Priority
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is related to and claims the benefit of priority to US Provisional Patent Application Serial No. 63/405,158, filed September 9, 2022.
Information Disclosure Statement
The Information Disclosure Statements filed 9/3/2024, 7/29/2025, 10/23/2025, 12/22/2025, 4/14/2026 and 9/1/2026 have been considered by the Examiner. The submissions are in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Claim Rejections - 35 USC § 112 – Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for inhibiting a stress-related disease or disorder, does not reasonably provide enablement for “treating” (as broadly defined) stress-related disease or disorder. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The test of enablement requires a determination of whether the disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention. That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term “undue experimentation,” it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Claim 1 broadly recites:
“a method of treating a stress-related disease or disorder in a subject comprising administering … R-MDMA…”
The specification defines treating at ¶ 0062 as follows:
“The terms “treat,” “treated,” “treating”, or “treatment” as used herein refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological condition, disorder or disease, or to obtain beneficial or desired clinical results… Treatment may also be preemptive in nature, i.e., it may include prevention of disease. Prevention of a disease may involve complete protection from disease, for example as in the case of prevention of infection with a pathogen or may involve prevention of disease progression. For example, prevention of a disease may not mean complete foreclosure of any effect related to the diseases at any level, but instead may mean prevention of the symptoms of a disease to a clinically significant or detectable level. Prevention of diseases may also mean prevention of progression of a disease to a later stage of the disease and prolonging disease-free survival as compared to disease-free survival if not receiving treatment and prolonging disease-free survival as compared to disease-free survival if not receiving treatment.”
See 0062. Emphasis added.
Thus, the claims are broadly drawn to treating – defined to encompass prophylactically preventing – a stress-related disease or disorder by administering R-MDMA. This is despite 1) the lack of sufficient support for prevention/prophylaxis of any single cancer whether in vitro or in vivo and 2) the lack of sufficient support for preventing.
The nature of the invention/Breadth of claim:
The invention relates to a method of treating stress-related diseases/disorders using R-MDMA. Treatment is defined broadly to include not only therapeutic intervention, but also prophylaxis and prevention, i.e., inhibiting or stopping disease/disorder before it arises. The breadth of the claims is beyond what the prior art or the specification can support. No evidence is provided that prevention had been achieved, or even attempted.
State and predictability of the art:
The state of the art of treating stress-related disease/disorder is recognized as being unpredictable. Recent literature underscores this concern with specificity.
Howlett et al. (Neuropsychopharmacology REVIEWS (2016) 41, 357–369) report:
The state of the art demonstrates that prevention of trauma and stress-related disorders, including PTSD, was highly uncertain and clinically underdeveloped. Howlett teaches that, despite advances in understanding the neurobiology of trauma, “clinical evidence for preventive interventions remain sparse,” and that further adequately controlled clinical testing was needed to establish effective preventive approaches. See abstract. The reference further teaches that there was insufficient evidence for any primary prevention strategy for PTSD and that more research was required. See p. 360. The reference further teaches no pharmacologic interventions to prevent PTSD currently have enough evidence to justify clinical use. The reference further teaches no pharmacologic interventions to prevent PTSD currently have enough evidence to justify clinical use. See p. 365, right column. Thus, the state of the art did not provide predictable or established means for preventing stress-related diseases/disorders such as PTSD.
Relative skill level:
One of ordinary skill in the art is one with access to reagents, tools and equipment used for diagnosing disease, performing tests and/or administering treatment to individuals. The skilled artisan also has many years of training and experience in either the clinical or laboratory environment or both. Therefore, it is clear that the level of skill of one in the art is high. However, this high level of skill is overcome in view of the limited teachings provided by the specification and the unpredictable state of the art, it would require the skilled artisan undue experimentation to make and use the invention commensurate to the scope of the claims.
The amount of direction or guidance provided and the presence or absence of working examples:
The specification provides several preclinical working examples showing R-MDMA receptor activity, neurite growth, fear-extinction effects, locomotor effects, and comparative safety/toxicity. However, the examples do not demonstrate prevention of PTSD or another stress-related disease/disorder in humans. Thus, while the specification provides direction for biological effects of R-MDMA, it provides little specific guidance for the full prophylactic scope, including which at-risk subjects to treat, when treatment should occur relative to trauma, and what regimen would prevent development of PTSD.
The quantity of experimentation necessary:
Because of the known unpredictability of the art, and in the absence of supportive experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed agents could be predictably used for treating (as defined) claimed diseases as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Claim Rejections - 35 USC § 112 – Not further limiting
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 50-52 and 61 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 50-52 contain a circular dependency. Claims 50 depends from Claim 52, Claim 51 depends from Claim 50, and Claim 52 depends from Claim 51. Accordingly, none of Claims 50-52 depend from a preceding independent claim in a manner that incorporates and further limits any limitation of that claim. The circular dependency therefore fails to comply with the requirements for dependent claims. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-12 and 15-61 are rejected under 35 U.S.C. 102a2 as being anticipated by Obidin et al. (US 11,939,312 B2).
Claimed invention
The overall invention is drawn to a method of treating a stress-related disease or disorder such as PTSD in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising R(-)-3,4-methylenedioxymethamphetamine (R-MDMA) to obtain therapeutic benefit (lessen avoidance behavior) while producing the pharmacological/neuroplastic benefit associated with R-MDMA and reducing adverse effects associated with conventional MDMA treatment.
Method
Specifically, claimed treatment and results/effects by administering compositions containing R-MDMA:
Claim 1 reads on a method of treating a stress-related disease or disorder…
Claim 20 reads on a method of decreasing side effects of 3,4-methylenedioxy-methamphetamine (MDMA) treatment…
Claim 30 reads on a method of inducing neurite outgrowth…
Claim 37 reads on a method of treating neuronal atrophy…
Claim 45 reads on a method of inducing structural neuroplasticity…
Claim 53 reads on a method of increasing brain-derived neurotrophic factor (BDNF) levels…
…in a subject by administering R-MDMA to lessen avoidance behavior.
Composition
Claims 60-61 are drawn to a pharmaceutical composition comprising R-MDMA and a pharmaceutically acceptable carrier such as saline or purified water (Claim 61)
Prior art
Obidin teaches treatment of a mental health disorder in a subject including, inter alia, PTSD, anxiety and depression with a therapeutically effective amount of a composition containing R-MDMA and a carrier including water. See abstract; Fig. 1; Claims 9 and 14-19; see Example 5.
With respect the recitation “to lessen avoidance behavior” in Claims 1, 20, 30, 37, 45, and 53, the phrase is interpreted as expressing the intended purpose or result of the positively recited administration of R-MDMA rather than requiring a separate manipulative step. The claims do not require a different composition, dose, route, patient population, or additional treatment step to accomplish the recited purpose. Obidin’s teaching of PTSD meets the limitations for Claim 2, 3, 21-23, 34-36, 42-44, 50- 52, and 57-59.
Regarding Claim 4 and Claim 27, as outlined above, Obidin teaches the composition containing R-MDMA depression and anxiety.
Regarding Claim 5-7 and Claim 28, as outlined above, Obidin teaches R-MDMA administered in an amount of between 50 mg and 300 mg, 100 mg and 300 mg, 150 mg and 300 mg, 200 mg and 300 mg, 200 mg and 250 mg, 62 mg and 285 mg, 62 mg and 235 mg, 141 mg and 285 mg, or 141 mg and 235 mg. See reference claims 10, 15. The dose administered to a subject in an amount of 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, or 10 mg/kg. See col. 44. This also meets the limitations of Claims 33, 41, 49 and 56.
Regarding Claim 8-10 and 29, Obidin teaches administration orally, sublingually, or intravenously/intramuscularly. See col. 46; claims 21-24, 27. Obidin teaches single dose or multi-dose. See col. bridging 7 and col. 8; col. 28, line 53.
Regarding Claim 11-12, Obidin teaches additional active compound combined with R-MDMA composition is an antidepressant or anxiolytic, such as an SSRI. See col. bridging 27 and col. 28.
Regarding Claim 60 and Claim 61, Obidin teaches a composition comprising R-MDMA and a carrier including water. See Example 5.
Regarding Claim 15 and Claim 16, Obidin teaches additional combination psychotherapy treatment including cognitive behavioral therapy (CBT). See Example 14; see also col. 69, line 1; col. 80, lines 31-32.
Regarding Claims 17-19, the recitation that R-MDMA is a partial agonist of 5-HT2A and that R-MDMA induces neurite growth represents identifying a property of R-MDMA. The prior art need not expressly teach and the POSA need not recognize this property of R-MDMA prior to the filing of the current application. This possession of property is evidenced by the current specification in stating “administration of R(−)-MDMA induces neurite outgrowth.” See ¶ 0103. Obidin further teaches the R-MDMA composition agonizes 5-HT2A. See col. 4, line 56 to col. 5, line 11. This also meets the neurite growth limitations of Claims 30-32, 38-40, and 46-48. And because promoting neurite growth induces neuroplasticity and combats neuronal atrophy the limitations of Claims 37 and 45.
Regarding Claims 20, Obidin teaches the R-MDMA composition has reduced toxicity and preferred in place of “MDMA”/racemic-MDMA to minimize the adverse effects associated with racemic-MDMA. See abstract.
Regarding Claims 24-26, the composition minimizes known side effects of racemic-MDMA including tachycardia (increased heart rate) and neurotoxicity including depression (mood disorder). See col. 72, line 6; claim 16.
Regarding Claims 53-56, the recitation that R-MDMA increases BDNF represents identifying a property of R-MDMA. Obidin teaches the R-MDMA composition agonizes 5-HT2A. See col. 4, line 56 to col. 5, line 11. Because the same ingredient and same dosage amounts are administered to the same patient population, and because increasing 5-HT2A causes an increase in BDNF, the administration of R-MDMA as disclosed by Obidin would lead to increase in BDNF at least as a result of increasing 5-HT2A.
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.
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.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Obidin et al. (US 11,939,312 B2) in view of Sabbagh et al. (US 9,399,039).
Claimed invention
Claim 13 limits claim 12, wherein the SSRI 1s fluoxetine, paroxetine, sertraline, escitalopram or citalopram.
Claim 14 limits claim 13, comprising administering the therapeutic agent prior to, concurrently with or after R(-)-MDMA.
Prior art
Obidin teaches additional active compound combined with R-MDMA composition is an antidepressant or anxiolytic, such as an SSRI. However, the reference does not teach a specific SSRI claimed, e.g., fluoxetine, paroxetine, sertraline, escitalopram or citalopram.
Each one of fluoxetine, paroxetine, sertraline, escitalopram or citalopram was already known as pharmaceutically suitable SSRI that can be administered for therapeutic effect in a human or animal. For example, Sabbagh teaches treating a neurodegenerative disease or condition, depression, a stress disorder, or an anxiety disorder in a person or animal with MDMA and an SSRI such as fluoxetine, paroxetine, sertraline, escitalopram or citalopram. See claims 8, 9, 15, and 20.
A person of ordinary skill in the art (POSA) would have found it obvious to combine either fluoxetine, paroxetine, sertraline, escitalopram or citalopram as the SSRI with R-MDMA to treat PTSD because Obidin teaches treatment of PTSD with R-MDMA can be combined with an SSRI, and Sabbagh teaches fluoxetine, paroxetine, sertraline, escitalopram and citalopram are suitable for therapeutic use as SSRI’s in the treatment of a depression, a stress disorder, or an anxiety disorder. Thus, a POSA would have selected any one of these known SSRIs for use in the SSRI combination with R-MDMA disclosed by Obidin, with a reasonable expectation of success. The administration of the SSRI and R-MDMA would result in the SSRI administered prior to, concurrent with or after R-MDMA.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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