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 . Claims 1, 3-27 and 34 filed December 01, 2025 are currently pending. Claims 1 and 13 are independent.
Election/Restrictions
Applicant’s election without traverse of Group (I), claims 1, 3-15 and 17-26 in the reply filed on 12/01/2025 is acknowledged.
Claims 27 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/01/2025.
Secondly, Applicant’s election without traverse of compound 33 in the reply filed on 12/01/2025 is acknowledged.
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Claims 15-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of Formula (I), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/01/2025
Priority
Acknowledgement is made of the national stage entry of PCT/US2021/033170 filed 05/19/2021 which claims priority to U.S. Provisional Application 63027557 filed 05/20/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/12/2023 and 12/01/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 (i.e., changing from AIA to pre-AIA ) 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:
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.
Claim(s) 1, 3-14 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Markowitz (WO2020/106998 published 05/28/2020; priority to U.S. Provisional 62770571 filed 11/21/2018).
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Markowitz (WO2020/106998 published 05/28/2020; priority to U.S. Provisional 62770571 filed 11/21/2018) teaches compounds of Formula (VI) that are potent inhibitors of short-chain dehydrogenase 15-PDGH (abstract [0068]-[0074], claims 56-62, claims 1, 71). Embraced within Markowitz is compound 219 as shown above which reads on the claimed structural limitations: R1 is cyclobutyl, R2 is amine, R7 is phenyl, X is CH and R6 is pyrimidinone wherein R11 is H (page 188, claims 56-62, claims 1, 71). As shown in Table 1, compound 219 comprises advantageous potency at inhibiting 15-PDGH with an IC50 of less than 2.5 nM (page 188). Applicant also teaches compound 409 as shown above, which comprises the same R1, R2, X and R6 of compound 219 above, except that compound 409 comprises a cyclobutyl at R7 instead of a phenyl group as found in compound 219 and R11 is methyl instead of hydrogen on the pyrimidinone R6 (page 232). As shown in Table 1, Markowitz teaches that modifying R11 from hydrogen to methyl as well as modifying the phenyl ring at R7 for a smaller substituent results in equivalent potency at inhibiting 15-PDGH as compound 219 (page 232). Markowitz further teaches that an isopropyl group is one of 6 suitable alternative moieties to replace the phenyl substituent at R7 of the presently claimed compound and still yield potency at inhibiting 15-PDGH ([0068]-[0074]). Regarding claim 26, Markowitz teaches formulating said 15-PDGH inhibitors with a pharmaceutically acceptable excipient (page 188, claims 56-62, claims 1, 71, 73).
Accordingly, said skilled artisan would have found it prima facie obvious to modify the hydrogen moiety at R11 of the pyrimidinone ring to a methyl substituent and modify the phenyl moiety at R7 of the 15-PDGH inhibitor 219 of Markowitz, for an isopropyl moiety, arriving at compound 33 of the present claims. MPEP 2143 provides rationale for a conclusion of obviousness including (B): Simple substitution of one known element for another to obtain predictable results;
In the present case, it was known in the art that modifying the R11 position from a hydrogen to a methyl as well as modifying the R7 position with a smaller ligand, such as a cyclobutyl results in equivalent potency at inhibiting 15-PDGH (see compound 219 vs 409 in Table 1). Coupled with the knowledge that Markowitz teaches that an isopropyl group is one of 6 suitable alternative moieties to replace the phenyl substituent at R7 of the presently claimed compound and still yield potency at inhibiting 15-PDGH ([0068]-[0074]), said skilled artisan would have readily predicted that the modified compound 219 of Markowitz comprising an isopropyl moiety at R7 and a methyl at R11 would be efficacious at inhibiting 15-PDGH in a subject in need.
Applicant is reminded of MPEP 2143 wherein it should be noted that the lead compound cases do not stand for the proposition that identification of a single lead compound is necessary in every obviousness rejection of a chemical compound. For example, one might envision a suggestion in the prior art to formulate a compound having certain structurally defined moieties, or moieties with certain properties. If a person of ordinary skill would have known how to synthesize such a compound, and the structural and/or functional result could reasonably have been predicted, then a prima facie case of obviousness of the claimed chemical compound might exist even without identification of a particular lead compound. Thus, Office personnel should recognize that in certain situations, it may be proper to reject a claimed chemical compound as obvious even without identifying a single lead compound.
In the present case, the prior art of Markowitz teaches that compounds comprising the structural defined moieties of R1 is cyclobutyl, R2 is amine, R7 is phenyl, X is CH and R6 is pyrimidinone wherein R11 is H or methyl comprises the advantageous property of inhibiting 15-PDGH with an IC50 of <2.5nM, coupled with the knowledge that an isopropyl group or a phenyl group are two of 7 suitable alternative moieties at R7 to effectively inhibit 15-PDGH ([0068]-[0074]). Said skilled artisan would have known how to synthesize such a compound based on the teachings of Markowitz, and the structural and/or functional result could reasonably have been predicted in view of the structure-activity relationship table of Table 1.
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621