Prosecution Insights
Last updated: April 19, 2026
Application No. 17/980,755

SYSTEMS AND METHODS FOR PREPARING BIOLOGICAL SAMPLES FOR GENETIC SEQUENCING

Final Rejection §103§112
Filed
Nov 04, 2022
Examiner
PHAM, KHAI QUYNH TIEN
Art Unit
1684
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Universal Diagnostics, S.A.
OA Round
2 (Final)
0%
Grant Probability
At Risk
3-4
OA Rounds
3y 2m
To Grant
0%
With Interview

Examiner Intelligence

Grants only 0% of cases
0%
Career Allow Rate
0 granted / 1 resolved
-60.0% vs TC avg
Minimal +0% lift
Without
With
+0.0%
Interview Lift
resolved cases with interview
Typical timeline
3y 2m
Avg Prosecution
11 currently pending
Career history
12
Total Applications
across all art units

Statute-Specific Performance

§101
8.7%
-31.3% vs TC avg
§103
43.5%
+3.5% vs TC avg
§102
19.6%
-20.4% vs TC avg
§112
26.1%
-13.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1 resolved cases

Office Action

§103 §112
DETAILED ACTION Status of the Claims Claims 1, 9- 11, and 19 are amended. Claims 23-25 are newly added. Claims 8 is canceled. Claims 1-7 and 9-25 are currently pending and are examined herein. The following Office Action is in response to Applicant's communication dated 01/30/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . New Claim Interpretations Necessitated by Amendments For purposes of examination, the claims are interpreted according to their plain language as would be understood by one of ordinary skill in the art. Where the claim language is internally inconsistent or unclear, the Office does not infer unstated limitations or supply missing relationships. The interpretations set forth below are adopted solely to permit examination and do not resolve ambiguities in the claim language. Claim 23 depend on claim 1 and recites that “ the first portion is the 5' end of the indexed DNA and the second portion of the indexed DNA is the 3' end of the strand.” However, claim 1 does not introduce or define “first portion” or “second portion” , nor does it specify the nucleic acid or structure to which such portions refer. In particular, claim 1 does not recite “indexed DNA” adapter sequences, or a splint structure having multiple complementary portions. As a result, it is unclear from the claim langue whether the recited “first portion” and “second portion” refer to portions of the captured DNA fragments, the indexed DNA, the splint DNA, or other nucleic acid involved in the method. For purposes of examination only, and to facilitate a complete analysis of the claim, the Examiner interprets the “first portion” and “second portion” recited in claim 23 as corresponding to portions of the indexed DNA fragments recited in claim 19, specifically the 5’ end and 3’ end of the indexed DNA strand to which adapter sequences of a splint DNA hybridize during circularization. This interpretation is adopted solely for examination and does not resolve the lack of clarity in the claim language. New Claim Rejections - 35 USC § 112 (b) Necessitated by Amendments 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 23 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. Claim 23 recites “the first portion” and the “the second portion” without providing proper antecedent basis in claim 1 from which claim 23 depends. Claim 1 does not introduce or define “the first portion” or “the second portion”, nor does it specify the nucleic acid or structure to which such portions refer. Because the claim introduced new element without prior reference or explanation, a one of ordinary skill in the art cannot determine with reasonable certainty the scope of protection. Hence, the metes and bounds of the claim are unascertainable. Modified Claim Rejections - 35 U.S.C. 103 Necessitated by Amendments 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. 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. 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. Myllykangas et al. and Weng et al. Claim(s) 1, 2, 5-7, 9-18, and 23-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Myllykangas et al. (BMC Biotechnol. 2011;11:122) in view of Weng et al. (US 20180363039 A1, of record). Regarding claim 1, Myllykangas discloses a method comprising: capturing a subset of deoxyribonucleic acid (DNA) fragments with one or more capture probes (e.g. capture oligonucleotides selectively hybridized to specific genomic DNA fragments [abstract, Fig. 1]. ); converting said captured DNA fragments into circular, single stranded DNA(ssDNA), wherein converting said captured DNA fragments into circular, ssDNA comprises binding a splint DNA segment to each of the captured DNA fragments (e.g. The capture oligonucleotide acts as a “splint” that anneals and thus bridges the two ends of the fragment and this leads to a partial circularization of the fragment.[abstract, result section on page 2, and Fig. 1]). Myllykangas does not explicitly state that the DNA fragments are from of cell free DNA (cfDNA) samples and that the barcode sequence is located within a splint DNA segment. Myllykangas discloses the use of target-specific sequences as molecular barcodes and explicitly discloses incorporation of index sequences directly into capture oligonucleotides to enable multiplexed sequencing and sample identification [page 9]. Weng discloses sample polynucleotides is a cell-free DNA or RNA (cfDNA or cfRNA)[ [paragraph 0066]. Further, Weng teaches incorporating barcode or index sequences into ligation products that are joined to target DNA prior to circularization, such that the barcode sequence becomes part of the circular DNA molecule subjected to rolling circle amplification and sequencing [paragraph 0004]. As of the application’ s effective filing date, in view of Weng, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to incorporate such barcode sequence into the splint oligonucleotide used to mediate circularization method of Myllykangas, rather than in a separate adapter or primer, as a predictable design choice to enable multiplexing while reducing additional processing steps. Further, because the method of Myllykangas operate on DNA fragments based on sequence complementarity and fragment structures, a person of ordinary skill in the art would reasonably expect the method to be applicable to cfDNA fragments taught by Weng. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B and E). Regarding claim 2 and 5 Myllykangas and Weng discloses a method of claim 1 as discussed fully above and incorporated here. Weng further discloses extracting cfDNA from a biological sample (e.g. methods for extracting cfDNA [paragraph 00128] from biological samples [paragraph 00127]) and converting the cfDNA prior to capturing the subset of DNA fragments with the one or more capture probes (e.g. converting unmethylated cytosine to uracil [paragraph 0105]).The biological sample comprises a member selected from the group consisting of plasma, blood, serum, urine, stool, and tissue ([paragraph 00127]). Regarding claim 6, 7, and 18, Myllykangas and Weng discloses a method of claim 1 as discussed fully above and incorporated here. Weng further discloses the one or more capture probes comprises one or more methylation capture probes and/or one or more mutation capture probes (e.g. capture probe hybridizes to a sequence variant [paragraph 0068], sequence variant comprise at least one mutation, including nucleotide variant, an insertion etc. [paragraph 0008]). Further, at least one of the one or more capture probes targets a differentially methylated region (e.g. capture probe hybridizes to a sequence variant [paragraph 0068], sequence variant comprises at least one mutation, including nucleotide variant, an insertion etc. [paragraph 0008]). The capture probes are used in a predetermined ratio to enrich methylated/unmethylated reads in target regions (e.g. capture probe hybridizes to a sequence variant [paragraph 0068], sequence variant comprises at least one mutation, including nucleotide variant, an insertion, methylation etc. [paragraph 0008]). Regarding claim 9, Myllykangas and Weng discloses a method of claim 1 as discussed fully above and incorporated here. Myllykangas teaches circularization of target DNA fragments using oligonucleotides that hybridize to complementary target sequences [page 2]. As hybridization requires sequence complementarity, the resulting circular DNA necessarily includes regions complimentary to the original DNA fragment. It would have been obvious to one of ordinary skill in the art to apply this teaching of cfDNA fragments, yielding a circular ssDNA having portion complimentary to the original cfDNA strand. Regarding claim 10, Myllykangas and Weng discloses a method of claim 1 as discussed fully above and incorporated here. Weng further discloses amplifying the circular DNA by performing rolling circle amplification (RCA) (e.g. performing RCA on the circular DNA templates. Fig. 6B, [paragraph 0089]). Regarding claim 11-14, Myllykangas and Weng discloses a method of claim 1 as discussed fully above and incorporated here. Weng further discloses sequencing the circular DNA using nanopore sequencing or single molecule real time sequencing (SMRT) (e.g. circularized polynucleotides subjected to sequencing reaction. Examples include Illumina, Life Technologies, Roche's 454 Life Sciences systems, Pacific Biosciences systems etc. [paragraph 0095]), wherein sequencing reads each having length of at least 900 bases. (e.g. circularization reaction conditions may be selected to favor self-joining of polynucleotides shorter than about 5000, 2500, 1000 etc. [paragraph 0073]). Regarding claim 15-17, Myllykangas and Weng discloses a method of claim 11 as discussed fully above and incorporated here. Weng further discloses performing (i) methylation target evaluation , or (ii) mutation target evaluation, or (iii) simultaneous methylation target and mutation target evaluation (e.g. sequencing data from amplification products can be used to detect sequence variants [paragraph 0099], sequence variant comprises at least one mutation, including nucleotide variant, an insertion etc. [paragraph 0008].) for determining that a subject has a disease or condition [paragraph 0126]. Regarding claim 23, Myllykangas and Weng disclose a method of claim 1 as discussed fully above and incorporated here. Myllykangas further discloses the first portion is the 5' end of the indexed DNA and the second portion of the indexed DNA is the 3' end of the strand (e.g. The capture oligonucleotide acts as a “splint” that anneals and thus bridges the two ends of the fragment and this leads to a partial circularization of the fragment.[abstract, result section on page 2, and Fig. 1]). Regarding claim 24, Myllykangas and Weng disclose a method of claim 1 as discussed fully above and incorporated here. While Myllykangas does not expressively recite a specific molar ratio between captured DNA and splint DNA, the reference discloses performing circularization reactions using defined oligonucleotide amounts (e.g. 1 μg of genomic DNA digested and circularized in the presence of a pool of 107 genomic circularization oligonucleotides [method, “Targeted genomic circularization” section]). Selection of a particular molar ratio between splint DNA and captured DNA represents optimization of a result effective variable. The discovery of an optimum or workable range, (e.g. 1:2 to 1:5 molar ratio of captured DNA fragments to splint DNA) would have been within the ordinary skill in the art through routine experimentations. See MPEP § 2144.05 (II), 2144.05 (III)(C); In re Aller, 220 F.2d 454. Regarding claim 25, Myllykangas and Weng disclose a method of claim 1 as discussed fully above and incorporated here. Weng further discloses the captured DNA fragments comprise DNA fragments having a length from 150 base pairs to 1000 base pairs.[paragraph 0131]. Weng et al., Myllykangas et al., and Glezer et al. Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weng et al. (US 20180363039 A1, of record) in view of Myllykangas et al. (BMC Biotechnol. 2011;11:122), and Glezerat al. (US 11359238 B2, of record). Regard claim 3, Myllykangas and Weng disclose a method of claim 2 as discussed fully above and incorporated here. Weng further disclosed method of converting the cfDNA via bisulfite treatment [paragraph 0105]. However, Myllykangas and Weng do not disclose conversion of the cfDNA comprises enzymatic treatment of the cfDNA. Glezer et al. discloses bisulfite-free approach for methylation analysis using the NEBNext® Enzymatic Methyl-seq product [paragraph 0187]. Method involves first protects 5mC and 5hmC from deamination by TET2 and an oxidation enhancer, followed by APOBEC deamination of unprotected cytosines to uracil [paragraph 0187]. As of the application’ s effective filing date, in view of Weng, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to substitute bisulfite cfDNA conversion of Weng with the enzymatic cfDNA conversion of Glezer. Weng teaches method for determining the sites of 5-methylcytosine in genome at the sequence level involves bisulfite modification of DNA. Glezer teaches that there is another well-known alternative to bisulfite sequencing for analyzing DNA methylation, using enzymes instead of harsh chemicals to convert DNA. Glezer explicitly teaches enzymatic process minimizes DNA damage, leading to higher sensitivity, greater mapping efficiency, more uniform GC coverage, and the ability to detect more CpGs with fewer sequencing reads [column 84, lines 61-column 85, line 19]. One of ordinary skill in the art would have had a reasonable expectation of success as of the application' s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since substituting enzymatic conversion for bisulfite-mediated conversion would have a predictable result and a reasonable expectation of success as both function to determine the sites of 5-methylcytosine and the methylation as per Glezer et al. uses a commercially available kit. The substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A and E.). Weng et al., Myllykangas et al., and Fan et al. Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weng et al. (US 20180363039 A1, of record) in view of Myllykangas et al. (BMC Biotechnol. 2011;11:122), and Fan et al. (US 20050026183 A1, of record). Regard claim 4, Myllykangas and Weng disclose a method of claim 1 as discussed fully above and incorporated here. Weng further discloses sequencing of circularized cfDNA to detect methylation states across predetermined loci. However, Weng does not disclose the use of methylated DNA control samples to serve as a reference or normalization element in evaluating target methylation levels. Fan discloses methylation analysis workflows in which reference samples, known methylation status DNA, are incorporated int assays to provide internal standards for differential methylation detection and comparison between biological samples and known methylation states (e.g. “plasmid control DNAs with known methylation status, spiked into human genomic DNA in a 1:1 ratio” [paragraph 0104], Fig. 5 and Fig. 6). Fan further teaches comparing methylated CpG dinucleotide sequences in biological sample to reference levels to determine altered methylation patterns associate with cancer [paragraph 0124]. As of the application’ s effective filing date, in view of Weng, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to include methylated DNA control samples as part of the methylation detection workflow of Myllykangas and Weng, in order to calibrate assay performance, detect bisulfite conversion efficiency, and provide reference intensities against which to compare the methylation status of cDNA targets. The inclusion of control DNA molecules as internal references, taught by Fan, represents a routine assay calibration consistent with standard molecular diagnostic practice and would have yield predictable improvements in data reliability, consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A and G.). Weng et al., Myllykangas et al., Fan et al., and Glezer et al. Claim(s) 19-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weng et al. (US 20180363039 A1, of record) in view of Myllykangas et al. (BMC Biotechnol. 2011;11:122), Glezerat al. (US 11359238 B2, of record) and Fan et al. (US 20050026183 A1, of record). Regarding claim 19, Weng discloses a method comprising: Extracting DNA from a biological sample of a human subject to obtain a DNA sample [paragraph 0050]; adding an index primer to the converted DNA; amplifying the indexed DNA; amplifying the circular, ssDNA using rolling circle amplification; creating a library of DNA from the amplified, circulars ssDNA [Fig. 6A-6B, paragraphs 0089 and 0090]); sequencing the library using third generation sequencing to produce sequencing results (e.g. single-molecule real-time sequencing [paragraph 0061] However, Weng does not disclose adding control DNA molecules to the DNA sample; converting unmethylated cytosines to uracils of the DNA in the DNA sample using enzymatic conversion; and capturing a subset of indexed DNA with one or more capture probes, wherein each of said capture probes are targeted to a pre-determined mutation locus or a pre-determined methylation locus; converting said captured, indexed DNA into circular, single stranded DNA(ssDNA), wherein converting said captured, indexed DNA into circular, ssDNA comprises binding a splint DNA segment to the indexed DNA, wherein the splint DNA comprises a segment of barcode DNA, a first adapter complementary to a first portion of the captured, indexed DNA, and a second adapter complementary to a second portion of the captured, indexed DNA; Fan discloses methylation analysis workflows in which reference samples, known methylation status DNA, are incorporated int assays to provide internal standards for differential methylation detection and comparison between biological samples and known methylation states (e.g. “plasmid control DNAs with known methylation status, spiked into human genomic DNA in a 1:1 ratio” [paragraph 0104], Fig. 5 and Fig. 6). Fan further teaches comparing methylated CpG dinucleotide sequences in biological sample to reference levels to determine altered methylation patterns associate with cancer [paragraph 0124]. Weng further discloses bisulfite/chemical conversion context but does not explicitly recite converting unmethylated cytosine to uracil using enzymatic means. Glezer discloses bisulfite-free approach for methylation analysis using the NEBNext® Enzymatic Methyl-seq product [column 58, lines 36-47]. Method involves first protects 5mC and 5hmC from deamination by TET2 and an oxidation enhancer, followed by APOBEC deamination of unprotected cytosines to uracil [column 85, lines 3-19]. As discussed in claim 1, Myllykangas discloses circularization of target DNA using oligonucleotides that hybridize to complementary target sequences [abstract, Fig. 1] and further teaches incorporation of barcode or index sequences into oligonucleotides involved in sequencing library preparation [page 9]. As of the application’s effective filing date, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to modify the method of Weng to incorporate the circularization and probe mediated capture strategies taught by Myllykangas in order to improve target specific sequencing accuracy and error suppression in cfDNA methylation analysis. Weng already teaches the core architecture of the claimed method including capture-probe-mediated hybridization of target DNA, ligation to barcoded adapters, circularization, rolling-circle amplification, and sequencing for variant and methylation analysis. Myllykangas recognizes that the usual two-step sample preparation for targeted NGS, (1) selectively captured target sequence and (2) sample preparation DNA molecules to render them compatible with any given NGS sequencing platform, often time-consuming, prone to experimental errors and difficult to automate. Hence, Myllykangas disclosed a method of integrating both NGS library preparation and capture of specific genomic targets. [page 2]. Incorporating Myllykangas’s circularization and probe design into Weng’s workflow represents applying a known solution to a known problem, namely improving sensitivity and accuracy, while lower sample preparation time. A person of ordinary skill in the art would have been motivated to combine these teachings because both references address similar technical problem (detection of sequence variants in low abundance DNA) using compatible techniques (capture probe, circularization, amplification, and sequencing). Further, the inclusion of control DNA molecules as internal references, taught by Fan, represents a routine experimental control wildly used in methylation assays to normalize conversion efficiency and sequencing bias. Likewise, replacing bisulfite conversion with enzymatic conversion of unmethylated cytosines to uracils, as taught by Glezer, would have been an obvious substitution because both techniques perform the same chemical function and Glezer explicitly teaches enzymatic conversion as a known alternative to bisulfite treatment with reduced DNA degradation [column 84, lines 61-column 85, line 19]. Accordingly, the claim method is the result of combining familiar elements according to known methods to yield predictable results, rendering claim 19 obvious, consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, A, B and G). Regard claim 20, Weng, Myllykangas, Fan, and Glezer disclose a method of claim 19 as discussed fully above and incorporated here. Although Weng does not expressly disclose the sequencing reads each having length of at least 900 bases, Weng teaches circularization reaction conditions may be selected to favor self-joining of polynucleotides shorter than about 5000, 2500, 1000 etc. [paragraph 0073]. As set forth in MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Regard claim 21, Weng, Myllykangas, Fan, and Glezer disclose a method of claim 19 as discussed fully above and incorporated here. Weng further discloses method comprises determining that a subject has a disease or condition based at least in part on the methylation target and/or mutation target evaluation [paragraph 0126]. Regard claim 22, Weng, Myllykangas, Fan, and Glezer disclose a method of claim 19 as discussed fully above and incorporated here. Fan further discloses methylation analysis workflows in which reference samples, known methylation status DNA, are incorporated int assays to provide internal standards for differential methylation detection and comparison between biological samples and known methylation states (e.g. “plasmid control DNAs with known methylation status, spiked into human genomic DNA in a 1:1 ratio” [paragraph 0104], Fig. 5 and Fig. 6). Fan further teaches comparing methylated CpG dinucleotide sequences in biological sample to reference levels to determine altered methylation patterns associate with cancer [paragraph 0124]. Response to Arguments Applicant’s argument filed 01/30/2026 have been fully considered but are not persuasive for the reasons set forth below. While applicant has amended the claims and presented arguments traversing prior rejections, the amendments and arguments do not overcome the rejections as presently applied. Hence, the rejections maintained. RE: Applicant argues that Weng does not disclose that converting capture DNA fragments into circular single-stranded DNA comprises binding a splint DNA segment to the indexed DNA, and therefore contends that the prior 102 rejections were improper. In response: As set forth in the present rejection, then claims are no longer rejected under §102 based solely on Weng. Instead, the claims are rejected under 35 U.S.C. §103 over Myllykangas in view of Weng. While Weng does not explicitly recite the use of a splint DNA to mediate circularization, Myllykangas expressly teaches circularization of captured DNA fragments using oligonucleotides that hybridize to complementary target sequences, thereby functioning as splint oligonucleotide to join the ends of DNA fragments. Accordingly, Applicant’s argument directed to the absent of splint DNA in Weng does not address the combined teachings upon in the present rejection. RE: Applicant argues that the prior art does not disclose splint DNA comprising a segment of barcode DNA. In response: Myllykangas teaches incorporating of barcode sequences into oligonucleotides used in sequencing library preparation [page 9], and Weng teaches incorporating barcode into ligation products joined to target DNA prior to circularization, such that the barcode becomes part of the circular DNA subjected to amplification and sequencing [paragraph 0004]. In view of these teachings, a PHOSITA would have been motivated to incorporate the barcode sequence into the splint DNA, consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, E). RE: Applicant asserts that amendment of independent claim 1 to expressly recite splint DNA render the prior rejection moot. In response: The present rejection expressly relied on Myllykangas for splint-mediated circularization and on Weng for technique incorporating barcode sequences into ligation products that become part of the circular DNA constructed (the barcode concept is suggested by Myllykangas). RE: Applicant further contends that the claimed configuration provides unique benefits not taught or suggested by prior art. In response: The asserted benefits represent expected result for combining known techniques for barcoding, circularization, and multiplexed sequencing. The recognition of such advantages does not render the claimed subject matter nonobvious. Conclusion 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 Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 ET. 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, Heather Calamita can be reached at (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. /KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684 /JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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Prosecution Timeline

Nov 04, 2022
Application Filed
Oct 27, 2025
Non-Final Rejection — §103, §112
Jan 30, 2026
Response Filed
Mar 04, 2026
Final Rejection — §103, §112 (current)

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