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 .
DETAILED ACTION
Claims 1-19 are pending.
Response to Amendment
Applicant added new claim 19.
The rejection of claims 1-18 under 35 U.S.C. 103 is withdrawn.
The rejection of claims 1-18 on the ground of nonstatutory double patenting is withdrawn in view of the Terminal Disclaimer filed on 11/26/2025.
Claim Rejections - 35 USC § 112
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 1-18 remain rejected and new claim 19 is 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 suppressing immune checkpoints in mice and in vitro, does not reasonably provide enablement for suppressing immune checkpoints in a human subject in need thereof. 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.
In making a determination that a disclosure does not satisfy the enablement requirement, the factors that may be considered include: (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. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
Nature of the invention. The claims are drawn to a method for suppressing immune checkpoints, comprising administering, as an active ingredient, to a human subject in need thereof a plant fermentation product comprising a mixture of (a) to (g).
Breadth of the claims. The breadth of the claimed invention is exceedingly large and fails to receive adequate support in the specification. Claims 1-19 encompass suppressing immune checkpoints in a human subject in need thereof.
State of the prior art and Unpredictability. No prior art teachings show the suppression of immune checkpoints in a human in need thereof comprising administering the recited composition. Prior art Higashi (WO-2016093104A1, published 06/2016, of record in IDS filed on 03/15/2021) teaches administering the composition to mice and reports an aging suppressing effect in the mice (Abstract, claims 1 and 9, [0070]). Reference Marshall (Alternatives to Laboratory Animals 51.2 (2023): 102-135) reports the failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades, and reports the majority of these failures are due to unexpected toxicity, safety issues revealed in human trials that were not apparent in animal tests, or lack of efficacy (Abstract). Fruhwein et al. report the issue of translating preclinical findings into human treatments is particularly evident in cancer research, and despite promising preclinical results, fewer than 15% of clinical trials successfully progress beyond phase I, with cancer research consistently exhibiting the highest rates of failure. Fruhwein et al. report that, even when murine models show initial promise, the success rate of translating these findings into human treatments is less than 8% (page 2 left column last para.). Fruhwein et al. also report the translation of findings from animal studies, particularly murine models, to successful human clinical applications remains fraught with challenges (page 2 right column para. 3). Therefore, the claimed method for suppressing immune checkpoints in a human in need thereof is highly unpredictable.
Guidance in the specification and working examples. The guidance in the specification is not commensurate in scope with the claimed invention. The test Examples were all done in mice. The description is limited to administering the composition to mice, followed by laparotomy to extract the thymus, the spleen, and the kidney (page 17-18). The thymuses of the old mice had atrophy whereas the group which was administered the plant fermentation did not show atrophy the thymus (page 18 “Result”). The specification discloses the immune checkpoint expression increased with aging and was further higher in tumor bearers, but the expression was reduced in mice which took the plant fermentation product (Test Example 2). The gene expressions of PD-1, PD-L1, and Ctla4 in the thymus of mice generally increase with aging, the increments are all reduced by the plant fermentation product (Test Example 4). In vitro test discloses autoclaved aqueous solution of the plant fermentation product has an inhibitory activity on binding of PD-1 receptor and ligand (PD-L1 and PD-L2) (Test Example 5). The specification fails to provide guidance pertaining to suppressing of immune checkpoints in a human in need thereof.
Amount of experimentation necessary. The above-mentioned details establish that one skilled in the art would not be able to make or use the full scope of claimed invention with a reasonable expectation of success and without undue experimentation.
Taking these factors into account, undue experimentation would be required by one of ordinary skill in the art to practice the full scope of the claimed invention. Thus, the claims are not fully enabled by the disclosure.
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.
Claim 19 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 19 recites the limitation "the immune checkpoint measured" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 19 depends, recite the limitation “immune checkpoint” but does not recite the limitation “measured immune checkpoint”.
Response to Arguments
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive.
Applicant’s argument regarding antibody drugs against immune checkpoint and against PD-1 and PD-L1 used as anticancer agents has been considered but is not persuasive, since the argument is not commensurate in scope with the claims which do not include antibodies.
Applicant argues that specific antibodies for PD-1 and PD-L1 are commercially available as a novel anticancer but the product of the present application is a plant fermentation product that suppresses the biosynthesis of PD-1 and PD-L1 in vivo (though in mice) by oral administration instead of suppressing the binding reaction of the antigen PD-1 and the ligand PD-L1. Applicant argues the present specification, while not providing data showing suppression of all the immune checkpoints, provides sufficient support to the present claim scope.
In response to the argument, the claims are drawn to a method of suppressing immune checkpoints in a human subject in need thereof. As acknowledged by Applicant, the disclosure states the claimed product suppresses the biosynthesis of PD-1 and PD-L1 in vivo in mice. As explained above, the art reports the failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades, and reports the majority of these failures are due to unexpected toxicity, safety issues revealed in human trials that were not apparent in animal tests, or lack of efficacy. Thus, undue experimentation would be required by one of ordinary skill in the art to practice the full scope of the claimed invention.
Conclusion
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.
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/MARY A CRUM/ Examiner, Art Unit 1657
/THANE UNDERDAHL/ Primary Examiner, Art Unit 1699