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 .
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Status
Claims 1-2, 6, 8, 10, 12-24 are pending.
Claims 6, 10, and 21-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/13/2025.
Claims 1-2, 8, 12-20, and 24 are being examined on the merits.
Abstract
The objection to the abstract is withdrawn in light of Applicant’s amendments.
Specification
The objection to the specification is withdrawn in light of Applicant’s amendments. Applicant’s amendment to the specification to properly denote trade names or marks used in commerce is acknowledged.
Claim Objections
The objection to claim 13 is withdrawn in light of Applicant’s amendment to the claim.
Claim Rejections - Improper Markush Group
Maintained
Claims 1-2, 8, 12-20, and 24 are rejected on the 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). 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.
The Markush grouping of “(a) an inactivated TP53 gene and/or (b) at least one of: (i) an inactivated Rb1 gene, (ii) an amplified CCNE1 gene or overexpression of a CCNE1 gene product, and (iii) an inactivated BRCA gene” is 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 scope of claims 1 and 2 is such that an implied relationship between a cancer sensitivity to KIF18A inhibitor treatment is associated with any one of the genetic markers by themselves or in combination. However, according to the specification, these genetic markers are not alternatively usable in determining increased sensitivity to KIF18A inhibitor treatment, given that in each example provided in Example 1 of the specification, cancer cells are only sensitive to KIF18A inhibition in the genetic background of a mutated TP53 gene (see Figure 1C-1,2). For example, an inactivated Rb1 gene alone would not lead one to believe that KIF18A inhibition would successfully treat the cancer (given the results in the HCC-1954 cell line, which has a mutant TP53 but is proficient for Rb1). Additionally, no evidence is supplied to indicate that inactivated BRCA alone or amplified CCNE1 alone is alternatively usable, given that the provided examples demonstrate inhibition in backgrounds in which the required biomarkers are present in combination with mutant TP53.
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.
Response to Remarks
The Examiner notes that claim 10 was included in the Improper Markush Group rejection in the Office Action of 12/10/2025 in error, as this claim was withdrawn at the time of examination as being drawn to a nonelected invention. The Examiner thanks Applicant for pointing this out in their Remarks, and the appropriate correction has been made above.
Applicant traverses the rejection of claims 1-2, 8, 12-20, and 24 for containing an improper Markush grouping of alternatives. Applicant's arguments filed 3/10/2026, pages 10-12 of Remarks, have been fully considered but they are not persuasive.
As stated in the rejection above and reiterated by Applicant in their Remarks, the members of a proper Markush grouping must “share a single structural similarity and a common use”. Applicant argues that the alternatives share a single structural similarity as “alterations in genes belonging to the same recognized class of tumor suppressor and oncogenes whose genetic lesions are enriched in chromosomally unstable cancers and that regulate cell-cycle progression/checkpoints, centrosome-cycle, and DNA repair”. This argument is not persuasive. The biomarkers listed do not share a single structural similarity that is related to their function as an indicator of KIF18A inhibitor sensitivity. Association with chromosomal instability does not equate to a structural similarity, as this grouping of genes/proteins lacks unity of invention given that each is a distinct biological entity with very different biological roles.
Applicant argues that the recited biomarkers “share a common use” and that the “data is consistent with” the biomarkers as being alternatively usable. The Examiner respectfully disagrees. Each piece of evidence presented on page 11 for inactive Rb1, amplified CCNE1, and inactive BRCA is directly referencing data that is obtained in the background of an inactive TP53. None of the evidence provided directly links Rb1, CCNE1, or BRCA to KIF18A inhibitor sensitivity on their own, but rather demonstrates their utility in combination with TP53. Applicant argues that the “alternatives share a common use as disclosed in the specification”, however no such evidence has been provided given that all evidence indicates that mutant TP53 is required in addition to at least one of the other genetic markers.
Therefore, the rejection of claims 1-2, 8, 12-20, and 24 for containing an Improper Markush Group is maintained.
Claim Rejections - 35 USC § 112b - Indefiniteness
The rejection of claims 1, 8, 15-18, and 24 under 35 U.S.C. 112(b) are withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112a – Enablement
Maintained in Part
Claims 1-2, 8, 12-20, and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treating a human subject having a neoplastic disease, comprising:
(I) assaying a sample obtained from the human subject and detecting (a) an inactivated TP53 gene and (b) at least one of: an inactivated Rb1 gene, (ii) an amplified CCNE1 gene and (iii) an inactivated BRCA gene, and;
(II) administering a KIF18A inhibitor to the human subject
does not reasonably provide enablement for establishing a relationship between KIF18A inhibition in an overexpression of a CCNE1 gene product background and successful cancer treatment. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Nature of the invention and breadth of the claims
The invention is in the class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The rejected claims are broadly directed to the administration of a KIF18A inhibitor (a nucleic acid, a polynucleotide, a polypeptide, a small molecule, etc.) to a human subject with any type of neoplastic disease/cancer with a specific genetic background. The rejected claims also encompass specifically administering any type of KIF18A inhibitor to any type of subject with any type of cancer wherein the subject has either an amplified CCNE1 gene or overexpression of a CCNE1 gene product.
Direction provided by the specification and working example
The specification provides examples in which human cell lines or human cell xenograft models in nude mice are treated with the KIF18A inhibitor compound 14 (Examples 1, 3, 4, 13, 14, and 15). The genetic content of cells examined in response to KIF18A C14 inhibitor treatment were from ovarian, breast, or prostate cancer cell lines with at least one of inactivated TP53, inactivated Rb1, amplified CCNE1, or an inactivated BRCA (see Figure 1C-1,2). The specification does not exemplify KIF18A inhibition in human cells with overexpression of CCNE1.
State of the art, level of skill in the art, and level of unpredictability
The claims encompass treating a human subject with a neoplastic disease wherein the subject has either an amplified CCNE1 gene or overexpression of a CCNE1 gene product, while only presenting evidence in the specification for amplified CCNE1. Jia et al. teaches that while it may be a common assumption, there is insufficient evidence in the literature to indicate that amplification of an oncogene always leads to overexpression of said oncogene (Jia et al., 2016, Abstract). Jia et al. also teaches that there are some instances in which gene amplification actually results in decreased expression (Introduction, pg 2, col 1).
Quantity of experimentation required
Given the level of unpredictability in terms of gene amplification vs. gene overexpression, there would be an undue amount of experimentation required for one skilled in the art to perform the method of treatment as claimed.
Conclusion
After consideration of the teaching of the specification and specific working examples, considering the breadth of the claims, and the unpredictability in the art, it is the conclusion that an undue and unreasonable amount of experimentation would be required to make and use the invention that is instantly claimed.
Response to Remarks
Applicant’s arguments, see pages 13-14 of Remarks, filed 3/10/2026, with respect to “a neoplastic disease” and “a KIF18A inhibitor” have been fully considered and are persuasive. Applicant argues on page 13-14 that the “molecular characteristic” of the neoplastic disease, rather than the “anatomical location”, is what defined the invention as claimed. Applicant argues that the specification provides evidence for “consistent, cross-tissue correlation” as a “predictive determinant of responsiveness to a KIF18A inhibitor”. This argument is persuasive, and as such the scope of the enablement as written above has been modified to include the “a neoplastic disease” claim language as previously (and currently) presented.
Applicant argues on page 14 that the specification provides results for “three structurally distinct KIF18A inhibitors” in addition to C14 as well as results indicating effectiveness of siRNA inhibitors in knocking down/inhibiting KIF18A. This argument is persuasive, and as such the scope of the enablement as written above has been modified to include the “a KIF18A inhibitor” claim language as previously (and currently) presented.
Applicant does not present an argument with regard to the enablement rejection of inclusion of CCNE1 overexpression in addition to CCNE1 amplification. As stated above, CCNE1 amplification (which has evidence with relation to KIF18A inhibition in the specification) is not equivalent to CCNE1 overexpression. Given that no arguments have been provided with regard to this particular rejection, the rejection above is “maintained in part” as the specification only provides enablement for CCNE1 amplification, not CCNE1 overexpression. As such, claims 1-2, 8, 12-20, and 24 remain rejected under 35 USC 112a.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 8, and 24 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Rajagopal (Rajagopal et al., WO 2018/231859 A1) is withdrawn in light of Applicant’s amendments to the claims.
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 1-2, 12-15, and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-16 and 18 of copending Application No. 18/580,564 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to the same limitations. Any additional limitations of '564 claims are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks
Applicant traverses the double patenting rejection above and argues that the provisional nonstatutory double patenting rejection should be withdrawn when it is the only rejection remaining in this application (page 15 of Remarks). However, as indicated in the rejections above, the double patenting rejection is not the only remaining rejection in this application and therefore the double patenting rejection is maintained.
Conclusion
No claims are 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 KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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