DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed January 28, 2026. Currently, claims 1-2,4-6 and 19-34 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
The new matter rejection has been withdrawn in view of the amendment to the claims to require at least 6.
The Written Description rejection has been withdrawn in view of the amendment to the claim to require the probe binds to particular amplicons.
The 102 rejection has been withdrawn in view of the amendments to the claims to require the probe binds to particular amplicons. Page 23-24 of the specification teaches these amplicons are 69-90bp. Thus, the claims no longer encompass very large regions for the DMR.
Election/Restrictions
Applicant's election without traverse of Group I and with traverse to 10 particular methylation markers, claims 1-17 in the paper filed June 12, 2025 is acknowledged.
The response requests rejoinder of all of the species because the claimed Markush group is small and can be made without a serious burden. This argument has been reviewed but is not persuasive. Each of the recited 19 CpG sites requires search and consideration that is different from each other CpG site. This requires a serious burden.
Claims 3-6, 10, 12-14, 16-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Objections
Newly added Claim 33 is objected to because the claim does not end in a period (see MPEP 608.01(m)). This objection may be overcome by inserting a period at the conclusion of Claim 33.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 23-34 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 pre-AIA the applicant regards as the invention.
Claims 23-34 recite “Roche UPL70”. This language is considered essential subject matter. Therefore, the claims are rejected as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the polynucleotide sequence of Roche UPL70. As provided in 2144.01(III) “The goal of the Office is to build a comprehensive database that can be used for, inter alia, assessing the prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database. In those instances in which prior art sequences are only referred to in a given application by name and a publication or accession reference, they need not be included as part of the “Sequence Listing”, unless the referred-to sequence is “essential material” per MPEP § 608.01(p).” Here, the sequence “Roche UPL70” is essential as it is required element of the claims. It is further noted 37 CFR 1.57(h)(1)
“authorizes the correction of noncompliant incorporation by reference statements that do not use the root of the words "incorporate" and "reference" in the incorporation by reference statement when the application as filed clearly conveys an intent to incorporate the material by reference. This correction can usually be made, for example, when an originally filed claim of an application identifies an amino acid or nucleotide sequence by database accession number. In making the determination of clear intent the examiner should consider the language used in referencing the sequence, the context in which it is disclosed, and any additional arguments or evidence presented by applicants.”
However, there is no indication of the sequence of the probe. No new matter may be added. Applicant may wish to provide evidence of the sequence available at the time of filing.
Claims 1-2, 4-6, 19-34 are directed nucleic acid sequences “according to”. It is unclear what “according to encompasses.” According to is not a recognized transitional phrase, therefore it is unclear what the claim encompasses. Applicant may wish to amend the claim to recite “wherein each marker-specific probe binds an amplicon formed by a PCR of genomic DNA using primer pairs comprising…..”
Claim 20 recites “all of the primer pairs”. The claim lacks proper antecedent basis. “All of the primer pairs” are not defined in Claim 1. Claim 1 provides a PCR to amplify bisulfite converted DNA. However, there are no primer pairs required by Claim 1. The primers listed in the wherein clause are not required elements, but only define boundaries of the amplicon. Clarification is required.
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.
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.
Claim(s) 1-2, 5-6, 19, 24-25, 27-30 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by GSM1465025 (September 10, 2014).
GSM1465025 teaches a method of processing a human colorectal cancer cell line for whole genome bisulfite sequencing (WGBS). GSM1465025 teaches the nucleic acid was processed to be cell free before performing WGBS. GSM1465025 teaches bisulfite treating adapter-ligation mixes before running on the Hi-Seq 2000 platform.
Whole genome bisulfite sequencing would cover the entire genome and thus would comprise the claimed methylation markers in Claims 2-3, and 14-15.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970);and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-2, 4-6, 19-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 7, 10-11, 174, 17, 20-23, 26-27, 29, 31, 33-47 of copending Application No. 17/619,116 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the conflicting claims are not identical, they are not patentable distinct from each other. Claims 1, 4-5, 7, 10-11, 174, 17, 20-23, 26-27, 29, 31, 33-47 of copending Application No. 17/619,116 are directed to methods of quantifying and analyzing the methylation of a plurality of genetic loci in cfDNA. Claims 10 are directed to 8-10 biomarkers, which encompasses at least 6. Claim 21-23, 38 encompass the instant DMR.
Response to Arguments
The Applicant requests that this rejection be held in abeyance until allowable subject matter is found in the pending application. This request has been noted and is denied. See 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance but includes no provision for holding rejections in abeyance. Thus, for the reasons above and those already of record, the rejection is maintained.
Claims 1-2, 4-6, 19-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of US Patent 11,851,711 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Although the conflicting claims are not identical, they are not patentable distinct from each other. Claims 1-9 of US Patent 11,851,711 are directed to methods of detecting methylation of a plurality of genetic loci consisting of 10 particular sites. These sites are the 10 sites listed in Claim 1.
Response to Arguments
The Applicant requests that this rejection be held in abeyance until allowable subject matter is found in the pending application. This request has been noted and is denied. See 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance but includes no provision for holding rejections in abeyance. Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
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 JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
April 1, 2026