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 mailed 02/03/2026 states that the instant application claims benefit of provisional applications 63/585,000, filed 09/25/2023, 63/513,140, filed 07/12/2023, and 63/493,428, filed 03/31/2023.
The provisional applications support the instant application. Therefore, the effective filing date is 03/31/2023.
Information Disclosure Statement
The information disclosure statements submitted 03/28/2024, 05/17/2024, 06/26/2024, 08/15/2024, 02/10/2026, and 05/18/2026 have been considered.
Restriction/Species Election
Applicant’s election without traverse of the following is acknowledged.
Applicant has elected i) sertraline as the monoamine antidepressant agent, ii) depressive disorder as the psychiatric disorder, and iii) N,N-dimethyltryptamine as the compound of formula I.
Claims 47-50 are hereby withdrawn being drawn to non-elected species.
Rejections
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 Rationales
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) 29-46 and 51-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chadeayne (US20210085671) in view of Cameron (ACS Chem. Neurosci. 2018, 9, 2344-2357), Barker (Psychopharmacology, 2022, 239:1749-1763), Liechti (US20220387456A1), Watts (Journal of Contextual Behavioral Science, 15, 2020, 92-102) and Iannuzzo (Psychiatry Research, 145, 2006, 21-37).
Chadeayne is drawn to a composition for administration comprising a first serotonergic drug and a second serotonergic drug (reference claim 1 and para. [0028]).
Regarding claims 29, 32, 34-35, Chadeayne in para. [0028] contemplates first serotonergic drugs including N,N-dibutyl tryptamine (N,N-Dibutyl-T), N,N-diethyl-T, N-Methyl-T, and 5-methoxy-N,N-dimethyl-tryptamine (5-methoxy-N,N-dimethyl-T). Chadeayne in the same paragraph notes that all of the compounds are purified psilocybin derivatives.
Chadeayne in reference claim 5 also contemplates the administration of sertraline as a second serotonergic drug. Chadeayne in para. [0258] also contemplates the administration of sertraline as a serotonergic drug. Note that the reference claim does not exclude the administration of the psilocybin derivative with a second serotonergic drug, including sertraline. That is one of ordinary skill would recognize that the psilocybin derivative can be the first serotonergic drug and sertraline can be the second serotonergic drug.
Regarding claims 34-35, Chadeayne in para. [0003]-[0004] discusses the administration of serotonergic drugs to affect conditions such as depression where it states “Many people worldwide are afflicted with psychological or mood disorders, such as depression, anxiety, compulsion, and post-traumatic stress disorder. Many of these conditions are believed to involve a person’s serotonin system-including interactions between (A) the neurotransmitter serotonin…and (B) several different subtypes of serotonin neurotransmitter receptors found in the human body.”
Chadeayne continues “A variety of compositions are known to modulate activity at the serotonin receptors. A number of pharmaceuticals (antidepressant, serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, etc.) have become available…Almost all these pharmaceutical target neurotransmitters, e.g., serotonergic receptors…and in different. All ten of the leading pharmaceutical products for treating mood disorders (such as depression…) target serotonin pathways.”
Therefore, the connection between serotonergic drugs and depression is well known and one of ordinary skill would find it obvious to administer a compound known to be a serotonergic drug to treat depression.
While Chadeayne discusses psilocybin derivatives similar in structure to N,N-dimethyltryptamine, it does not explicitly discuss N,N-dimethyl tryptamine, drug assisted psychotherapy, intravenous or intramuscular administration, doses, and MADRS or Becks Depression Inventory-II. This is addressed by Cameron, Barker, Liechti, Watts, and Iannuzzo.
Regarding claims 29, 43-46 and 51, Cameron on p. 2346, Figure 3 teaches the structure, synthesis, and biosynthesis of N,N-dimethyltryptamine, compound 1 (herein after DMT). The structure of 5-methoxy-N,N-DMT (Cameron, Fig. 2) is included for comparison.
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Further, Cameron on p. 2346, Table 1 teaches the affinity of DMT for various Serotonin receptors, establishing that DMT is either an agonist or partial agonist for major serotonin receptors and subtypes.
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Critically, Cameron on p. 2345, left col., para. 2-4 states “Structurally, the most striking aspect of DMT is its simplicity…Chemically, it is related to the natural compounds serotonin and melatonin, as all three molecules possess a tryptamine core. The DMT core structure is also a prominent feature of a class of medications known as the triptans; however, the effects of DMT on the central nervous system are quite distinct from these compounds….Importantly, the triptans demonstrate that it is possible to make slight modification to the structure of DMT to produce nonhallucinogenic analogues of great medicinal value. Other DMT analogues have shown promise for treating Alzheimer’s disease and depression in preclinical models.”
Cameron continues “Functionally, DMT is most similar to the serotonergic psychedelics – compounds that have ‘mind-manifesting’ properties and are infamous for their effects on perception. In fact, the structure of DMT constitutes the core of several important psychedelic compounds including lysergic acid, diethylamide (LSD) ibogaine, psilocybin, and 5-Meo-DMT.”
Cameron concludes this section states “Despite its simple structure, DMT binds with high affinity to a variety of neuroreceptors and elicits robust behavioral responses. An excellent review covering various aspects of DMT neuropharmacology was published recently, which we expand upon here…Additionally, we discuss the psychoplastogenic (plasticity-promoting) effects of DMT and its potential use for treating depression, addiction, and anxiety disorders.”
Cameron’s teachings make it clear that one of ordinary skill in the art would find it obvious to modify the composition of Chadeayne to include DMT in place of the psilocybin derivative of its claims.
Regarding claims 38-42, Barker teaches intravenous administration of DMT. Barker in its abstract states “As with all drugs, the route form, and/or dose of a substance administered or applied can play a defining role in its overall pharmacology and use as a therapeutic. This review will focus on these factors as they related to the psychedelic N,N-dimethyltryptamine (DMT).
Barker on p. 1751 sec. 2 states “Oral administration of DMT alone is rendered neurochemically inactive by MAO during first-pass metabolism. Thus, other routes for the administration of DMT have been designed to avoid or mitigate this fate. These have predominantly required intravenous (IV) or intramuscular (IM) administration…. Barker continues “Szára reported that the effects of intramuscular DMT (o.7 mg/kg) were like mescaline and LSD (visual illusions and hallucinations, distortion of body image, speech disturbance, mood changes, and euphoria or anxiety). Other studies using either IV or IM administrations [citations omitted] have observed similar results. The intramuscular effects of DMT (0.2-1 mg/kg) generally had a rapid onset (2-5 min) and lasted 30-60 min…”.
Barker’s teachings of doses does not explicitly teach the claimed dose amounts of claims 40-42. However, it would be well within the skillset of one of ordinary skill in the art to modify the dose amounts to arrive at the instant claims.
The MPEP section 2144.05, subsection II states “
The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the ingredients beneficially taught by the cited references), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
Regarding claim 30-33, Liechti is drawn to the administration of psilocybin in co-treatment to assist psychotherapy (title). Liechti in para. [0053]-[0054] states “The present invention shows that administering psychedelics with antidepressants can be advantageous. More specifically, the present invention provides for a method of enhancing positive acute and long-term therapeutic effects of a psychedelic, by pretreating an individual with an antidepressant, administering a psychedelic to the individual, and inducing a more positive psychological state in the individual with the antidepressant-psychedelic combination compared with the psychedelic alone. Administering the antidepressant (such as escitalopram…) before the psychedelic administration enhances the endogenous serotonin system prior to stimulating the 5-HT2 receptor with the psychedelic and overall induces a positive psychological state in an individual and relatively enhances the positive response to the psychedelic with the antidepressant. The overall goal of the present invention is to improve the positive over negative acute subjective effect response…to a psychedelic. The method can be used for any indication of psychedelic medication use and typically applies to indications where a positive experience after psychedelic use predicts the long-0term effect such as psychiatric disorders including (but not limited to) depression…”.
Liechti in para. [0059] lists sertraline as an alternative to escitalopram.
Liechti in para. [0064] states “The present invention documents that escitalopram treatment before the administration of a full and typical therapeutic dose of psilocybin improved the acute effects of psilocybin compared to its administration after a placebo treatment. Specifically, escitalopram pretreatment reduced psilocybin-induced bad drug effect, gear, anxiety, anxious ego-dissolution, nadir effects, cardio stimulants effects, and acute adverse effects compared to psilocybin alone thus resulting in an overall more favorable acute effect profile for psilocybin.”
Regarding claims 52 and 53, Watts in its abstract states “Psychedelic assisted therapy comprises three stages: Preparation, Psychedelic Session, and Integration.” Watts in sec. 5.3 states “Each psilocybin session consists of either one large or one small dose. Therapeutic contact consists of four preparation sessions, the two psilocybin sessions scheduled three weeks apart, and 4-7 integration sessions. Preparation 1 is a face to face meeting with the two therapist ‘guides’ that happens at the end of the initial screening visit; Preparation 2 is a phone call with the main guide conducted approximately 1 week before the first psilocybin session; Preparation 3 is a full afternoon of face-to-face preparation conducted the day before psilocybin 1 that ends when the client has had all their questions answer; Preparation 4 is a phone call the day before Psilocybin 2. The integration portion consists of four sessions that occur the day after Psilocybin 1, one week after Psilocybin 1, the day after Psilocybin 2, and 3 weeks after Psilocybin 2.”
Regarding claims 36 and 37, Iannuzzo teaches the HAM-D/MADRS Interview depression symptom rating scale. Iannuzzo in its abstract states “The Hamilton Rating Scale for Depression (HAM-D) and the Montgomery- Åsberg Depression Rating Scale (MADRS), two widely used depression scales, each have unique advantages and limitations for research. Iannuzzo in sec4.2 states “The HAM-D/MADRS Interview provides an easy-to-administer and reliable method of rating depression severity which may be used to improve consistency and validity of depression study findings.”
The core of the instantly claimed invention is drawn to a method for supplementing psychotherapy via administering of DMT to either an on-going treatment with an antidepressant and/or to regiment of drug-assisted psychotherapy involving combined administration of DMT and an antidepressant. The administration of tryptamines, including DMT, to treat depression is known within the art. Additionally, the administration of sertraline to treat depression is also known within the art. Chadeayne contemplates the combination of two serotonergic compounds, such as tryptamines and sertraline, to treat depression. The art in Cameron indicates that DMT is well-studied and its efficacy as a serotonergic compound is well known. As stated above, one of ordinary skill in the art would find it obvious to modify Chadeayne to include DMT in place of another tryptamine compound. The dependent claims that specify administration route and dose are made obvious by the art and what isn’t made explicitly obvious, one of ordinary skill could arrive at via simple modifications available within their skillset. The additional dependent claims that specify assessment via MADRS would be obvious as the art shows that this is a typically assessment that one of ordinary skill would be trained in or at least be knowledgeable of. Similarly, drug-assisted psychotherapy is a technique that is well known as well and it would be obvious to make use of the claimed method in a larger method of drug-assisted psychotherapy, especially so because the art teaches that DMT has similar affinity for serotonin receptors as other tryptamines, such as psilocybin.
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 combine the teachings of Chadeayne, Cameron, Barker, Liechti, Watts, and Iannuzzo to arrive at the instant claims. One of ordinary skill would find motivation to make the combinations as the art teaches the efficacy of DMT as a serotonergic compound is similar to that of other tryptamine compounds. See KSR Rationales A, B, and F.
Conclusion
No claims allowed.
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/LUISALBERTO GONZALEZ/Examiner, Art Unit 1624
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