DETAILED ACTION
Claims 1-20 were pending; claims 1 and 4 have been amended per the reply of 9/26/2025.
Claims 1-20 are pending and the subject of the Office Action below.
Priority
The instant application, filed May 9, 2022 is a Continuation of 15/446,933, filed March 1, 2017, now U.S. Patent 11,324,741 and having 3 RCE-type filing therein. 15/446,933 is a continuation of 14/584,985, filed December 29, 2014, now abandoned. 14/584,985 is a continuation of 12/995,121, filed February 28, 2011, now abandoned and having 1 RCE-type filing therein. 12/995,121 was a national stage entry of PCT/US2009/045720, with an international filing date of May 29, 2009 and claims priority from provisional application 61/057,743, filed May 30, 2008.
Claim Rejections - 35 USC § 103
(Maintained)
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 (i.e., changing from AIA to pre-AIA ) 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.
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, 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 negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Eckel et al. (“Eckel”) The Lancet 365, 2005, 1415-1428; Kuk et al. (“Kuk”) Obesity 14(2), 2006, 336-341; Janssen et al. (“Janssen”) International Journal of Obesity 23, 1999, 1035-1046 and Weber et al. (“Weber”) US 2006/0142290 A1 published June 29, 2006 with evidence provided by Van Gaal et al ("Van Gaal") International Journal of Obesity Related Metabolic Disorders 1998, 22, Abstract; and Casado et al. ("Casado") Nutrition Neuroscience 6(2) 2003, Abstract. All the references have been cited in the parent application, 12/995,121.
Claim 1 states, “[a] method of treating a visceral fat condition in a person with excessive visceral fat, where the amount of visceral fat increases the risk and/or severity of diabetes or hypertension, comprising administering to the person naltrexone or a pharmaceutically acceptable salt thereof and bupropion or a pharmaceutically acceptable salt thereof.”
Applicants’ invention is directed towards treating “a visceral fat condition” through the administration of a combination of two old pharmaceuticals, namely, naltrexone and bupropion. By way of background, Applicants explain that there are certain types of health risks that correlate with different species of obesity, such as obesity linked to visceral fat:
Health risks associated with obesity can depend on how and where the fat is stored. Cutaneous fat refers to fat that is near the skin's surface. Visceral fat, which may also be referred to as intra-abdominal or subcutaneous fat, typically surrounds internal organs. In contrast to subcutaneous fat, visceral fat has been shown to be a risk factor associated with a variety of serious medical disorders.
For example, whether a person is obese (BMI>30) or not, they can still experience visceral fat accumulation in the abdominal cavity (particularly, in the mesentery and/or in the greater omentum). This accumulation, in turn, is often positively correlated with elevated values of serum cholesterol, triglyceride, and/or blood glucose measured by the glucose tolerance test. Visceral fat accumulation also often positively correlates with the systolic and diastolic blood pressures, and accordingly is related to a heightened risk of diseases such as hypertension, diabetes, and hyperlipemia….These diseases are therefore thought to be treated, cured and/or prevented by decreasing visceral fat, by inhibiting visceral fat accumulation, and/or improving body fat distribution …. Hence, there is a need for an effective pharmacotherapy for decreasing visceral fat.
Specification, page 1, paras. 3 and 4.
Applicants further require their patient be a patient diagnosed with in need of treatment for a visceral fat condition, which would include metabolic syndrome1.
Eckel is brought in to show simply that “metabolic syndrome” is a condition that includes the symptoms one would like to have an effect upon the disorder. Eckel is also brought in to show that the goal for a patient with abdominal obesity (i.e. a metabolic syndrome) is a 10% weight loss in the first year, see the insert on page 1423. Eckel clearly defines that a patient with metabolic syndrome and abdominal fat should lose weight. The key link is that visceral fat reduction in metabolic syndrome is a necessary goal to be achieved, one would be motivated to treat these patient. This reference ties into Kuk, because while Kuk does not call out "metabolic syndrome” explicitly the syndrome is clearly implied. Moreover, Eckel teaches the patient population to lose weight.
Kuk is now provided to show how visceral fat (abdominal fat) can be measured and bolsters the argument for reducing weight in metabolic syndrome patients outlined by Eckel. Kuk outlines the predictive nature of visceral fat on all-cause mortality (Abstract). Stating, it is well established that “visceral fat is a strong, independent predictor of dyslipidemia and insulin resistance, and changes in visceral fat are associated with concomitant changes in glucose tolerance and insulin resistance,” (page 336, column 2, paragraph 2). Kuk goes on to describe the subjects in the study, the “patient population” (Table 1). There are “patients” with high blood pressure, high cholesterol, high triglycerides, and type 2 diabetes. The population also has a visceral fat area (L4-L5) of 174 ± 96 cm2, and a body mass index (BMI) of 26.4 ± 4.8. Table 2, page 339, shows the associations between the various fat depots and mortality. The result of the study was that only visceral fat mass and area were significant predictors of mortality (page 338, paragraph 2). Kuk goes on to explain one significant fact in weight loss, that being; visceral fat is substantially reduced in response to diet and exercise induced weight loss independent of age or sex, page 339, paragraph 2. This is followed by this key statement, “It is generally reported that weight loss in the order of 10% is associated with the corresponding reduction in visceral fat that approximates 35%, page 339, paragraph 2.
Kuk is brought in to show that a person of ordinary skill understands that weight loss will result in the reduction of visceral fat, thereby treating obesity and metabolic syndrome (generally all under the broad category of “a visceral fat condition”). Kuk doesn’t treat the patients with drugs, and doesn’t suggest doing so. Kuk does underscore that the primary importance of treating abdominal obesity, as waist circumference provides a reasonable approximation of visceral fat in the clinical setting, page 340, column 1, paragraph 3.
Janssen is brought in to show how weight reduction results in visceral fat reduction regardless of how the weight reduction is achieved. This is the reference for the following statement, “abdominally obese men and women both lose approximately 35% of their visceral adipose tissue in response to a ~10% weight loss," page 1044, paragraph 2.
Between the references of Kuk and Janssen there is a strong motivation in the art to treat morbidity, dyslipidemia, insulin resistance, and glucose tolerance by the reduction of visceral fat, i.e. weight loss.
Weber is brought in to show how weight loss can be achieved with a combination treatment of naltrexone and bupropion. A multicenter, randomized, blinded, placebo-controlled clinical trial are run with combination treatment of Bupropion-SR 150 mg po BID plus Naltrexone 50 mg po QD in Group 3, column 36, line 21. Weber states in claim 36 that the effective amount of the combination is defined as; naltrexone in about 5 mg to about 50 mg per day, and the amount of bupropion is about 30 mg to about 500 mg per day. Weber teaches an effective weight loss treatment capable of reducing weight in the required range to reduce visceral fat substantially as evidenced by Janssen.
With regards to specific inclusion criteria, such as the waist-to-hip measurement ratio of about 0.8 or greater, as required by claim 6, this is a measure of abdominal fat. This aspect of the patient population is demonstrated by Kuk's study. Moreover the BMI measurements that are set as limitations of instant claims are encompassed by the population of Kuk, Table 1. Lastly, the dosing forms, be it together, or separate, or sequential; are all taught by Weber. See claims 15-17 of Weber. Even the sustained release form is described by Weber, see claim 13. As to claims, requiring an effect, this is mere recitation of the outcome of the administration of the drugs to the patient population.
Van Gaal is provided to show that pharmacotherapy in general, one that “increases energy expenditure” (as shown by Casado), is capable of weight reduction and specifically that weight reduction reduces visceral fat levels. Van Gaal observed a decrease in total abdominal fat (18%), total subcutaneous fat (17%) and total visceral fat (22%) with pharmacological intervention. Van Gaal bolsters the teaching of Kuk, further showing that one of ordinary skill is well aware that the main goal of treating patients with obesity and its related morbidities, particularly metabolic complications is to reduce visceral fat. Not only is visceral fat reduction important (as also shown by Kuk), but visceral fat is reduced with a pharmacological treatment that increases energy expenditure.
The fact that the pharmacological treatment of Van Gaal increases energy expenditure is provided by Casado. Casado clearly shows that a pharmacological treatment that reduces food intake and increases energy expenditure will reduce weight and visceral fat.
A person of ordinary skill would know that the patient population instantly claimed is substantially similar and obvious in light of the teaching of Eckel, Kuk, and Janssen. These three reference show that a person with excess visceral fat and metabolic syndrome are prone to multiple metabolic conditions that may be mitigated through the reduction in visceral fat levels. Reduction of visceral fat will occur with reduction of weight, this is shown by Janssen and Van Gaal, as a result of a pharmacological regimen that reduces food intake and increases energy expenditure (as Weber has shown the instantly claimed drugs and doses of those drugs are capable of). Therefore, a person of ordinary skill in the art would have a reasonable expectation of taking the treatment regimen of Weber, which reduces food intake and increases energy expenditure, and applying the regimen to the patient population Kuk to result in the pharmacological visceral fat reduction required based on the knowledge of Van Gaal. The invention as a whole was prima facie obvious at the time of invention.
In regards to claims 2 and 3, directed to the amount of the two drugs and how they enhance the treatment. This is taught in Weber, he teaches the effective amount of the drugs.
In regards to claim 4 (and claim 9), wherein said person has an amount of visceral fat that increases the risk and/or severity of at least one disease or condition selected from coronary heart disease, cancer, diabetes, glucose intolerance, hyperinsulinemia, hypertension, periodontal disease, and metabolic syndrome. The art teaches metabolic syndrome.
Claims 5-8, 10-11, 17-20 are directed to waist-to-hip measurement ratio and other inclusion criteria for the patient, and other known ways to determine the fat content in the abdomen/viscera. This was discussed above in Kuk and Weber, the patients discussed above would all be included in this treatment protocol and meet the limitation of these claims.
Claims 12-16 are directed to the “recitation of the positive outcome” of the treatment of a specific patient with a specific amount of the 2 drugs, give the amounts are known in the art and the patients included to be treated are articulated above, patients with excess visceral fat and metabolic markers of that state, the outcomes would be inherent to treating the patient with the drug. As such these claims are obvious.
Response to Applicant’s Arguments: Applicant points out that Eckel does not teach the administration of either naltrexone or bupropion. Applicant also points out that Janssen does not teach the administration of either naltrexone or bupropion. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Since Weber cures this by showing the exact dosing of naltrexone or bupropion, this reference is used to provide this fact.
Applicant states that one skilled in the art would not have combined the cited references to arrive at the claimed invention with a reasonable expectation of success. None of the references, whether individually or in combination, teach or suggest the treatment of the claimed patient population with the claimed combination of naltrexone and bupropion. Applicant's arguments have been fully considered but they are not persuasive. As one would predict visceral fat loss when general weight loss is achieved. That is precisely what the art shows and therefore one would predict this outcome regardless how the weight loss is achieved as this is the teaching in the art when looking at Van Gaal and Casado.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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 MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 Metabolic syndrome is a well-established disorder of energy utilization and storage in a person possessing three of the five following medical conditions: abdominal (central) obesity; elevated blood pressure; elevated fasting plasma glucose; high serum triglycerides; and low HDL levels.