Detailed Action
Claims 6 and 8 are rejected to and under examination.
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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 18/285,521, filed on 10/04/2023.
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 6 and 8 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 reducing an anxiety symptom in a subject in need thereof comprising administering an effective amount of L-ergothioneine or a salt thereof to a subject, does not reasonably provide enablement for preventing an anxiety symptom comprising administering L-ergothioneine or a salt thereof to a subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: Claim 6 is drawn to a method of preventing or reducing an anxiety symptom, comprising administering L-ergothioneine or a salt thereof to a human. Claim 8 is drawn to the method of claim 6, wherein the L-ergothioneine or a salt thereof is administered to a human adult in an amount of 2 to 50 mg per day in terms of L-ergothioneine.
However, the nature of the invention is complex in that prevention of anxiety or an anxiety symptom, as claimed, is undeterminable and not a guaranteed outcome, and efficacy of the claimed L-ergothioneine in the context of the claimed method is not demonstrated as L-ergothioneine does not show absolute prevention of the claimed anxiety symptoms in all humans.
Breadth of the Claims: The claims are broad in that the claims recite a method for preventing anxiety symptoms, comprising administering L-ergothioneine or a salt thereof to a human. A human, as claimed, can be interpreted as any human with or without anxiety at baseline, and thus the Applicant’s claimed method of prevention would be interpreted as prophylactic administration to a human without prior history of anxiety symptoms. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the Specification and Existence of Working Examples: The specification describes administering L-ergothioneine to humans and measuring anxiety symptom change using the State Trait Anxiety Inventory (STAI). The Applicant’s results show further decrease in state anxiety in the test group receiving L-ergothioneine as measured by STAI, compared to the control group. However, no working examples are given for preventing anxiety symptoms, comprising administering L-ergothioneine or a salt thereof to a human. While it is noted that the applicant has shown some data for efficacy of L-ergothioneine in reducing anxiety symptoms, the applicant is not enabled for prevention of anxiety symptoms as claimed.
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped. It is known in the art that anxiety is highly dependent on multiple unpredictable factors including individual genetic disposition, demographic, environmental exposures, and that treatments for anxiety can vary in efficacy between individuals.
Cleveland Clinic. Anxiety Disorders, [online], [retrieved on 12/30/2025]. https://my.clevelandclinic.org/health/diseases/9536-anxiety-disorders (Year:2024) - explains that there are various manifestations of anxiety and that they are not entirely preventable.
Amount of Experimentation Necessary: The quantity of experimentation necessary to carry out the claimed invention is high, as the skilled artisan could not rely on the prior art or instant specification to teach a method of preventing an anxiety symptom, comprising administering L-ergothioneine or a salt thereof to a human.
In order to carry out the claimed invention, one of ordinary skill in the art would have to administer the claimed L-ergothioneine as a regular, prophylactic dosing over the course of a long enough period of time under conditions where it would be certain that anxiety symptoms would develop, which would be an impossible experimental setup due to the duration and the lack of a true control group.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 6 and 8 are not considered to be fully enabled by the instant specification.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over
Kato, M., et. al. (JP6086568B2; Published 03/01/2017, translation provided herein) in view of
Nakamichi, N. (Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice), Brain and Behavior, Vol. 6, no. 6, pp. 1-10 (Year: 2016), further in view of Cheah, I.K. (Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?), Biochemical and Biophysical Research Communications, Vol. 478, no. 1, pp. 162-167 (Year: 2016).
To the extent that the method in claim 6 is drawn to reducing an anxiety symptom, the following 35 U.S.C 103 rejection applies.
(Of Note: the Applicant defines an anxiety symptom to include a wide range of cognitive symptoms, such as: anxiety, fear, tension, worries, heartache,
loneliness, poor memory, lethargy, nervousness, distress, mental agitation, and decreased
positive thinking. Therefore, all references encompass the Applicant’s claimed anxiety symptoms.)
Kato teaches a method of reducing depression, administering L-ergothioneine to mice,
and teaches that mice that were fed L-ergothioneine showed reduced immobility time on
forced swimming tests, a routine test for depression in animal models (See page 4; paragraph 0017).
Nakamichi teaches a method of reducing depressive symptoms comprising administering L-ergothioneine or a salt thereof to mice (See e.g. Abstract; page 1). Nakamichi also teaches that Ergothioneine is an antioxidant known to prevent oxidative damage to DNA and protein, and increased oxidation has been previously been linked to depression (See e.g. Page 2; paragraph 1).
However, neither Kato or Nakamichi teach, through working example, their respective methods used in humans at the Applicant’s dosing range of 2 to 50 mg of L-ergothioneine per day.
While Kato does not teach, through working example, the Applicant’s claimed dosing range of 2 to 50 mg of L-ergothioneine per day in humans, Kato suggests that a preferrable dosing range for human adults to be 3 to 50 mg of ergothioneine per day and that exact dosing can be appropriately adjusted depending on gender, body weight, age, period of ingestion, severity of symptoms, and the like (See page 4; paragraph 0015). 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).
Kato also teaches that it has been confirmed that in mice, L-ergothioneine permeates the cell membrane by membrane transporter OCTN1, and that OCTN1 is expressed in a wide range of tissues in humans, including the brain. Kato also teaches that it has been confirmed that human OCTN1 is able to incorporate L-ergothioneine into cells (See page 5; paragraph 0018).
Cheah teaches that Ergothioneine accumulates naturally in the human body in tissues predisposed to higher levels of oxidation (See e.g. Abstract; page 1). Cheah also teaches that levels of Ergothioneine were measured to be lower with increasing age, significantly above 60 years of age, and that a subset of subjects with mild cognitive impairments showed decreased Ergothioneine levels, compared with age matched subjects.
Kato, Nakamichi and Cheah all draw a nexus between Ergothioneine and anxiety/depression related cognitive symptoms. While, Kato and Nakamichi teach an experimental study where administration of Ergothioneine was directly observed to effect depression in mice, Cheah further provides motivation to explore this effect in humans through an observational study that showed Ergothioneine levels decrease with both age and established cognitive impairment in humans.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to reduce depression in a human by administering L-ergothioneine in an amount of 2 mg to 50 mg, based upon the beneficial teachings of Kato, Nakamichi and Cheah. One skilled in the art, before the effective filing date of the claimed invention, would have had sufficient motivation and a reasonable expectation of success to combine Kato’s teaching of reducing depression by administering L-ergothioneine in a dosing range of 3 mg to 50 mg per day in human adults, as well as L-ergothioneine uptake into the brain occurring through the same transporter in both mice and humans, Nakamichi’s teaching that L-Ergothioneine fed orally in mice showed large increase in concentrations in plasma and brain, and that mice who were fed L-Ergothioneine showed decreased immobility time in forced swim tests, showing increase in cognition and antidepressive activity, and Cheah’s teaching that decreased L-ergothioneine levels in humans are associated with cognitive impairments, to arrive at the Applicant’s claimed method of reducing an anxiety symptom, comprising administering L-ergothioneine or a salt thereof to a human, in an amount of 2 to 50 mg per day.
Conclusion
No claims are allowed.
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/OROD MOTEVALLI/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628