DETAILED ACTION
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
The instant application, filed 09/11/2023, is a national stage entry of PCT/EP2022/056406, filed 03/11/2022, which claims domestic priority to U.S. provisional application no. 63/160,068, filed 03/12/2021.
Claim Amendments
The amendment filed on 09/11/2023 is acknowledged and entered.
Claims 1-39 are cancelled;
Claims 40-59 are added.
Claims 40-59 are pending.
Information Disclosure Statement
The Information Disclosure Statement filed on 12/05/2023, 03/1920 24, 10/15/2024, and 03/10/2025 are acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statements are considered.
Restriction/Election
Applicant’s election without traverse of Group I in the reply filed on 03/12/2026 is acknowledged. Applicant’s further election of the following species is also acknowledged:
Species A: Applicant elects “reducing an effect of substance withdrawal” (see claim 41)
Species A1: Applicant elects “cocaine” (see claims 41-44)
Species B: Applicant elects “DFosB” (see claims 48, 49, and 52)
Species C: Applicant elects “WAY100635” (see claim 56).
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species does not make a contribution over the prior art of record.
Status of Claims
Claims 40-59 are pending in the instant application. Claims 45-47, 50, 51, 53, and 57-59 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species. Therefore, claims 40-44, 48, 49, 52, and 54-56 read on an elected invention and species and are therefore under consideration in the instant application.
Drawings
The drawings filed on 09/22/2023 are objected to under 37 CFR § 1.83(a) for the following reasons:
The different data types are indistinguishable in Figures 38A, 40A, 42A, 44A, 46A, 51, and 52. The original figures rely on color-coding of the data, a feature not available in the black and white drawings. The figures must be remade with shapes or line-types used to describe the different data points.
The gel bands are indistinguishable in Figures 13C, 15C, 17A-D (wherein the gels are not labeled using a figure label designator) 18, 20B, 20C, 22A-D (wherein the gels are not labeled using a figure label designator). The figures must be remade with figures wherein the gel bands are distinguishable.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). 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.
Claim Rejections - 35 U.S.C. § 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.
Claims 40-44, 54, and 55 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated O’Sullivan and Murphy (Brain and Neuroscience Advances, Volume 3, Poster number: PM166 (SP) published January 2019).
The instant claims are drawn to a method of treating substance use disorder comprising the administration of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), wherein the substance is cocaine. The claims are further drawn to reducing an effect of substance withdrawal.
O’Sullivan and Murphy teach administering 5-MeO-DMT to subjects experiencing a cocaine based substance use disorder (see instant claims 40 and 42-44). O’Sullivan and Murphy further teach the administration of 5-MeO-DMT as a single acute dose of 10 mg/kg or 20mg/kg (see instant claims 54 and 55). O’Sullivan and Murphy teach that 5-MeO-DMT reduced despair-like behavior and reversed cocaine-induced behavioral abnormalities including anxiety and depression. The disclosure further notes that substance-induced depression is a major risk factor for driving relapse to drug use.
Regarding claim 41, although O’Sullivan and Murphy do not explicitly state “reducing an effect of substance withdrawal,” this limitation is inherent to the disclosed method of O’Sullivan and Murphy since O’Sullivan and Murphy teach the administration of the same compound to the same subject having a substance use disorder. Thus administration of the same compound in the same amount to the same subject will necessarily produce the same effects as claimed in instant claim 41. A method carried out under conditions that necessarily produce a result inherently possess that results, even if the result is not recognized or necessarily disclosed by the prior art. In the instant case, O’Sullivan and Murphy’s method of administering 5-MeO-DMT to cocaine-experienced animals in the amounts as claimed will inherently produce the effects as claimed in claim 41.
The teachings set forth above are applied to each claim individually, and the claims herein stand rejected.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claim 48, 49, and 52 is rejected under 35 U.S.C. § 103 as being unpatentable over O’Sullivan and Murphy (as applied to claims 40-44, 54, and 55, above), in view of Seltenhammer et al. (J Addict Rs Ther, Volume 7, Issue 5, published October 1, 2016), hereinafter Seltenhammer.
The instant claims are further drawn to a method wherein 5-MeO-DMT modulates gene expression of a DFosB as a biomarker present in the subject’s blood or urine
The teachings of O’Sullivan and Murphy are as set forth above.
O’Sullivan and Murphy teach wherein 5-MeO-DMT reverses the majority of measured molecular changes in gene and protein expression induced by repeated cocaine administration across multiple brain structures (see instant claims 48, 49, and 52).
However, O’Sullivan and Murphy fail to teach wherein the biomarker whose gene expression is modulated by 5-MeO-DMT is DFosB, and also fails to teach wherein the biomarker is detected in the subject’s blood or urine.
The deficiencies of O’Sullivan and Murphy are remedied by Seltenhammer, who teaches that highly stable 35-37 kDa isoforms of DFosB accumulate in the nucleus accumbens of chronic human drug users (page 2). The disclosure further teaches that the isoforms were detectable by immunoblotting, and that peripheral blood and urine samples were routinely collected from the same drug abusing subjects, and subjected to quantitative toxicological analysis by gas chromatography-mass spectrometry (page 3). Thus, Seltenhammer establishes both that DFosB can be measured as a specific biomarker of chronic drug abuse in humans, and that its peripheral blood and urine detection is considered standard, as it is routinely collected in the evaluation of drug addicted patients.
A person of ordinary skill in the art would be motivated to combine the teachings of O’Sullivan and Murphy with Seltenhammer, because O’Sullivan and Murphy demonstrates that cocaine 5-MeO-DMT induced gene expression changes. A person of ordinary skill in the art, seeking to monitor the ability of 5-MeO-DMT to modulate cocaine induced molecular changes using a clinically accessible biological sample, would be directly motivated to measure DFosB—the primary accumulating biomarker identified by Seltenhammer. Both blood and urine are routinely collected from such patients, and a person of ordinary skill in the art would expect reasonable success in detecting changes in DFosB levels, as the teachings of O’Sullivan and Murphy indicate that 5-MeO-DMT is capable of inducing gene expression changes.
Claim 56 is rejected under 35 U.S.C. § 103 as being unpatentable over O’Sullivan and Murphy (as applied to claims 40, 42-44, 54, and 55, above), in view of Krebs-Thomson et al. (Psychopharmacology, Volume 189, pages 319-329, published September 30, 2006), hereinafter Krebs-Thomson.
The instant claims are further drawn to the further administration of a therapeutically effective amount of antidote reversal agent WAY100635.
The teachings of O’Sullivan and Murphy are as set forth above.
O’Sullivan and Murphy teach that 5-MeO-DMT is an agonist of 5-HT1A.
O’Sullivan and Murphy fail to teach the co-administration of WAY100635 as an antidote reversal agent.
The deficiencies of O’Sullivan and Murphy are remedied by Krebs-Thomson, who teach the administration of WAY100635 at 1mg/kg as a selective 5-HT1A antagonist directly in combination with 5-MeO-DMT (Figure 4). Krebs-Thomson disclose wherein WAY100635 pretreatment decreases the behavioral effects of 5-MeO-DMT, such as decreased locomotor activity, reduce investigatory behavior, and disrupted prepulse inhibition (Abstract, pages 322-325, Figures 1-4). Krebs-Thomson. That is, WAY100635 is capable of successfully counteracting the effects of 5-MeO-DMT when co-administered with the drug.
A person of ordinary skill in the art would be motivated to combine the teachings of O’Sullivan and Murphy with those of Krebs-Thomson, because O’Sullivan and Murphy establish that the therapeutic effects of 5-MeO-DMT in cocaine-experienced subjects are mediated through 5-HT1A receptor agonism. Krebs-Thomson directly demonstrates that co-administration of 5-MeO-DMT and WAY100635 selectively antagonizes the 5-HT1A-mediated behavioral effects of 5-MeO-DMT. Given the demonstrated pharmacological interaction between 5-MeO-DMT and WAY100635 demonstrated by Krebs-Thomson, a person of ordinary skill in the art would recognize that co-administering WAY100635 provides a means to selectively modulate 5-MeO-DMT receptor activity profile in the therapeutic context disclosed by O’Sullivan and Murphy, with a reasonable expectation of success.
Correspondence
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on +1 (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is +1 (571) 273-8300.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
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