DETAILED ACTION
The Applicant’s filing, received 06 September 2023, has been fully considered. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
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
The preliminary amendment received 11 December 2023 has been entered.
Claims 128-147 are pending.
Claims 128-147 are rejected.
Priority
This application is a CON of PCT/IB2022/000103, filed 07 March 2022
which claims benefit of 63/158,245, filed 08 March 2021
and claims benefit of 63/297,668, filed 07 January 2022.
Therefore, the effective filing date of the claimed invention is 08 March 2021.
Information Disclosure Statement
The information disclosure statements (IDS) received 12 December 2023, 15 February 2024, 08 August 2024, and 19 August 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, these information disclosure statements have been considered by the examiner.
Drawings
The replacement drawings received 11 December 2023 are not accepted, and are objected to as noted below.
The drawings are objected to because separate views are not labeled with a number followed with a capital letter as required by 37 C.F.R. 1.84(u)(1) (see MPEP 608.02 V.). In particular:
FIG. 10 at replacement sheet 13/37 shows “Fig. 2.1.” however, there is no Fig. 2.1 filed;
Replacement sheet 33/37 shows “Fig. 22” which should be deleted because the figures are already labeled as “Fig. 22A” and “Fig. 22B”;
Replacement sheet 34/37 shows “Fig. 23” which should be deleted because the figures are already labeled as “Fig. 23A”, “Fig. 23B”, “Fig. 23C”, and “Fig. 23D”;
Replacement sheet 35/37 shows “Fig. 24” which should be deleted because the figures are already labeled as “Fig. 24A” and “Fig. 23B” (note “Fig. 23B” (emphasis added)); and
Replacement sheet 37/37 shows “Fig. 26” which should be deleted because the figures are already labeled as “Fig. 26A”, “Fig. 26B”, “Fig. 26C”, “Fig. 26D”, and “Fig. 26E”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The substitute specification received 11 December 2023 has been entered.
Review of the mark-up and clean copy appear to provide amendments to the brief description of the drawings section to be consistent with newly filed drawings.
Claim Objections
Claim 146 is objected to because of the following informalities: The claim contains more than one period, (i.e., ‘.’) (e.g., ‘a.’, ‘b.’, ‘c.’ and ‘d.’). The MPEP at 608.01(m) states that each claim begins with a capital letter and ends with a period, and that periods may not be used elsewhere in the claims except for abbreviations. A potential amendment that could overcome this objection would be to replace the periods with parentheses, e.g., replace ‘a.’ with ‘a)’.
Claim 146 is further objected to because of the following informalities: The space between the word “agonist” and the subsequent comma in line two of step d. should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 128-145 are 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 128 is indefinite for reciting “identifying or measuring a first state” and “identifying or measuring a second state” because the claim previously recites a “computer-implemented method…” and therefore it is not clear as to whether the steps of identifying or measuring a first and second state wherein the first and second state comprise one or more of a (1) a physiological parameter, (2) a biological state, or (3) an emotional state, are active physical steps (e.g., measuring brain activity using electroencephalogram (EEG)) for obtaining the data to perform an evaluation, or if the steps of “identifying or measuring” are limited to using the computer to analyze previously obtained data. The limitation “identifying” is interpreted to encompass steps of using a computer to analyze data, i.e., a computer-implemented method, and further encompass observation and/or evaluation of a biological or emotional state (e.g., sweating or mood); and the limitation “measuring” is interpreted to encompass active physical steps of obtaining data, e.g., measuring a physiological parameter using an EEG.
Claims 129-145 are indefinite for depending from claim 128 and for failing to remedy the indefiniteness of claim 128.
Claim 135 recites the limitation "the symptoms" in line three. There is insufficient antecedent basis for this limitation in the claim, because the previous claims do not recite any symptoms for the conditions, and therefore it is not clear which symptoms are being referred to.
Claims 136-140 are indefinite for depending from claim 135 and for failing to remedy the indefiniteness of claim 135.
Claim 137 recites the limitation "the condition" in line one. There is insufficient antecedent basis for this limitation in the claim, because claim 135 recites more than one condition, and therefore it is not clear which condition claim 137 is referring to.
Claim 138 recites the limitation "the second amount" in line five. There is insufficient antecedent basis for this limitation in the claim, because the claims do not previously recite a second amount.
Claim 138 further recites the limitation " the one or more 5-HT agonist" in lines five and six. There is insufficient antecedent basis for this limitation in the claim, because the claims do not previously recite a one or more 5-HT agonist.
Claim 139 recites the limitation "the condition" in line one. There is insufficient antecedent basis for this limitation in the claim, because claim 135 recites more than one condition, and therefore it is not clear which condition claim 139 is referring to.
Claim 140 is indefinite for depending from claim 139 and for failing to remedy the indefiniteness of claim 139.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 128-147 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a law of nature without significantly more. The claims recite: (a) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgement, opinion); and (b) a law of nature (e.g., naturally occurring relationships).
Claim Interpretations
Independent claim 128 recites the limitations “identifying or measuring a first state of the individual” and “identifying or measuring a second state of the individual.” The limitation “identifying” is interpreted to encompass steps of using a computer to analyze data, i.e., a computer-implemented method, and further encompass observation and/or evaluation of a biological or emotional state (e.g., sweating or mood); and the limitation “measuring” is interpreted to encompass active physical steps of obtaining data, e.g., measuring a physiological parameter using an EEG.
Independent claim 146 recites the limitations “identifying or measuring a first state of the individual” and “identifying or measuring a second state of the individual.” The limitation “identifying” is interpreted to encompass observation and/or evaluation of a biological or emotional state (e.g., sweating or mood), and further encompass observation and/or evaluation of data obtained by ‘measuring’ a state (e.g., evaluating an EEG result); and the limitation “measuring” is interpreted to encompass active physical steps of obtaining a measurement, e.g., measuring a physiological parameter using an EEG.
Subject matter eligibility evaluation in accordance with MPEP 2106.
Eligibility Step 1: Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter?
Claims 128-145 recite a computer-implemented method for identifying a therapeutically effective dose of a 5-HT receptor agonist administered to an individual (i.e., a process); and claims 146-147 recite a method for treating a mental, a behavioral, or a neuropsychiatric condition treatable with a 5-HT receptor agonist, or symptoms thereof, in an individual (i.e., a process).
Therefore, these claims are encompassed by the categories of statutory subject matter, both being processes, and thus, satisfy the subject matter eligibility requirements under step 1.
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two whether the recited judicial exception is integrated into a practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception, examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
To the extent that claim 128 can be interpreted to be a computer-implemented method of analyzing data, independent claim 128 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
at step (a) identifying a first state of the individual by performing an evaluation on the individual, wherein the first state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state (i.e., mental processes, e.g., observation and/or evaluation);
at step (c) identifying a second state of the individual by performing an evaluation on the individual, wherein the second state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state subsequent to administering the 5-HT receptor agonist (i.e., mental processes, e.g., observation and/or evaluation); and
at step (d) determining the therapeutically effective dose of the 5-HT receptor agonist based at least in part on a comparison between the first and second states of the individual (i.e., mental processes, e.g., observation and/or evaluation).
Independent claim 146 is not computer-implemented and recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
at step a) identifying a first state of the individual by performing an evaluation on the individual, wherein the first state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state (i.e., mental processes, e.g., observation and/or evaluation); and
at step c) identifying a second state of the individual by performing a second evaluation subsequent to administering the first amount of the one or more 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, wherein the second state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state (i.e., mental processes, e.g., observation and/or evaluation).
Independent claims 128 and 146, and those claims dependent therefrom, recite a law of nature by associating a therapeutically effective dose of the 5-HT receptor agonist with either a physiological, biological, or emotional state of an individual, i.e., a correlation that is the consequence how the dose of the 5-HT receptor agonist is metabolized by the individual (MPEP 2106.04(b)).
Dependent claims 129-131, 133, 135-140, 142, 145, and 147 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claim 129 further recites:
the physiological parameter comprises one or more of a brain activity, blood pressure, a heart rate, or a breathing rate (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 130 further recites:
identifying or measuring the biological state comprises evaluating a biological sample comprising one or more of serum, plasma, whole blood, urine, or sweat (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 131 further recites:
the emotional state comprises one or more of a mood rating, a sleep rating, a coping rating, a stress rating, an anxiety rating, or a memory rating (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 133 further recites:
the emotional state is identified or measured by administering to the individual one or more questionnaires and receiving the individual's responses to the one or more questionnaires (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 135 further recites:
the therapeutically effective dose is effective in treating or managing a mental, a behavioral, or a neuropsychiatric condition, or the symptoms thereof, in the individual (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 136 further recites:
treating or managing the mental, the behavioral, or the neuropsychiatric condition, or the symptoms thereof, comprises one or more of improving motivation or cognitive engagement in the individual (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 137 further recites:
the condition is induced by one or more of stress or anxiety (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 138 further recites:
the first and second state comprise at least a physiological parameter comprising a brain activity (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 139 further recites:
the condition is one or more of an attention condition, a cognitive condition, addiction, anxiety, apathy, or depression (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 140 further recites:
the attention condition is attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD) (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 142 further recites:
the second state is identified or measured at least twenty minutes or more after the first state is identified or measured (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 145 further recites:
the therapeutically effective dose of the 5-HT receptor agonist is for treating brain inflammation or brain fog following insult in the individual (i.e., mental processes, e.g., observation and/or evaluation).
Dependent claim 147 further recites:
the first and second state comprise at least a physiological parameter comprising a brain activity (i.e., mental processes, e.g., observation and/or evaluation).
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pen and paper (e.g., determining the therapeutically effective dose of the 5-HT receptor agonist based at least in part on a comparison between the first and second states of the individual), and therefore recite judicial exceptions from the mental process grouping of abstract ideas.
Therefore, claims 128-147 recite an abstract idea. Additionally, the methods as a whole provide steps for observing and/or identifying a natural correlation of compounds and possible physical effects for use as a possible treatment
[Step 2A Prong One: YES]
Eligibility Step 2A Prong Two: In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)(III)).
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
Dependent claims 129-131, 133, 135-137, 139, 140, 142, and 145 do not further recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional elements in independent claim 128 include:
a computer;
at steps a) and c) ‘measuring’; and
at step (b) administering the 5-HT receptor agonist to the individual.
The additional elements in independent claim 146 include:
at steps a. and c. ‘measuring’;
at step b. administering to the individual a first amount of one or more 5-hydroxytryptamine (5-HT) receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof; and
at step d. administering to the individual a second amount of one or more 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, thereby treating or managing the mental, the behavioral, or the neuropsychiatric condition, or the symptoms thereof, in the individual.
The additional elements in dependent claim 132 include:
the physiological parameter is identified or measured using at least one of an electroencephalogram (EEG), a magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), PET transcranial functional ultrasound imaging, or a biosensor.
The additional elements in dependent claim 134 include:
the first or second state is identified or measured using a wearable device or a mobile device.
The additional elements in dependent claim 138 include:
subjecting the individual to one or more auditory stimulus or one or more visual stimulus subsequent to step (b); and
wherein the second amount of the one or more 5-HT agonist is based at least in part on a change in brain activity between the first state and the second state.
The additional elements in dependent claim 141 include:
the 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, is administered to the individual in an amount of about 0.01 mg to about 100 mg.
The additional elements in dependent claim 143 include:
transmitting the therapeutically effective dose of the 5-HT receptor agonist to the individual, a caregiver, or both.
The additional elements in dependent claim 144 include:
the 5-HT receptor agonist is administered to the individual in need thereof as an oral formulation, an intravenous formulation, a subcutaneous formulation, a dental formulation, a buccal formulation, a nasal formulation or an inhalation formulation.
The additional elements in dependent claim 147 include:
subjecting the individual to one or more auditory stimulus or one or more visual stimulus subsequent to step (b); and
wherein the second amount of the one or more 5-HT agonist is based at least in part on a change in brain activity between the first state and the second state.
The additional element of a computer (claim 128) invokes a computer and/or computer-related components merely as a tool for use in the claimed process, such that it amounts to no more than mere instructions to apply the exceptions using a generic computer (MPEP 2106.05(f)), and therefore is not an improvement to computer functionality itself, or an improvement to any other technology or technical field, and thus, does not integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(1)).
The additional element of transmitting the therapeutically effective dose of the 5-HT receptor agonist to the individual, a caregiver, or both (claim 143) is merely a post-solution activity of transmitting data for use in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional elements of measuring a first state and a second state of the individual (claims 128 and 146); and the physiological parameter is identified or measured using at least one of an electroencephalogram (EEG), a magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), PET transcranial functional ultrasound imaging, or a biosensor (claim 132) are merely a pre-solution activity that is part of the data gathering process used in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional element of the first or second state is identified or measured using a wearable device or a mobile device (claim 134) is merely a pre-solution activity that is part of the data gathering process used in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional element of subjecting the individual to one or more auditory stimulus or one or more visual stimulus subsequent to step (b) (claims 138 and 147); is merely a pre-solution activity that is part of the data gathering process used in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional elements of administering the 5-HT receptor agonist to the individual (claim 128); administering to the individual a first amount of one or more 5-hydroxytryptamine (5-HT) receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof (claim 146); the second amount of the one or more 5-HT agonist is based at least in part on a change in brain activity between the first state and the second state (claims 138 and 147); the 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, is administered to the individual in an amount of about 0.01 mg to about 100 mg (claim 141); and the 5-HT receptor agonist is administered to the individual in need thereof as an oral formulation, an intravenous formulation, a subcutaneous formulation, a dental formulation, a buccal formulation, a nasal formulation or an inhalation formulation (claim 144); are merely pre-solution activities that are part of the data gathering process used in the claimed process – nominal or tangential additions to the claims that do not meaningfully limit the claims, and therefore do not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g) & 2106.04(d)(2)(factor c.)).
The additional element of administering to the individual a second amount of one or more 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, thereby treating or managing the mental, the behavioral, or the neuropsychiatric condition, or the symptoms thereof, in the individual (claim 146); does not effect a particular treatment or prophylaxis for a disease or medical condition, and therefore does not integrate the judicial exception(s) into a practical application (MPEP 2106.04(d)(2)).
Thus, the additionally recited elements claims 128-145 merely invoke a computer and/or computer related components as tools; and/or amount to insignificant extra-solution activity; and/or do not effect a particular treatment or prophylaxis for a disease or medical condition; and the additionally recited elements claims 146-147 amount to insignificant extra-solution activity; and/or do not effect a particular treatment or prophylaxis for a disease or medical condition; and as such, when all limitations in claims 128-147 have been considered as a whole (i.e., the analysis takes into consideration all the claim limitations and how those limitations interact and impact each other when evaluating whether the exception is integrated into a practical application), the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 128-147 are directed to an abstract idea (MPEP 2106.04(d)) and a law of nature (MPEP 2106.04(b)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
Dependent claims 129-131, 133, 135-137, 139, 140, 142, and 145 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 128 and 146 and dependent claims 132, 134, 138, 141, 143, 144, and 147 are identified above, and carried over from Step 2A Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of a computer (claim 128) and transmitting data (claim 143) are conventional computer components and/or functions (see MPEP at 2106.05(b) and 2106.05(d)(II) regarding conventionality of computer components and computer processes).
The additional elements of measuring a first state and a second state of the individual (claims 128 and 146); and the physiological parameter is identified or measured using at least one of an electroencephalogram (EEG), a magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), PET transcranial functional ultrasound imaging, or a biosensor (claim 132) is conventional. Evidence of conventionality is shown by:
Muthukumaraswamy (“The use of magnetoencephalography in the study of psychopharmacology (pharmaco-MEG).” Journal of Psychopharmacology, 2014, vol. 28(9), pp. 815-829).
Muthukumaraswamy reviews the physiological and technical basis of pharmaco-MEG and contrasts it with other pharmacological neuroimaging techniques, and further reviews various studies that have utilized pharmaco-MEG across a range of neurotransmitter systems such as GABA, glutamate, acetylcholine, dopamine and serotonin (Abstract). Muthukumaraswamy further shows resting-state MEG data following intravenous administration (2 mg) of the classical hallucinogen psilocybin, wherein ten networks were identified in the data, seven of which showed a significant reduction in activity following psilocybin (page 820, col. 1, para. 1; and Figure 4).
The additional element of the first or second state is identified or measured using a wearable device or a mobile device (claim 134) is conventional. Evidence of conventionality is shown by:
Muthukumaraswamy (as cited above).
Muthukumaraswamy reviews pharmaco-MEG in comparison to other neuroimaging methods for psychopharmacology, including electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) (pages 821-822). One of skill in the art would recognize that an EEG test can comprise wearing an elastic cap fitted with electrodes.
The additional elements of subjecting the individual to one or more auditory stimulus or one or more visual stimulus subsequent to step (b) (claims 138 and 147) are conventional. Evidence of conventionality is shown by:
Lowe et al. (“The Therapeutic Potential of Psilocybin.” Molecules, 2021, vol. 26, no. 2948, pp. 1-33).
Lowe et al. reviews the potential of psilocybin in the treatment of neuropsychiatry-related conditions (Abstract) and shows various factors that affect therapeutic/clinical outcome of psilocybin administration, e.g., the environment setting, including the use of music and/or art and the use of religious and spiritual imagery (page 19, Table 6, #3).
The additional elements of administering the 5-HT receptor agonist to the individual (claim 128); administering to the individual a first amount of one or more 5-hydroxytryptamine (5-HT) receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof (claim 146); the second amount of the one or more 5-HT agonist is based at least in part on a change in brain activity between the first state and the second state (claims 138 and 147); the 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, is administered to the individual in an amount of about 0.01 mg to about 100 mg (claim 141); and the 5-HT receptor agonist is administered to the individual in need thereof as an oral formulation, an intravenous formulation, a subcutaneous formulation, a dental formulation, a buccal formulation, a nasal formulation or an inhalation formulation (claim 144); are conventional. Evidence of conventionality is shown by:
Hirschfeld et al. (“Dose-response relationships of psilocybin-induced subjective experiences in humans.” Journal of Psychopharmacology, 2021, vol. 35(4), pp. 384-397).
Hirschfeld et al. reviews questionnaire ratings after oral psilocybin administration in order to provide a meta-analysis to obtain linear dose-response relationship estimates using available study data obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale (Abstract). Hirschfeld et al. concluded that psilocybin intensified almost all characteristics of altered states of consciousness asses with the given questionnaires, and that subjective experiences are not only determined by dose, but also by individual and environmental factors (Abstract). Hirschfeld et al. shows a conclusion that psilocybin intensified almost all characteristics of ASC (altered state of consciousness) that were measured by the given questionnaires, and noted that even though the subjective psilocybin experience is also determined by non-pharmacological variables, the meta-analysis established robust dose-response relationships for most factors and scales, which may be used as a general reference for relating expected and observed dose-specific effects (page 394, col. 2, para. 1).
The additional element of administering to the individual a second amount of one or more 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, thereby treating or managing the mental, the behavioral, or the neuropsychiatric condition, or the symptoms thereof, in the individual (claim 146) is conventional. Evidence of conventionality is shown by:
Zeiss et al. (“Rediscovering Psilocybin as an Antidepressive Treatment Strategy.” Pharmaceuticals, 2021, vol. 14, no. 985, pp. 1-14).
Zeiss et al. reviews the current state of research in the potential mechanisms of psilocybin, its antidepressant potential, and the associated risks and adverse effects of psilocybin, to provide an update on a controversial topic discussed in psychopharmacology, and shows studies included in the review that found high treatment effect sizes for psilocybin as an antidepressant (Abstract). Zeiss et al. further shows a graphical summary of a pharmacological model and an extra-pharmacological model depicting the mechanisms of action of psilocybin (Figure 1) and further shows that numerous studies suggest beneficial effects of psilocybin in the treatment of depression, and that these effects appear to be long lasting, with overall good safety and tolerability provided that psilocybin is administered in a safe and professional environment (page 10, Conclusions).
Therefore, when taken alone (i.e., individually), all additional elements in claims 128-145 and in claims 146-147 do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as an ordered combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 128-147 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 146 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Griffiths et al. (“Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.” Journal of Psychopharmacology, 2016, vol. 30(12), pp. 1181-1197, as cited in the Information Disclosure Statement received 12 December 2023).
Independent claim 146 encompasses a method for treating a mental, a behavioral, or a neuropsychiatric condition treatable with a 5-HT receptor agonist, or symptoms thereof, in an individual in need thereof, comprising: identifying or measuring a first state of the individual by performing an evaluation on the individual, wherein the first state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state; administering to the individual a first amount of one or more 5-hydroxytryptamine (5-HT) receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof; identifying or measuring a second state of the individual by performing a second evaluation subsequent to administering the first amount of the one or more 5-HT receptor agonist, or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, wherein the second state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state; and administering to the individual a second amount of one or more 5-HT receptor agonist , or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof, thereby treating or managing the mental, the behavioral, or the neuropsychiatric condition, or the symptoms thereof, in the individual.
Griffiths et al. teaches a randomized, double-blind, cross-over trial that investigated the effects of a very low dose vs. a high dose of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up.
Regarding independent claim 146, Griffiths et al. shows a study that provides the most rigorous evaluation to date of the efficacy of a classic hallucinogen for treatment of depressed mood and anxiety in psychologically distressed cancer patients (page 1182, col. 1, para. 3); a two-session, double-blind cross-over study design that compared the effects of a low versus high psilocybin dose on measures of depressed mood, anxiety, and quality of life, as well as measures of short-term and enduring changes in attitudes and behavior (page 1182, col. 1, para. 5); psilocybin session 1 occurred, on average, approximately 1 month after study enrollment, with session 2 occurring approximately 5 weeks later, and data assessments occurred (1) immediately after study enrollment, i.e., baseline assessment; (2) on both session days, i.e., during and at the end of the session; (3) approximately 5 weeks after each session, i.e., post-session 1 and post-session 2 assessments; (4) approximately 6 months after session 2, i.e., 6-month follow-up (page 1182, col. 2, para. 1); cardiovascular measures (blood pressure, heart rate) and monitor ratings (questionnaire rating or scoring several dimensions of the participant’s behavior or mood) were obtained at ten minutes before and 30, 60, 90, 120, 180, 240, 300, and 360 minutes after administration (page 1184, col. 2, para. 2; and Table 2); subjective drug effect measures were assessed 7 hours after psilocybin administration (page 1185, col. 1, para. 1); therapeutically relevant measures were assessed at baseline, 5 weeks after each session, and 6-month follow-up (page 1185, col. 1, para. 2). Griffiths et al. further shows that the present study demonstrated the efficacy of a high dose of psilocybin administered under supportive conditions to decrease symptoms of depressed mood and anxiety, and to increase quality of life in patients with a life-threatening cancer diagnosis.
Thus, Griffiths et al. anticipates instant claim 146.
Claim Rejections - 35 USC § 103
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.
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.
Claims 128-131, 133, 135, 138, 139, 141-144, and 147 are rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (“Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.” Scientific Reports, 2017, vol. 7:13187, pp. 1-11) and Nicholas et al. (“High dose psilocybin is associated with positive subjective effects in healthy volunteers.” Journal of Psychopharmacology, 2018, vol. 32(7), pp. 1-18).
Independent claim 128 broadly encompasses identifying a therapeutically effective dose of a 5-HT receptor agonist administered to an individual, comprising steps of identifying or measuring a first state of the individual by performing an evaluation on the individual, wherein the first state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state; administering the 5-HT receptor agonist to the individual; identifying or measuring a second state of the individual by performing an evaluation on the individual, wherein the second state comprises one or more of (1) a physiological parameter, (2) a biological state, or (3) an emotional state subsequent to administering the 5-HT receptor agonist; and determining the therapeutically effective dose of the 5-HT receptor agonist based at least in part on a comparison between the first and second states of the individual.
Dependent claims 129-131, 133, 135, 138, 141-144, and 147 further define the characteristics of the first and second states being measured and how the measurements are obtained, and further define the characteristics of the condition being measured and treated.
Carhart-Harris et al. teaches psilocybin for treatment-resistant depression, and measuring cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist).
Nicholas et al. teaches a method to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects.
Regarding independent claims 128, Carhart-Harris et al. shows a study focused on changes in brain function before versus after psilocybin in patients with treatment-resistant depression who received two doses of the drug (10 mg followed by 25 mg, one week apart) (page 2, para. 2); and arterial spin labelling (ASL) and blood oxygen level dependent (BOLD) resting state functional connectivity (RSFC), were used to measure changes in cerebral flood flow (CBF) and functional connectivity (FC) before (baseline) and one day after treatment with psilocybin (i.e., one day after the 25 mg dose) (page 2, para. 2). Carhart-Harris et al. further shows that it has been suggested that the days subsequent to a psychedelic experience constitute a distinct phase, referred to as the ‘after-glow’, that is characterized by mood improvements and stress relief, and therefore, the rationale for scanning one day post-treatment was to capture brain changes related to this so-called after-glow that might correlate with current mood improvements and/or longer-term prognoses, and thus, had predicted that resting-state CBF and FC would be altered post treatment and correlate with immediate and longer-term clinical improvements (page 2, para. 2).
Regarding independent claims 128, Carhart-Harris et al. does not show determining the therapeutically effective dose of the 5-HT receptor agonist based at least in part on a comparison between the first and second states of the individual (i.e., the second dose given in Carhart-Harris et al. was predetermined).
Regarding independent claims 128, Nicholas et al. shows a study with the primary objective of evaluating the pharmacokinetics of escalating doses of psilocybin as the base in healthy adult volunteers (page 4, para. 2); participants completed questionnaires after each psilocybin dose (page 6, para. 4), and drug concentration in plasma and urine were measured using a validated assay incorporating high-performance liquid chromatography and mass spectrometry (page 8, para. 2); and the study provided a conclusion that while there were no statistically significant differences in the rate of complete mystical experiences at 0.60 mg/kg versus 0.45 mg/kg or 0.30 mg/kg doses of oral psilocybin, there were significant does-related differences on the transcendence of time and space MEQ subscale, with participants reporting significant positive persisting effects 30 days after their final dose and an average moderate increase in their overall sense of well-being or life satisfaction, which suggests that the “complete” mystical experience may not necessarily be a prerequisite for positive outcomes in certain samples (page 13, para. 2).
Regarding dependent claim 129, Carhart-Harris et al. further shows measuring brain mechanism using fMRI technology before and after treatment with the serotonin agonist psilocybin (Title; and Abstract).
Regarding dependent claim 130, Carhart-Harris et al. further shows cerebral blood flow and blood oxygen-level dependent resting-state functional connectivity were measured (Abstract).
Regarding dependent claim 131, Carhart-Harris et al. further shows using psilocybin for treating treatment-resistant depression (Title; and Abstract).
Regarding dependent claim 133, Nicholas et al. further shows that subjective effects of psilocybin doses were assessed using the Mystical Experience Questionnaire and the Persisting Effects Questionnaire (Abstract).
Regarding dependent claim 135, Carhart-Harris et al. further shows that treatment with psilocybin produced rapid and sustained antidepressant effects (page 2, para. 5).
Regarding dependent claims 138 and 147, Nicholas et al. further shows preparing the treatment environment (setting) with an audio system connected to wireless headphones through which participants could listen to a pre-selected playlist of music (page 4, para. 5); and Carhart-Harris et al. further shows patients completed pre-treatment and one-day post-treatment fMRI scanning (page 2, para. 4) and study results that suggest that changes in brain activity observed just one day after a high dose psychedelic experience are very different to those found during the acute psychedelic state (page 4, para. 2).
Regarding dependent claim 139, Carhart-Harris et al. further shows the present study focuses on changes in brain function before versus after psilocybin in patients with treatment-resistant depression (page 2, para. 2).
Regarding dependent claim 141, Carhart-Harris et al. further shows administering two doses of psilocybin (10 mg followed by 25 mg, one-week apart) (page 2, para. 2).
Regarding dependent claim 142, Carhart-Harris et al. further shows measuring changes in cerebral blood flow and functional connectivity one day after treatment with psilocybin (page 2, para. 2).
Regarding dependent claim 143, Nicholas et al. further shows that participants were contacted by telephone seven days after each psilocybin session and again 30 days post-dose (page 6, para. 3).
Regarding dependent claim 144, Nicholas et al. further shows that participants were given doses of oral psilocybin (Abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Carhart-Harris et al. by incorporating methods for evaluating the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects, as shown by Nicholas et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Carhart-Harris et al. with the methods of Nicholas et al., because Nicholas et al. shows that pharmacokinetic measures were associated with dose but no with Mystical Experience Questionnaire total scores or rate of a mystical experience. This modification would have had a reasonable expectation of success given that both Carhart-Harris et al. and Nicholas et al. disclose methods for administering psilocybin to effect a therapeutic response.
Claims 132 and 134 are rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, and Scholkmann et al. (“Effects of psilocybin on functional connectivity measured with fNIRS: Insights from a single-subject pilot study.” Matters, 2019, vol. 5(11), pp. 1-11).
Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, do not show the physiological parameter is identified or measured using at least one of an electroencephalogram (EEG), a magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), PET transcranial functional ultrasound imaging, or a biosensor (claim 132) or the first or second state is identified or measured using a wearable device or a mobile device (claim 134).
Dependent claims 132 and 134 further define the types of neuroimaging devices used to measure a physiological parameter.
Scholkmann et al. teaches using functional near-infrared spectroscopy (fNIRS) optical neuroimaging to investigate psilocybin-induced changes in brain hemodynamics and oxygenation.
Regarding dependent claim 132, Scholkmann et al. shows a study to investigate the potential of optical neuroimaging with fNIRS to detect changes in a subject’s brain resting-state functional connectivity (RSFC) after intake of psilocybin (page 2, para. 3).
Regarding dependent claim 134, Scholkmann et al. shows that the functional near-infrared spectroscopy instrumentation comprised light sources and detectors that were placed on the head of the subject with help of a specific cap (page 7, para. 2).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, by incorporating methods for obtaining fNIRS measurements in a subject before and after psilocybin administration, as shown by Scholkmann et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, with the methods of Scholkmann et al., because Scholkmann et al. shows that fNIRS has the advantage over fMRI of having a higher temporal resolution, delivering information about hemodynamics and cerebral tissue oxygenation independently, and not requiring motionless measurements, which reduces the possibility of experimental stress (page 2, para. 2). This modification would have had a reasonable expectation of success given that both Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, and Scholkmann et al. disclose methods for evaluating the therapeutic effects of psilocybin administration.
Claims 136, 137, 140, 145 are rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, and Hutten et al. (“Self-Rated Effectiveness of Microdosing with Psychedelics for Mental and Physical Health Problems Among Microdosers.” Frontiers in Psychology, 2019, vol. 10, no. 672, pp. 1-9, as cited in the Information Disclosure Statement received 15 February 2024).
Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, do not show treating or managing the mental, the behavioral, or the neuropsychiatric condition, or the symptoms thereof, comprises one or more of improving motivation or cognitive engagement in the individual (claim 136); the condition is induced by one or more of stress or anxiety (claim 137); the attention condition is attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD) (claim 140); or the therapeutically effective dose of the 5-HT receptor agonist is for treating brain inflammation or brain fog following insult in the individual (claim 145).
Dependent claims 136, 137, 140, and 145 further define characteristics of the condition being treated.
Hutten et al. teaches that there is a growing interest in the use of psychedelic substances for health-related purposes, including symptom relief for disorders like anxiety, depression, and pain, and provides a study aimed to investigate, by means of an online questionnaire, the self-rated effectiveness (SRE) of microdosing with psychedelics for mental and physiological disorders compared to the conventional prescribed treatment and to regular doses of psychedelics, including psilocybin (page 5, col. 2, paras. 2-3).
Regarding dependent claim 136, Hutten et al. shows that self-medication with MDP (MicroDosing with Psychedelics) was experienced to be more effective compared to conventional treatments in cases of anxiety, ADHD/ADD, and physiological disorders such as pain (page 7, col. 1, para. 2).
Regarding dependent claim 137, Hutten et al. shows the most frequently diagnosed disorders in the study sample were stress-related disorders, i.e., depression and anxiety (page 8, col. 1, para. 2).
Regarding dependent claim 140, Hutten et al. shows that respondents were asked whether a medical doctor or therapist diagnosed them with a psychiatric, neurological, or physical disorder, and when affirmed, they were asked which of the pre-set orders applied: depression, anxiety/panic disorder, attention deficit hyperactivity disorder (ADHD) or attention deficit disorder (ADD), bipolar disorder, schizophrenia, obsessive compulsive disorder (OCD), autism/Asperger syndrome, antisocial behavior disorder, borderline personality disorder, substance abuse disorder, Tourette’s, Parkinson’s, epilepsy, migraine, cluster headache, multiple sclerosis (MS), and/or chronic pain (page 2, col. 2, para. 4).
Regarding dependent claim 145, Hutten et al. shows mental and physiological diagnoses that include migraine and cluster headache (page 2, col. 2, para. 4) (i.e., are symptoms of brain inflammation).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, by incorporating methods for investigating the effectiveness of psychedelics such as psilocybin for symptomatic relief for mental and physiological disorders, as shown by Hutten et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, with the methods of Hutten et al., because Hutten et al. shows results of an online questionnaire that showed the self-rated effectiveness of microdosing with psychedelics to alleviate symptoms of a range of mental or physiological diagnoses is higher compared to conventionally offered option, and that these effects were specific for ADHD/ADD and anxiety disorders (Abstract: Results and Conclusion). This modification would have had a reasonable expectation of success given that both Carhart-Harris et al. and Nicholas et al. as applied to claims 128-131, 133, 135, 138, 139, 141-144, and 147 above, and Hutten et al. disclose methods for evaluating the therapeutic effects of psilocybin administration.
Conclusion
No claims are allowed.
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this application.
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/STEVEN W. BAILEY/Examiner, Art Unit 1687
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