IP Library › Granted Patent US 12,545,963
Granted Patent B1
US 12,545,963 · App. 18/965,294 · Granted Feb 10, 2026

Personalized methods of detecting circulating tumor DNA

Inventors: Jared Robert Maguire (San Francisco, CA); Clement S. Chu (San Francisco, CA); Imran Saeedul Haque (San Francisco, CA); Eric Andrew Evans (San Bruno, CA); Noah Welker (Half Moon Bay, CA)
Assignee: Myriad Women's Health, Inc.
C12Q1/6886C12Q1/6806C12Q1/6869C12Q2600/156
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,545,963
App. No.
18/965,294
Granted
Feb 10, 2026
Kind
B1
Abstract

The present disclosure relates to a laboratory execution system that provides for automation of laboratory processes. A centralized data management system may be dynamically updated and used to facilitate management of components of the laboratory execution system, such as an automation system and an analytics results management system that may facilitate complex analytical functions, such as synthesizing raw test data. Potential workflows include the detection of specific molecules of interest.

Claims (35)

1 . A personalized method for detecting circulating tumor DNA (ctDNA) in a patient comprising:

(a) obtaining a tumor sample and a non-tumor sample from a subject with a history of cancer;

(b) sequencing DNA from the tumor sample and sequencing DNA from the non-tumor sample, thereby obtaining sequences of DNA from the tumor sample and sequences of DNA from the non-tumor sample, and determining a set of at least 10 tumor-specific somatic mutations that are specific to the subject; and

at one or more timepoints subsequent to (a) and (b):

(c) obtaining a fluid sample of whole blood, plasma, or serum from the subject;

(d) extracting cell-free DNA (cfDNA) from the fluid sample;

(e) sequencing the cfDNA, thereby obtaining a plurality of sequence reads; and

(f) detecting the presence or absence of a sequence read comprising any one of the set of at least 10 tumor-specific somatic mutations that are specific to the subject, wherein the presence of a sequence read in the plurality of sequence reads corresponding to one or more of the set of at least 10 tumor-specific somatic mutations that are specific to the subject indicates the presence of ctDNA.

2 . The method of claim 1 , wherein the fluid sample is plasma.

3 . The method of claim 1 , wherein sequencing DNA from the tumor sample and sequencing DNA from the non-tumor sample comprises whole genome sequencing.

4 . The method of claim 1 , wherein sequencing DNA from the tumor sample and sequencing DNA from the non-tumor sample comprises targeted sequencing.

5 . The method of claim 4 , wherein the targeted sequencing comprises sequencing exons.

6 . The method of claim 1 , further repeating (c)-(f) at one or more times during a cancer treatment, following completion of a cancer treatment, while the subject is in remission, or coinciding with or prior to surgery.

7 . The method of claim 1 , wherein the set of at least 10 tumor-specific somatic mutations that are specific to the subject comprises at least 50 tumor-specific somatic mutations that are specific to the subject.

8 . The method of claim 1 , wherein the set of at least 10 tumor-specific somatic mutations that are specific to the subject comprises at least 500 tumor-specific somatic mutations that are specific to the subject.

9 . The method of claim 1 , wherein the cancer patient has or had a cancer selected from adrenal cancer, anal cancer, bile duct cancer, bladder cancer, bone cancer, a central nervous system (CNS) cancer, breast cancer, Castleman disease, cervical cancer, colon or rectum cancer, endometrial cancer, esophagus cancer, a Ewing sarcoma, eye cancer, gallbladder cancer, a gastrointestinal carcinoid cancer, Hodgkin disease, Kaposi sarcoma, kidney cancer, laryngeal and hypopharyngeal cancer, leukemia, liver cancer, lung cancer, lymphoma, malignant mesothelioma, multiple myeloma, myelodysplastic syndrome, nasal cavity or paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, oral cavity or oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymus cancer, thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstrom macroglobulinemia, and Wilms tumor.

10 . The method of claim 1 , wherein the non-tumor sample is blood or plasma.

11 . A personalized method for detecting circulating tumor DNA (ctDNA) in a patient comprising:

(a) obtaining a tumor sample and a non-tumor sample from a subject with a history of cancer;

(b) sequencing DNA from the tumor sample and sequencing DNA from the non-tumor sample, thereby obtaining sequences of DNA from the tumor sample and sequences of DNA from the non-tumor sample;

(c) obtaining from the sequences of DNA from the tumor sample and the non-tumor sample a set of at least 10 tumor-specific somatic mutation sequences that are present in the sequences of DNA from the tumor sample and not present in the sequences of DNA from the non-tumor sample; and

at one or more timepoints subsequent to (a)-(c):

(d) obtaining a fluid sample of whole blood, plasma, or serum from the subject;

(e) extracting cell-free DNA (cfDNA) from the fluid sample;

(f) sequencing the cfDNA, thereby obtaining a plurality of sequence reads; and

(g) detecting the presence or absence of a sequence read comprising any one of the set of at least 10 tumor-specific somatic mutations that are specific to the subject, wherein the presence of a sequence read in the plurality of sequence reads corresponding to one or more of the set of at least 10 tumor-specific somatic mutations that are specific to the subject indicates the presence of ctDNA.

12 . The method of claim 11 , wherein the fluid sample is plasma.

13 . The method of claim 11 , wherein sequencing DNA from the tumor sample and sequencing DNA from the non-tumor sample comprises whole genome sequencing.

14 . The method of claim 11 , wherein sequencing DNA from the tumor sample and sequencing DNA from the non-tumor sample comprises targeted sequencing.

15 . The method of claim 14 , wherein the targeted sequencing comprises sequencing exons.

16 . The method of claim 11 , further repeating (d)-(g) at one or more times during a cancer treatment, following completion of a cancer treatment, while the subject is in remission, or coinciding with or prior to surgery.

17 . The method of claim 11 , wherein the set of at least 10 tumor-specific somatic mutations that are specific to the subject comprises at least 50 tumor-specific somatic mutations that are specific to the subject.

18 . The method of claim 11 , wherein the set of at least 10 tumor-specific somatic mutations that are specific to the subject comprises at least 500 tumor-specific somatic mutations that are specific to the subject.

19 . The method of claim 11 , wherein the cancer patient has or had a cancer selected from adrenal cancer, anal cancer, bile duct cancer, bladder cancer, bone cancer, a central nervous system (CNS) cancer, breast cancer, Castleman disease, cervical cancer, colon or rectum cancer, endometrial cancer, esophagus cancer, a Ewing sarcoma, eye cancer, gallbladder cancer, a gastrointestinal carcinoid cancer, Hodgkin disease, Kaposi sarcoma, kidney cancer, laryngeal and hypopharyngeal cancer, leukemia, liver cancer, lung cancer, lymphoma, malignant mesothelioma, multiple myeloma, myelodysplastic syndrome, nasal cavity or paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, oral cavity or oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skin cancer, small intestine cancer, stomach cancer, testicular cancer, thymus cancer, thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstrom macroglobulinemia, and Wilms tumor.

20 . The method of claim 11 , wherein the non-tumor sample is blood or plasma.

Assignments (3)
SECURITY INTEREST Recorded Aug 1, 2025
From: MYRIAD GENETICS, INC.; MYRIAD GENETIC LABORATORIES, INC.; MYRIAD WOMEN’S HEALTH, INC.; ASSUREX HEALTH, INC.; GATEWAY GENOMICS, LLC
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES IV, LP, AS ADMINISTRATIVE AGENT FOR SECURED PARTIES
Reel/Frame 072309/0932 →
CHANGE OF NAME Recorded Feb 6, 2025
From: COUNSYL, INC.
To: MYRIAD WOMEN'S HEALTH, INC.
Reel/Frame 070126/0666 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 4, 2025
From: MAGUIRE, JARED ROBERT; CHU, CLEMENT; HAQUE, IMRAN SAEEDUL; EVANS, ERIC ANDREW; WELKER, NOAH
To: COUNSYL, INC.
Reel/Frame 070100/0576 →
Continuity (7)
Continuation 18357799 · Jul 24, 2023
Continuation 17883414 · Aug 8, 2022
Continuation 17678829 · Feb 23, 2022
Continuation 17383273 · Jul 22, 2021
Continuation 16784761 · Feb 7, 2020
Continuation 15465553 · Mar 21, 2017
Provisional Application 62311899 · Mar 22, 2016
References Cited (71)
US 6306597B1 · Macevicz · 2001 [cited by applicant]
US 7115400B1 · Adessi et al. · 2006 [cited by applicant]
US 7232656B2 · Balasubramanian et al. · 2007 [cited by applicant]
US 7323305B2 · Leamon et al. · 2008 [cited by applicant]
US 10597717B2 · Maguire et al. · 2020 [cited by applicant]
US 11932910B2 · Maguire et al. · 2024 [cited by applicant]
US 12024749B2 · Maguire et al. · 2024 [cited by applicant]
US 20080160580A1 · Adessi et al. · 2008 [cited by applicant]
US 20080286795A1 · Kawashima et al. · 2008 [cited by applicant]
US 20120208705A1 · Steemers et al. · 2012 [cited by applicant]
US 20130225452A1 · Pollack et al. · 2013 [cited by applicant]
US 20130261019A1 · Lin et al. · 2013 [cited by applicant]
US 20130296183A1 · Eggan et al. · 2013 [cited by applicant]
US 20140342354A1 · Evans et al. · 2014 [cited by applicant]
US 20150080266A1 · Volkmuth et al. · 2015 [cited by applicant]
US 20150301058A1 · Schettini et al. · 2015 [cited by applicant]
US 20150376700A1 · Schnall-Levin et al. · 2015 [cited by applicant]
US 20160053301A1 · Raymond et al. · 2016 [cited by applicant]
WO WO2011103236A2 · 2011 [cited by applicant]
WO WO2013112923A1 · 2013 [cited by applicant]
WO WO2014015084A2 · 2014 [cited by applicant]
WO WO2014151117A1 · 2014 [cited by applicant]
WO WO2016040901A1 · 2016 [cited by applicant]
Altschul et al., “Basic Local Alignment Search Tool”, Journal of Molecular Biology, 1990, pp. 403-410, vol. 215, 1990 Academic Press Limited. [cited by applicant]
Botezatu et al., “Genetic Analysis of DNA Excreted in Urine: A New Approach for Detecting Specific Genomic DNA Sequences from Cells Dying in an Organism”, Clinical Chemistry, vol. 46, No. 8, May 22, 2000, pp. 1078-1084. [cited by applicant]
Branton et al., “The potential and challenges of nanopore sequencing”, Nat. Biotechnol., vol. 26, 2008, pp. 1146-1153. [cited by applicant]
Browning et al., “Haplotype phasing: Existing methods and new developments”, Nat. Rev. Genet., vol. 12, Apr. 1, 2012, pp. 703-714. [cited by applicant]
Butler et al., “Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease,” PLOS One, 10(8):e0136407, pp. 1-14 (Aug. 28, 2015). [cited by applicant]
Chan et al., “Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing”, Clinical Chemistry, vol. 59… [cited by applicant]
Chen et al., “Microsatellite alterations in plasma DNA of small cell lung cancer patients”, Nature Medicine, vol. 2, No. 2, Sep. 1996, pp. 1033-1035. [cited by applicant]
Dawson et al., “Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer”, The New England Journal of Medicine, 2013, vol. 368, No. 13, pp. 1199-1209 and Supplemental Appendix. [cited by applicant]
Diehl et al., “Circulating mutant DNA to assess tumor dynamics”, Nat Med., 2008, vol. 14, No. 9, pp. 985-990. [cited by applicant]
Duncavage et al., “Hybrid Capture and Next-Generation Sequencing Identify Viral Integration Sites from Formalin-Fixed, Paraffin-Embedded Tissue”, The Journal of Molecular Diagnostics, May 3, 2011, vol. 13, No. 3, pp. 32… [cited by applicant]
Fan et al., “Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood”, PNAS, vol. 105, No. 42, Oct. 21, 2008, pp. 16266-16271. [cited by applicant]
Fierer et al., “The influence of sex, handedness, and washing on the diversity of hand surface bacteria”, Proc. Nat'l Adad. Sci., vol. 105, Nov. 18, 2008, pp. 17,994-17,999. [cited by applicant]
Forshew et al., “Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA,” Sci Transl Med, 4(136):136ra68, 13 pages (May 30, 2012). [cited by applicant]
Garcia-Murillas et al., “Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer”, Sci Transl Med., 2015, vol. 7, No. 302, 13 pages. [cited by applicant]
Gnirke et al., “Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing,” Nature Biotechnology, Feb. 2009, vol. 27, No. 2 (pp. 182-189). [cited by applicant]
Gudmundsson et al., “Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility”, Nat Genet., vol. 41, No. 10, Oct. 2009, pp. 1122-1126. [cited by applicant]
Hamady et al., “Error-correcting barcoded primers allow hundreds of samples to by pyrosequenced in multiplex”, Nature Methods, vol. 5, No. 3, 2008, pp. 235-237. [cited by applicant]
Henikoff et al., “Amino acid substitution matrices from protein blocks”, Proceedings of the National Academy of Sciences USA, vol. 89, Nov. 1992, pp. 10915-10919. [cited by applicant]
Higgins et al., “Clustal: a package for performing multiple sequence alignment on a microcomputer,” Dec. 15, 1988, Gene, vol. 73, No. 1, pp. 237-244. [cited by applicant]
Hopp et al., “A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification,” Bio/Technology, Oct. 1988, vol. 6, pp. 1204-1210. [cited by applicant]
Horhota et al., “Glycerol nucleoside triphosphates: synthesis and polymerase substrate activities”, Organic Letters, Sep. 8, 2006, vol. 8, No. 23, pp. 5345-5347. [cited by applicant]
International Search Report and Written Opinion issued in corresponding International Application No. PCT/US2017/023482, dated Jul. 27, 2017 (13 pages). [cited by applicant]
Karlin et al., “Applications and statistics for multiple high-scoring segments in molecular sequences”, Proc. Natl. Acad. Sci., vol. 90, Jun. 1993, pp. 5873-5877. [cited by applicant]
Koide et al., “Fragmentation of cell-free fetal DNA in plasma and urine of pregnant women,” Prenatal Diagnosis, vol. 25, No. 7, Jul. 2005, pp. 604-607. [cited by applicant]
Koren et al., One chromosome, one contig: Complete microbial genomes from long-read sequencing and assembly, Curr. Opin. Microbiol. vol. 23, Dec. 1, 2014, pp. 110-120. [cited by applicant]
Krishnan et al., Barcodes for DNA Sequencing with guaranteed error correction and capability, Electronics Letter, vol. 47, 2011, pp. 236-237. [cited by applicant]
Langmead et al., “Ultrafast and memory-efficient alignment of short DNA sequences to the human genome”, Genome Biology, Mar. 4, 2009, vol. 10, No. 3 (pp. 1-10). [cited by applicant]
Leary et al., “Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing,” Science Translational Medicine, Feb. 24, 2010, vol. 2, No. 20 (pp. 1-8). [cited by applicant]
Lefrancois et al., Efficient yeast ChiP-Seq using multiplex short-read DNA sequencing, BMC Genomics, vol. 10, 2009, pp. 1-18. [cited by applicant]
Ley et al., “CDNA Sequencing of a Cytogenetically Normal Acute Myeloid Leukaemia Genome,” Nature, 456(7218):66-72 (Nov. 6, 2008). [cited by applicant]
Li et al., “The Sequence Alignment/Map format and SAMtools”, Bioinformatics, vol. 25, No. 16, 2009, pp. 2078-2079. [cited by applicant]
Lipson et al., “Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade”, J Immunother Cancer. 2014, 7 pages. [cited by applicant]
Lo et al., “Presence of fetal DNA in maternal plasma and serum”, The Lancet, vol. 350, Aug. 16, 1997, pp. 485-487. [cited by applicant]
Lutz-Freyermuth et al., “Quantitative determination that one of two potential RNA-binding domains of the A protein component of the U1 small nuclear ribonucleoprotein complex binds with high affinity to stem-loop II of … [cited by applicant]
Martin et al., “GAP Domains Responsible for Ras p21-Dependent Inhibition of Muscarinic Atrial K+ Channel Currents”, Science, vol. 255, No. 5041, Jan. 10, 1992, pp. 192-194. [cited by applicant]
Mertes et al., “Targeted enrichment of genomic DNA regions for next-generation sequencing”, Briefings in Functional Genomics, 2011, vol. 10, No. 6, pp. 374-386. [cited by applicant]
Metzker, Michael, “Sequencing technologies—the next generation”, Nature Reviews, vol. 11, Jan. 2010, pp. 31-46. [cited by applicant]
Needleman, et al., “A General Method Applicable to the Search for Similarities in the Amino Acid Sequence of Two Proteins,” J. Mol. Biol, vol. 48, pp. 443-453 (1970). [cited by applicant]
Newman et al., “An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage” Nature Medicine, May 2014, vol. 20, No. 5, pp. 548-554 and Supplementary Information (pp. 1-22). [cited by applicant]
Pereira et al., “Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers,” PLoS One 10(12):e0145754, p. 1-13 and Figure S1 and Table S1, 15 pages total (2… [cited by applicant]
Skinner et al., “Use of the Glu-Glu-Phe C-terminal Epitope for Rapid Purification of the Catalytic Domain of Normal and Mutant ras GTPase-activating Proteins”, The Journal of Biological Chemistry, vol. 266, No. 22, Aug.… [cited by applicant]
Su et al., “Human Urine Contains Small, 150 to 250 Nucleotide-Sized, Soluble DNA Derived from the Circulation and May Be Useful in the Detection of Colorectal Cancer”, Journal of Molecular Diagnostics, vol. 6, No. 2, Ma… [cited by applicant]
Takai et al., “Clinical Utility of Circulating Tumor DNA for Molecular Assessment in Pancreatic Cancer,” Nature Scientific Reports, 5:18425, p. 1-10 and Supplementary Information, 43 pages total (2015). [cited by applicant]
Thermo Fisher Scientific. “Ion AmpliSeq™ Designer provides full flexibility to sequence genes of your choice” Application Note. Ionu AmpliSeq™ Custom Panels. 4 pages, available via URL: <assets.thermofisher.com/TFS-Asse… [cited by applicant]
Turner et al., “Massively parallel exon capture and library-free resequencing across 16 genomes”, Nat. Methods, 6:315-316, 2009. [cited by applicant]
Voelkerding et al., “Next-Generation Sequencing: From Basic Research to Diagnostics”, Clinical Chemistry, vol. 55, No. 4, 2009, pp. 641-659. [cited by applicant]
Wagle et al., “High-throughput detection of actionable genomic alterations in clinical tumor samples by targeted, massively parallel sequencing”, Cancer Discovery, 2012, vol. 2, No. 1, pp. 82-93. [cited by applicant]
Woo et al., “Profiling of exome mutations associated with progression of HBV-related hepatocellular carcinoma”, PLoS One, 2014, vol. 9, No. 12, 15 pages. [cited by applicant]