DETAILED ACTION
This office action is in response to the Applicant’s filing dated November 14th, 2025.
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
This application is a 371 of PCT/US2021/031192 filed on May 6th, 2021; and has a PRO of 63/022,129 filed on May 8th, 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of Claims
Claims 1-2, 5-7, 18-19, 23, 30, 33, 36, 40, 47, 53-54, 56, 58-59, 63 and 68 are pending in the
instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on April
28th, 2023. Acknowledgment is made of Applicant’s amendment of claims 2, 5, 7, 18-19, 23, 36, 40, 47,
53-54, 56, 58-59, 63 and 68; and the cancelation of claims 3-4, 8-17, 20-22, 24-29, 31-32, 34-35, 37-39,
41-46, 48-52, 55, 57, 60-62, 64-67 and 69-78.
Election/Restrictions
Applicant’s election without traverse of Group I and species election of PLK1 inhibitor onvansertib and colorectal cancer in the reply filed on November 14th, 2025 is acknowledged.
Claims 30, 33, 36 and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 November 14th, 2025.
Claim Objections
Claim 2 is objected to because of the following informalities: Claim 2 recites “(1) during the subject is treated for cancer”, but it is unclear as written. Appropriate correction is required.
Claims 19 and 56 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
Claims 1-2, 18, 23, 47, 53-54, 58-59, 63 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCT03829410 (https://clinicaltrials.gov/study/NCT03829410 ?tab=history&a=2); as evidenced by Naser et al (PLOS One, (2014), 9(11), e113350, 1-12).
Regarding claims 1-2, 18, 23, 47, 53-54, 58-59, 63 and 68, NCT03829410 teaches the oral administration of 12 mg/m2 of onvansertib (addressing claim 58) for 5 consecutive days, in combination with FOLFRI and avastin (addressing claim 68) in each consecutive 14 day course in a 28 day cycle (addressing claim 59[iv]), to patients with metastatic colorectal cancer (addressing claim 53) with a KRAS mutation (addressing claim 47); including Kras mutations in exons 2, 3 or 4 in primary tumor or metastasis (pages 9-10, Study Description; page 12, Phase 1b; page 17, Inclusion Criteria [2]). Naser et al, cited for evidentiary purposes only, teaches that exon 2 comprises codons 12 and 13, exon 3 comprises codon 61 and exon 4 comprises codons 117 and 146 (addressing claim 54) (page 7, right column, last paragraph). NCT03829410 further teaches that blood samples obtained at baseline and subsequent time points, from day 1 of each course (addressing claim 23) up to 28 days after the last dose of the study drug, were analyzed for the presence of circulating tumor DNA (ctDNA [including Kras mutations]) (addressing claims 2 and 18); for a reduction in mutant allelic burden as the study is focused on patients with mutations at the mutations in exons 2, 3 or 4 as discussed above (page 15, Secondary Outcome Measures, [5]).
Regarding claim 63, NCT03829410 teaches the oral administration of 12 mg/m2 of onvansertib as discussed in the above rejection (page 12, Phase 1b). The prior art is silent regarding Cmax, AUC, Tmax and T1/2 pharmacokinetic parameters. However: the claimed Cmax, AUC, Tmax and T1/2 pharmacokinetic parameters will inevitably flow from the teachings of the prior art (see above rejection), since the same dose of onvansertib is being administered to the same subjects (patients with colorectal cancer). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding Cmax, AUC, Tmax and T1/2 pharmacokinetic parameters, by practicing the method taught by the prior art: NCT03829410, one will also be achieving the claimed Cmax, AUC, Tmax and T1/2 pharmacokinetic parameters, even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage (Cmax, AUC, Tmax and T1/2 pharmacokinetic parameters) of the method taught by the prior art (NCT03829410).
MPEP 2112 (I) states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
Thus, the teachings of NCT03829410 anticipate the methods of instant claims 1-2, 18, 23, 47, 53-54, 58-59, 63 and 68.
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 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03829410 (https://clinicaltrials.gov/study/NCT03829410 ?tab=history&a=2); as evidenced by Naser et al (PLOS One, (2014), 9(11), e113350, 1-12), cited for evidentiary purposes only; in view of Yi et al (International Journal of Cancer, (2017), 140, 2642-2647); as evidenced by Favero et al (Annals of Oncology, (2014), 26, 64-70), cited for evidentiary purposes only.
Regarding claims 5-7, NCT03829410 anticipates the methods of claims 1-2, 18, 23, 47, 53-54, 58-59, 63 and 68 as described in the above rejection.
NCT03829410 does not explicitly disclose the use of Variant Allele Frequency or Mutant Allele Frequency metrics to calculate the reduction of mutant allelic burden.
Yi et al teaches that circulating tumor DNA (ctDNA) mutation levels may be quantified using Mutant Allele Frequency (MAF) measurements, and further discloses that tumor burden has been shown to directly correlate to ctDNA levels in patients and the frequency of ctDNA molecules carrying mutations (page 2642, Abstract, lines 8-9; page 2643, right column, lines 11-12; page 2646, left column, first paragraph). Favero et al, cited for evidentiary purposes only, teaches that MAF is defined as the fraction of reads with a mutation at each genomic position (page 66, Figure 1, lines 11-12); e.g. the total mutation count at a given position is a variable used for calculating MAF. A person of ordinary skill in the art would have recognized that such quantitative ctDNA analysis techniques express mutation levels using metrics derived from detected mutation reads, including MAF values and other quantitative measures derived from mutation read counts.
It would have been prima facie obvious to a person of ordinary skill in the art to apply the known ctDNA quantification techniques taught by Yi, including determining MAF, when analyzing the KRAS mutations detected in blood samples of the NCT03829410 study in order to determine changes in mutant allelic burden. Applying MAF analysis to the KRAS ctDNA mutations detected in the NCT03829410 study would have represented the predictable use of a known analytical technique for quantifying ctDNA mutation levels, yielding the expected result of determining changes in the mutant allelic burden.
“[T]he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Taken together, all of this all of this would result in the methods of instant claims 5-7 with a reasonable expectation of success.
Conclusion
Claims 1-2, 5-7, 18, 23, 47, 53-54, 58-59, 63 and 68 are rejected.
Claims 2, 19 and 56 are objected to.
No claim is allowed.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691