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 .
Status of Claims
Claims 1, 9, 13-17, 20-21, 26, and 30 are pending in the instant application.
Claims 2-8, 10-12, 18-19, 22-25, 27-29, and 31-35 have been canceled.
Withdrawn Rejections/Objections
Applicant’s amendment is sufficient to overcome the objection to the specification for minor informalities. This objection is hereby withdrawn.
Applicant’s cancellation of Claim 24 renders the objection thereof moot. This objection is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claim 30 under 35 U.S.C 112(a) and the rejection of Claim 30 under 35 U.S.C. 112(b). These rejections are hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claims 1, 3-5, 9, and 13 under 35 U.S.C. 102. This rejection is hereby withdrawn.
Applicant’s cancellation of Claims 18-19 and 22-25 render the rejection thereof under 35 U.S.C. 103 moot. Applicant’s amendment is sufficient to overcome the rejection of Claim 26 under 35 U.S.C. 103. This rejection is hereby withdrawn.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The rejection of Claim 14 under 35 U.S.C. 103 as being unpatentable over Sard et. al. (WO 2006/047032 A2; cited on Applicant’s Information Disclosure Statement filed August 8th, 2024; cited in non-final rejection mailed June 13th, 2025; hereinafter referred to as Sard 1) in view of Meanwell (“Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design”, J. Med. Chem., 61, 5822-5880, 2018; cited in non-final rejection mailed June 13th, 2025; hereinafter referred to as Meanwell) is maintained.
This rejection is extended to Claims 1, 9, 13, and 30.
Applicant has traversed this rejection on the basis that no motivation would have led a skilled artisan to select and modify compound 16 in Sard 1.
The Examiner does not find this persuasive.
As noted in the non-final rejection mailed June 13th, 2025, Sard 1 teaches the following compound as compound 16:
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wherein R is cyclopropylmethyl.
While Sard 1 does not disclose activity of this compound specifically, at Claim 16, Sard 1 teaches a method of increasing the activity of a serotonin receptor comprising contacting a serotonin receptor with a compound of Claim 9, which includes compound 16, above.
In addition to compound 16, at Figure 1, Sard 1 teaches compound 13, having the same structure as noted above, wherein R is CH2CH2CH3, with a compound code of O-3952. At Page 50, Table 2, Sard 1 teaches compound O-3952 as being an activator of 5-HT2A and 5-HT2C, thereby reading on the limitations of instant Claim 30. Compound 13 reads on a compound of Formula I as instantly recited at Claims 1, 9, and 13 when R1 and R2 are methyl, R3 is CH2CH2CH3 and Z is H, differing only in the presence of the aryl fluorine atom.
As noted in the non-final rejection mailed June 13th, 2025, at Page 5822, first column, Meanwell teaches “early applications of fluorine as a bioisostere focused on the relatively simple replacement of hydrogen atoms in drug molecules”, and further, at Page 5823, under “Fluorine as a Bioisostere of the Hydorgen atom in Alkyl Moieties,” Meanwell states, “Replacing hydrogen atoms with fluorine atoms has been explored extensively in drug design, most commonly to replace those bound to an aromatic ring…”
Applicant’s traversal of the rejection of Claim 14 did not raise objection to the bioisosteric replacement of fluorine with hydrogen being non-obvious, but rather was based on the assertion Sard 1 did not teach that the compound was active as a 5-HT2 receptor agonist. For the reasons noted above, this is not the case. Therefore, the substitution of the fluorine atoms in the compounds taught by Sard 1 for a hydrogen atom would have been obvious to a person having ordinary skill in the art, with reasonable expectation of success, as the compounds taught by Sard 1 were taught to be 5HT2 receptor agonists. Per MPEP 2144.09, I., “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).”
The rejection of Claim 17 under 35 U.S.C. 103 as being unpatentable over Sard et. al. (“SAR of psilocybin analogs: Discovery of a selective 5-HT2c agonist”, Bioorganic & Medicinal Chemistry Letters, 15, 4555-4559, 2005; cited on Applicant’s Information Disclosure Statement filed August 8th, 2024; cited in non-final rejection mailed June 13th, 2025; hereinafter referred to as Sard 2) in view of Pirali et. al. (“Applications of Deuterium in Medicinal Chemistry”, Journal of Medicinal Chemistry, 62, 5276-5297, 2019; cited in non-final rejection mailed June 13th, 2025; hereinafter referred to as Pirali) is maintained.
This rejection is extended to Claims 1 and 30.
Applicant traverses this rejection on the basis that Sard 2 provides no reason for starting with compound 14, referenced in the non-final rejection mailed June 13th, 2025 and that compound 14 further differs from the instantly claimed compounds by having a methylene linker between the amine moiety and the indole, as opposed to an ethylene linker.
The examiner does not find this argument persuasive.
As noted in the non-final rejection mailed June 13th, 2025, Sard 2 teaches the following group of compounds:
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With respect to Applicant’s assertion that compound 14 shows reduced affinity and selectivity for the 5-HT2c receptor, this argument is not persuasive. The instantly claimed compounds and limitation of instant Claim 30 are drawn to agonist activity of a 5-HT2 receptor. The fact that compound 14 has reduced activity over other 5-HT2 receptors does not negate its activity and status in the art as a 5-HT2 receptor. With regard to the length of the linker, the instantly claimed compounds as recited at Claims 1 and 14 are homologous to compound 14 as taught by Sard 2. Per MPEP 2144.09, II., “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).”
Further, at Page 4558, first paragraph, Sard 2 teaches decreasing the linker from ethylene to methylene resulted in poorer activity against the 5-HT2 receptors. Therefore, a person having ordinary skill in the art would reasonably expect success in activating a 5-HT2 receptor by generating a homolog of compound 14 by replacing the aforementioned methylene linker with an ethylene linker as instantly claimed.
As applicant has not traversed the motivation for substituting CH3 for CD3 as noted in the non-final rejection mailed June 13th, 2025, this rejection holds. For clarity of the record, the motivation for substituting CD3 for CH3 is restated below.
As taught by Pirali, incorporation of deuterium in bioactive compounds is a well-established practice in the art.
At Page 5276, Second Column, Second Paragraph, Pirali teached C-D bonds are more stable to oxidative processes compared to C-H bonds.
At Page 5278, Second Column, Third Paragraph, Pirali teaches deuterated compounds generally result in reduced clearance, increased Cmax and t1/2.
Further, at Page 5292, Second Column, Second Paragraph, Pirali teaches “nowarays deuterium has also been used for bioisoteric replacements when fluorine replacement is unfeasible”.
Taken together, applying KSR exemplary rationale D, it would have been prima facie obvious to a person having ordinary skill in the art to modify the compound taught by Sard 2, noted above, substituting CD3 for CH3 in the R3 position and extending the methylene linker to an ethylene linker with reasonable expectation of success.
Allowable Subject Matter
Claims 14-16, 20-21, and 26 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1, 9, 13, 17, and 30 are rejected.
Claims 14-16, 20-21, and 26 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624