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 .
The preliminary amendment filed April 12, 2024 canceling claims 1-30 and adding new claims 31-50 is acknowledged and has been entered.
Claims 31-50 are pending and will be examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 18, 2024, June 12, 2025, September 23, 2025, December 18, 2025, February 3, 2026, April 22, 2026, July 1, 2026 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
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) 31-50 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carrell et al. (US 11401552 B2; August 2022).
With regard to claim 31, Carrell teaches a method of detecting hypermethylation of differentially methylated regions (DMRs), the method comprising:
detecting a methylation status of at least one methylation site within each of two or more differentially methylated regions (DMRs) of cell-free DNA from blood or plasma of a human subject suspected of having colorectal cancer and/or advanced adenoma, wherein a first of the two or more DMRs comprises a methylation locus within gene ALK and a second of the two or more DMRs comprises a methylation locus within gene LONRF2, wherein detecting the methylation status comprises determining whether at least one methylation site within each of the two or more DMRs are hypermethylated (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 32, Carrell teaches a method of claim 31, wherein the methylation locus within gene ALK comprises ALK '434 (SEQ ID NO: 17) (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 33, Carrell teaches a method of claim 31, wherein the methylation locus within gene LONRF2 comprises LONRF2 '281 (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 34, Carrell teaches a method of claim 31, wherein the methylation locus within gene LONRF2 comprises LONRF2 '387 (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 35, Carrell teaches a method of claim 31, wherein the methylation status is detected using quantitative polymerase chain reaction (qPCR) (col. 10, where PCR is described).
With regard to claim 36, Carrell teaches a method of claim 31, wherein the method comprises amplification of the DMR LONRF2 '281 (SEQ ID NO: 19) using an oligonucleotide primer pair (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 37, Carrell teaches a method of claim 31, wherein the method comprises amplification of the DMR LONRF2 '387 (SEQ ID NO: 20) using an oligonucleotide primer pair (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 38, Carrell teaches a method of claim 31, wherein the method comprises amplification of the DMR ALK '434 (SEQ ID NO: 17) using an oligonucleotide primer pair (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 39, Carrell teaches a method of claim 31, wherein the subject is suspected of having early-stage colorectal cancer (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 40, Carrell teaches a method of claim 31, wherein the methylation status is detected using one or more members selected from the group consisting of methylation sensitive restriction enzyme quantitative polymerase chain reaction (MSRE-qPCR), Methylation-Specific PCR, Methylation Specific Nuclease-assisted Minor-allele Enrichment PCR, and next-generation sequencing (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 41, Carrell teaches a method of claim 31, wherein the method further comprises detecting a methylation status of at least one methylation site within a third DMR comprising a methylation locus of gene PDGFD, at least one methylation site within a fourth DMR comprising a methylation locus of gene FGF14, and at least one methylation site within a fifth DMR comprising a methylation locus of gene JAM2 (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 42, Carrell teaches a method of claim 31, wherein each of the two or more DMRs comprise from one to fifteen methylation sensitive restriction enzyme (MSRE) cleavage sites (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 43, Carrell teaches a method of using methylation sensitive restriction enzyme quantitative polymerase chain reaction (MSRE-qPCR), the method comprising:
(a) contacting cell-free DNA from blood or plasma of a human subject suspected of having colorectal cancer and/or advanced adenoma with one or more methylation sensitive restriction enzymes; (b) performing qPCR of enzyme-digested DNA, or amplicons thereof; and (c) detecting the methylation status of at least one methylation site found within each of two or more differentially methylated regions (DMRs) of DNA, wherein a first of the two or more DMRs comprises a methylation locus within gene ALK and a second of the two or more DMRs comprises a methylation locus within gene LONRF2 (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 44, Carrell teaches a method of claim 43, wherein the method comprises amplification of the DMR LONRF2 '281 (SEQ ID NO: 19) using an oligonucleotide primer pair (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 45, Carrell teaches a method of claim 43, wherein the method comprises amplification of the DMR LONRF2 '387 (SEQ ID NO: 20) using an oligonucleotide primer pair (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 46, Carrell teaches a method of claim 43, wherein the method comprises amplification of the DMR ALK '434 (SEQ ID NO: 17) using an oligonucleotide primer pair (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 47, Carrell teaches a method of claim 43, wherein the subject is suspected of having early-stage colorectal cancer (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 48, Carrell teaches a method of claim 43, wherein the method further comprises detecting a methylation status of at least one methylation site within a third DMR comprising a methylation locus of gene PDGFD, at least one methylation site within a fourth DMR comprising a methylation locus of gene FGF14, and at least one methylation site within a fifth DMR comprising a methylation locus of gene JAM2 (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 49, Carrell teaches a method of claim 43, wherein each of the two or more DMRs comprise from one to fifteen methylation sensitive restriction enzyme (MSRE) cleavage sites (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
With regard to claim 50, Carrell teaches a method of claim method of screening for colorectal cancer, the method comprising:
determining a methylation status for each of the following, in deoxyribonucleic acid of a human subject suspected of having colorectal cancer and/or advanced adenoma: (a) a methylation locus within gene ALK; and (b) a methylation locus within gene LONRF2 (Fig 3, Fig 6, paragraph 102, for example and Table 2, where multiple markers are included and differential methylation is the focus of Carrell).
Conclusion
No claims are allowed. All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
