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 .
The claims dated 6/8/2026 are under consideration.
The amendments and arguments presented in the papers filed 6/8/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 3/16/2026 listed below have been reconsidered as indicated.
a) The rejections of claim(s) 2-9, 11 and 14-18 under 35 U.S.C. 103 as being unpatentable over Ahlquist (WO 2015/153283 A1) are withdrawn in view of the amendments to the claims.
b) The rejections of claim(s) 2-9, 11, 13-18 and 22 under 35 U.S.C. 103 as being unpatentable over Ahlquist (WO 2015/153283 A1) in view of Kisiel (US 2016/0090634 A1) are withdrawn as Kisiel is not eligible as prior art.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
Claim Interpretation
Claim 2 encompasses determining a methylation profile in any differentially methylation region (DMR) from ELOVL2 in a DNA sample obtained from a subject having or suspected of having a gastrointestinal neoplasm by treating the sample with a reagent that modifies DNA in a methylation-specific manner. The claim further requires at least one DMR from MAXchr7.25896389-25896501.
Claim 7 further limits the DMRs of claim 2 to those within ELOVL2 and also comprises an increased methylation percentage as compared to a control DNA sample from a subject that does not have a gastrointestinal neoplasm.
Claim 8 further limits the DMRs of claim 2 to those within ELOVL2 also comprises an increased hypermethylation ratio as compared to a control DNA sample from a subject that does not have a gastrointestinal neoplasm.
Claim 9 further limits the DMRs of claim 2 to those within ELOVL2 also are associated with an area under a ROC curve (AUC) greater than or equal to 0.5, and wherein the ROC curve discriminates between a subject having or suspected of having a gastrointestinal neoplasm and a control DNA sample.
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) 2-9, 11, 14-18 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist (WO 2015/153283 A1; previously cited) in view of Aboelsoud (Hepatology. October 2014. 60(4 Suppl):798A-799A).
The following are new rejections necessitated by the amendments to the claims.
Regarding claims 2, 17, 18 and 22, Ahlquist teaches treating DNA from subjects with gastrointestinal neoplasm with bisulfite (p. 55).
The treated DNA is amplified with primers specific for markers in an MSP assay (p. 57-58). The markers included ELOVL2 (Table 1A) that is amplified with a primer identified as SEQ ID NO: 26 (Table 1B), which has the identical sequence as presently claimed SEQ ID NO: 5. Ahlquist further teaches a primer for ELOVL2 identified as SEQ ID NO: 27 (Table 1B), which as the identical sequence as presently claimed SEQ ID NO: 6.
Ahlquist teaches that designing primer for DMRs was known and within the skill of the ordinary artisan (p. 55, lines 21-27; p. 57, lines 8-25 and lines 26-31).
Ahlquist does not teach primers specific for MAX.chr7.25896389-25896501.
However, Aboelsoud teaches MAX.chr7.25896389-25896501 is a known methylation marker (p. 799A).
It would have been prima facie obvious to have combined the use of the ELOVL2 primers of Ahlquist with primers for MAX.chr7.25896389-25896501 in view of Aboelsoud. One would be motivated to do so to detect the CRC of Ahlquist and/or the cholangiocarcinomas of Aboelsoud.
The modification has a reasonable expectation of success because it simply involves designing primers for a MSP PCR assay which Ahlquist clearly demonstrates is within the skill of the ordinary artisan. The claimed primer sequences of claim 22 for MAX.chr7.25896389-25896501 are obvious variants of those that may be designed for detecting hypermethylation of MAX.chr7.25896389-25896501. Absent unexpected results, the claimed primers are rendered obvious.
Regarding claim 3, Ahlquist teaches determining the presence or absence of methylation at one or more CpG sites using the primers and a MSP assay as noted above.
Regarding claim 4, Ahlquist teaches the above DMR, which overlap with those identified in the specification. The markers of Ahlquist also thus must be present in a coding region, a non-coding region or regulatory region of the ELOVL2 gene. Aboelsoud also teaches the above DMR, which overlap with those identified in the specification. The markers of Aboelsoud also thus must be present in a coding region, a non-coding region or regulatory region of the MAX.chr7.25896389-25896501 region.
Regarding claim 5, Ahlquist teaches determining the methylation frequency (p. 9 and 25).
Regarding claim 6, Ahlquist teaches determining the methylation pattern (p. 25).
Regarding claim 7, Ahlquist teaches the DMR in ELOVL2 gene (Table 1A) has an increased methylation percentage as compared to a subject that does not have a gastrointestinal neoplasm.
Regarding claim 8, Ahlquist teaches the DMR in ELOVL2 gene (Table 1A) has an increased hypermethylation ratio as compared to a subject that does not have a gastrointestinal neoplasm.
Regarding claim 9, Ahlquist teaches the DMR in the ELOVL2 gene (Table 1A and 4B) as a marker has an AUC greater than 0.5 (p. 31).
Regarding claim 11, Ahlquist further teaches performing methylation specific PCR using primers for QKI and PDGFD (Table 1A).
Regarding claims 14 and 16, Ahlquist teaches the sample is a colon cancer tissue sample (p. 53-56).
Regarding claim 15, Ahlquist teaches the sample is from the upper gastrointestinal tract (p. 49).
Examiner’s response to the traversal of the 103 rejections
The Remarks argue Ahlquist alone and Ahlquist and Kisiel do not render the claim obvious (p. 5-8).
The arguments have been fully considered but are not persuasive as they do not address the above rejections necessitated by the amendments to the claims.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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