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 1-2, 6, 8-10, 12-26, and 28-29 are pending in the instant application
Claims 3-5, 7, 11, and 27 have been canceled.
Claims 28-29 stand withdrawn.
Withdrawn Rejections/Objections
Applicant’s amendment is sufficient to overcome the rejection of Claims 1-23 and 25-26 under 35 U.S.C. 112(a). Applicant’s cancellation of Claims 3-5, 7, and 11 renders the rejection thereof moot. This rejection is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claims 1-5, 7-9, 11, and 13-17 under 35 U.S.C. 112(b). Applicant’s cancellation of Claims 3-5, 7, and 11 renders the rejection thereof moot. This rejection is hereby withdrawn.
Applicant’s cancellation of Claims 3-5, 7, and 11 under 35 U.S.C. 103 renders the rejection thereof moot. This rejection is hereby withdrawn.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 Claims 1, 6, 8-10, 12-13, 15-19, and 25-26 under 35 U.S.C. 103 as being unpatentable over Martin et. al. (WO 2019/090088 A1; cited on Applicant’s Information Disclosure Statement filed April 21st, 2023 and October 23rd, 2023; cited in non-final rejection mailed October 29th, 2025; hereinafter referred to as Martin) in view of McCurdy & Cohen (Drug Design Org, https://www.drugdesign.org/chapters/bioisosterism/, last modified Feb 2007; obtained from the internet October 2nd, 2025; cited in non-final rejection mailed October 29th, 2025; hereinafter referred to as McCurdy) is maintained.
Applicant has traversed this rejection on the basis that the central piperidine is correlated with “surprising and unexpected integrated stress response (ISR) activity” (See Page 21, Second Paragraph of Applicant’s remarks filed January 27th, 2026), and that McCurdy does not provide any teaching or suggestion that the bioisosteric substitutions would be appropriate or advantageous in the structural frameworks disclosed in Martin.
The examiner does not find this argument persuasive.
For clarity of the record, as noted in the non-final rejection mailed October 29th, 2025, at Page 69, entry 135, Martin teaches the following compound:
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This compound reads on a compound of formula (I) when the variables are recited as follows:
R1 is H.
R2 is H.
R2a is H.
R3 is phenyl, further substituted by two R7 groups, wherein one R7 is fluoro and the second R7 is chloro.
R4a, R4b, R4c, R4d, R4e, and R4f are each H.
R5 is H.
R6 is R11, wherein R11 is methyl, substituted by R13, wherein R13 is A2, wherein A2 is 5-membered heterocyclyl substituted by R16a wherein R16a is R17, wherein R17 is methyl, further substituted three R18 groups, wherein each R18 is fluoro.
At Page 92, Lines 26-27, Martin teaches pharmaceutical compositions comprising the above compound.
This compound differs from a compound of formula (I) only in that the nitrogen in the core piperidine ring is substituted with an oxygen, thereby replacing the core piperidine ring with a tetrahydropyran ring. This substitution would have been recognized by a person having ordinary skill in the art as a bioisosteric replacement.
McCurdy teaches at page 12 that -o- is a bivalent bioisostere to -NH-:
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At Page 15, McCurdy teaches bioisosteric replacements are useful to improve potency, improve selectivity, reduce toxicity, and improve bioavailability.
Regarding Applicant’s argument that the ISR activity of the instantly claimed compounds is surprising and unexpected, the examiner does not find this persuasive, as Martin demonstrates ISR activity of the disclosed compounds at pages 181-182 and Table 2. Therefore, the instantly claimed compounds and the compound disclosed by Martin have a shared utility. Applicant has not demonstrated surprising or unexpected ISR activity over the compounds disclosed by Martin.
Therefore, a person having ordinary skill in the art would reasonably expect the substitution of the piperidine ring instantly disclosed for a tetrahydropyran ring as taught by Martin would result in compounds with ISR activity, as the bioisosterism of -NH- and -O- is known in the art. Given the rest of the structure of the aforementioned molecule taught by Martin is preserved, a person having ordinary skill in the art would expect ISR activity from the instantly disclosed compounds, which are arrived at by a bioisosteric substitution. The motivation in generating such compounds, as noted in the non-final rejection mailed October 29th, 2025 is that bioisosteres are known in the art to produce compounds that could have improved potency, improved selectivity, reduced toxicity, and improved bioavailability. Therefore, this results in the practice of Claims 1, 6, 8-10, 12-13, 15-19, and 25-26 with reasonable expectation of success.
Allowable Subject Matter
Claims 2, 14, and 20-24 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, 6, 8-10, 12-13, 15-19, and 25-26 are rejected.
Claims 2, 14, and 20-24 are objected to.
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 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