DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 19 March 2026 has been entered.
Comments
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
Claims 15-16, 31, and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim.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 13 December 2024.
Claims 1-3, 8-9, 11, 13-16, 19, 25-27, 29, 31, and 43 are pending in the application.
Claims 1-3, 8-9, 11, 13-14, 19, 25-27, and 29 are examined in the instant Office action.
Withdrawn Rejections
The 35 U.S.C. 112 and 35 U.S.C. 103 rejections are withdrawn in view of amendments filed to the instant set of claims on 19 March 2026.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
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 25-27 and 29 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.
The term “maximum different ratio” in each of claims 25 and 29 is a relative term which renders the claim indefinite. The term “maximum different ratio” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear as to relative to what ratios the different ratio is maximum. For the purpose of examination, any different ratio is interpreted to be the “maximum different ratio”.
Claim Rejections - 35 USC § 103
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.
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) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mouliere et al. [WO 2020/094775 A1; on IDS of 8/20/2025] in view of He et al. [Am J Cancer Res, volume 4, 2014, pages 394-410; on attached 892 form].
The document of Mouliere et al. studies enhanced detection of target DNA by fragment size analysis [title].
Claim 25 is drawn to a method for cancer detection, recurrence monitoring, and treatment response assessment [abstract, Figure 1, and claim 39 of Mouliere et al.].
The method comprises obtaining a chromosome instability index in the biological sample. The chromosome instability index measures the degree of genomic structural variation based on CNAs across genomic regions of sequencing data of the biological sample [page 4, line 32 to page 5, line 4 of Mouliere et al.].
The method comprises determining a probability that the biological sample is derived from a cancer patient based on fragment size. The method comprises obtaining a cfDNA sample from the biological sample [abstract of Mouliere et al.].
The method comprises constructing a sequencing library from the cfDNA sample and sequencing the library to generate sequencing reads and extracting a plurality of fragment size metrics from the sequencing reads [page 9, line 20 to page 10, line 5 and claims 30-31 of Mouliere et al.].
The method comprises processing a machine learning model input comprising the statistical features using a first machine learning model to predict a probability value indicating the likelihood pf the biological sample being derived from a cancer patient, wherein the model comprises SVM [claim 11 of Mouliere et al.].
The method comprises determining a probability that the biological sample is derived from a cancer patient based on a protein tumor marker content [abstract and Figure 1 of Mouliere et al.].
The method comprises determining the proportion of mitochondrial DNA fragments below 150 bp in the biological sample [claims 30-31 of Mouliere et al.].
The method comprises obtaining a concentration of cfDNA in the biological sample [page 1, lines 10-30 of Mouliere et al.].
The method comprises determining a cancer predicting score that measures a probability that the biological sample is derived from a cancer patient [abstract and Figure 1 of Mouliere et al.].
The method comprises treating a subject with a cancer therapy [page 1, lines 1-10 of Mouliere et al.].
However, Mouliere et al. does not specifically teach a quantity termed “a chromosome instability index”. Mouliere et al. does not teach a cancer predicting score. Mouliere et al. does not teach. Mouliere et al. does not teach a different ratio between the cumulative distribution of SNV and SNP in the sample.
The document of He et al. teaches genome-wide prediction of cancer driver genes based on SNP and cancer SNV data [title]. The Section bridging pages 395-398 of He et al. teaches calculating SNV/SNP ratios for genes.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the cancer analysis of Mouliere et al. to include a chromosome instability index and cancer prediction scores wherein the motivation would have been that Mouliere et al. suggests the equivalent for the analogous purpose of assessing cancer [page 4, line 32 to page 5, line 4 of Mouliere et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the cancer analysis of Mouliere et al. in view of the SNV to SNP ratio of He et al. wherein the motivation would have been that the SNV to SNP ratio of He et al. is an additional manner of assessing for cancer within the genome [Section bridging pages 395-398 of He et al.]. There would have been a reasonable expectation of success in combining Mouliere et al. and He et al. because both studies analogously measure the degree of cancer in the genome.
Allowable Subject Matter
Even though the claims recite judicial exceptions, the core limitations of the claims involve using machine learning in the form of SVM, LASSO, or GBM, which is too complex to be performed in the human mind.
Claims 1-3, 8-9, 11, and 19 are free of the prior art because the prior art does not teach the mathematical manipulations recited in the claims.
Claim 26-27 and 29 are free of the prior art because the prior art does not teach the mathematical equation of finding bTMB for the purpose of assessing cancer in a subject.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/ Primary Examiner, Art Unit 1686 22 March 2026