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 .
Election/Restrictions
Applicant’s election of the invention of Group I (claims 1-12) and the species of Example 24, shown below, in the reply filed on 08/31/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
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Examiner searched the above compound and found it to be free of the art. Examiner expanded the search to encompass Examples 19-23 as in claim 10. Examiner then expanded the search to species with the following core structure.
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Claims 5 and 13-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and/or invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/31/2026.
Priority
Examiner acknowledges that, according to the Filing receipt received 04/09/2026, that the instant application 18/713,496 filed 05/24/2024 is a 371 of PCT/US2022/080348 filed 11/22/2022 which claims benefit of U.S. provisional application 63/282,878 filed 11/24/2021. All of the instant claims have been awarded the effective filing date of 11/24/2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 12/17/2024 (7 total) and 06/22/2026 (3 total) are in compliance with the provisions of 37 CFR 1.97 and have been considered in full, except where lined through. A signed copy of list of references cited from the IDS is included with this Office Action.
Examiner notes that the following references were not considered as a copy of the document was not submitted with its respective IDS.
IDS filed 06/22/2026 (8 pages): Foreign Patent Document #27 (WO2 023/193085 A1), Non-patent Literature Documents #8 (Fell, Jay B. et al.) and #9 (REGISTRY).
IDS filed 06/22/2026 (10 pages): Foreign Patent Documents #18 (WO 2021211864 A1) and #28 (WO 2022087375 A1).
Claim Rejections – Improper Markush Grouping
Claims 1-4, 6-9, and 11-12 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) the species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the Specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons:
The variable structure of Formula (I) is defined as seen below:
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The variable rings X, B, Y, and Z vary greatly in their respective sizes, levels of saturation, identity and number of heteroatoms, and substituents such that their activity is expected to vary greatly. The only common structure shared between compounds is that of the pyrimidine fused to variable ring B, wherein pyrimidines do not share a common use or establish a substantial structural feature from which its use may flow. Moreover, a search for even a fraction of the species within the scope of Formula (I) (see Election/Restriction search scope above) yields thousands of possible compounds.
Clearly no ‘‘single structural similarity’’ can be seen.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claim(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. § 134 and 37 CFR41.31 (a) (1) (emphasis provided).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites “The compound of claim 1 selected from Examples 1-49”. However, Examples 1-49 are not depicted in claim 10. The claims should be complete in and of themselves without incorporation of figures by reference. Examiner suggests that Applicant amend claim 10 to depict each of the structures of Examples 1-49.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 6-9, and 11 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wang et al. (WO 2022/132200 A1; effectively filed March 2021; IDS filed 12/17/2024).
Wang et al. discloses the following compounds which are KRAS inhibitors (p. 738, 740, 742, 753, 755, 756, 772).
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Wang et al. additionally discloses pharmaceutical compositions comprising the disclosed compounds and a pharmaceutically acceptable excipient (p. 6, par. [000036]).
The compounds of Wang et al. are within the scope of the instant claims wherein ring X is as in claim 3 and/or claim 4, ring Y is as in claim 7 or naphthyl substituted by halo, hydroxyl, and alkyl or alkenyl, ring Z is as in claim 8 (wherein P is heterocycloalkyl with at least two heteroatoms N and O) or claim 9, and the moiety containing ring B is as below.
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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.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2022/132200 A1; effectively filed March 2021; IDS filed 12/17/2024) as applied to claims 1-4, 6-9, and 11 above, and further in view of Patani et al. (Chemical Reviews; 1996).
Wang et al. teaches the following compound, as in the above rejection.
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Wang et al. does not teach a compound that is identical to one of Examples 1-49 as in claim 10. However, this limitation is obvious in view of Patani et al.
Patani et al. teaches that fluorine and hydrogen are monovalent atoms that are considered classical bioisosteres (p. 3149, col. 1). Patani et al. teaches that bioisosteres elicit similar biological activity due to common physicochemical properties (p. 3148, col. 2, par. 2). Patani et al. teaches that hydrogen and fluorine are sterically similar due to their similar van der Waal’s radii, but they can differ in their pharmacological effect due to the electronegativity of fluorine (p. 3149, col. 1, par. 5). Patani et al. teaches that hydrogen and fluorine substitutions have been made in pharmacological studies in order to observe differences in properties such as affinity and activity (p. 3149, col. 2 – p. 3150, col. 1, par. 1).
It would have been prima facie obvious for one of ordinary skill in the art to substitute the fluorine on the napthyl group of the compound of Wang et al. with a hydrogen, yielding claimed compound Example 23 shown below.
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One would have been motivated to do so, with reasonable expectation of success, in order to examine whether fluorination (or lack thereof) of the compound of Wang et al. yields different effects in its KRAS binding affinity and pharmacological activity for purposes of developing a KRAS inhibitor for the treatment of cancers.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2022/132200 A1; effectively filed March 2021; IDS filed 12/17/2024) as applied to claims 1-4, 6-9, and 11 above.
Wang et al. discloses as above.
While Wang et al. does not explicitly teach a composition comprising a compound of Formula (I) and an additional anti-cancer agent, this limitation is obvious over Wang et al.
Wang et al. additionally teaches that the compounds and pharmaceutical compositions thereof may be co-administered with other anti-neoplastic compounds, such as chemotherapy (p. 34, par. [0000208]).
It would have been prima facie obvious for one of ordinary skill in the art to combine the composition of Wang et al. with a chemotherapeutic compound. One would have been motivated to do so, with reasonable expectation of success, in order to yield an additive effect of combining two agents for treatment of cancer.
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 1, 6-9, and 11-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 3-4 of copending Application No. 18/555,640 (allowed, patent not yet issued) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are directed toward compounds, including those below, and compositions comprising the compounds, a pharmaceutically acceptable carrier, and an anti-cancer agent.
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The compounds are within the scope of Formula (I) as in instant claims 1 and claims 6-9 wherein ring X is a bridged saturated heterocycloalkyl and n is 2. The claims of the ‘640 application therefore anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MADELINE E BRAUN/Examiner, Art Unit 1624 09/21/2026
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