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 .
Election/Restrictions
Applicant’s election without traverse of the invention of Group I and Compound 169 in the reply filed on 01/06/2026 is acknowledged.
Examiner searched Compound 169 and did not find art. Examiner expanded the search to encompass all of Formula (I) and did not find art.
Claim 1 is directed to an allowable product, notwithstanding formal matters addressed herein. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 83-86, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 09/16/2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Priority
Examiner acknowledges that, according to the Filing receipt received 05/29/2024, that the instant application 18/249,774 filed 04/20/2023 is a 371 of PCT/US2021/056694 filed 10/26/2021 which claims benefit of U.S. provisional applications 63/133,046 filed 12/31/2020 and 63/106,156 filed 10/27/2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 04/20/2023 and 10/02/2024 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1-2, 4, 7, 16, 24, 31, 34, 37-39, 44, 62, 67, 69, 71 and 83 are objected to because of the following informalities: "(C1-C3 haloalkyl)", "(C3-C6 cycloalkyl)", and "(C1-C3 alkyl)" do not require parentheses when not bound to another moiety (e.g., “C1-C3 alkyl” vs “-O-(C1-C3 alkyl)”). Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 83 is 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 treating a 5HT2A-related disorder selected from a condition associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, an effect of PCI selected from microvascular obstruction (MVO), myocardial injury, reduced cardiac function, or a major adverse cardiac event (MACE), and Raynaud's, does not reasonably provide enablement for treating a 5HT2A-related disorder generally. 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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill level.
The nature of the invention claims a method of treating 5HT2A-related disorders comprising administering to an individual in need thereof a compound of Formula (I). 5HT2A-related disorders encompass a broad scope of diseases, from Alzheimer’s disease and depression to cardiovascular disease. These disorders are not considered predictable in the art, nor are they treated using the same methods or medicaments. For example, depression is often treated using talk therapy and SSRI’s, while cardiovascular diseases can be treated by administration of beta blockers and anticoagulants.
The state of the art, with regards to Alzheimer’s disease, is that Alzheimer’s disease is progressive, irreversible, and incurable. Risk factors that can lead to the onset of Alzheimer’s can be environmental or genetic in nature, and the etiology of the illness is still not completely understood. The main theoretical construct for the progression of Alzheimer’s disease is the “amyloid cascade hypothesis”, which posits that amyloid plaques and Aβ-peptides are the cause of the progressive neurodegeneration that characterizes the disease (De Strooper et al.; p. 603, col. 1). However, research and clinical studies have shown that the multicausality of dementia diverges from the once linear hypothesis of the amyloid cascade as the main causal factor (Scheltens et al.; p. 508, col. 2). Current treatment for Alzheimer’s disease includes supportive care form family and caregivers, while four drugs have been approved for the treatment of the dementia phase of Alzheimer’s disease: cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and the glutamate antagonist memantine (Scheltens et al.; p. 511, col. 2). However, it should be noted that these drugs cannot reverse the disease and only provide amelioration of existing symptoms, and additionally are mechanistically discrete from the instant invention.
It is maintained by the examiner that applicant has not enabled the instant claims in view of the current state of the art, as the applicant fails in the specification to demonstrate the ability of the claimed invention to treat 5HT2A-related disorders generally. Furthermore, said disorders have no reasonable expectation to be predictably cured or prevented.
The breadth of the claims
The claims are very broad insofar as the instant claims recite a method of treating 5HT2A-related disorders comprising administering to an individual in need thereof a compound of Formula (I).
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As far as examiner is aware, no compounds have been described in the art (including the instantly claimed compounds) that can treat such a broad array of diseases and disorders.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction or guidance for treating 5HT2A-related disorders generally. The working examples are limited to in vitro assays demonstrating the activity of the claimed compounds of Formula (I) when binding to 5HT2A receptors and cells expressing 5HT2A. See the specification, pages 284-289.
The quantity of experimentation necessary
Due to the known unpredictability in the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed compounds would be capable of treating 5HT2A-related disorders generally.
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Allowable Subject Matter
Claims 84-86 are objected to for depending upon a rejected base claim and incorporate the informalities of claim 83.
The instantly claimed invention is free of the art. The closest prior art is CHEMCATS (RN 1368454-82-1; previously cited) which discloses a compound with a core structure containing isoxazole bound to a phenyl group. However, there is no suggestion in the art to modify the compound in order to arrive at the instant invention.
Additionally, Teegarden et al. (WO 2006/055734 A2; 2006) discloses 3-phenyl-pyrazole 5-HT2A modulators. Teegarden et al. does not teach or suggest substituting the pyrazole with isoxazole in order to arrive at the instant invention.
Conclusion
Claim 83 is rejected. Claims 1-2, 4, 7, 16, 24, 31, 34, 37-39, 44, 62, 67, 69, 71 and 84-86 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.E.B./Examiner, Art Unit 1624 03/16/2026
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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