Prosecution Insights
Last updated: April 19, 2026
Application No. 18/337,131

METHOD AND KIT FOR DETECTING CELL-FREE DNA METHYLATION

Non-Final OA §102§112
Filed
Jun 19, 2023
Examiner
FLINDERS, JEREMY C
Art Unit
1684
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Dalian Gentalker Bio-Tech Co. Ltd.
OA Round
1 (Non-Final)
64%
Grant Probability
Moderate
1-2
OA Rounds
3y 9m
To Grant
80%
With Interview

Examiner Intelligence

Grants 64% of resolved cases
64%
Career Allow Rate
378 granted / 586 resolved
+4.5% vs TC avg
Strong +15% interview lift
Without
With
+15.2%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
48 currently pending
Career history
634
Total Applications
across all art units

Statute-Specific Performance

§101
8.8%
-31.2% vs TC avg
§103
33.2%
-6.8% vs TC avg
§102
26.1%
-13.9% vs TC avg
§112
21.1%
-18.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 586 resolved cases

Office Action

§102 §112
DETAILED ACTION Status of the Claims Claims 1-20 are currently pending and are examined herein. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Information Disclosure Statement The information disclosure statement (IDS) submitted on 06/19/2023 is 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 § 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. Claim s 1- 20 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 in ventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claims 1- 2 , 11, and 13 contain the trademark/trade names Illumina®, Diagenode ®, NextSeq ®, Hiseq ®, and Miseq ® . Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe commercially available photoresists and, accordingly, the identification/description is indefinite. Given that a trademark or trade name is used to identify a source of goods, and not the goods themselves, it is suggested that Applicant amend the claims to properly define the products used for library preparation and sequencing (e.g. using generic descriptions). Claims 2-20 depend from claim 1 and are therefore similarly rejected. Claim 13 recites the limitation "step 5" of claim 1. There is in sufficient antecedent basis for this limitation in the claim, since there is no step 5 in the claims. Therefore, the metes and bounds of the claim are unascertainable. As per MPEP 2173 : It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112 , second paragraph as indefinite. Further, as per MPEP 2173 .02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. Claim Rejections – 35 U.S.C. 102 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 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 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. Shen et al. Claims 1-30 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Shen et al. ( Nature Protocols , 2019, 14:2749-2780). Regarding claim 1 , Shen discloses a construction method of a sequencing library for cell-free DNA (cfDNA) methylation (e.g., as per the Abstract) , comprising the following steps: step 1, extracting whole blood cfDNA (e.g., as per the Extraction and quantification of circulating cfDNA from plasma section on p p. 27 6 3 -2764 ) , and constructing a cfDNA library by end repair, A-tailing, and ligation of Illumina sequencing platform-specific index adapters (e.g., as per the Library preparation of cfDNA section on p p. 2753 -2754 ) ; step 2, mixing the cfDNA library constructed in step 1 with a filler DNA constructed in advance (e.g., as per the λ filler DNA generation section on pp. 2759-2763) to obtain a mixture of the cfDNA library and the filler DNA (e.g., as per the Library preparation—end repair and A-tailing section on pp. 2763-2766 ) ; step 3, co-immunoprecipitating anti-5-methylcytosine (5mC) antibody with the mixture of the cfDNA library and the filler DNA obtained in step 2 (e.g., as per the MeDIP —part 1 & 2 section on pp. 2766-2770 ) , and capturing and purifying methylated DNA fragments in the mixture to obtain captured product fragments (e.g., as per the MeDIP —part 1 & 2 section on pp. 2766-2770 ) ; and step 4, conducting amplification and enrichment on the product fragments obtained in step 3 (e.g., as per the Library amplification section on pp. 2772-2773 ) , and purifying, recovering and screening amplified products with magnetic beads to obtain a final sequencing library (e.g., as per the Library amplification section on pp. 2772-2773) . Regarding claim 2 , Shen discloses the above method , wherein the cfDNA in step 1 is extracted and obtained by a QlAamp Circulating Nucleic Acid Kit (e.g., as per the Extraction and quantification of circulating cfDNA from plasma section on pp. 2763-2764) . Regarding claim 3 , Shen discloses the above method , wherein the end repair and the A-tailing in step I are completed by means of an End Repair & A-Tailing Enzyme Mix reaction system (e.g., as per the Library preparation—end repair and A-tailing section on pp. 2763-2766 ) . Regarding claim 4 , Shen discloses the above method , wherein no sequencing adapter is added to the filler DNA in step 2 (e.g., as per Fig. 2 and the Filler DNA generation section on p. 2753 ) . Regarding claim 5 , Shen discloses the above method , wherein the filler DNA in step 2 comprises six polymerase chain reaction (PCR) amplicons of different sizes and CpG densities, five fragments of different CpG densities are methylated, one fragment is unmethylated, and methylated and unmethylated fragments have a mass ratio of 1:1 (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757 ) . Regarding claim 6 , Shen discloses the above method , wherein the six PCR amplicons of different sizes and CpG densities are 1CpG, 5CpG, 10CpG, 15CpG, 20LCpG, and 20SCpG (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757) . Regarding claim 7 , Shen discloses the above method , wherein the methylated fragments are 1CpG, 5CpG, 10CpG, 15CpG, and 20LCpG fragments (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757) . Regarding claim 8 , Shen discloses the above method , wherein the unmethylated fragment is a 20SCpG fragment (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757) . Regarding claim 9 , Shen discloses the above method , wherein the filler DNA in step 2 is obtained by performing a PCR with λ DNA as a template, purifying and recovering, and methylating, purifying and recovering a resulting PCR fragment (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757) . Regarding claim 10 , Shen discloses the above method , wherein the filler DNA in step 2 comprises 50% wt / wt methylated fragments and a 50% wt / wt unmethylated fragment (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757) . Regarding claim 11 , Shen discloses the above method , wherein the capturing in step 3 is completed by means of a Diagenode MagMeDIP Kit and a Diagenode iPure Kit V2 (e.g., as per the MeDIP —part 1 & 2 section on pp. 2766-2770) . Regarding claim 1 2 , Shen discloses the above method , wherein the amplification and enrichment in step 4 is performed by ligation-mediated polymerase chain reaction (LM-PCR) (e.g., as per the Library amplification section on pp. 2772-2773) . Regarding claim 13 , Shen discloses the above method , wherein the Illumina sequencing platform in step 5 is one selected from the group consisting of Illumina NextSeq 500, Illumina Hiseq2000, Illumina Hiseq2500, and Illumina Miseq (e.g., as per the Sequencing section on p. 2755) . Regarding claim 14 , Shen discloses a method for detecting cfDNA methylation, comprising steps of: sequencing a sequencing library obtained by the construction method according to claim 1 on an Illumina sequencing platform (e.g., as per the Sequencing section on p. 2755 ) , and bioinformatically analyzing acquired experimental data to know about the cfDNA methylation (e.g., as per the Bioinformatic analysis section on p. 2755 ) . Regarding claim 15 , Shen discloses a kit for the method for detecting cfDNA methylation according to claim 14, wherein the kit comprises the following components: components for next-generation sequencing (NGS) library preparation, a filler DNA fragment, components for co-immunoprecipitation, methylation capture, and purification and recovery, and components for library enrichment (e.g., as per the Material s section on pp. 2755-2759) . Regarding claim 16 , Shen discloses the above kit , wherein the components for NGS library preparation mainly comprise enzymes desired for end repair, A-tailing and adapter ligation in the NGS library preparation and Illumina sequencing platform-specific adapters (e.g., as per the Materials section on pp. 2755-2759) . Regarding claim 1 7 , Shen discloses the above kit , wherein the filler DNA fragment comprises six PCR amplicons of different sizes and CpG densities, five fragments of different CpG densities are methylated, and one fragment is unmethylated; the six PCR amplicons of different sizes and CpG densities are ICpG , 5CpG, 1OCpG, 15CpG, 20LCpG, and 20SCpG; the five fragments of different CpG densities are ICpG , 5CpG, 1OCpG, 15CpG, and 20LCpG fragments; and the one fragment is a 20SCpG fragment (e.g., as per the Materials section on pp. 2755-2759) . Regarding claim 1 8 , Shen discloses the above kit , wherein primers desired for the PCR have nucleotide sequences shown in SEQ ID NOs: 1 to 12 (e.g., as per the Filler DNA generation section on p. 2753 and Table 1 on p. 2757) . Regarding claim 1 9 , Shen discloses the above kit , wherein the components for co-immunoprecipitation comprise buffer reagents desired for the co-immunoprecipitation, an antibody protein, magnetic beads for the methylation capture, and reagents and an Elution Buffer desired for the purification and recovery (e.g., as per the Materials section on pp. 2755-2759) . Regarding claim 20 , Shen discloses the above kit , wherein the components for library enrichment comprise an enzyme and a buffer desired for library amplification, and magnetic beads desired for product recovery and purification and fragment screening (e.g., as per the Materials section on pp. 2755-2759) . Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JEREMY FLINDERS whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-1022 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 10-6:00 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, FILLIN "SPE Name?" \* MERGEFORMAT Heather Calamita can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571)272-2876 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JEREMY C FLINDERS/ Primary Examiner, Art Unit 16 84
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Prosecution Timeline

Jun 19, 2023
Application Filed
Mar 15, 2026
Non-Final Rejection — §102, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
64%
Grant Probability
80%
With Interview (+15.2%)
3y 9m
Median Time to Grant
Low
PTA Risk
Based on 586 resolved cases by this examiner. Grant probability derived from career allow rate.

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