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 .
Status of the Application
The Amendment filed March 19, 2026 is acknowledged.
Claims 1-15 were pending. Claims 1, 5-6 and 9 are being examined on the merits. Claims 3-4 and 7-8 are canceled. Claims 2 and 10-15 were withdrawn and are now canceled.
Response to Arguments
Applicant’s arguments filed March 19, 2026 have been fully considered.
The following objections and rejections are WITHDRAWN in view of Applicant’s arguments and amendments to the specification and claims:
Objections to the Specification
Objections to claims 3 and 4-9
Rejection of claims 1 and 3 under 35 USC § 101
Double patenting rejections
The following rejections are MODIFIED in view of Applicant’s arguments and amendments to the claims:
Prior art rejections
Response to arguments regarding prior art rejections
The prior art rejections are modified in view of the instant claim amendments. However, to the extent that Applicant’s arguments are relevant to the modified rejections, the Examiner notes the following.
Applicants argue that the prior art rejections based on Goering should be withdrawn because Goering is directed to prostate cancer and does not teach detecting the methylation state of the recited genes in a sample from a patient with bladder cancer (Remarks, p. 7).
The Examiner agrees. The rejections based on Goering are withdrawn.
Applicant states:
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168
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(Remarks, p. 7).
The Examiner agrees in part and disagrees in part. The Examiner agrees that Lind uses cells present in urine sediment in their assay, and further that Lind does not teach performing the detection in a cell free component. However, as to the claim 1 “urine sample”, the Examiner disagrees that the limitation should be construed so narrowly as to exclude urine sediment. The specification does not define “urine sample” in a way that would exclude urine sediment. Further, the prior art, e.g., Renard1 (Identification and Validation of the Methylated TWIST1 and NID2 Genes through Real-Tie Methylation-Specific Polymerase Chain Reaction Assays for the Noninvasive Detection of Primary Bladder Cancer in Urine Samples, European Urology, 58, 96-104, 2010), describes urine sediment as being comprised within a “urine sample” (p. 98, right col., para. 1). Thus, to the extent that urine sediment is a component of a urine sample, then the Lind urine sediment component reads on the instantly claimed “urine sample”.
The prior art rejections are modified in view of the instant claim amendments.
Information Disclosure Statement
The Information Disclosure Statements submitted October 29, 2025 and December 1, 2025 have each been considered.
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.
Claims 1 and 5-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lind2 (US Patent App. Pub. No. 2013/0210011 A1).
Regarding independent claim 1 and dependent claims 5-6, Lind teaches …
A method of detecting the presence or absence of methylation markers, the method comprising: detecting, optionally with amplification, in DNA present in a urine sample from an individual suffering from bladder cancer, the presence or absence of methylation markers in a CpG island, optionally in a promoter region, of at least one gene selected from GDF15, TMEFF2, VIM; or NID2 in combination with TWIST1 (para. 6: “methods and biomarkers … for detection of … cancer … in biological samples (e.g., … urine samples …)”; para. 8: “gene methylation levels were quantified”; para. 8: “[t]he methylation levels of GDF15, TMEFF2, and/or VIM were significantly higher in bladder cancer tissues … In urine samples, the panel achieved a sensitivity of 94% and specificity of 100%”; para. 19: “obtaining DNA from a biological sample … determining the level, presence or frequency of methylation of one or more nucleic acid[s] … compris[ing] a … CpG island [which] … is present in … a promoter”); para. 53: “a two-gene panel (TWIST1 and NID2)”; para. 71: “detecting bladder neoplasia through detecting both the level (presence, absence, score, frequency) of markers in a urine sample obtained from the mammal”; para. 106: methylation-specific qPCR amplification with patient samples).
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 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lind (US Patent App. Pub. No. 2013/0210011 A1) as applied to claim 1 above, and further in view of Song3 (US Patent App. Pub. No. 2014/0155279 A1).
Regarding dependent claim 9, Song teaches that the urine sample is a cell-free urine
sample (para. 136) from a bladder cancer patient (para. 37). Song additionally teaches that assays that use a cell-free DNA fraction from urine have higher sensitivity and specificity for detecting tumor-derived DNA markers than the traditionally used fractions (paras. 135-137).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Lind method to incorporate the cell-free urine sample of Song. Lind teaches the need for diagnostic assays with high sensitivity and specificity for use in clinical settings to detect cancer (para. 4). Song teaches that using the cell-free DNA fraction from urine results in an assay with higher sensitivity and specificity compared to traditionally used fractions. Therefore, one of ordinary skill in the art would have been motivated to incorporate the Song cell-free fraction into the Lind method to increase the sensitivity and specificity of the Lind method. The ordinary artisan would have had an expectation of success, as Lind teaches that the method can be performed on a variety of tissues and fluids (para. 62).
Conclusion
Claims 1, 5-6 and 9 are being examined, and are rejected. No claims are 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 CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Renard is incorporated-by-reference in Lind at paras. 53-54. Renard was additionally cited in the Information Disclosure Statement submitted October 30, 2023.
2 Lind was cited in the Information Disclosure Statement submitted October 30, 2023.
3 Song was cited in the Information Disclosure Statement submitted October 30, 2023.
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