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 .
Response to Amendments
The amendments made to the claims 11/10/2025 have been entered.
Information Disclosure Statement
No new information disclosure statement (IDS) has been submitted.
Priority
The filing receipt mailed 08/13/2021 states the instant application is a CON of PCT/EP2020/052010 filed 01/28/2020 which claims foreign benefit of EPO 19153957.6 filed 01/28/2019.
A copy of the EPO document was submitted 08/13/2021 and supports the instant claims. Therefore, the effective filing date is 01/28/2019.
Withdrawn Objections
In view of the amendments, the objections made in the prior office action have been withdrawn.
Withdrawn Rejection
In view of the amendments made the 112(a) scope of enablement rejection and 112(b) rejections made in the previous action have been withdrawn.
Applicant’s arguments have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made.
New Rejection
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 1-19, 21-23, 25-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the combination of specific caloric restriction and vitamin C in specific doses, does not reasonably provide enablement for the general combination of caloric restriction and vitamin C. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The following Wands Factors have been considered if not explicitly stated: (A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims
Claim 1 now specifies KRAS mutant cancers consisting of colorectal, lung, and pancreatic cancer. The claim still states “comprising administering a fasting mimicking diet and vitamin C to a patient in need thereof”
Currently, only dependent claim 15 specifies a dose amount of vitamin C. Claim 1 is open to all amounts of vitamin C when the synergistic effect argued has only been shown for specific doses of vitamin C, which is 4 g/kg twice a day (see below).
Instant specification, p. 9, Figure 3
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Nature of the Invention, Amount of direction and working examples
The invention is drawn to a method of treating specific KRAS mutant cancers via administering to a patient in need thereof vitamin C in an unspecified amount while the patient is undergoing a fast mimicking diet.
“fasting mimicking diet” is defined in the specification on p. 6 which states “ ‘Fasting mimicking diet’ (FMD) refers to previously described formulations to mimic the effects of fasting.” Prior to this, the instant specification p. 2, l. 16 states “Fasting mimicking diet (FMD) is low in calories, proteins and sugars but high in saturated fats and, as fasting, it is able to reduce the level of cancer risk factors such as glucose and IGF-1, which are the major players involved in DSS and DSR.”
A specific example of a fasting mimicking diet is found on p. 6, l. 24-31, shown below.
Fasting Mimicking Diet
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The specification also discusses a “short-term starvation” (STS) diet in relation to an FMD. A detailed discussion of STS is found on p. 17, l. 17-25. Here the specification states the following:
STS conditions
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This paragraph connects STS and FMD conditions, however, exact conditions for STS are not detailed within the specification. Therefore, the most detailed explanation of conditions that were tested and shown to have efficacy are those discussed above under FMD.
Applicant has argued that the combination of a fasting mimicking diet and vitamin C showed a synergistic increase over the administration of the two methods separately. Figure 1.a, reproduced here, shows this effect as discussed in the specification p. 8, l. 18-24 and p. 17, l.11-30.
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State of the prior art
A 2014 review by Wilson (Asia-Pacific Journal of Clinical Oncology, 2014; 10: 22-37) discusses the use of high-dose intravenous vitamin C as a singular anti-cancer agent (title). Wilson on p. 23, sec Does Vitamin C (at high plasma concentrations) have antitumor activity in rodent systems? discusses dosing and plasma concentrations in mice. Wilson points to Chen and states “Chen et al. demonstrated that vitamin C (4 g/kg intraperitoneal [IP] once or twice daily) reduced tumor growth and weight by 41-53% using ovarian (Ovcar5), pancreatic (PAN01) and glioblastoma (9 L) tumor cell lines in mice. The effective plasma concentration that decreased survival by 50% (EC50) was less than 10 mM in 75% of the tumor cells tested, but in contrast cytotoxicity was not evident in normal cells at ascorbate concentrations exceeding 20 mM.” Wilson continues “Epsey et al. demonstrated that vitamin C (4 g/kg) inhibited the growth rate of PAN02 pancreatic tumors by approximately 40%, and also augmented the effect of concurrently administered gemcitabine (30 mg/kg). This dose of vitamin C in rodents is equivalent to 1.5 g/kg in humans.”
Fasting is reported as a possible clinical application against certain cancers in Nencioni (Nature Reviews, vol. 18, 2018).
The synergistic effect of administering vitamin C while a patient is in a fasted state to treat the specific KRAS mutant cancers was not reported until 2020, in Di Tano (Nature Communications, 2020:11:2332).
Level of predictability and quantity of experimentation
The working examples show a predictable synergistic effect when administering 4 g/kg twice a day during a fasting state. However, it is not clear if the doses less than this amount would also have a synergistic effect when combined with a fasting-mimicking diet.
Considering the above, one of ordinary skill in the art could not predictability practice the claimed methods within the current scope of the claims.
As claims 2-19, 21-23, and 25-27 are dependent on claim 1, they are also rejected.
Examiner’s Comments
Proposed amendments have been submitted by the applicant (See interview summary and attached proposed amendments). It was determined that the proposed amendments do not rectify the 112(a) issue detailed above.
Conclusion
No claims allowed.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624