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
This Office Action is responsive to the Response to Election/Restriction filed 11/07/2025.
Claims 1-54 are pending.
Priority
This application claims the following priority:
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Information Disclosure Statement
The instant information disclosure statement is 160 pages long and cites over 1600 references. The applicant has an obligation to call the most pertinent prior art to the attention of the U.S. Patent and Trademark Office in a proper fashion. Burying one reference in one hundred other IDS references is like citing nothing. PENN YAN BOATS, INC. v. SEA LARK BOATS, INC., et. al. 175 USPQ 260 (S.D. Fla. 1972). Golden Valley Microwave Foods, Inc. v. Weaver Popcorn Co. Inc., 24 USPQ2d 1801 (U.S. District Court Northern District of Indiana, July 22, 1992), Molins PLC v. Textron, Inc., 48 F.3d 1172, 1184, 33 USPQ2d 1823 (Fed. Cir. 1995).
The examiner respectfully requests that Applicant point to the most pertinent prior art.
Election/Restrictions
Applicant’s election without traverse of:
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, in the reply filed on 11/07/2025, is acknowledged.
In the course of the search, the Election of Species requirement was withdrawn.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Objections
Claim 1 is objected to because of the following informalities:
-In claim 1, line 3, following “regimen,” the term “comprising” should be replaced with - -wherein the method comprises- -, for grammatical clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2-5, 34-47, 49-50, and 53-54 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 2 recites the limitation "the dose" in line 1. There is insufficient antecedent basis for this limitation in the claim.
-Claim 53 recites the limitation "side effect of SSRI washout" in line 2. There is insufficient antecedent basis for this limitation in the claim.
-In claim 54, lines 8-9, the phrase “(e.g. paresthesias such as electric shock sensations),” renders the claim indefinite because it is not clear if the parenthetical recitation is a further limitation, i.e., Markush group member, or if it is exemplary of “sensory disturbances,” and does not further limit the claim.
In view of compact prosecution, for the purpose of applying prior art, this phrase is interpreted as exemplary and as not further limiting the claim.
All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency.
Claim Rejections - 35 USC § 103
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 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 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 1-50 and 52-54 are rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris (Psilocybin with psychological support for treatment-resistant depression: six-month follow up,” Psychopharmacology, published 2018, IDS of 07/11/2023) in view of Keks (Switching and stopping antidepressants, Australian Prescriber, published 2016, PTO-892), Nutt (Psychedelic drugs-a new era in psychiatry? Dialogues in Clinical Neuroscience, published 2019, PTO-892), WO 2023/0277568 to Bridges (effectively filed 07/10/2020, PTO-892 of 08/13/2025), Jha (When Discontinuing SSRI Antidepressants Is a Challenge: Management Tips, American Jn. of Psychiatry, published 2018, PTO-892), and Collett (Dosage Regimens, published 2016, PTO-892).
Independent claim 1 recites:
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Carhart-Harris teaches a method of treating treatment resistant depression with psilocybin (title, abstract). Carhart-Harris teaches its patients as previously receiving SSRI’s (Table 1, pg. 623).
Regarding claim 1, while Carhart-Harris teaches a method of administering psilocybin after ceasing of SSRI therapy, it differs from that of instant claim 1 in that it does not teach the method of ceasing SSRI therapy, i.e., ceasing SSRI therapy 1-35 days prior to administration of psilocybin.
Keks teaches that switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects, and teaches that all antidepressant switches must be carried out cautiously and under close observation. Conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before the new antidepressant is started. Keks teaches that clinical expertise is needed for more rapid or cross-taper switching as drug toxicity may result (abstract).
Keks further teaches that gradual dose reduction over days to weeks reduces the risk and severity of complications (abstract).
Keks further teaches that the usual recommended period for antidepressant dose reduction is a minimum of four weeks, but that abrupt cessation may at times be unavoidable on clinical grounds, and further teaches that the time frame for dose reduction also depends on individual risk for withdrawal symptoms, patient preference and experience during withdrawal, and drug characteristics such as half-life. Some patients experience little discomfort despite abrupt cessation, while others are severely affected. In a minority, withdrawal symptoms are not diminished by extending the duration of dose taper. Such patients may prefer rapid cessation and a briefer withdrawal period (pg. 76, Col. 2 “Withdrawing antidepressants”).
Keks teaches that a number of strategies are available for switching between antidepressants, and that individual patient factors and illness factors may require considerable modification of a switching strategy. The most conservative strategy, with the lowest risk of drug interactions, is to gradually taper the dose of the first antidepressant to minimize withdrawal symptoms, then start a washout period equivalent to five half-lives of the drug. The second antidepressant is then introduced according to the starting dose recommendations. As the conservative switch can take quite a long time and usually includes at least several days where the patient is not on an antidepressant, a compromise strategy is the moderate switch. Here the washout period can generally be shortened to about two days. Direct and cross-taper switch methods can also be used (pgs. 77-78, “Switching Strategies” and Table 2).
In conclusion, Keks states, “Switching antidepressants involves drug cessation, which may cause withdrawal symptoms and relapse or exacerbation of the psychiatric illness. Gradual antidepressant withdrawal reduces the risk of complications. If the washout period is not long enough (defined by half-life of the drug), introducing a new antidepressant can cause drug interactions leading to toxicity, particularly serotonin syndrome. Switching from one antidepressant to another requires careful observation and caution” (pg. 79, “Conclusion”).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select the cessation of SSRI therapy 1-35 days prior to administration of psilocybin, to arrive at steps a) and c) of instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- Carhart-Harris teaches a method of treating treatment resistant depression with psilocybin, wherein patients were previously treated with SSRIs,
-Nutt teaches psilocybin for the treatment of depression (pg. 142, paragraph spanning Cols. 1 and 2; paragraph spanning pgs. 142 and 143; Table 1, pg. 144), and teaches that SSRIs desensitize 5-HT2A receptors to psilocybin, reducing its effects, and that stopping SSRIs is necessary (pg. 145, Col. 1, last full paragraph),
-Keks teaches that when switching from one antidepressant to another, it can be done gradually or immediately depending on the patient and the clinical circumstances, and
- "[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," MPEP 2144.05(II).
As such, an ordinary skilled artisan would have been motivated to make such a selection to predictably arrive at the most therapeutically effective method of ceasing SSRI therapy in order to begin psilocybin therapy, such that the method is optimized to minimize withdrawal effects of the SSRI and maximize psilocybin 5-HT2A receptor effect.
Further regarding claim 1, and regarding claims 9-33, and 48 while the combination of Carhart-Harris, Nutt, and Keks teaches a method of administering psilocybin comprising instant steps a) and c), it differs from that of instant claim 1 in that it does not teach step b).
Bridges teaches the administration of psilocybin with an additional compound, such as the benzodiazepine lorazepam (abstract).
Bridges teaches that the benzodiazepine is formulated in the same composition as the psilocybin or is formulated in a separate composition from the psilocybin ([0073]).
Bridges teaches that “The benzodiazepine may be administered to the patient to dampen anxiety-producing effects of the psilocybin. As a result, the benzodiazepine may decrease the intensity of the experience of the subject being administered the psilocybin. Therefore, benzodiazepine may be administered in order to limit, stop, or prevent any negative side effects (such as psilocybin induced anxiety or psilocybin-induced anxiety) from the psilocybin or psilocin that the patient may experience” ([0077]).
See also pg. 20, claims 10-11, 13-16, 19-20, 39, 42-44.
Jha teaches management tips when discontinuing SSRI antidepressants is a challenge (title).
Jha teaches that benzodiazepines for anxiety or agitation can be used if discontinuation symptoms of an SSRI are severe (pg. 1182, Col. 1, 1st full paragraph).
Collett teaches that the design of a dosage regimen determines the therapeutic benefit for patients. The principles of clinical pharmacokinetics are applied to design a dosage regimen for a patient that ensures the appropriate formulation of drug is chosen for an appropriate route of administration. One the basis of the patient’s drug handling parameters, which require an understanding of absorption, distribution, metabolism and excretion, the dosage regimen for the medicine in a particular patient, can be optimized. The pharmacist needs to ensure the appropriate regimen is prescribed to achieve optimal efficacy and minimal toxicity (pg. 2, 1st paragraph).
Collett teaches that clinical pharmacokinetics provides a basic understanding of the principles required to design a dosage regimen, wherein pharmacokinetics provides a mathematical basis to assess the time course of drug and their concentration in the body and enables absorption, distribution, metabolism, and excretion (ADME) to be quantified (pg. 2, 2nd paragraph).
Collett teaches that the design of the regimen, i.e. formulation, route of administration, dose size, and dose frequency, are important factors which influence what plasma concentration is achieved and maintained in the body over the prescribed course of drug treatment. Collett further teaches that other factors that require consideration are patients’ individual needs and lifestyles (pg. 3, 3rd paragraph).
Collett teaches that to understand how the design of dosage regimen influences the time course of a drug in the body, consideration of the complex pharmacokinetic process of drug input, output, and distribution within the body must be considered (pg. 3, last paragraph). Collett teaches that pharmacokinetic models are hypothetical constructs which describe the fate of a drug in a biological system following its administration. The purpose of modeling is to characterize the ADME profile for a drug to indicate how the drug is handled by the patient and to characterize basic parameters (pg. 4, 1st paragraph).
Collett teaches that the greater the rate of drug input relative to the rate of drug output from the body compartment over the net absorption phase, the higher will be the peak concentration achieved in the body or plasma following oral administration of a single dose of drug.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to add at least once daily administration a benzodiazepine 1-35 days prior to administration of psilocybin, to the combined method of Carhart-Harris, Nutt, and Keks, to arrive at instant claim 1 and claims 9-33, and 48. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Jha teaches that benzodiazepines can be used for anxiety or agitation when SSRIs are being discontinued,
-Bridges teaches that co-administering psilocybin and a benzodiazepine dampens the anxiety-producing effects of the psilocybin and limits negative side effects,
-Collett teaches that its known in the art to modify dosage regimens to optimize therapeutic effects, and
- "[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," MPEP 2144.05(II).
As such, an ordinary skilled artisan would have been motivated to make such an addition to predictably arrive at a method that it optimized to minimize SSRI cessation side effects and/or minimize psilocybin negative side effects.
Specifically regarding the specific combination of days of ceasing SSRI therapy and beginning benzodiazepine therapy, an ordinary skilled artisan would have been motivated to modify the dosage regimen, to predictably arrive at a method that minimizes the withdrawal effects of SSRI cessation, while maximizing the therapeutic effects of psilocybin, and minimizing the time between ending one depression therapy and beginning another.
Regarding claims 2, 6, 34-47, and 49-50, while the combination of Carhart-Harris, Nutt, Keks, Bridges, Jha, and Collett, teaches a method of administering psilocybin comprising ceasing SSRI therapy 1-35 days prior to psilocybin administration, administering one or more benzodiazepine at least once daily, at least 1-35 days prior to psilocybin administration, and administering psilocybin, it differs from that of claims 2, 6, 34-47, and 49-50, in that it does not explicitly teach cessation of the SSRI therapy during the titration period, immediate cessation of an SSRI, and the percentage by which SSRI therapy is reduced on different days.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify ceasing SSRI therapy immediately or in a titration period wherein the maintenance dose is decreased incrementally, in the combined method of Carhart-Harris, Nutt, Keks, Bridges, Jha, and Collett, to arrive at instant claims 2, 6, 34-47, and 49-50. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Keks teaches that abrupt cessation is sometimes required due to clinical grounds or patient preference,
-Keks teaches that antidepressant dose reduction of a minimum of four weeks is usually recommended and that the time frame for dose reduction depends on individual risk for withdrawal symptoms, patient illness, patient preference and experience during withdrawal, and individual drug characteristics such as half-life,
-Keks teaches that the lowest risk of drug interactions is to gradually taper the dose of the antidepressant to minimize withdrawal symptoms, and then start a washout period equivalent to five half-lives of the drug,
-Keks teaches that since the gradual taper can take a long time and can include several days where the patient is not on an antidepressant, a moderate switch can be implemented wherein the washout period can be shortened to about two days,
-Keks teaches that a direct and cross-taper switch method can also be applied,
-Collett teaches that the design of a dosage regimen determines the therapeutic benefit for a patient and is dependent on the patient’s drug handling parameter of absorption, distribution, metabolism, and excretion, and
- "[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," MPEP 2144.05(II).
As such, an ordinary skilled artisan would have been motivated to make such modifications, to predictably arrive at the most therapeutically effective and safe method of ceasing SSRI therapy in a patient to decrease withdrawal symptoms, while minimizing the time between treatments for depression.
Regarding claims 3-5 and 7-8, the combination of Carhart-Harris, Nutt, Keks, Bridges, Jha, and Collett, does not explicitly teach the timing of the administration of the benzodiazepine in relation to the SSRI discontinuation and/or withdrawal period.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the timing of the administration of the benzodiazepine, to arrive at instant claims 3-5 and 7-8. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Jha teaches that for those experiencing anxiety or agitation during SSRI discontinuation, benzodiazepine therapy can be used to treat these symptoms,
-Bridges teaches that administration of benzodiazepine with psilocybin can decrease the negative side effects of psilocybin, such as anxiety,
-Collett teaches that the design of a dosage regimen determines the therapeutic benefit for a patient and is dependent on the patient’s drug handling parameter of absorption, distribution, metabolism, and excretion, and
- "[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," MPEP 2144.05(II).
As such, an ordinary skilled artisan would have been motivated to make such a modification to predictably arrive at a benzodiazepine dose regimen that optimizes the treatment of the anxiety and/or agitation experienced by SSRI withdrawal, while optimizing the treatment of the negative side-effects of the psilocybin therapy.
Regarding claim 52, Bridges teaches lorazepam and other benzodiazepines (abstract, [0003], [0006], [0029], [0074]-[0077], [0128], [0130], pg. 21, claims 17-18).
Regarding claims 53-54, Jha teaches that administration of benzodiazepine during SSRI cessation decreases anxiety and/or agitation.
Thus, claims 1-50 and 52-54 are rendered obvious.
Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris (Psilocybin with psychological support for treatment-resistant depression: six-month follow up,” Psychopharmacology, published 2018, IDS of 07/11/2023), Keks (Switching and stopping antidepressants, Australian Prescriber, published 2016, PTO-892), Nutt (Psychedelic drugs-a new era in psychiatry? Dialogues in Clinical Neuroscience, published 2019), WO 2023/0277568 to Bridges (effectively filed 07/10/2020, PTO-892 of 08/13/2025), Jha (When Discontinuing SSRI Antidepressants Is a Challenge: Management Tips, American Jn. of Psychiatry, published 2018, PTO-892), and Collett (Dosage Regimens, published 2016, PTO-892). as applied to claims 1-50 and 52-54 above, and further in view of MayoClinic (Selective Serotonin Reuptake Inhibitors (SSRIs), published 2020, PTO-892).
The combination of Carhart-Harris, Nutt, Keks, Bridges, Jha, and Collett is applied as discussed above and incorporated herein.
While the combination of Carhart-Harris, Nutt, Keks, Bridges, Jha, and Collett teaches a method of administering psilocybin comprising ceasing SSRI therapy 1-35 days prior to psilocybin administration, administering one or more benzodiazepine at least once daily, at least 1-35 days prior to psilocybin administration, and administering psilocybin, it differs from that of instant claim 51, in that it does not teach species of SSRIs.
MayoClinic teaches citalopram, escitalopram, fluoxetine, paroxetine, and sertraline as approved SSRIs to treat depression (pg. 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select citalopram, escitalopram, fluoxetine, paroxetine, and/or sertraline, as the SSRI taught in the combination of Carhart-Harris, Nutt, Keks, Bridges, Jha, and Collett, to arrive at instant claim 52. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because Carhart-Harris teaches its subjects as previously administered SSRIs and MayoClinic teaches citalopram, escitalopram, fluoxetine, paroxetine, and sertraline as FDA approved SSRIs to treat depression.
As such, an ordinary skilled artisan would have been motivated to select citalopram, escitalopram, fluoxetine, paroxetine, or sertraline as the SSRIs taught by Carhart-Harris since these SSRIS are approved by the FDA to treat depression.
Thus, claims 1-54 are rendered obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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/LAUREN WELLS/Examiner, Art Unit 1622