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 .
Priority
Instant application 17/760,861 filed on 03/16/2022 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
The amendment filled on 09/26/2025 has been entered.
Applicant cancelled claims 36-70 and added new claims 71-84.
Claims 71-84 are pending.
Election/Restrictions
Applicant’s election without traverse of Group III, directed to compounds in the reply filed on 09/26/2025 is acknowledged.
It should be noted that Applicant cancelled all claims directed to compounds of formula (I). Further, Applicant cancelled all claims directed to a method for treating cancer.
Regarding species election, Applicant’s election without traverse of
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in the reply filed on 09/26/2025 is acknowledged.
Applicant submitted:
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Claims 76-80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/26/2025.
Examination will begin with the elected species. In accordance with the MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP 803.02, the Examiner will attempt to determine whether the entire scope of the claims is patentable. Applicants' elected species, as shown above, does make a contribution over the prior art. Therefore, according to MPEP 803.02: should the elected species appear allowable; the search of the Markush-type claim will be extended. The search and examination should be continued until either (1) prior art is found that anticipates or renders obvious a species that falls within the scope of a proper Markush grouping that includes the elected species, or (2) it is determined that no prior art rejection of any species that falls within the scope of a proper Markush grouping that includes the elected species can be made. The Examiner need not extend the search beyond a proper Markush grouping.
It should be noted that the instant compounds have utility as synthetic intermediates for the preparation of inhibitors of the enzyme CTPS1 of formula (I) using AlMe3 and compounds of formula (III) (see instant specification e.g., Scheme 5a on page 46).
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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:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 71, 72, 73, 74, 75, 83 are rejected under 35 U.S.C. 103 as being unpatentable over Coulter (WO2006050908A1 – made of record on the IDS).
Coulter teaches inhibitors of 11β-HSD1 (see page 5):
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Further, Coulter teaches the following compounds (see scheme A, page 25):
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The above compounds fall under instant formula (II)
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wherein
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X is CH, Y is CR2, Z is CR3, R2 is H, R3 is H, R4 and R4 are R4b and R5b, R4b and R5b are each independently H, R is H or C2 alkyl (Et) and R1 corresponds to A variable.
Regarding claim 72, Coulter teaches compounds wherein X is N, Y is CR2, and Z is CR3, R2 is H and R3 is H (see Scheme F):
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For example,
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falls under instant formula (II) wherein
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X is N, Y is CR2, Z is CR3, R2 is H, R3 is H, R4 and R4 are R4b and R5b, R4b and R5b are each independently H, R is C2 alkyl (Et) and R1 corresponds to A variable.
Regarding claim 83, the above compound falls under instant formula (II) wherein R is ethyl.
Coulter does not teach a compound in which A is alkyl substituted by CN in one single embodiment.
However, Coulter teaches general formula (I) and list C1-6 alkyl substituted by CN (R5) as an option for A:
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The above compounds disclosed by Coulter are useful as intermediates for the preparation of inhibitors of 11β-HSD1 (see scheme A):
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Since Coulter suggests C1-6 alkyl substituted by CN as an option for A - applying KSR prong (A) and/or (B) - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select alkyl substituted by CN from the list of A variables disclosed by Coulter. One of ordinary skill in the art would have been motivated to follow Coulter’s suggestions to prepare further inhibitors of 11β-HSD1 with a reasonable expectation of success. Regarding instant claims 73-75, Coulter suggests C1-6 alkyl substituted by CN, therefore one of ordinary skill would test C1-5, C1-3 and C1 alkyls.
MPEP 2143 teaches that 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.
Claims 71-75 and 82-84 are rejected under 35 U.S.C. 103 as being obvious over Quddus (US- 11,987,753-B2 (also published as WO-2020083975-A1) in view of WO-2019106146-A1 (publication date 06/06/2019) and in view of Wermuth (C. G. Wermuth, in The Practice of Medicinal Chemistry, Academic Press 1996, pp 203-237).
The applied reference (Quddus, US 11,987,753-B2) has a common Applicant (Step Pharma S.A.S.) with the instant application. Based upon the earlier effectively filed date (10/23/2018) of the reference,
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it constitutes prior art under 35 U.S.C. 102(a)(2).
Quddus teaches CTPS1 inhibitors of formula (I) (see abstract and summary of the invention – columns 7 and 8):
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Quddus teaches intermediates of formula (II) for preparation of the above CTPS1 inhibitors of formula (I) (see column 13):
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Further, Quddus teaches (see Column 44, Method I):
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Furthermore, for example, Quddus teaches the following intermediate (see column 43):
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The above compound disclosed by Quddus differs from the instant elected species:
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only in R1 position.
The compound disclosed by Quddus bear cyclopropane moiety whereas the instant elected species bear CH2CN group at the corresponding position (R1).
Quddus is silent about R1 substituted by CN group.
However, WO-2019106146-A1 teaches inhibitors of the enzyme CTPS1 of formula (I):
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WO-2019106146-A1 does not teach C1-5 alkyl substituted by CN.
However, WO-2019106146-A1 teaches formula (I) wherein R1 is C1-5 alkyl substituted by CF3.
Wermuth teaches that CF3 may be exchange for CN because CF3 and CN are isosteres often used in medicinal chemistry (see page 205 right column and Fig. 13.29, page 207):
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Further, Wermuth teaches that CN and CF3 groups have comparable effects on electronics, but CN will increase the overall hydrophilicity (see page 205 right column):
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Since Wermuth teaches that CN and CF3 may be used as alternative electron-withdrawing groups, therefore, one of ordinary skill in the art would have been motivated to substitute CF3 by CN to prepare compounds bearing alkyl substituted by CN. It should be noted that the essential part of the molecule remains unchanged, thus, one of ordinary skill would expect retention of activity. The skilled person would be motivated to use the compounds as alternative intermediates for preparation of further CTPS1 inhibitors.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 71-75 and 82-84 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12371419-B2 in view of and in view of WO-2019106146-A1 and in view of Wermuth (C. G. Wermuth, in The Practice of Medicinal Chemistry, Academic Press 1996, pp 203-237).
This rejection applies to the elected species.
Claims of U.S. Patent No. 12371419-B2 recite a compound of Formula (II):
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The compounds recited in claims of US 12371419 differ from the instant compounds only in one position, the position corresponding to instant R1 variable.
US-12371419-B2 – claim 5
Instant Elected Species
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The compound recited in claim 5 of US 12371419 bear cyclopropane moiety whereas the instant elected species bear CH2CN group at the corresponding position (R1).
WO-2019106146-A1 teaches inhibitors of the enzyme CTPS1 of formula (I):
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WO-2019106146-A1 does not teach C1-5 alkyl substituted by CN.
However, WO-2019106146-A1 teaches formula (I) wherein R1 is C1-5 alkyl substituted by CF3.
Wermuth teaches that CF3 may be exchange for CN because CF3 and CN are isosteres often used in medicinal chemistry (see page 205 right column and Fig. 13.29, page 207):
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Further, Wermuth teaches that CN and CF3 groups have comparable effects on electronics, but CN will increase the overall hydrophilicity (see page 205 right column):
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Since Wermuth teaches that CN and CF3 may be used as alternative electron-withdrawing groups, therefore, one of ordinary skill in the art would have been motivated to substitute CF3 by CN to prepare compounds bearing alkyl substituted by CN. It should be noted that the essential part of the molecule remains unchanged, thus, one of ordinary skill would expect retention of activity. The skilled person would be motivated to use the compounds as alternative intermediates for preparation of further CTPS1 inhibitors.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/I.S./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621