DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/23/2026 has been entered.
Claims 1-15, 17, and 23 are cancelled.
Claim 24 is newly added.
Claims 16, 18-22, and 24 are under current examination.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention 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 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16, 18-22, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Suzuki et al. (US 2002/0086855 A1, published July 4, 2002, included on IDS submitted 12/15/2023), hereafter “Suzuki 2002”, in view of Kalayoglu (EP 2982373 A1, published February 10, 2016; of record) and Suzuki et al. (“A Fermentation Product of Phytosterol Including Campestenone Reduces Body Fat Storage and Body Weight Gain in Mice” J Nutr Sci Vitaminol, 2007, 53, 63-67, included on IDS submitted 02/19/2021), hereafter “Suzuki 2007”.
Regarding instant claim 16, Suzuki 2002 teaches a method for therapeutic or preventive treatment of obesity comprising administering to a mammal a therapeutically effective amount of a medicament comprising at least one 24-alkylchlolest-5-en-3-one (see entire document, particularly abstract and claim 1). Suzuki 2002 teaches that 24-alkylcholest-4-en-3-ones, 24-alkylcholest-5-en-3-ones, and the like may be used as active ingredients (paragraphs [0020]-[0025]). Preferred examples of the 24-alkylcholest-5-en-3-one include 5-sitosten-3-one, 5-campesten-3-one, and a mixture thereof (paragraphs [0011] and [0025]). Suzuki 2002 demonstrates that 5-campesten-3-one, 4-sitosten-3,6-dione, and 4-stigmasten-3-one show reductions in body weight gain compared to the control group (see Figure 6). Also see the table at paragraph [0048] showing the effects of various cholestenones (including 4-cholesten-3-one) and 5-sitosten-3-one on body weight gain, serum lipid, and feed intake.
The medicament can be administered orally or parenterally; examples of parenteral administrations include transdermal preparations (paragraph [0029]). The medicament can include pharmaceutical additives suitably chosen by those skilled in the art, for example, emulsifiers (paragraph [0030]). They further teach that mice fed with feed supplemented with 5-sitosten-3-one showed remarkable decreases of body fat (subcutaneous fat and intraperitoneal fat) (paragraph [0042]). Suzuki 2002 teaches oral doses that comprise 1 mg to 5,000 mg of phytostenone based on 100 g (paragraph [0031]), and teaches that body weight decreases were observed in mice treated with 5-sitosten-3-one in added amounts of 0.1%, 0.3%, and 0.5% (paragraph [0059]). Suzuki 2002 further teaches that doses of the medicament should be appropriately increased or decreased depending on factors such as the age and conditions of a patient and route of administration, and generally the dose may be within 1 to 5,000 mg per day (paragraph [0029]).
Regarding instant claim 18, as noted above, Suzuki 2002, teaches that preferred examples of the 24-alkylcholest-5-en-3-one active ingredient include 5-sitosten-3-one, 5-campesten-3-one, and a mixture thereof (paragraph [0011]).
Regarding instant claim 19, as noted above, Suzuki 2002 demonstrates that 4-stigmasten-3-one shows reductions in body weight gain compared to a control group (see Figure 6).
Regarding instant claim 20, as noted above, Suzuki 2002 demonstrates that 4-sitosten-3,6-dione shows reductions in body weight gain compared to a control group (see Figure 6 and Table at [0048]).
While Suzuki 2002 exemplifies the oral administration of 24-alkylcholest-5-en-3-ones for the reduction of subcutaneous fat, they teach that the medicament can be administered both orally or parenterally, including via transdermal preparations (paragraph [0029]). From these teachings, one of ordinary skill in the art would reasonably expect the use of a transdermal medicament comprising 24-alkylcholest-5-en-3-ones such as 5-sitosten-3-one, 5-sitosten-3-one, and combinations thereof, would have a similar effect on subcutaneous fat reduction.
Further, Kalayoglu teaches compositions for reducing subcutaneous fat that are transdermally administered (claims 1-4 and 6) and teaches that transdermal administration may provide a depot effect whereby a compound applied to the skin may result in slow release of the active ingredient into the bloodstream and a more sustained therapeutically effective concentration in the bloodstream (paragraph [0096]). Transdermal administration was capable of demonstrating reduced weight gain and improved serum lipids (paragraph [0354]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use a transdermal medicament comprising 24-alkylcholest-5-en-3-ones such as 5-sitosten-3-one, 5-campesten-3-one, or a mixture thereof in the method of treating obesity, including the reduction of subcutaneous fat, taught by Suzuki 2002, as suggested by Kalayoglu.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success to use a dosage form that results in a more sustained therapeutically effective concentration of active ingredient in the bloodstream and which is capable of delivering active ingredients for reducing subcutaneous fat and improving serum lipids, as suggested by Kalayoglu. There is a reasonable expectation of success as Suzuki 2002 teaches that 24-alkylcholestenones and their analogues deriving from plant sterols (24-alkylcholesterols) have an extremely potent decreasing effect on serum lipid and body fat, and are useful as an active ingredient of a medicament for the treatment of obesity (paragraph 0008]); they further teach that the medicament can be administered both orally or parenterally, including via transdermal preparations (paragraph [0029]).
While Suzuki 2002 demonstrates that 5-campesten-3-one, 4-sitosten-3,6-dione, and 4-stigmasten-3-one individually demonstrate reductions in body weight gain compared to a control group, and suggests that combinations 24-alkylcholest-4-en-3-ones, 24-alkylcholest-5-en-3-ones, and the like may be used as active ingredients (paragraphs [0020]-[0025]), Suzuki 2002 does not explicitly teach a phytostenone-containing composition comprising a combination of a 5-en-3-one derivative of phytosterol, a 4-en-3-one derivative of phytosterol, and a 4-en-3,6-dione derivative of phytosterol in an amount of 50% by weight or more (instant claim 16) or 50-60% by weight (instant claim 22), nor the specific phytostenone combination of instant claim 21. Suzuki 2002 does not teach a higher weight percentage reduction of subcutaneous fat than visceral fat (instant claim 24).
Suzuki 2007 teaches the anti-obesity effects of a fermentation product of phytosterols which is a phytostenone mixture (see entire document, particularly abstract). The phytostenone-containing composition (TO-001) contains the phytosterol derivatives campest-5-en-3-one, campest-4-en-3-one, β-sitost-5-en-3-one, β-sitost-4-en-3-one, phytost-4-en-3,6-dione and phytosterols (Table 1 on pg. 64). From the instant specification (paragraph [0047]), "phytost-4-en-3,6-dione" is a mixture of campest-4-en-3,6-dione, sitost-4-en-3,6-dione, stigmast-4-en-3,6-dione, and brassicast-4-en-3,6-dione. The phytostenone-containing compositions of Suzuki 2007 are thus consistent with the components recited in instant claims 16 and 18-21. Suzuki 2007 teaches that composition contains “approximately” 16% campestenone, 29% β-Sitostenone, 3% phytoste-4-en-3,6-dione, and 52% phytosterol (pg. 63-64, “Materials”) and that the content of phytostenone was “about” 50% (pg. 67, column 1, paragraph 2).
Suzuki 2007 teaches that phytostenones have anti-obesity action by reducing blood triglycerides and body fat accumulation (pg. 63, column 1, paragraph 3) and that this particular composition decreased both visceral and subcutaneous fat in mice fed with it (pg. 67, column 1, paragraph 3). Suzuki 2007 demonstrates that the TO-001 combination is capable of reducing a higher weight percentage of subcutaneous fat than visceral fat. See, for one example, Table 2, TO-001 at 0.25% compared to the control; subcutaneous fat weight gain is decreased from 0.40 g to 0.30 g for subcutaneous fat (a 25% decrease), while the total of three types of visceral fat weight gain is decreased from 3.72 g to 2.92 g (a 21.5% decrease).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the composition of Suzuki 2007 which includes the combination of 5-en-3-one derivatives of phytosterol, 4-en-3-one derivatives of phytosterol, and 4-en-3,6-dione derivatives of phytosterol at about 50% in the method of treating obesity, including the reduction of subcutaneous fat, of Suzuki 2002.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success as Suzuki 2007 teaches that phytostenones have anti-obesity action by reducing blood triglycerides and body fat accumulation (pg. 63, column 1, paragraph 3) and that this particular composition significantly decreased both visceral and subcutaneous fat (pg. 67, column 1, paragraph 3). They further teach that all of the phytostenones in the mixture have similarities in physiological activity to campest-5-en-3-one (pg. 67, column 1, paragraph 3). There is a reasonable expectation of success as the medicaments and methods of Suzuki 2002 are similarly taught to treat obesity and improve lipid metabolism (paragraph [0008]), and the medicaments of Suzuki 2002 similarly comprise a phytostenone or mixtures of phytostenones comprising campest-5-en-3-one.
Regarding the recited weight percentages of phytosterol derivatives in the phytostenone-containing composition, as noted above, Suzuki 2007 teaches derivatives at “about 50%” of the composition (pg. 67, column 1, paragraph 2), and “approximately” 48% (pg. 63-64, “Materials”), which is interpreted as overlapping or close to the recited range. Per MPEP 2144.05, “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)” and “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”.
Suzuki 2002 further teaches that doses of medicament can be appropriately increased or decreased depending on factors such as the age and conditions of a patient and route of administration (paragraph [0029]), suggesting that the amount of the active phytostenones in the composition can be routinely optimized to meet the specific needs of a patient. From MPEP 2144.05 II. A., "[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).
Response to Arguments
Applicants’ arguments filed 03/23/2026 have been fully considered.
Regarding the claim rejections under 35 USC § 103, Applicant argues that the Office has failed to specifically identify all of the requirements of the amended claims. Particularly, Applicant argues that there is no suggestion in the art of record of the claimed phytosterol derivatives in an amount of 50% by weight or more based on the weight of the phytostenone-containing composition; Applicant argues that Suzuki 2007 teaches away from including a higher percentage by stating “the weight-loss effect of TO-001 was potent even though the levels of campest-5-en-one and 3,6-dione compound were comparatively low” and does not suggest that a higher percentage of phytostenones would be desired to reduced subcutaneous fat.
These arguments are unpersuasive. As set forth above, the combined teachings of the prior art render obvious the instant claims. Particularly, Suzuki 2007 teaches derivatives at “about 50%” of the composition (pg. 67, column 1, paragraph 2), and “approximately” 48% (pg. 63-64, “Materials”), and is interpreted as overlapping or close to the recited range. Per MPEP 2144.05, “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)” and “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”. Suzuki 2002 further teaches that doses of medicament can be appropriately increased or decreased depending on factors such as the age and conditions of a patient and route of administration (paragraph [0029]), suggesting that the amount of the active phytostenones in the composition can be routinely optimized to meet the specific needs of a patient. From MPEP 2144.05 II. A., "[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).
However, the Examiner notes that, per MPEP 2144.05 III. A., “Applicants can rebut a prima facie case of obviousness by showing the criticality of the range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).” Applicant is encouraged to provide or point to evidence on the record demonstrating the criticality of the claimed range.
The argument that Suzuki 2007 teaches away from increasing the amount of phytostenones is unpersuasive as Suzuki 2007 does not criticize, discredit, or otherwise discourage such an increase. Suzuki 2007 also demonstrates that increasing the concentration of the administered composition (which comprises phytostenones) provides a greater effect on body fat accumulation compared to the control (see Table 2).
Applicant further reiterates arguments that the Office has failed to provide the appropriate motivation to combine Kalayoglu with Suzuki 2002 as the references disclose medicaments of different compound classes and mechanisms of action and the skilled artisan would not be motivated to combine them. Applicant similarly reiterates that the formulations of Suzuki 2002 and Suzuki 2007 are formulated to have a mechanism of action for oral administration not transdermal administration; the Example section of Suzuki 2002 does not provide any data for transdermal preparations or data for transdermal preparations and only provides data for oral preparations.
In response, the Examiner respectfully maintains the position regarding these arguments set forth in the Office Action mailed 07/23/2025. Particularly, per MPEP 2123: “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)”. Suzuki 2002 expressly teaches that the medicament can be administered both orally and parenterally, including transdermal preparations (paragraph [0029]), and that those skilled in the art can suitably choose pharmaceutical additives for preparation of a medicament (paragraph [0030]). The Examiner maintains that Suzuki 2002 reasonably suggests administration via transdermal preparations and that the formulation of such preparations is within the purview of an ordinary skilled artisan.
Further, the Examiner maintains that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Here, Kalayoglu provides motivation to the skilled artisan for the transdermal administration of compositions for reducing subcutaneous fat in order to result in a sustained therapeutically effective concentration of the active ingredient in the bloodstream. Both Kalayoglu and Suzuki 2002 teach the transdermal administration of active agents for reducing subcutaneous fat and improving serum lipids. From the combined teachings of the prior art, the skilled artisan would be motivated to apply the teachings of Kalayoglu regarding the beneficial properties of transdermal administration of serum lipid-lowering active agents to the method of Suzuki 2002.
In view of the foregoing, and as further set forth in the above rejections, the Examiner maintains that the balance of evidence indicates that the prior art renders obvious the instantly claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
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