least 5% of baseline body weight at week 12 would be similarly better responders to the combination in the treatment of obese patients with major depressive disorder and thus would be motivated to continue the treatment for maintaining the effects in those patients. This is what a person of ordinary skill in the corresponding art would do.
Thus, the instant claims would have been obvious over the claims of the patent.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,033,543 in view of Clinical Trial titled “A Study of Naltrexone SR/ Bupropion SR in Overweight or Obese Subjects With Major Depression” (Clinical trial.gov ID: NCT00624858, Version 3: 9/4/2008; hereafter, NCT00624858) and Jain et al. (OBESITY RESEARCH Vol. 10 No. 10 October 2002).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a method of providing weight loss therapy to a patient who is suffering from major depressive disorder (MDD) and is also overweight or obese, comprising administration of naltrexone or a pharmaceutically acceptable salt thereof and bupropion or a pharmaceutically acceptable salt thereof in the same escalating dosing schedule.
As to the new limitation, the claims of the patent is silent about assessing whether the patient loses at least 4% or 5% of initial body weight after 12 weeks and “continuing to administer only if the patient loses at least 4% or 5% of initial body weight after 12 weeks”.
However, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention was made to assess the percentage change from baseline in total body weight at 12 weeks and to continue administration of the combination for those who lost at least 5 % of initial body weight because of the following reasons. NCT00624858 already discloses assessing the percentage change from baseline in total body weight at 12 and 24 weeks (p3, Secondary Outcomes Measure). Also, NCT00624858 discloses the patient continues administration of naltrexone SR 32 mg/ bupropion SR 360 mg 12 weeks after assessing the percentage change from baseline in total body weight as stated above. In addition, it was well-known in the art that assessing percent change from baseline body weight (initial body weight) as efficacy measure is commonly performed at week 12 in weight loss therapy and the percent change from the initial weight at week 12 can be a basis for adjusting the treatment as evidenced by Jain et al. (abstract and p1052, col 2, last para-p1053, col 1, para 1). Jain et al. further teach that those who lost at least 5% of baseline body weight after the treatment with bupropion SR are more likely to improve depressive symptoms in obese patients with depressive symptoms (abstract and p1052, col 2, last para-p1053, col 1, para 1. Thus, the skilled artisan would have recognized that patients who lost at least 5% of baseline body weight at week 12 would be similarly better responders to the combination in the treatment of obese patients with major depressive disorder and thus would be motivated to continue the treatment for maintaining the effects in those patients. This is what a person of ordinary skill in the corresponding art would do.
Thus, the instant claims would have been obvious over the claims of the patent.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611