Office Action Predictor
Application No. 17/669,988

SYNTHETIC POLYNUCLEOTIDES AND METHOD OF USE THEREOF IN GENETIC ANALYSIS

Non-Final OA §102§103
Filed
Feb 11, 2022
Examiner
LAFAVE, ELIZABETH ROSE
Art Unit
1684
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Personal Genome Diagnostics INC.
OA Round
3 (Non-Final)
47%
Grant Probability
Moderate
3-4
OA Rounds
4y 1m
To Grant
99%
With Interview

Examiner Intelligence

47%
Career Allow Rate
15 granted / 32 resolved
Without
With
+58.5%
Interview Lift
avg trend
4y 1m
Avg Prosecution
48 pending
80
Total Applications
career history

Statute-Specific Performance

§101
11.5%
-28.5% vs TC avg
§103
23.3%
-16.7% vs TC avg
§102
29.8%
-10.2% vs TC avg
§112
33.1%
-6.9% vs TC avg
Black line = Tech Center average estimate • Based on career data

Office Action

§102 §103
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 . Office Action: Notice A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/3/2025 has been entered. Claim Status Per Applicant amendments 10/3/2025; claims 1, 5, 6, 8, 12, 21, and 25 have been amended. No new matter has been added. No claims have been cancelled. Claims 1-3 and 5-27 are under examination on the merits. Election/Restrictions As previously noted in the previous Office Action, mailed 11/25/2024, Applicant's argument to the restriction requirement mailed on September 4, 2024 and applicant’s subsequent reply filed on October 21, 2024 is acknowledged. The traversal regarding claims 5, 10, 17, 19, 21-27 is not found persuasive for the following reasons, and is therefore maintained. For claim 5, each tissue type has distinct characteristics requiring treatment methods, leading to different search strategies. For claim 10, each species has a unique structure and effect on the sequences, necessitating searches in different technical areas. For claim 17, each gene has a distinct sequence and structure, with proteins encoded by the genes having different structural characteristics, requiring separate search strategies. For claim 19, the modified bases have different structures and distinct effects on the nucleic acid sequences. For claim 27, the different variants again require different structural searches and effects on sequences. For claims 21-24, each disease and disorder have different causes, etiologies, and associated treatments, requiring distinct search strategies. For claims 25-26, each drug type has a different effect on cancer and can be used on different types of cancer, necessitating separate searches. The election requirement for claim 16 is withdrawn. Applicant’s elections, mailed October 21, 2024, are; Claim 5: plasma Claims 10, 27: single nucleotide variant (SNV) Claim 17: epidermal growth factor receptor (EGFR) Claim 19: 5-methylcytosine Claims 21-24: cancer, tissue type of origin is lung Claims 25-26: chemotherapy drug and species of tyrosine kinase inhibitors Thus, claims 1-27 are under examination based on these merits and the non-elected species for the above claims remain withdrawn from consideration. Information Disclosure Statement The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. The information disclosure statements (IDS) submitted on 7/10/2025 and 10/3/2025 are being considered by the examiner. Rejections Maintained Claim Rejections - 35 USC § 102 Claims 1-3, 5, 7-24 and 27 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Collins et al. (WO2017/205827 A1, published 11/30/2017). This rejection is modified, as necessitated by Applicants' amendments. Regarding claim 1, Collins teaches a method for validating assay performance, comprising; generating synthetic nucleic acid fragments or samples with known characteristics or alleles (i.e., synthetic origin) (Paragraph 87, lines 1-4), combining these synthetic samples with controls or wild-type fragments (i.e., quality controls) (Paragraph 25, lines 1-5; Paragraph 385, lines 1-10), followed by performing validation steps or quality control image data to compute on various dilutions, validate and verify tests or assays with known allele or synthetic fragments (Paragraph 229, lines 1-10). Further, Collins teaches that the previously described method involves the amount of data collected from a single molecule array is very different from a sequencing-based test; including whole-genome sequencing (i.e., next generation sequencing), where many of sequencing reads will map to chromosomes that are not being tested (Paragraph 377, lines 1-5). Regarding claim 2, Collins teaches analyzing variations or selective identification throughout the genomic loci (Paragraph 20, lines 1-5) with high accuracy (Paragraph 2, lines 1-5). Regarding claim 3, Collins teaches methods including selectively labeling one or more nucleic acid sequences or variants, clustered in specific regions of interest, including; genes, functional regions, promotors, exons, introns, telomeric regions or centromeric regions (Paragraph 103, lines 15-20). Regarding claim 5, Collins teaches that the test samples or genetic sample is selected from the group consisting of a cell-free DNA sample, whole blood, serum, plasma, urine, saliva, sweat, fecal matter, and/or tears from the subject (Paragraph 258, lines 17-25). Regarding claim 7, Collins teaches these methods for assaying, as described above, may also be used to detect germline variants (Paragraph 686, lines 1-2) or somatic cell hybrids (Paragraph 20, lines 1-5) in cancer or in other disease or conditions to improve combinatorial analyses (Paragraph 20, lines 1-5). Regarding claim 8, Collins teaches that these methods for assaying, as described above, are high throughput screening or next generation sequencing (NGS) intended for compounds or samples with properties of interest (Paragraph 564, lines 1-7). Specifically, Collins teaches that in the above example the quantity of tumor cfDNA may be measured and may be used to determine the size, growth rate, aggressiveness, stage, prognosis, diagnosis and other attributes of the tumor and the patient (Paragraph 695, lines 1-5). Regarding claim 9, Collins teaches a method for creating single nucleotide polymorphisms (SNPs) or variants (SNVs) and mutations via allele-specific extension (AMASE) protocol which allows incorporation of nucleotides through matched and mismatched 3'-end primers or molecular tags dependent on reaction speed (Paragraph 433, lines 1-5). Further, Collins teaches nucleotide analogues having modifications or the addition of molecular tags in the chemical structure of the base, sugar and/or phosphate, specifically included in the 5’ position (Paragraph 116, lines 1-15). Specifically, Collins teaches that the previously described method can be applied to samples that are scanned individually—meaning that they are not pooled or mixed together and for sequencing-based approaches to prenatal testing, samples are barcoded and then pooled and sequenced as a batch (Paragraph 170, lines 1-5). Regarding claims 10-11, Collins teaches a method for typing SNPs or SNVs (Paragraph 334, lines 1-8) comprising exposing the same to allow hybridization for later detection following oligonucleotide design and primer extension with specified start and end positions or levels (Paragraph 514, lines 1-5, via specific increments or array members (Paragraph 513, lines 1-10; Paragraph 514, lines 1-5), occurring both downstream and upstream of target or variant position (Paragraph 513, lines 1-10; Paragraph 515, lines 1-5). Regarding claims 12-15, MPEP 2131.03 highlights that when the prior art discloses a specific example or a range that falls within the claimed range, the claimed range is anticipated. Regarding claim 12, Collins teaches interrogating or generating SNPs or SNVs in groups of one, two, three, four, five, ten, twenty, fifty or more times, until an informative variation is detection (Paragraph 382, lines 10-18). Regarding claim 13, Collins teaches generating probe products based on specified genomic locations or base pairs using hybridization-ligation processes and specifically highlighting eight separate variants (Figures 59-60; Paragraphs 664-665, lines 1-10). Regarding claim 14, Collins teaches tagging nucleotide sequences having lengths from 5 to 250 (Paragraph 252, lines 1-10). Regarding claim 15, Collins teaches molecular arrays comprising at least 10 molecular species, but more preferably 50-100 species (Paragraph 275, lines 1-8). Regarding claims 16-17, Collins teaches a method to select genes comprising one or more mutation or substitution, inversion, insertion, or deletion in nucleotide sequences; originating from specifically the epidermal growth factor receptor (EGFR) gene (Paragraph 84, lines 1-20). Regarding claim 18, Collins teaches that samples (i.e., synthetic) may be fragmented, amplified, denatured or otherwise modified before an assay is performed or before they are immobilized on the array (Paragraph 85, lines 5-10; Paragraph 92, lines 1-2) such that they form a singular distinct molecular species and are used to interrogate the same locus (Paragraph 110, lines 1-5). Regarding claim 19, Collins teaches that the modified base of the previously described fragmented sample for analysis, is 5-methylcytosine (Paragraph 552, lines 1-5). Regarding claim 20, Collins teaches detecting copy neutral changes (i.e., inversions, translocation) (Paragraph 686, lines 1-2), where translocations (i.e., native, translocated) that have known breakpoints or varying fractional composition via modified bases or unique labels (Paragraph 685, lines 1-5) may be assayed (Figure 68A; Paragraph 687, lines 1-10). Regarding claims 21-24, Collins teaches a method for validating assay performance, comprising; generating synthetic nucleic acid fragments or samples with known characteristics or alleles (i.e., synthetic origin) (Paragraph 87, lines 1-4), combining these synthetic samples with controls or wild-type fragments (i.e., quality controls) (Paragraph 25, lines 1-5; Paragraph 385, lines 1-10), followed by performing validation steps or quality control image data to compute on various dilutions, validate and verify tests or assays with known allele or synthetic fragments (Paragraph 229, lines 1-10). Collins teaches methods of detecting rare events in disease detection or minimal residual disease in patients with cancer and early detection of relapse by detecting mutation within a wild type background using a specialized assay or array (Paragraph 9, lines 1-5), specifically teaching the difficulty in detecting highly specified locus or disease versus more common events (Paragraph 10, lines 1-5). Further, Collins teaches that the previously described method involves the amount of data collected from a single molecule array is very different from a sequencing-based test; including whole-genome sequencing (i.e., next generation sequencing), where many of sequencing reads will map to chromosomes that are not being tested (Paragraph 377, lines 1-5). Further, Collins teaches the sample source or target of interest, including, whole blood, serum, plasma, urine, saliva, sweat, fecal matter, tears, intestinal fluid, mucous membrane samples, lung tissue, tumors, transplanted organs, and/or fetus (Paragraph 87, lines 5-15), originating from an animal, including human (Paragraph 89, lines 1-5) is a genomic variant (Paragraph 84, lines 1-5). Additionally, Collins teaches that these genomic variants include, one or more substitution, inversion, insertion, deletion, or mutation in nucleotide sequences (e.g., DNA and RNA) and proteins (e.g., peptide and protein), one or more microdeletion, or one or more rare allele (Paragraph 84, lines 5-10; Paragraph 88, lines 1-10). Specifically, Collins teaches that this detection method for specified disorders is targeted towards cancer studies for genetic variation related to metastasis, presence, absence, and/or risk of a disease or drug toxicity (Paragraph 84, lines 15-20). Regarding claim 27, Collins teaches a method of detecting genetic variation in a genetic or synthetic sample (Paragraph 84, lines 1-5), which comprises selecting genetic locus or loci of interest (i.e., SNV), and quantifying the amount of the relative amounts of different locus variants (i.e., two alleles of a given DNA sequence) (Paragraph 99, lines 1-10). Collins teaches each and every limitation of claims 1-3, 5, 7-24 and 27, and therefore Collins anticipates claims 1-3, 5, 7-24 and 27. Applicant’s Response: The Applicant argues that Collins does not anticipate the claimed invention because it fails to disclose key elements of newly amended claims 1 and 21. Specifically, Collins does not teach validating the performance of a next-generation sequencing (NGS) assay, generating synthetic variant DNA fragments with known allele frequencies, or using molecular barcodes for distinguishing synthetic variants from wild-type DNA in test samples. The Applicant further asserts that Collins merely discloses positive controls and tagged probes as detection methods, not the generation or combination of barcoded synthetic fragments for assay validation. Further, the Applicant asserts that any teachings in Collins are not arranged or combined in the same way as the claims and therefore, the amended claims are novel in view of Collins. Examiner’s Response to Traversal: Applicant’s arguments have been carefully and fully considered but are not found persuasive, as discussed below. The Applicant argues that Collins fails to disclose critical limitations of amended claim 1, including validating the performance of a next-generation sequencing (NGS) assay, generating synthetic variant DNA fragments with known allele frequences, and utilizing molecular barcodes to distinguish synthetic variants from wildtype (WT) DNA. These arguments are not found persuasive. Firstly, the Applicant argues that Collins does not teach synthesizing synthetic variant DNA fragments with known allele frequencies. Collins teaches validating assay performance using synthetic nucleic acid fragments with known characteristics (i.e., synthetic origin) combined with WT or control fragments (Paragraphs 25, 87, 229, 385), followed by assay validation steps including computing performance across dilutions and verifying assays with known alleles. Furthermore, Collins teaches use of specimens of “synthetic origin” (Paragraph 87), which under the broadest reasonable interpretation encompasses deliberately synthesized DNA fragments. Where synthetic variants are designed to contain specific substitutions, the allele frequencies are inherently known. Anticipation may depend on inherent characteristics that are necessarily present, even if not explicitly stated (see MPEP 2112). Additionally, the Applicant asserts that Collins does not teach combining variant and WT DNA to create synthetic standards. Collins teaches configuring probes to target known genetic variations (i.e., SNPs, mutations and structural changes such as amplifications, deletions, inversions and translocations) (Paragraphs 225-229), aligning with the claimed use of synthetic fragments bearing known allele frequencies for test development and performance validation. This directly addresses the Applicant’s assertion that Collins does not teach validation of assay performance, as Collins provides explicit support for validation using synthetic and wild-type mixtures. Further, this showcases that Collins indicates a purposeful design for evaluating assay accuracy utilizing synthetic fragments with known variants or alleles. Therefore, a person of ordinary skill in the art would recognize that combining synthetic variant fragments with WT sequences constitutes a synthetic standard suitable for assay calibration. Second, with respect to NGS, Collins explicitly refers to “whole genome sequencing” (Paragraph 377, lines 1-5) which is a recognized form of NGS. Collins also teaches sequencing-based and high-throughput methods (Paragraph 564, lines 1-7), demonstrating familiarity with NGS technology. These disclosures counter Applicant’s argument that Collins fails to teach validation in the context of NGS, as Collins expressly references such platforms and their role in assay evaluation. Further, in this same vein, the Applicant asserts that Collins only teaches arrays and does not teach use of synthetic standards in NGS assays. While Collins teaches array-based detection (Paragraphs 513-514), it also teaches sequencing assays in conjunction with or as orthogonal validation methods (Paragraph 229). Under the broadest reasonable interpretation, Collins’ teachings that synthetic standards may be applied to sequencing assays is sufficient to anticipate the claimed use in NGS. That Collins may prefer arrays does not limit the scope of its disclosure (MPEP 2131). Third, regarding molecular barcoding, Collins teaches the use of molecular tags and nucleotide analogs incorporated into synthetic DNA for identification purposes (Paragraph 116, 433), and further described DNA barcodes for interrogation (Paragraph 266, lines 1-10). Additionally, Collins states that probes may be configured to target known genetic variations (Paragraph 682), which supports the interpretation that synthetic variant sequences with known attributes are intended to be included and tracked across samples, further implying the use of sequence-specific identifiers or barcodes. Thus, Collins provides a framework for using synthetic fragments bearing known characteristics, tracked and distinguished via barcoding or tagging systems for reliable test sample construction. Accordingly, this directly addresses the Applicant’s argument that Collins fails to disclose or suggest the use of barcoded synthetic variant DNA fragments distinguishable from WT sequences in assay validation contexts. Overall, the Applicant argues that Collins does not teach the claimed elements arranged in the same way. However, anticipation requires only that each limitation is disclosed or taught, either expressly or inherently, in a single prior art reference, not that the reference duplicate the Applicant’s specific arrangement or intended application. See In re Gleave, 560 F.3d 1331, 90 USPQ2d 1235 (Fed. Cir. 2009). Collins teaches synthetic nucleic acids, variants and WT mixtures, and their use in validating sequencing-based assays, therefore meeting the amended claimed limitations. Accordingly, Collins discloses each limitation of independent, amended claims 1 and 21, as well as dependent claims 2-3, 5, 7-20, 22-24, and 27. Therefore, the rejection under 35 USC § 102 is maintained. Claim Rejections - 35 USC § 103 Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Collins et al. (WO2017/205827 A1, published 11/30/2017), as applied to claims 1-3, 5, 7-24 and 27 above, and in view of Ossandon et al. (“Circulating Tumor DNA Assays in Clinical Cancer Research”, Journal of the National Cancer Institute, published 6/20/2018). Collins teaches a method for validating assay performance on variations throughout the genome, as compared to wild-type samples, as discussed above. Regarding claim 6, Collins teaches method of analyzing DNA samples, including messenger RNA (mRNA), extracellular DNA, genomic DNA, circulating free DNA (cfDNA) and copy DNA (cDNA), where DNA fragments of specific size ranges are enriched to increase sensitivity of testing (Paragraph 8, lines 1-15; Paragraph 88, lines 1-10). Collins does not teach or suggest circulating tumor DNA (ctDNA). However, Ossandon teaches that ctDNA is an important form of cell-free DNA when mutated RAS gene fragments were detected in patient blood samples (Abstract). Further, Ossandon teaches that ctDNA comprises up to 1% of total circulating DNA in cancer patients and can be identified and differentiated from other cfDNA by fragment size and/or variations in genetic abnormalities compared to normal cells (Introduction, Paragraph 2). Specifically, Ossandon teaches that ctDNA fragments from apoptotic tumors range from 180 bp to 1000 bp—and these fragments can be used to detect cancer-specific genetic variations (Introduction, Paragraph 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods of Collins to specifically analyze ctDNA as taught by Ossandon because ctDNA serves as a specific biomarker for cancer detection and monitoring via a blood sample (Introduction, Paragraph 2). The inclusion of ctDNA analysis would enhance the diagnostic capabilities of Collins’ method by providing cancer-specific genetic information. One of ordinary skill in the art would have had a reasonable expectation of success in making this modification because both Collins and Ossandon teach analysis of cell-free nucleic acids, and the DNA analysis methods taught by Collins would be readily applicable to ctDNA analysis. Furthermore, Ossandon teaches specific guidelines on ctDNA fragment sizes and detection methods that could be directly implemented within Collins’ existing framework for nucleic acid analysis (Abstract). Applicant’s Response: The Applicant argues that Collins does not anticipate the claimed invention because it fails to disclose key elements of newly amended independent claims 1 and 21. Specifically, Collins does not teach validating the performance of a next-generation sequencing (NGS) assay, generating synthetic variant DNA fragments with known allele frequencies, or using molecular barcodes for distinguishing synthetic variants from wild-type DNA in test samples. The Applicant further asserts that Collins merely discloses positive controls and tagged probes, not the generation or combination of barcoded synthetic fragments for assay validation and therefore, the amended claims are novel in view of Collins. Therefore, as a result of these failed anticipations of independent claim 1, the teachings of Collins in view of Ossandon, do not allow one of ordinary skill in the art to arrive at the conclusion of instant claim 6. Examiner’s Response to Traversal: Applicant’s arguments have been carefully and fully considered but are not found persuasive, as discussed below. As of note, the Applicant’s argument relies solely on the asserted deficiencies of Collins discussed in connection with amended claim 1. As addressed above, Collins teaches each limitation of amended independent claim 1, including validation of sequencing assays using synthetic variant DNA fragments and WT controls. More so, claim 6 adds only the use of circulating tumor DNA (ctDNA) as the sample type. While Collins does not expressly disclose ctDNA, Ossandon clearly teaches ctDNA as a relevant and important form of cell-free DNA in cancer diagnostics, including details on how ctDNA can be enriched, distinguished from other cfDNA, and used to detect tumor-associated genetic abnormalities. Thus, one of ordinary skill in the art would have found it obvious to apply the validated assay methods taught by Collins to ctDNA samples in view of Ossandon. Therefore, the rejection of claim 6 under 35 USC § 103 is maintained. Claims 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Collins et al. (WO2017/205827 A1, published 11/30/2017), as applied to claims 1-3, 5, 7-24 and 27 above, and in view of Tong et al. (“Drug combination approach to overcome resistance to EGFR tyrosine kinase inhibitors in lung cancer”, Cancer Letters, published 10/1/2017). This rejection is modified, as necessitated by Applicants' amendments. Collins teaches a method for validating assay performance on variations throughout the genome, as compared to wild-type samples, as discussed above. Regarding claims 25-26, Collins teaches a method for validating assay performance, comprising; generating synthetic nucleic acid fragments or samples with known characteristics or alleles (i.e., synthetic origin) (Paragraph 87, lines 1-4), combining these synthetic samples with controls or wild-type fragments (i.e., quality controls) (Paragraph 25, lines 1-5; Paragraph 385, lines 1-10), followed by performing validation steps or quality control image data to compute on various dilutions, validate and verify tests or assays with known allele or synthetic fragments (Paragraph 229, lines 1-10). Specifically, Collins teaches an assay for detecting drug resistance in a mutated (i.e., cancer) sample through monitoring drug toxicity and pharmacokinetic variability (Paragraph 258, lines 10-15) via the utilization of specialized probes (Paragraph 258, lines 15-25), which detect genetic variation through distinguishing an optical signal from a single label from the rest of the optical signals from background or multiple labels (Paragraph 258, lines 15-25; Paragraph 681, lines 1-5). Further, Collins teaches that the previously described method involves the amount of data collected from a single molecule array is very different from a sequencing-based test; including whole-genome sequencing (i.e., next generation sequencing), where many of sequencing reads will map to chromosomes that are not being tested (Paragraph 377, lines 1-5). Collins does not teach or suggest the specified chemotherapy drug type for detection, tyrosine kinase inhibitors for EGFR. Tong teaches that EGFR tyrosine kinase inhibitors (TKIs) are a critical treatment for lung cancer patients with EGFR mutations (Lung cancer, its conventional treatment and molecular targeted therapy: Paragraph 1). Specifically, Tong teaches that EGFR TKIs showed remarkable progression-free survival compared to conventional chemotherapy, where 90% of activating mutations in EGFR responded (Drug resistance to EGFR-TKIs, Primary Resistance: Paragraph 1). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Collins’ method of detecting drug resistance to specifically analyze resistance to EGFR tyrosine kinase inhibitors as taught by Tong. The motivation would have been that Tong demonstrates EGFR TKIs are a crucial treatment for lung cancer patients with EGFR mutations, making detection of resistance critically important for patient care. One of ordinary skill in the art would have had a reasonable expectation of success in making this modification because, Collins already teaches methods for detecting drug resistance and cancer mutations. Further, Tong provides specific guidance on EGFR mutations and TKI resistance mechanisms, and therefore, the combination merely requires applying Collins’ known detection methods to a specific, well-characterized drug resistance scenario detailed by Tong. Applicant’s Response: The Applicant argues that Collins does not anticipate the claimed invention because it fails to disclose key elements of newly amended claim 1, which are features encompassed in newly amended independent claim 25. Specifically, Collins does not teach validating the performance of a next-generation sequencing (NGS) assay, generating synthetic variant DNA fragments with known allele frequencies, or using molecular barcodes for distinguishing synthetic variants from wild-type DNA in test samples. The Applicant further asserts that Collins merely discloses positive controls and tagged probes, not the generation or combination of barcoded synthetic fragments for assay validation and therefore, the amended claims are novel in view of Collins. Therefore, as a result of these failed anticipations of amended claim 1, incorporated into amended claim 25, the teachings of Collins in view of Tong, do not allow one of ordinary skill in the art to arrive at the conclusion of instant claims 25-26. Examiner’s Response to Traversal: Applicant’s arguments have been carefully and fully considered but are not found persuasive, as discussed below. As of note, the Applicant’s argument relies solely on the assertion that amended claim 25, as in the case of amended claim 1, is not obvious in view of Collins alone since aspects of claim 1 were incorporated into instant claim 25 as an amendment. As addressed above, Collins teaches each limitation of amended claim 1, including validation using synthetic fragments and test samples containing known allele variants. Further, claims 25-26 adds only the use of tyrosine kinase inhibitors (TKIs) for EGFR in the context of drug resistance monitoring. While Collins does not expressly mention EGFR TKIs, Tong clearly teaches that EGFR TKIs are standard treatment for lung cancer and discusses resistance mechanisms in patients with EGFR mutations. One of ordinary skill in the art would have been motivated to apply Collins’ known assay validation and resistance detection methods to the well-characterized TKI resistance detection methods to the well-characterized TKI resistance scenario described in Tong. Therefore, the rejection of claims 25-26 under 35 USC § 103 is maintained. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30. 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 on 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. /ELIZABETH ROSE LAFAVE/Examiner, Art Unit 1684 /HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
Read full office action

Prosecution Timeline

Feb 11, 2022
Application Filed
Nov 20, 2024
Non-Final Rejection — §102, §103
Mar 25, 2025
Response Filed
May 30, 2025
Final Rejection — §102, §103
Oct 03, 2025
Request for Continued Examination
Oct 07, 2025
Response after Non-Final Action
Oct 20, 2025
Non-Final Rejection — §102, §103
Mar 27, 2026
Response Filed

Precedent Cases

Applications granted by this same examiner with similar technology. Study what changed to get past this examiner.

Patent 12584166
METHOD AND SYSTEM FOR DETECTING MTDNA MUTATIONS
2y 5m to grant Granted Mar 24, 2026
Patent 12577557
PRODUCTION AND TRACKING OF ENGINEERED CELLS WITH COMBINATORIAL GENETIC MODIFICATIONS
2y 5m to grant Granted Mar 17, 2026
Patent 12577559
Method for Creating a cDNA Sequencing Library
2y 5m to grant Granted Mar 17, 2026
Patent 12577514
METHOD OF PRODUCING BIOCHIPS
2y 5m to grant Granted Mar 17, 2026
Patent 12529049
CHARACTERIZATION AND LOCALIZATION OF PROTEIN MODIFICATIONS
2y 5m to grant Granted Jan 20, 2026

AI Strategy Recommendation

Click below to generate an AI-powered prosecution strategy using examiner precedents, rejection analysis, and claim mapping.
Powered by AI — typically takes 5-10 seconds

Prosecution Projections

3-4
Expected OA Rounds
47%
Grant Probability
99%
With Interview (+58.5%)
4y 1m
Median Time to Grant
High
PTA Risk
Based on 32 resolved cases by this examiner