DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
2. Claims 45-56 and 58-69 are pending.
Claims 45-56 and 58-69 are examined on the merits.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
3. 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.
4. 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.
5. The rejection of claim(s) 45-56 and 58-69 under 35 U.S.C. 103 as being unpatentable over ClinicalTrials.gov ID NCT01954836 (7 pages, First posted October 7, 2016), and further in view of Rattue, Grace. (MedicalNewToday 1-14, February 11, 2012), Nencioni et al., WO 2018/138090 A1 (effective filing date 26 January 2017) and Longo et al., US 2011/0118528 A1 (published May 19, 2011) is maintained.
Applicant sets forth case law regarding the transitional phrase, “consisting of” and states “… with the closed language, “consisting of’,…the claimed method steps are limited only to fasting-mimicking periods before and after each chemotherapy cycle. The claims as amended do exclude any actions, except the administration of an anti-cancer agent, that may take place during each of the plurality of therapy cycles. “, see Remarks submitted July 10, 2025, page 2, last paragraph (para.); and page 3, 3rd para.
Applicant reiterates their claimed invention and pointedly states the alleged misgivings of each reference, see pages 4 and 5 within the Remarks.
Applicant asserts, “ClinicalTrials.gov does not provide any information even remotely connected to the schedule of fasting presently claimed, Nencioni does not describe any cancer treatment Longo does not describe multiple cycles of short-term fasting and Rattue describes experiments on mice with cancer.”, see page 5, 3rd paragraph.
And more specifically, Applicant argues “Nencioni is completely silent with regard to cancer treatment because endometrial hyperplasia is not cancer, as described on pages 1 and 2.
Longo is completely silent with regard to multiple cycles of short-term fasting as presently claimed.
Finally, the newly cited reference Rattue only describes recent findings regarding the efficacy of fasting during cancer therapy in patients, particularly in the context of chemotherapy, and refers only to patients who tolerated fasting when administered in the two days before or the day after treatment, thus being eligible to participate in the clinical trial.
Moreover, Rattue, as the other cited references, is completely silent with regard to FMD, which is a fasting-mimicking diet and therefore different from a fast.
It is pointed out that Rattue (e.g., pages 2 and 3) refers to a previous publication regarding general fasting during chemotherapy in patients (attached hereto), which discusses fasting simply as a potential adjuvant to chemotherapy, aimed at improving the patient's condition in the short term.
No mention is made to FMD diet.
Therefore, Applicant respectfully traverses the rejection because Rattue provides no further relevant teaching beyond what has already been disclosed in the previously cited documents.”, page 4.
Applicant’s arguments, points of view and Safdie et al. (AGING 1(12): 1-20, December 2009) reference have been carefully considered but found unpersuasive.
ClinicalTrial #NTC01954836 teaches food deprivation, wherein the caloric intake is less than 400kcal in combination with multiple chemotherapy cycles are administered to patients with ovarian cancer or breast cancer, see claims 45-49 and 67-69. The reduced caloric intake begins 36 to 48 hours before chemotherapy, see claims 45-47 and 60-64.
Applicant’s arguments cite what Nencioni does not teach, while the reference is replete with the specifics of the fasting-mimicking diet (FMD) cycles to prevent effects of toxicity from chemotherapy treatment of a gynecological disorder. Nencioni teaches FMD components, caloric intake percentage, kcals, days and cycles, which limit side effects for patients undergoing chemotherapy (DNA damaging agents) treatment, see rejection herein and document.
Contrary to Applicant’s assertion, “Longo is completely silent with regard to multiple cycles of short-term fasting as presently claimed”, Longo cites time periods of FMD, components of the FMD, chemotherapy treatments given to patients with cancer in order to protect normal cells from deleterious effects, see rejection herein and document.
Rattue makes clear that reduction of caloric intake or fasting and chemotherapy in combination does hinder the growth and spread of tumors, however defined periods of time for FMD with chemotherapy cycles need to be tailored to cancer patients at risk for additional maladies as unrestricted fasting may not be a reliable course of action for patients with different and diverse cancers, see rejection herein and document.
The combination of references teaches the claimed inventions. The combination of these teachings does not differ from Applicant’s claimed inventions. Hence, the same results would render the same effects as espoused by Applicant. Applicant has not presented any scientific evidence that would dissuade the Office from the combination of references. The combination of references would not change the principle of operation of the prior art invention being modified, hence the teachings of the references are sufficient to render the claims prima facie obvious.
Moreover, the modification of the primary reference in light of the secondary references is proper because the applied references are so related that the appearance of features shown in one would suggest the application of those features to the other. See In re Rosen, 673 F.2d 388, 213 USPQ 347 (CCPA 1982); In re Carter, 673 F.2d 1378, 213 USPQ 625 (CCPA 1982), and In re Glavas, 230 F.2d 447, 109 USPQ 50 (CCPA 1956). Further, it is noted that case law has held that a designer skilled in the art is charged with knowledge of the related art; therefore, the combination of old elements, herein, would have been well within the level of ordinary skill. See In re Antle, 444 F.2d 1168,170 USPQ 285 (CCPA 1971) and In re Nalbandian, 661 F.2d 1214, 211 USPQ 782 (CCPA 1981). The combination of references would not change the principle of operation of the prior art invention being modified, hence the teachings of the references are sufficient to render the claims prima facie obvious. For the reasons of record and cited herein, the rejection is maintained.
The Brief Summary of the Trial states “…a randomized controlled pilot trial 30 female patients with gynecological cancer (ovarian and breast cancer) and 4-6 scheduled chemotherapies will be randomized to fast 60-72 hours during the first half of chemotherapies or during the second half of chemotherapies and to proceed normocaloric food intake during the other cycles. Sequence of fasting and normocaloric food intake will be randomized. Assessments of adverse effects, quality of life and laboratory values take place 24 and 7 days after each chemotherapy.” see page 3.
The Detailed Description of the Trial states “[w]ithin a randomized controlled pilot trial 30 female patients with gynecological cancer disease (ovarian and breast cancer) in all stages and 4-6 scheduled chemotherapies will be randomized to fast 60-72 hours during half of chemotherapies and to have normocaloric food intake during the other chemotherapies. Fasting is defined as caloric restriction to below 400kcal energy intake/day with free intake of water and tea. Sequences of fasting and normocaloric food intake will be randomized. Assessments of adverse effects, quality of life, fatigue and laboratory values will take place 24 and 7 days after each chemotherapy. Statistical analyses will compare the summarized differences of fasted and non-fasted chemotherapy cycles, that means a total of max. 60-90 chemotherapies with accompanying fasting will be compared to 60-90 non-fasted chemotherapies.”, see Detailed Description on page 3.
“Intervention
Behavioral: initial fasting
modified fasting with daily caloric intake of <400kcal by juices starting 36 to 48 h before begin of chemotherapy and lasting to 24 h after end of chemotherapy applied in the first half of scheduled 4 or 6 chemotherapy cycles
Behavioral: Secondary fasting
modified fasting with daily caloric intake of <400kcal by juices starting 36 to 48 h before begin of chemotherapy and lasting to 24 h after end of chemotherapy applied in the second half of scheduled 4 or 6 chemotherapy cycles
Study Arms
Experimental: Initial fasting
Fasting during chemotherapy of the first half of chemotherapy cycles (1 and 2 of four or 1 to 3 of six cycles)
Interventions:
Behavioral: initial fasting
Active Comparator: Secondary fasting
Fasting during the second half of chemotherapy cycles (3 and 4 of four cycles or 4 to 6 of six cycles)
Interventions:
Behavioral: Secondary fasting” see ClinicalTrials.gov page 4.
Outcome Measures
Primary Outcome Measures:
1.
Quality of life, modified FACT-O[ Time Frame: 24 h and 7 days after chemotherapy cycle]
Secondary Outcome Measures:
1.
Fatigue[ Time Frame: 24 h and 7 days after chemotherapy cycle]
2.
Intensity of adverse effects structured criteria Likert scales[ Time Frame: 24 h and 7 days after chemotherapy cycles]
3.
Laboratory assessments (blood count, liver, renal function)[ Time Frame: 24 h and 7 days after chemotherapy cycles]”,
see ClinicalTrials.gov archive, page 5.
ClinicalTrials.gov ID NCT01954836 does not explicitly teach the methods, wherein the FMD is restricted for a period of 30-42 hours before each therapy cycle and 18-30 hours after each therapy cycle, wherein the therapy includes specific chemotherapeutic agents, DNA alkylating agents, topoisomerase inhibitors, cyclophosphamide, topoisomerase inhibitors, doxorubicin, carboplatin, docetaxel and the FMD composition provides a daily caloric intake reduced by 50-90% and caloric intake is 100-350 kcal/day.
However, Rattue does teach “…chemotherapy combined with fasting delayed tumor growth and/or limited the spread of tumors, and improved survival,”, see page 2.
The human trial discussed in Rattue “…did not include cancer patients who had risk factors, such as diabetes, or had already lost over 10% of their normal weight. In addition, fasting can result in headaches and lower blood pressure, which for some patients could make driving and other activities dangerous.”, see page 2. Hence, defined periods of fasting would be advantageous to a host of patients with cancer.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of all references to subject cancer patients to Applicant’s designated periods of FMD time before and after each therapy cycle because continuous fasting, as well as unrestricted fasting may not be a reliable course of action for all cancer patients, see page 3.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in Rattue, while fasting is able to delay the growth and spread of tumors, as well as fasting cycles are as effective as chemotherapy, FMD should be judiciously applied to the cancer treatment regimen and patient dependent because some individuals cannot tolerate fasts due to preexisting conditions, already underweight, and the FMD may induce or provoke additional maladies such as headaches or low blood pressure, see pages 1 and 2.
In addition, Nencioni teaches a diet composition for the treatment of a gynecological cancer comprising a FMD in cycles providing less than 50%-90% of the normal caloric intake, see abstract; page 4, lines 9-20; and page 9, lines 14-16. Nencioni also teaches nutrients contained in the FMD in Table 2 on pages 6 and 7, also see page 5, lines 25 and 26. “[T]he fasting mimicking diet component comprises proteins in an amount that is less than 15% of the total calories provided by the fasting mimicking diet component.
Preferably, the fasting mimicking diet component comprises sugars in an amount that is less than 15% of the total calories provided by the fasting mimicking diet component.”, see page 8, lines 10-15. Hence, this recited FMD contains all the necessary micronutrients to prevent malnutrition.
“[T]he fasting mimicking diet component comprises at least 60% calories from fatty acids, 2-5% calories from glycerol and up to 5% calories from plant-based proteins and a maximum of 35% calories from carbohydrates.”, see page 8, lines 25-28.
Moreover, Longo teaches administering chemotherapy to a patient within nutritional methods and formulations that are capable of reducing cancer growth, see abstract; and page 6, sections 0085, 0087 and 0090, as well as the entire document.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of all references to meet the nutritional requirements that do not lead to chronic weight loss and/or nutrition, as well as administer a traditional anticancer therapeutic agent, such as a chemotherapeutic agent.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in all the references that defined multiple cycles of short-term fasting including necessary nutrients with multiple chemotherapy cycles is well tolerated and effective in treating cancers including gynecological cancer, see all documents in their entirety; and particularly, Nencioni, page 12, lines 23-27; and Longo’s Experiments and Cases, particularly Experiment 1 and Case 1 on pages 8 and 9 and section 0077 spanning pages 4 and 5.
Conclusion
6. 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.
7. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached on 571-272-5205. 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.
ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
10 September 2025
/Alana Harris Dent/Primary Examiner, Art Unit 1643