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 .
Status of the Claims
Claims 1, 35, 40, 43, 47-49, 56, 63-67, and 74-77 are under examination. Acknowledgement is made of Applicant’s amendments filed on November 26, 2025, cancelation of claims 70-71, and addition of claims 75-77.
Priority
Application 17/416,367 filed June 18th, 2021 is a 371 national stage entry of PCT/US2019/067953 filed December 20th, 2019; which claims priority to provisional applications 62/784,229 and 62/784,222 filed December 21st, 2018.
Information Disclosure Statement
The listing of references in the response filed November 26, 2025 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) submitted on November 26, 2025 was filed after the mailing date of the non-final rejection on May . The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections and Objections
Objections
Applicant’s amendment of claim 67 has removed all instances of the acronym “CNS” and has thus overcome the objection. Therefore, the objection has been withdrawn.
Claim Rejections - 35 USC § 112
112(a)
Applicant’s amendment of claim 67 to include only the enabled Rett syndrome, Fragile X syndrome, and Angelman syndrome has overcome the scope of enablement rejection in the previous Office action. Therefore, the rejection has been withdrawn.
Response to Arguments
35 USC § 103
Applicant's arguments filed on November 26, 2025 with respect to the rejection of claims 1, 4, 9, 14, 19, 23, 27, 31, 35, 40, 43, 47-49, 56, 57, 63, 67, 70-71, and 74 under 35 U.S.C. § 103 as being unpatentable over compounds of Robichaud (WO 2018/013613 A1) in view of Barillari ("Classic Bioisosteres," In Bioisosteres in Medicinal Chemistry, Wiley-VCR, 2012, p. 15-29) have been fully considered but they are not persuasive.
In summary, Applicant argues one would not have been motivated to modify the compounds taught by Robichaud because Robichaud provides no motivation to choose compounds 3, 15, 51, and 54 of Robichaud as the lead compound to be modified, and that Barillari et al. provides no teachings or guidance that would motivate one skilled in the art to modify the teachings of Robichaud. Applicant further cites Kim et al. (“Synthesis and biological evaluation of novel 2-pyridinyl-[ 1,2,3 ]triazoles as inhibitors of transforming growth factor beta 1 type 1 receptor. Bioorg Med Chem Lett. 2004; 14(10):2401-2405), which teaches that aryl and heteroaryl can exert different functional activities and thus isosteres do not necessarily have the same functional activity.
In response, Applicant’s argument is not found persuasive. Regarding Applicant’s arguments that one would not have been motivated to select compounds 3, 15, 51, or 54, MPEP § 2143 I.B, Example 9 states, “The Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound: ‘Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound.’ Eisai, 533 F.3d at 1357, 87 USPQ2d at 1455.”
In the instant case, Compound 54 is explicitly recited in claim 31 of Robichaud as one of about 80 compounds. Thus, Compound 54 is exemplified as a compound of Formula (1-A). Therefore, one would have been motivated to select Compound 54 as one of 80 explicitly recited among hundreds or thousands of possible compounds. In addition, because Barillari teaches that N and CH are isosteres per Grimm’s Hydride Displacement Law (p. 16) and that “the substitution of phenyl ring with pyridine is widely used to improve metabolic stability” (p. 19), one would have been motivated to modify Compound 54 of Robichaud to arrive at instantly claimed Compound 23.
Regarding the argument that isosteres may not have equivalent functionalities, although Kim teaches that isosteres with aryl vs. heteroraryl subsitutents do not necessarily have the same functional activity, the compounds taught by Kim are not structurally similar to the steroid compounds taught by Robichaud. The core of a triazole bonded to a pyridine in Kim is not structurally similar to the steroid core of the compounds in Robichaud. Thus, the fact there is a difference in activity in Kim does not teach away from replacing aryl (e.g. phenyl) substituents in the compounds of Robichaud with heteroaryl substitutents (e.g. pyridine).
In addition, Robichaud teaches compounds both where RY (using the nomenclature of instant Formula (I)) is phenyl, such as Compound 3, and where RY is pyridine or a homolog thereof, including Compound 15, as well as methods of using these compounds to treat Rett syndrome, Fragile X syndrome, or Angelman syndrome (claim 65 of Robichaud teaches a composition of compounds of claims 1-47 to treat CNS-related disorders; claim 67 teaches wherein the disorder is Rett syndrome, Fragile X syndrome, or Angelman syndrome). Thus, pyridine and benzene have ostensibly similar functionalities as RY groups of the steroid compounds taught by Robichaud.
Since Applicant does not present any evidence or showing that substituting the benzene ring of compound 54 of Robichaud with a pyridine ring would lead to unexpected results (e.g., the loss of TBPS activity), the argument is not found persuasive for the reasons set forth herein.
Therefore, the rejection is maintained but revisited and modified in view of the claim amendments.
New Claim Rejections
Claim Rejections - 35 USC § 103
Claims 1 and 75-76 are rejected under 35 U.S.C. 103 as being unpatentable over Robichaud (WO 2018/013613 A1) in view of Barillari ("Classic Bioisosteres," In Bioisosteres in Medicinal Chemistry, Wiley-VCR, 2012, p. 15-29).
Robichaud teaches the following compound (claim 30, p. 236), cited as Compound 3 by Applicant in the response filed November 26, 2025 and in Table 2 (p. 210) of Robichaud:
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315
490
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Robichaud does not teach the above wherein RY is
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56
71
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as recited in instant claim 75 or
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67
75
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as recited in claim 76.
Barillari teaches that N and CH are isosteres per Grimm’s Hydride Displacement Law (p. 16) and that “the substitution of phenyl ring with pyridine is widely used to improve metabolic stability” (p. 19). Barillari also teaches that H and F are isosteres.
Regarding claims 1, 75 and 76, it would have been obvious to modify Compound 3 of Robichaud by replacing the phenyl ring with pyridine. One would have been motivated to select Compound 3 because it is recited in the claims of Robichaud, and would have been motivated to substitute the phenyl ring with pyridine to improve the metabolic stability of the compound, as taught by Barillari. In doing so, one would arrive at the compounds of claims 1, 75, and 76 with a reasonable expectation of success.
Allowable Subject Matter
Claim 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.
The following is a statement of reasons for the indication of allowable subject matter:
Although the following Ry
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56
71
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is made obvious over Robichaud Compound 3 in view of Barillari, it would not have been obvious to convert the phenyl of Robichaud directly to
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81
68
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as in instant claim 77 based on the prior art.
Robichaud also teaches the following Formula (1-A-4) (claim 20):
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188
244
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wherein RX can be H, RY1 can be H (claim 21), b can be 0, and RY2 can be heteroaryl substituted with 0-5 occurences of -CN (claim 23). Although
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70
88
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would fall under RY2 as claimed by Robichaud claim 23 and Formula (1-A-4), it would not be obvious to arrive at this particular group based on the teachings of Robichaud.
Conclusion
Claims 1, 35, 40, 43, 47-49, 56, 63-67, and 74-76 are rejected.
Claim 77 is 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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLIVER D. HEES whose telephone number is (571)272-9840. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, AMY L. CLARK can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OLIVER D HEES/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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