Detailed Action
The present office action is in response to the amendments filed 07 Apr 2026.
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
Claims 1-2, 4-9, and 13 of the pending application have been examined on the merits. Claims 3, 46,53, 58, and 64 are withdrawn (see “Response to Applicant Election” below). Acknowledgement is made of the amendments filed 07 Apr 2026. Acknowledgement is made of the cancellation of claims 10-12, 14-45, 54-57, and 59-63.
Priority
Applicants identify the instant application, Serial #: 18/533,332, filed 08 Dec 2023, as claiming foreign priority from Foreign Application #: CN202211574036.1, filed 08 Dec 2022. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 08 Dec 2022. It is noted, however, that applicant has not filed a certified copy of the 202211574036.1 application as required by 37 CFR 1.55.
The claimed priority date is therefore not recognized and the application has the effective filing date of 08 Dec 2023.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 14 Jun 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Election
Applicant’s election without traverse of Group I, claims 1-9 and 13, in the reply filed on 07 Apr 2026 is acknowledged. Applicant’s election without traverse of compound 9a (below) as the species of compound in the reply filed on 07 Apr 2026 is acknowledged. A search for this species returned prior art.
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Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 46-53, 58, and 64 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04 Mar 2026.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
Claims 1-2, 4-9, and 13 are 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.
Regarding claims 1-2, 4, and 7-9, the phrase “ester” renders the claim indefinite because the person having ordinary skill in the art would be unsure what it means to create an ester out of the claimed compounds. There are no obvious places on the claimed compounds of Formula (I) on which to create ester bonds and it is unclear which esters are included in the scope of this limitation. Claims 5 and 13 is rejected for failing to remedy the deficiencies of the independent claims.
Regarding claim 2, the claim includes the limitation, “X1 and X2 are independently H, OH, halogen, CF3, NH2, substituted or unsubstituted C1-C4 alkyl, or absent…X3 is C or N…” However, claim 2 does not explain how X1 may be H, OH, halogen, CF3, NH2, or substituted or unsubstituted C1-C4 alkyl when X3 is N, and violate the valence rules. The artisan would not be sure how to properly implement these limitations. Applicant may overcome this rejection by amending the claims with an explanation how the artisan may implement this limitation.
Regarding claim 6, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 6 recites the broad recitation
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, and the claim also recites
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which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 1-2, 4-6, 9, and 13 are rejected on the basis that it contains 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). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Regarding claim 1, the Markush grouping of substituents B, W(R1)-R2, and Ring A in Formula (I)
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are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The claims define Ring A as substituted or unsubstituted rings chosen from aromatic, heteraromatic, carboatomic, or heteroatomic. B is defined as substituted or unsubstituted alkyl, alkylaminoacyl, carboatomic ring, heteroatomic ring, aromatic ring, heteroatomic ring, condensed ring, or one of the following rings:
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W(R1)-R2 is defined even broader when W is C or N, resulting in many combinations of rings or chain groups the artisan can choose from. The variability of the definitions for each of the rings in the claimed structure of formula II results in there being no shared structural similarity that a person of ordinary skill in the art would recognize. Further, based on the breadth of the structures claimed, the artisan would have no reasonable expectation of success that all compounds claimed would have the same use.
Regarding claims 2, 4-6, 9, and 13, the dependent claims do not remedy the deficiencies of the independent claim and are rejected.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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) 1-2, 4-9, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2022/132200, hereinafter ‘200, further in view of US 2026/0015363 (filed 15 Jan 2026 and has an effective filing date of 01 Jul 2022), hereinafter ‘363.
In the remarks filed 07 Apr 2026, applicant elected Group I, claims 1-9 and 13, and the following species of Formula (I) (below) which reads on claims 1-2, 4-9, and 13:
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Claims 9 and 13 are further directed to a pharmaceutical composition comprising a compound of Formula (I) and at least one pharmaceutically acceptable excipient, carrier, or diluent (claim 9) created for different routes of administration (claim 13).
‘200 teaches compounds of Formula (I) which are pan-KRAS inhibitors (Abstract; paragraph [00007]).
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Ring A may be aryl, R4 may be a halogen, W may be
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where X is CH2 and two R7s may combine to form a spiro heterocycle, R6 may combine with itself to form a cycloalkyl, L may be -C1-C4 alkyl-NH-, and B may be
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where Y3 and Y4 join to create
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where J is CH2 (paragraphs [000086]-[0000113]). ‘200 further teaches Example 331 (below) which has the same core structure as the instantly claimed Compound 9a (paragraph [0000998]):
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Example 331 inhibits various KRas mutants with a IC50 of ≤2 nM and inhibits KRas-mediated phosphorylation of ERK in AsPC-1 cells with an IC50 of 4 nM (pgs. 707 and 720). ‘200 further teaches compositions of the reference compounds and a pharmaceutically acceptable carrier, excipient, or diluent and that the compositions may be formulated by well-known methods to be administered via different routes (paragraph [0000193]). The difference between Example 331 and the instantly elected compound is the substituent off the piperidine moiety. The instantly elected compound contains an oxygen heterocycle attached as a spiro substituent whereas Example 331 has a hydroxyl group and methyl group attached at the same carbon of the piperidine moiety.
‘363 teaches compounds which are useful as KRAS inhibitors including A-13B and A-16A (paragraphs [0215]-[0217] and [0221]-[0225].
Compound
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A-13B
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A-16A
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A-16A has the same stereo chemistry of the spiro heterocycle attached to the piperidine as the instant claims. Compound A-13B inhibits AsPC-1 cells with a IC50 of 18.8 nM and A-16A inhibits AsPC-1 cells with an IC50 of 5.7 nM (paragraph [0318]).
Based on the teachings of ‘200 and ‘363, a person of ordinary skill in the art would swap the substituents on the piperidine of Example 331, taught by ‘200, with the spirocyclic substituent taught by ‘363 to form the instantly elected compound. The artisan would be motivated to perform this substitution to decrease the minimum inhibitory concentration of the compound against AsPC-1 cells. There would be a reasonable expectation of success that this substitution would maintain the anti-KRas activity of Example 331, as taught by ‘363. In performing this substitution, the artisan would create the instantly elected compound and so the instant claims are rejected.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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