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
Filing Receipt and Priority
The filing receipt received 04/03/2024 states the that instant application is a 371 of PCT/US22/31423, filed 05/27/2022 which claims benefit of provisional applications 63/194,863, filed 05/28/2021, and provisional application 63/270,989, filed 10/22/2021.
The provisional application 63/194,863 supports claims to alcohol abuse disorder but no other use disorders. Provisional application 63/194,863 supports broadly use disorders.
Claims drawn to alcohol abuse disorder have an effective filing date (EFD) of 05/28/2021.
All other claims have an EFD of 10/22/2021
Information Disclosure Statement
The information disclosure statement submitted 05/16/2025 has been considered.
Third Party Submission
The third party IDS submission received 01/22/2025 has been considered.
Claim Objection
Claim 84 is objected to because the claim states “wherein the synthetic mescaline or a salt thereof is characterized by one or more additional characteristics.” The term “characteristic” is not defined in the instant specification. Language in the instant specification and in the claim implies additional components including alcohols, water, ions (chloride, Li, Al,), or organic compounds. Characterization of a compound within the organic arts is typically measurements aimed at the physical properties of a compound (NMR, XRPD, etc.).
Rejections
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1 and 81-99 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 alcohol use disorders, does not reasonably provide enablement for all substance use disorders. 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.
Additionally, claims 98 and 99 are enabling for treatment of alcohol abuse disorders but not enabling for prevention of alcohol use disorders.
The following WANDS factors have been considered if not explicitly discussed: (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 states “A method for treating a substance use disorder comprising (a) identifying a subjecting who has a substance use disorder; and (b) orally administering a pharmaceutical composition comprising synthetic mescaline or a salt thereof to the subject and accompanying said administration with a therapy session.”
Essentially, the claim is drawn to a method of administering mescaline to a patient with a drug abuse disorder in a therapy setting.
This is emphasized in dependent claims 92 and 96.
Claims 98 and 99 further emphasize this as they specifically include “a first therapy session” and a “second therapy session”.
Regarding the term “treatment”, the instant specification defines “treatment” and “treating” to include “prophylactic benefit”. “Prophylactic benefit” implies that the claimed method can prevent the onset of alcohol use disorder.
Nature of the invention
The invention involves administering mescaline specifically in a therapy session.
Working Examples and Guidance Provided
The instant specification does not list any working examples of their claimed method(s) as an effective method for treating any abuse disorder. The instant specification starting on p. 9 details a study design. Para. [0265] states “This trial will follow a double-blind, placebo-controlled, single-ascending dose study in healthy volunteers to assess the safety, tolerability, PK, and PD of orally administered mescaline or a salt thereof. Para. [0273] further states “Evaluation Endpoints” which are detailed in para. [0274].
See the written description rejection below for further discussion.
State of the Art
Mescaline as a compound used to treat alcohol use disorder is known within the art as discussed in Agin-Liebes (ACS Pharmacol. Transl. Sci. 2021, 4, 543-552, published March 2021, of the record). Agin-Liebes on p. 545 states “Mescaline is a naturally occurring phenethylamine and a serotonin-2A/2C receptor agonist that can be prepared synthetically or extracted from the peyote or San Pedro cactus….Peyote has long been used in the treatment of chronic alcoholism among members of the Native American Church.” Agin-Liebes discusses mescaline as a compound that was self-reported to have a positive impact on drug abuse disorders (p. 544, Table 1) but Agin-Liebes does not explicitly detail what these other drug abuse disorders are. Additionally, the results given by Agin-Liebes are self-reported results and would not necessarily indicate a strong positive impact on the clinical use of mescaline in a therapy setting. The historical use of peyote in treatment for alcoholism enables mescaline use for alcoholism. However, this is not enabling for all substance use disorders.
Further, the art does not discuss mescaline having any preventative effect towards alcohol use disorder or substance use disorders.
Level of Predictability
Considering the significant lack of evidence within the instant specification and within the art showing efficacy of mescaline against general drug abuse disorders, there is a significant level of uncertainty should one of ordinary skill in the art attempt to use mescaline or mescaline salts to treat and/or prevent general drug use disorders.
Written Description – Method of treating
Claims 1, 81-99 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant specification does not list any working examples of their claimed method(s) as an effective method for treating any abuse disorder. The instant specification starting on p. 9 details a study design. Para. [0265] states “This trial will follow a double-blind, placebo-controlled, single-ascending dose study in healthy volunteers to assess the safety, tolerability, PK, and PD of orally administered mescaline or a salt thereof. Para. [0273] further states “Evaluation Endpoints” which are detailed in para. [0274].
The instant specification in para. [0268]-[0269] details safety monitoring parameters. However, this section does not detail baseline parameters and does not detail how one of ordinary skill in the art would know that the claimed method is efficacious. Similarly, there is no discussion to determine a baseline for a patient who has just started treatment that would indicate that the claimed method is having a positive effect. The instant disclosure relies on what is known within the art to give an outline of a method that expects a successful result.
The instant specification is simply prophetic which is not sufficient to indicate to one of ordinary skill that the claimed method has been reduced to practice.
Claim Rejections - 35 USC § 112(b)
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.
Indefiniteness
Claim 96 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 96 states “wherein the psychological monitoring comprises monitoring for negative psychological reactions to treatment.”
The instant specification does not explicitly define this limitation and there are also no examples that could be considered “negative psychological reactions”. Therefore, one of ordinary skill in the art would not know the metes and bounds of the claim.
Claim Rejections - 35 USC § 103
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.
KSR Rationale
The MPEP in section 2143, subsection I gives examples of Rationales for supporting a conclusion of obvious. These rationales are non-exhaustive and include (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claim(s) 1, 81-99 is/are rejected under 35 U.S.C. 103 as being unpatentable over Young (US 2012/0108510) in view of Agin-Liebes (ACS Pharmacol. Transl. Sci. 2021, 4, 543-552, published March 2021, of the record), Patel (Br. J. Cardiol, 2009;16:281-6) Eischens (Journal of Psychedelic Studies 2(1), pp. 36-44, 2018), Glucksman (Journal of the American Academy of Psychoanalysis, Vol. 11, No. 4, 475-491, 1983) and Cassels (ACS Chem. Neurosci. 2018, 9, 2448-2458).
Claims 1 and 98 are drawn to methods comprising administering mescaline in combination with therapy. Claim 1 includes first (a) identifying a subject who has a substance use disorder. Claim 98 claims a method comprising a first step of (a) administering a first treatment of mescaline and a first therapy session followed by (b) a second treatment 5 to 12 days after the first treatment which involves a second administration of mescaline and a second therapy session.
Dependent claims 81-83 and 85-86 are drawn to specific salt forms of mescaline (81-83) and concentrations (claim 85-86).
Dependent claim 84 appears to require an additional component.
Dependent claim 87 claims a tablet or capsule form of mescaline.
Dependent claims 88-90 specify the substance use disorder. Claim 88 claims a number of substance use disorders where claims 89 and 90 specify alcohol use disorders including alcohol abuse, alcohol dependence, and alcoholism.
Dependent claim 91 specifies that the subject has had reduced substance consumption prior to step b (of claim 1).
Dependent claim 92 specifies an additional “preparatory therapy session prior to step (b).
Dependent claims 93-96 include physiological and psychological monitoring.
Dependent claim 97 includes a “treatment holiday between 2 weeks to 12 months.”
Dependent claim 99 includes additional “maintenance treatments”.
Young in its abstract describes “methods of using compounds that act to increase oxytocin release…for treating or reducing the severity of psychotherapeutic or social disorders such as autism, and in particular the use of these compounds as an adjunct to psychotherapeutic counseling or behavioral therapy.” Young in para. [0016] states “It is contemplated that drugs that stimulate the release of [oxytocin] will enhance trust, social information processing, empathy and general social genitive function during behavioral therapy or counseling sessions…thereby increasing their efficacy of these sessions.” This teaching at least makes obvious the combination of administering drugs or a compound during a therapy session.
Young in para. [0026] states “In other embodiments, the oxytocin releasing agent is a serotonin receptor agonist, and in particular embodiments, it is a 5-HT 1a or 5-HT 2a/c agonist such as buspirone…mescaline…or salts thereof.” Therefore, the limitations of claim 1 are made obvious at least over these teachings.
Regarding claim 84, Young in para. [0089] further contemplates the addition of water as a carrier in therapeutic compositions formulated as solutions, microemulsions, or liposomes.
Regarding claims 85-86, Young in para. [0087] contemplates dosages of oxytocin releasing compounds. Larger doses are contemplated in para. [0088] which are doses of between about 0.05-250 mg per 50kg of body weight.
Regarding claim 87, Young contemplates capsule and tablet forms in para. [0092].
Regarding claims 88-90, Young discusses alcohol abuse disorder and/or alcohol addiction (see para. [0004], para. [0052], and para. [0054]), however, these are in relation to other social behavior disorders including bipolar disorder and depression.
Agin-Liebes specifically states on p. 545 “Mescaline is a naturally occurring phenethylamine and a serotonin-2A/2C receptor agonist that can be prepared synthetically or extracted from the peyote or San Pedro cactus….Peyote has long been used in the treatment of chronic alcoholism among members of the Native American Church.” Therefore, one of ordinary skill in the art would find it obvious to include the therapy sessions of Young with administration of mescaline to treat alcoholism.
Regarding claims 81-83, Young contemplates salts of oxytocin-releasing compounds, such as mescaline, but does not specifically state which salts.
Patel is drawn to pharmaceutical salts (title). Patel in sec. What is a Pharmaceutical Salt indicates that, within the pharmaceutical arts, salt forms can be elucidated via their nomenclature. Specifically, Patel states “The drug name can provide a clue as to the type of salt, as small charged molecules such as sulphate, hydrochloride nitrate, etc. are all only ever used to form ionic drug salts…”. Patel in this section also states “A salt is the product generated upon neutralization of an acid or base. Pharmaceutical salts are important in the process of drug development, as concerting an acidic or basic drug into a salt via a simple neutralization reaction has the ability to change the physicochemical properties of a drug. Use different chemical species to neutralize the parent drug can produce a diverse series of compounds, and this process is traditionally used to improve drug solubility and drug dissolution rates.”
Therefore, one of ordinary skill in the art would find it obvious to generate an salt form of mescaline via simple addition of either sulfuric acid or hydrochloric acid to mescaline.
Regarding claims 92, 97, 98 and 99, Young does not discuss specific details of therapy sessions of therapy regiment. Eischen is drawn to psychedelic therapy as a treatment approach for alcohol use disorders (title). Eischen in sec. Introduction para. 2 states “Common treatment models for [alcohol use disorders] AUDs including screening and brief interventions, specialized treatment programs, and mutual help groups. Brief interventions are typically utilized in primary care setting after a patient has been identified as abusing alcohol. The goal of a brief intervention may be to limit the alcohol use of the patient prior to the development of an AUD. Specialized treatment may include components of withdrawal management, therapy, pharmacotherapy, and residential or outpatient rehabilitation.”
The claim limitations of claims 92 and 97 are drawn to the inclusion of preparatory therapy sessions (claim 92) and a “treatment holiday” or period where medication is paused (claim 97). Similarly, claims 98 and 99 include limitations where the method of treating substance use disorder includes a first treatment and first therapy session and then a second treatment and second therapy session. Claim 99 specifically includes maintenance treatments with accompanying maintenance therapy sessions. While these details are not explicitly disclosed within the cited references, one of ordinary skill in the art would find them obvious as general therapy practice. A therapist often performs follow-up therapy sessions depending on the therapy regiment and this is also applicable to second administrations. These limitations are obvious as one of ordinary skill in the art would find it routine within the general therapy practice to perform a first treatment and therapy session, followed by either a second treatment and therapy session and/or maintenance treatment and maintenance sessions until the patient has successfully been treated.
Regarding claim 91, Eischen on p. 37, para. 1 states “Formal treatment typically occurs within the initial months of an individual’s recovery…”.
Regarding claims 93-96, Young does not discuss physiological monitoring of the patient. Glucksman discusses physiological responses during psychotherapeutic sessions (title). Glucksman on p. 475, para. 2 states “Normal as well as pathological physiological responses can provide use with a great deal of information about a patient in the course of therapy. They may serve as reliable, objective indicators of significant affects, conflicts, fantasies, and resistances. Glucksman on p. 477, para. 1 continues “Symptom exacerbation or reduction is frequently accompanied by physiological changes. For example, the systematic desensitization of phobias is usually, though not always, associated with decreased autonomic nervous system activity. A high degree of psychological defensiveness or resistance is usually correlated with decreased autonomic nervous system activity…”. Glucksman in the following paragraph then states “During the past decade biofeedback has emerged as a mode of treatment for various psychophysiological disorders including migraine and muscle contraction headaches, pain, hypertension, cardiac arrhythmias, and asthma. Biofeedback essentially helps the patient modify voluntary and autonomic nervous system activity by means of direct feedback of physiological functions; e.g., patients can modify blood pressure by means of periodic, repetitive feedback of their systolic and diastolic blood pressure levels.”
This teaching from Glucksman shows that physiological monitoring of blood pressure, pulse, respiratory, and body temperature is a technique that is well known within the art to produce a positive effect on the therapy session. Therefore, it would be obvious to include physiological monitoring within the method described in Young.
Further, the claim limitation “psychological monitoring” is also implied within these teachings. Therapy itself is a form of psychological monitoring. That is, assuming a regular session where no compounds are being administered, a therapist is performing psychological monitoring on a patient in an unaltered mental state. The inclusion of administering a compound to induce an altered mental state, as described in Young and in Eischen, would therefore also include psychological monitoring for positive and negative psychological reactions. This limitation is therefore a part of routine practice within the psychotherapy art.
In addition to the teachings above, Cassels in sec. Introduction, History, and Occurrence, para. 1 teaches that the compound mescaline is a classic hallucinogen. Cassel in para. 2 states “Current use of pure mescaline, either isolated from natural sources or synthesized in the laboratory, seems to be infrequent, possibly due to the relatively high doses required to attain a full psychedelic experience.” This teaching, in combination with Young and Eischen, provides motivation to specifically use mescaline in methods to treat alcohol use disorder as Eischen teaches psychedelics as effective compounds for augmented psychotherapy to treat AUD and Young teaches the combination of therapy sessions with administering compounds to enhance the efficacy of psychotherapy sessions.
The art teaches the combination of therapy sessions with administering compounds that enhance said sessions to treat social behavior disorders. The art also teaches that the compound mescaline is known to be effective in treating alcoholism. The timing and frequency of administering mescaline with therapy sessions, which can be repeated in second or in subsequent maintenance session, is well within the skillset of one of ordinary skill. Additionally, physiological and psychological monitoring are also well known within the arts and one of ordinary skill could easily practice them.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to have combined the teachings of Young, Agin-Liebes, Patel, Glucksman, and Cassels to arrive at the instant claims with a reasonable assumption of success. One of ordinary skill would be motivated to make the combination as the art teaches that administering mescaline to treat AUD is well known and that the combination of this administration with therapy sessions is a practice that is also well known to be effective.
Conclusion
No claims allowed.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624