Granted Patent
B2
US 12,241,123 · App. 17/392,203 · Granted Mar 4, 2025
Methods of lowering the error rate of massively parallel DNA sequencing using duplex consensus sequencing
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, a method Duplex Consensus Sequencing (DCS) is provided. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors will result in errors in only one strand. This method uniquely capitalizes on the redundant information stored in double-stranded DNA, thus overcoming technical limitations of prior methods utilizing data from only one of the two strands.
Claims (17)
1. A method of sequencing a double stranded nucleic acid, the method comprising:
(a) ligating a first adapter to a first end of the double stranded nucleic acid, wherein the first adapter is a Y-adapter, wherein the Y-adapter comprises (i) a first strand haying a 5′-arm and a 3′-portion, and (ii) a second strand having a 5′-portion and a 3′-arm, wherein the 3′-portion of the first strand is substantially complementary to the 5′-portion of the second strand, and the 5′-arm of the first strand is not substantially complementary to the 3′-arm of the second strand, and ligating a second adapter to a second end of the double stranded nucleic acid, wherein the second adapter is a hairpin adapter, thereby forming a nucleic acid template;
(b) annealing a first primer to the nucleic acid template, wherein the first primer comprises a sequence that is complementary to a portion of the first adapter, or a complement thereof;
(c) sequencing a first portion of the nucleic acid template by extending the first primer, thereby generating a first read comprising a first nucleic acid sequence of at least a first portion of the double stranded nucleic acid;
(d) annealing a second primer to the nucleic acid template, wherein the second primer comprises a sequence that is complementary to a sequence within a loop of the hairpin adapter, or a complement thereof; and
(e) sequencing a second portion of the nucleic acid template by extending the second primer, thereby generating a second read comprising a nucleic acid sequence of at least a second portion of the double stranded nucleic acid.
2. The method of claim 1 , wherein the ligating of the first adapter comprises ligating a 3′-end of the first strand of the Y-adapter to a 5′-end of the forward strand of the double stranded nucleic acid, and ligating a 5′-end of the second strand of the Y-adapter to a 3′-end of the reverse strand of the double stranded nucleic acid.
3. The method of claim 1 , wherein the first primer anneals to the second strand of the Y-adapter.
4. The method of claim 1 , wherein the second adapter comprises a nucleic acid having a 5′-end, a 5′-portion, the loop, a 3′-portion and a 3′-end, and the 5′-portion of the second adapter is substantially complementary to the 3′-portion of the second adapter.
5. The method of claim 4 , wherein the ligating of the second adapter comprises ligating the 5′-end of the second adapter to a 3′-end of the forward strand of the double stranded nucleic acid and ligating the 3′-end of the second adapter to a 5′-end of the reverse strand of the double stranded nucleic acid.
6. The method of claim 1 , wherein the method further comprises, after (a) and prior to (b), generating amplicons of the nucleic acid template.
7. The method of claim 6 , wherein the method of generating amplicons of the nucleic acid template comprises a polymerase chain reaction.
8. The method of claim 7 , wherein the polymerase chain reaction comprises a bridge PCR amplification method.
9. The method of claim 1 , wherein the sequencing of (c) and the sequencing of (e) comprise a process comprising sequencing by synthesis.
10. The method of claim 1 , wherein the first adapter comprises one or more of a sample barcode sequence, a molecular identifier sequence, or both a sample barcode sequence and a molecular identifier sequence.
11. The method of claim 1 , wherein the second adapter comprises one or more of a sample barcode sequence, a molecular identifier sequence, or both a sample barcode sequence and a molecular identifier sequence.
12. The method of claim 6 , wherein the generating of amplicons comprises attaching the nucleic acid template to a substrate.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Dec 6, 2023
From: UNIVERSITY OF WASHINGTON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065790/0278 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 15, 2021
From: SALK, JESSE; LOEB, LAWRENCE A.; SCHMITT, MICHAEL
To: UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION
Reel/Frame 057810/0319 →
Continuity (7)
Continuation
14386800
Provisional Application
61613413
· Mar 20, 2012
Provisional Application
61625623
· Apr 17, 2012
Provisional Application
61625319
· Apr 17, 2012
References Cited (400)
US 5308751A
· Ohkawa et al.
· 1994
[cited by applicant]
US 6251610B1
· Gupte et al.
· 2001
[cited by applicant]
US 6498023B1
· Abarzua
· 2002
[cited by examiner]
US 6582908B2
· Fodor et al.
· 2003
[cited by applicant]
US 6958225B2
· Dong
· 2005
[cited by applicant]
US 7214490B2
· Su et al.
· 2007
[cited by applicant]
US 7267966B2
· Dong et al.
· 2007
[cited by applicant]
US 7297778B2
· Matsuzaki et al.
· 2007
[cited by applicant]
US 7406385B2
· Sorenson
· 2008
[cited by applicant]
US 7452699B2
· Makrigiorgos et al.
· 2008
[cited by applicant]
US 7459273B2
· Jones et al.
· 2008
[cited by applicant]
US 7476503B2
· Turner et al.
· 2009
[cited by applicant]
US 7741463B2
· Gormley et al.
· 2010
[cited by applicant]
US 7754429B2
· Rigatti
· 2010
[cited by applicant]
US 8029993B2
· Mikawa
· 2011
[cited by applicant]
US 8148068B2
· Brenner et al.
· 2012
[cited by applicant]
US 8153375B2
· Travers et al.
· 2012
[cited by applicant]
US 8318434B2
· Cuppens
· 2012
[cited by applicant]
US 8715967B2
· Casbon et al.
· 2014
[cited by applicant]
US 8735064B2
· Micklem et al.
· 2014
[cited by applicant]
US 8741606B2
· Casbon et al.
· 2014
[cited by applicant]
US 9080210B2
· Van Eijk et al.
· 2015
[cited by applicant]
US 9085798B2
· Chee
· 2015
[cited by applicant]
US 9249460B2
· Pushkarev et al.
· 2016
[cited by applicant]
US 9260753B2
· Xie et al.
· 2016
[cited by applicant]
US 9476095B2
· Vogelstein et al.
· 2016
[cited by applicant]
US 9598731B2
· Talasaz
· 2017
[cited by applicant]
US 9745627B2
· Van Eijk et al.
· 2017
[cited by applicant]
US 9752188B2
· Schmitt et al.
· 2017
[cited by applicant]
US 9783847B2
· Chee
· 2017
[cited by applicant]
US 9834822B2
· Talasaz
· 2017
[cited by applicant]
US 9862995B2
· Patel
· 2018
[cited by applicant]
US 9898577B2
· Van Eijk et al.
· 2018
[cited by applicant]
US 9920366B2
· Eltoukhy et al.
· 2018
[cited by applicant]
US 20040209299A1
· Pinter et al.
· 2004
[cited by applicant]
US 20070020640A1
· McCloskey et al.
· 2007
[cited by applicant]
US 20070172839A1
· Smith et al.
· 2007
[cited by applicant]
US 20080167195A1
· Li et al.
· 2008
[cited by applicant]
US 20080261204A1
· Lexow
· 2008
[cited by applicant]
US 20090093378A1
· Bignell
· 2009
[cited by applicant]
US 20100222238A1
· Smith et al.
· 2010
[cited by applicant]
US 20110301042A1
· Steinmann et al.
· 2011
[cited by applicant]
US 20120058468A1
· McKeown
· 2012
[cited by applicant]
US 20120165202A1
· Porreca et al.
· 2012
[cited by applicant]
US 20120238738A1
· Hendrickson et al.
· 2012
[cited by applicant]
US 20120244525A1
· Hendrickson
· 2012
[cited by applicant]
US 20140057799A1
· Johnson et al.
· 2014
[cited by applicant]
US 20180363048A1
· Bielas
· 2018
[cited by applicant]
US 20180363049A1
· Bielas
· 2018
[cited by applicant]
US 20210277467A1
· Vogelstein
· 2021
[cited by applicant]
US 20220010376A1
· Salk et al.
· 2022
[cited by applicant]
US 20220017961A1
· Salk et al.
· 2022
[cited by applicant]
US 20220195523A1
· Salk et al.
· 2022
[cited by applicant]
US 20220290231A1
· Salk et al.
· 2022
[cited by applicant]
US 20240035088A1
· Salk et al.
· 2024
[cited by applicant]
US 20240084385A1
· Salk et al.
· 2024
[cited by applicant]
EP 2893040B1
· 2019
[cited by applicant]
WO 2006113422
· 2006
[cited by applicant]
WO 2011021102
· 2011
[cited by applicant]
WO 2012042374A2
· 2012
[cited by applicant]
WO 2012061832
· 2012
[cited by applicant]
WO 2012129363A2
· 2012
[cited by applicant]
WO 20130142389A1
· 2013
[cited by applicant]
WO 2015100427A1
· 2015
[cited by applicant]
WO 20170100441A1
· 2017
[cited by applicant]
Myllykangas et al., “Overview of Sequencing Technology Platforms,” First Online 2011. Bioinformatics for High Throughput Sequencing, Chapter 2, pp. 11-25. (Year: 2011).
[cited by examiner]
Guo et al., “A randomized lentivirus shRNA library construction,” 2007. Biochemical and Biophysical Research Communications, vol. 348, pp. 272-276. (Year: 2007).
[cited by examiner]
Hirst et al., “Next generation sequencing based approaches to epigenomics,” 2010. Briefings in Functional Genomics, vol. 9, Issue 6, pp. 455-465. (Year: 2010).
[cited by examiner]
USPTO, U.S. Appl. No. 16/118,305, Notice of Allowance, dated Sep. 23, 2021.
[cited by applicant]
Ameur A, Stewart JB, Freyer C, Hagstrom E, Ingman M, Larsson N-G, et al. UltraDeep Sequencing of Mouse Mitochondrial DNA: Mutational Patterns and Their Origins. PLoS Genet. 2011;7:e1 002028.
[cited by applicant]
Bainbridge MN, Wang M, Burgess DL, Kovar C, Rodesch M, D'Ascenzo M, et al. Whole exome capture in solution with 3 Gbp of data. Genome Bioi. 2010;11: R62:1-8.
[cited by applicant]
Bentley, David R. et al., “Accurate whole human genome sequencing using reversible terminator chemistry,” Nature 456:53-59 (2008).
[cited by applicant]
Borodina, T. et al. “Chapter five—A Strand-Specific Library Preparation Protocol for RNA Sequencing” Methods in Enzymology, 2011, vol. 500, pp. 79-98.
[cited by applicant]
Boyd SO, Marshall EL, Merker JD, Maniar JM, Zhang LN, Sahaf B, et al. Measurement and Clinical Monitoring of Human Lymphocyte Clonality by Massively Parallel V-D-J Pyrosequencing. Science Translational Medicine. 2009;1 …
[cited by applicant]
Campbell PJ, Pleasance ED, Stephens PJ, Dicks E, Rance R, Goodhead I, et al. Subclonal phylogenetic structures in cancer revealed by ultra-deep sequencing. Proc Natl Acad Sci USA. 2008; 105:13081-6.
[cited by applicant]
Carlson CA, Kas A, Kirkwood R, Hays LE, Preston BD, Salipante SJ, et al. Decoding cell lineage from acquired mutations using arbitrary deep sequencing. Nat Methods. 2012;9:78-80.
[cited by applicant]
Casbon JA, Osborne RJ, Brenner S, Lichtenstein CP. A method for counting PCR template molecules with application to next-generation sequencing. Nucleic Acids Research. 2011 ;39:e81-e.
[cited by applicant]
Cervantes RB, Stringer JR, Shao C, Tischfield JA, Stambrook PJ. Embryonic stem cells and somatic cells differ in mutation frequency and type. Proc Natl Acad Sci USA. 2002;99:3586-90.
[cited by applicant]
Chiu RWK, Akolekar R, Zheng YWL, Leung TY, Sun H, Chan KCA, et al. Noninvasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ. 2011 ;342:c7401.
[cited by applicant]
Chiu, R.W.K. et al., “Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma,” PNAS 105:20458-20463 (2008).
[cited by applicant]
De Grassi A, Segala C, Iannelli F, Volorio S, Bertario L, Radice P, et al. Ultradeep Sequencing of a Human Ultraconserved Region Reveals Somatic and Constitutional Genomic Instability. PLoS Biol. 2010;8:e1000275.
[cited by applicant]
Diehl, Frank et al., “Basic—Alimentary Tract—Analysis of Mutations in DNA Isolated From Plasma and Stool of Colorectal Cancer Patients”, Gastroenterology 135:489-498 (2008).
[cited by applicant]
Diehl, Frank et al., “Detection and quantification of mutations in the plasma of patients with colorectal tumors,” PNAS 102:16368-16373 (2005).
[cited by applicant]
Ding L, Ley T J, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 21 05;481 :506-9.
[cited by applicant]
Ding, Li et al., “Analysis of next-generation genomic data in cancer: accomplishments and challenges,” Human Molecular Genetics, 19:R188-R196 (2010).
[cited by applicant]
Druley TE, Vallania FLM, Wegner OJ, Varley KE, Knowles OL, Bonds JA, et al. Quantification of rare allelic variants from pooled genomic DNA, Nat Methods. 2009;6 :263-5.
[cited by applicant]
Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, et al. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obsbet Gynecol. 2011;204:205e1-…
[cited by applicant]
Ewing, B. et al. “Base-Calling of Automated Sequencer Traces Using Phred. II. Error Probabilities” Genome Research (1998) vol. 8, pp. 186-194.
[cited by applicant]
Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake Sr. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA. 2008;105:16266-71.
[cited by applicant]
Flaherty P, Natsoulis G, Muralidharan O, Winters M, Buenrostro J, Bell J, et al. Ultrasensitive detection of rare mutations using next-generation targeted resequencing. Nucleic Acids Research. 2012;40:e2-e.
[cited by applicant]
Fleischhacker, M. et al., “Circulating nucleic acids (CNAs) and cancer—A survey,” Biochimica et Biophysica Acta. 1775:181-232 (2007).
[cited by applicant]
Fong, Siew Lee et al., “Comparison of 7 Methods for Extracting Cell-Free DNA from Serum Samples of Colorectal Cancer Patients,” Clinical Chemistry, 55:587-598 (2009).
[cited by applicant]
Fordyce SL, Avila-Areas MC, Rockenbauer E, B0rsting C, Frank-Hansen R, Petersen FT, et al. High-throughput sequencing of core STR loci for forensic genetic investigations using the Roche Genome Sequencer FLX platform. B…
[cited by applicant]
Forshew, T. et al. “Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA” Science Translational Medicine (2012) vol. 4, Issue 136, 136ra68, 14 pages.
[cited by applicant]
Fu GK, Hu J, Wang P-H, Fodor SPA. Counting individual DNA molecules by the stochastic attachment of diverse labels. Proc Natl Acad Sci USA. 2011;108:9026-31.
[cited by applicant]
Garcia-Garcera M, Gigli E, Sanchez-Quinto F, Ramirez O, Calafell F, Civit S, et al. Fragmentation of contaminant and endogenous DNA in ancient samples determined by shotgun sequencing; prospects for human palaeogenomics…
[cited by applicant]
Gordon, David J. et al., “Causes and consequences of aneuploidy in cancer,” Nature Reviews Genetics 13:189-203 (2012).
[cited by applicant]
Greaves LC, et al. (2009) Quantification of mitochondrial DNA mutation load. Aging Cell 8:566-572.
[cited by applicant]
Haag-Liautard C, et al. (2008) Direct estimation of the mitochondrial DNA mutation rate in
[cited by applicant]
He Y, Wu J, Dressman DC, Iacobuzio-Donahue C, Markowitz SD, Velculescu VE, et al. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature. 2010;464:610-4.
[cited by applicant]
Howell N, Kubacka I, Mackey DA (1996) How rapidly does the human mitochondrial genome evolve? Am J Hum Genet 59:501-509.
[cited by applicant]
Hyman RW, Herndon CN, Jiang H, Palm C, Fukushima M, Bernstein D, et al. The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization embryo transfer. J Assist Reprod Genet. 2012;29:105-1…
[cited by applicant]
Jabara CB, Jones CD, Roach J, Anderson JA, Swanstrom R. Accurate sampling and deep sequencing of the HIV-1 protease gene using a Primer ID. Proc Natl Acad Sci USA. 2011;108:20166-71.
[cited by applicant]
Jazin EE, Cavelier L, Eriksson I, Oreland L, Gyllensten U (1996) Human brain contains high levels of heteroplasmy in the noncoding regions of mitochondrial DNA. Proc Natl Acad Sci USA 93:12382-12387.
[cited by applicant]
Jiang, Hui et al., “SeqMap: mapping massive amount of oligonucleotides to the genome,” Bioinformatics 24:2395-2396 (2008).
[cited by applicant]
Kanagawa T. Bias and artifacts in multitemplate polymerase chain reactions (PCR). J Biosci Bioeng. 2003;96:317-23.
[cited by applicant]
Kao, Wei-Chun et al., “BayesCall: A model-based base-calling algorithm for high-throughput short-read sequencing,” Genome Research 19:1884-1895 (2009).
[cited by applicant]
Kasai H, et al.(1993) Formation, inhibition of formation, and repair of oxidative 8-hydroxyguanine DNA damage. Basic Life Sci 61:257-262.
[cited by applicant]
Kaur M, Makrigiorgos GM. Novel amplification of DNA in a hairpin structure: towards a radical elimination of PCR errors from amplified DNA. Nucleic Acids Res. 2003;31:26e1-7.
[cited by applicant]
Kennedy SR, Loeb LA, Herr AJ (2012) Somatic mutations in aging, cancer and neurodegeneration. Meeh Ageing Dev 133(4):118-26.
[cited by applicant]
Khaidakov M, Heflich RH, Manjanatha MG, Myers MB, Aidoo A (2003) Accumulation of point mutations in mitochondrial DNA of aging mice. Mutat Res 526:1-7.
[cited by applicant]
Kinde et al., Supporting Information corresponding to “Detection and quantification of rare mutations with massively parallel sequencing”, PNAS USA 108:9530-9535, Jun. 7, 2011.
[cited by applicant]
Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B. Detection and quantification of rare mutations with massively parallel sequencing. Proc Natl Acad Sci USA. 2011;108:9530-5.
[cited by applicant]
Kircher, Martin et al., “Improved base calling for the Illumina Genome Analyzer using machine learning strategies,” Genome Biology 10:R83 (2009).
[cited by applicant]
Kirsch, Stefan et al., “Sequence error storms and the landscape of mutations in cancer,” PNAS 109:14289-14290 (2012).
[cited by applicant]
Kivioja et al., “Counting absolute numbers of molecules using unique molecular identifiers,” Nature Methods 9, 72-74, Jan. 1, 2012.
[cited by applicant]
Kozarewa I, Ning Z, Quail MA, Sanders MJ, Berriman M, Turner OJ. Amplification free Illumine sequencing-library preparation facilitates improved mapping and assembly of (G+C)-biased genomes. Nat Methods. 2009; 6:291-5.
[cited by applicant]
Kraytsberg Y, Nicholas A, Caro P, Khrapko K (2008) Single molecule PCR in mtDNA mutational analysis: Genuine mutations vs. damage bypass-derived artifacts. Methods 46:269-273.
[cited by applicant]
Kunkel, TA. Mutational specificity of depurination. Proc Natl Acad Sci USA. 1984; 81:1494-98.
[cited by applicant]
LaTuga MS, Ellis JC, Cotton CM, Goldberg RN, Wynn JL, Jackson RB, et al. Beyond bacteria: a study of the enteric microbial consortium in extremely low birth weight infants. PLoS ONE. 2011; 6:e27858.
[cited by applicant]
Lecroq B, Lejzerowicz F, Bechar D, Christen R, Esling P, Baerlocher L, et al. Ultradeep sequencing of foraminiferal microbarcodes unveils hidden richness of early monothalamous lineages in deep-sea sediments. Proc Natl …
[cited by applicant]
Ledergerber, Christian et al., “Base-calling for next-generation sequencing platforms,” Briefings in Bioinformatics 12:489-497 (2011).
[cited by applicant]
Li, Heng et al., “Fast and accurate short read alignment with Burrows-Wheeler transform,” Bioinformatics 25:1754-1760 (2009).
[cited by applicant]
Li, Heng et al., “Mapping short DNA sequencing reads and calling variants using mapping quality scores,” Genome Research, 18:1851-1858 (2008).
[cited by applicant]
Liang, Kuo-Ching et al., “Bayesian Basecalling for DNA Sequence Analysis Using Hidden Markov Models,” IEEE/ACM Transactions on Computational Biology and Bioinformatics, 4:430-440 (2007).
[cited by applicant]
Liao, Gary J.W. et al., “Targeted Massively Parallel Sequencing of Maternal Plasma DNA Permits Efficient and Unbiased Detection of Fetal Alleles,” Clinical Chemistry 57:92-101 (2011).
[cited by applicant]
Lin MT, Simon DK, Ahn CH, Kim LM, Beal MF (2002) High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. Hum Mol Genet 11:133-145.
[cited by applicant]
Lindahl T, Wood RD. Quality control by DNA repair. Science. 1999;286:1897-1905.
[cited by applicant]
Lo, Y.M. Dennis et al., “Quantitative Analysis of Fetal DNA in Maternal Plasma and Serum: Implications for Noninvasive Prenatal Diagnosis,” Am. J. Hum. Genet. 62:768-775 (1998).
[cited by applicant]
Lunter, Gerton et al., “Stampy: A statistical algorithm for sensitive and fast mapping of Illumina sequence reads,” Genome Research 21:936-939 (2011).
[cited by applicant]
Lynch AM, Sasaki jC, Elespuru R, Jacobson-Kram D, Thybaud V, et al. New and emerging technologies for genetic toxicity testing. Environ Mol Mutagen. 2011;52(3):205-23.
[cited by applicant]
Mackelprang R, Waldrop MP, DeAngelis KM, David MM, Chavarria KL, Blazewicz SJ, et al. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw. Nature. 2011 ;480:368-71.
[cited by applicant]
McBride T J, Preston BD, Loeb LA (1991) Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry 30:207-213.
[cited by applicant]
McCloskey ML, Stager R, Hansen RS, Laird CD. Encoding PCR products with batch-stamps and barcodes. Biochem Genet. 2007; 45:761-7.
[cited by applicant]
McKernan, Kevin Judd et al., “Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding,” Genome Research 19:1527-1541 (2009).
[cited by applicant]
Mertes, Florian et al., “Targeted enrichment of genomic DNA regions for next-generation sequencing,” Briefings in Functional Genomics, 10:374-386 (2011).
[cited by applicant]
Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11:31-46.
[cited by applicant]
Meyer, M. et al. “Targeted high-throughput sequencing of tagged nucleic acid samples” Nucleic Acids Research (2007) vol. 35, No. 15, e97, 5 pages.
[cited by applicant]
Meyerhans A, Vartanian JP, Wain-Hobson S. DNA recombination during PCR. Nucleic Acids Research. 1990;18:1687-91.
[cited by applicant]
Meyerson, Matthew et al., “Advances in understanding cancer genomes through second-generation sequencing,” Nature Reviews Genetics, 11:685-696 (2010).
[cited by applicant]
Miner BE, Stager RJ, Burden AF, Laird CD, Hansen RS. Molecular barcodes detect redundancy and contamination in hairpin-bisulfite PCR. Nucleic Acids Research. 2004;32:e135.
[cited by applicant]
Minot S, Sinha R, Chen J, Li H, Keilbaugh SA, Wu GO, et al. The human gut virome: interindividual variation and dynamic response to diet. Genome Res. 2011; 21:1616-25.
[cited by applicant]
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008; 105:10513-8.
[cited by applicant]
Narayan, A. et al. “Ultrasensitive Measurement of Hotspot Mutations in Tumor DNA in Blood Using Error-Suppressed Multiplexed Deep Sequencing” Cancer Research (2012) vol. 72, No. 14, pp. 3492-3498.
[cited by applicant]
Nasu A, Marusawa H, Ueda Y, Nishijima N, Takahashi K, Osaki Y, et al. Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing. PLoS ONE. 2011;6:e24907.
[cited by applicant]
Nielsen, Rasmus et al., “Genotype and SNP calling from next-generation sequencing data,” Nature Reviews Genetics, 12:443-451 (2011).
[cited by applicant]
Out AA, van Minderhout IJHM, Goeman JJ, Ariyurek Y, Ossowski S, Schneeberger K, et al. Deep sequencing to reveal new variants in pooled DNA samples. Hum Mutat. 2009;30:1703-12.
[cited by applicant]
Ozsolak, F., Platt, A.R., Jones, D.R., Reifenberger, J.G., Sass, L.E., Mcinerney, P., Thompson, J.F., Bowers, J., Jarosz, M., and Milos, P.M. (2009). Direct RNA sequencing. Nature 461, 814-818.
[cited by applicant]
Parsons T J, et al. (1997) A high observed substitution rate in the human mitochondrial DNA control region. Nat Genet 15:363-368.
[cited by applicant]
Quail MA, Kozarewa I, Smith F, Scally A, Stephens PJ, Durbin R, et al. A large genome center's improvements to the Illumina sequencing system. Nat Methods. 2008;5:1005-10.
[cited by applicant]
Quinlan, Aaron R. et al., “Pyrobayes: an improved base caller for SNP discovery in pyrosequences,” Nature Methods, 5:179-181 (2008).
[cited by applicant]
Redon, Richard et al., “Global variation in copy number in the human genome,” Nature 444:444-454 (2006).
[cited by applicant]
Rizzo, J. et al. “Key Principles and Clinical Applications of “Next-Generation” DNA Sequencing” Cancer Prevention Research (2012), vol. 5, No. 7, pp. 887-900.
[cited by applicant]
Roberts, Short template amplicon and multiplex megaprimer—enabled relay (STAMMER) sequencing, a simultaneous approach to higher throughput sequence-based typing of polymorphic genes, Immunogenetics, vol. 62, 253-60 (201…
[cited by applicant]
Salk J, Fox E, Loeb L. Mutational heterogeneity in human cancers: origin and consequences. Annual Review of Pathology. 2009;5:51-75.
[cited by applicant]
Schmitt et al., Corrected Supporting Information corresponding to “Detection of ultra-rare mutations by next-generation sequencing”, PNAS, Sep. 4, 2012, 109(36) 14508-14513, Corrected SI dated Mar. 27, 2013.
[cited by applicant]
Schmitt et al., Supporting Information corresponding to “Detection of ultra-rare mutations by next-generation sequencing”, PNAS, Sep. 4, 2012, 109(36) 14508-14513.
[cited by applicant]
Schmitt, Michael W. et al., “Detection of ultra-rare mutations by next-generation sequencing,” PNAS 109:14508-14513 (2012).
[cited by applicant]
Schwarzenbach, H. et al., “Cell-free nucleic acids as biomarkers in cancer patients,” Nature Reviews, 11, 426-437, 2011.
[cited by applicant]
Schweiger, Michal R. et al., “Genome-Wide Massively Parallel Sequencing of Formaldehyde Fixed-Paraffin Embedded (FFPE) Tumor Tissues for Copy-Number- and Mutation-Analysis,” PLOS One 4:e5548 (2009).
[cited by applicant]
Sehnert, Amy J. et al., “Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA from Maternal Blood,” Clinical Chemistry 57:1042-1049 (2011).
[cited by applicant]
Shen Y, Wan Z, Coarfa C, Drabek R, Chen L, Ostrowski EA, et al. A SNP discovery method to assess variant allele probability from next-generation resequencing data. Genome Res. 2010;20:273-80.
[cited by applicant]
Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26:1135-45.
[cited by applicant]
Shibutani S, Takeshita M, Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature. 1991;349:431-4.
[cited by applicant]
Shiroguchi et al., Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodes, PNAS 109, 1347-1652, Jan. 9, 2012.
[cited by applicant]
Shiroguchi et al., Supporting Information corresponding to “Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodes”, PNAS, ePub 109(4): 1347-1352), Jan. …
[cited by applicant]
Song S, et al. (2005) DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity. Proc Natl Acad Sci USA 102:4990-4995.
[cited by applicant]
Sparks, Andrew B., et al., “Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy,” Prenatal Diagnosis, 32:3-9 (2012).
[cited by applicant]
Stiller M, Green RE, Ronan M, Simons JF, Du L, HeW., et al. Patterns of nucleotide misincorporations during enzymatic amplification and direct large-scale sequencing of ancient DNA. Proc Natl Aced Sci USA. 2006; 103:135…
[cited by applicant]
Stoneking M (2000) Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet 67:1029-1032.
[cited by applicant]
Teer, Jamie K. et al, “Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding,” Genome Research 20:1420-1431 (2010).
[cited by applicant]
Thomas DC, Roberts JD, Sabatino RD, Myers TW, et al. Fidelity of mammalian DNA replication and replicative DNA polymerases. Biochemistry. 1991;30:11751-9.
[cited by applicant]
Travers KJ, Chin CS, Rank DR, Eid JS, Turner SW. A flexible and efficient template format for circular consensus sequencing and SNP detection. Nucleic Acids Res. 2010; 38:159e1-8.
[cited by applicant]
Vandenbroucke I, Van Marek H, Verhasselt P, Thys K, Mostmans W, Dumont S, et al. Minor variant detection in amplicons using 454 massive parallel pyrosequencing: experiences and considerations for successful applications…
[cited by applicant]
Vermulst M, et al. (2007) Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet 39:540-543.
[cited by applicant]
Wagle, Nikhil et al., “High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing,” AACR Cancer Discovery 2:82-93 (2011).
[cited by applicant]
Wang C, Mitsuya Y, Gharizadeh B, Ronaghi M, Shafer RW. Characterization of mutation spectra with ultra-deep pyrosequencing: application to HIV-1 drug resistance. Genome Res. 2007;17:1195-201.
[cited by applicant]
Wiemann, S. et al. “Simultaneous On-Line DNA Sequencing on Both Strands with Two Fluorescent Dyes” Analytical Biochemistry, 1995, vol. 224, pp. 117-121.
[cited by applicant]
Yang J, Yang F, Ren L, Xiong Z, Wu Z, Dong J, et al. Unbiased parallel detection of viral pathogens in clinical samples by use of a metagenomic approach. J Clin Microbial. 2011 ;49:3463-9.
[cited by applicant]
Zagordi O, Klein R, Daumer M, Beerenwinkel N. Error correction of next-generation sequencing data and reliable estimation of HIV quasispecies. Nucleic Acids Research. 2010;38:7400-9.
[cited by applicant]
EPO, Application No. EP13764186.6, Extended European Search Report, dated Sep. 8, 2015.
[cited by applicant]
EPO, Application No. EP13764186.6, Examination Report, dated May 13, 2016, 6 pages.
[cited by applicant]
EPO, Application No. EP13764186.6, Examination Report, dated Jan. 31, 2017, 7 pages.
[cited by applicant]
EPO, Application No. EP13764186.6, Examination Report, dated Aug. 10, 2017, 7 pages.
[cited by applicant]
EPO, Application No. EP13764186.6, Examination Report, dated Jun. 8, 2018, 5 pages.
[cited by applicant]
EPO, Application No. EP13764186.6, Examination Report, dated Oct. 4, 2018, 6 pages.
[cited by applicant]
EPO, Application No. EP20166917.3, Extended European Search Report, dated Sep. 30, 2020. 6 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,019, Non-Final Office Action, dated Nov. 19, 2018. 16 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,072, Non-Final Office Action, dated Dec. 14, 2018. 16 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 15/660,785, Notice of Allowance, dated Dec. 27, 2018. 17 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,091, Notice of Allowance, dated Mar. 4, 2019. ___ pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,019, Final Office Action, dated Jun. 7, 2019. 17 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,091, Second Notice of Allowance, dated Jun. 10, 2019. 8 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,072, Notice of Allowance, dated Jun. 26, 2019. 16 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,045, Non-Final Office Action, dated Jul. 25, 2019. 20 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/120,019, Notice of Allowance, dated Oct. 30, 2019. 15 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,045, Notice of Allowance, dated Nov. 15, 2019. 16 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,068, Non-Final Office Action, dated Nov. 20, 2019. 28 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,069, Non-Final Office Action, dated Nov. 26, 2019. 28 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,066, Non-Final Office Action, dated Dec. 23, 2019. 33 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,382, Non-Final Office Action, dated Jan. 24, 2020. 35 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/514,931, Non-Final Office Action, dated Jan. 29, 2020. 37 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,068, Notice of Allowance, dated Feb. 28, 2020.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,066, Notice of Allowance, dated Mar. 6, 2020.
[cited by applicant]
USPTO, U.S. Appl. No. 16/411,069, Notice of Allowance, dated Mar. 6, 2020.
[cited by applicant]
USPTO, U.S. Appl. No. 16/514,931, Notice of Allowance, dated Jun. 1, 2020. 5 pgs.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,382, Notice of Allowance with notice of references cited, dated Jul. 15, 2020.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,382, Corrected Notice of Allowance with notice of references cited, dated Jul. 29, 2020.
[cited by applicant]
USPTO, U.S. Appl. No. 16/908,611, Non-Final Office Action, dated Oct. 9, 2020. 42 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/118,290, Non-Final Office Action, dated Dec. 14, 2020. 33 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/008,395, Non-Final Office Action, dated Jan. 7, 2021, 20 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/118,305, Non-Final Office Action, dated Jan. 13, 2021.
[cited by applicant]
USPTO, U.S. Appl. No. 16/908,611, Notice of Allowance, dated Jan. 29, 2021. 11 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/119,471, Non-Final Office Action, dated Feb. 2, 2021, 32 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/118,286, Non-Final Office Action, dated Mar. 1, 2021.
[cited by applicant]
USPTO, U.S. Appl. No. 17/008,395, Notice of Allowance, dated Apr. 15, 2021, 13 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/118,290, Notice of Allowance, dated Apr. 20, 2021. 5 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/119,471, Notice of Allowance, dated May 24, 2021, 11 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,398, Non-Final Office Action, dated May 27, 2021, 20 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/118,286, Notice of Allowance, dated Jun. 23, 2021, 8 pages.
[cited by applicant]
USPTO, International Search Report and Written Opinion for PCT/US2013/032665, 14 pgs, dated Jul. 9, 2013.
[cited by applicant]
Lewis Silkin, Opposition against European Patent No. 2828218, dated May 4, 2021, 7 pages.
[cited by applicant]
Margaret Dixon, Opposition against European Patent No. 2828218, dated May 4, 2021, 23 pages.
[cited by applicant]
Withers & Rogers, Opposition against European Patent No. 2828218, dated May 4, 2021, 28 pages.
[cited by applicant]
Clark, T. et al. “Direct Detection and Sequencing of Damaged DNA Bases” Genome Integrity, 2011, vol. 2, No. 10, 9 pages.
[cited by applicant]
Craig et al., “Identification of genetic variants using bar-coded multiplexed sequencing,” Nature Methods 5 887-93 + supplemental material (Oct. 2008).
[cited by applicant]
Evans et al., “NEB Expressions” New England BioLabs (2007) (IPR2022-00816 Ex. 1014).
[cited by applicant]
Hodges et al., “Genome-wide in situ exon capture for selective resequencing,” Nature Genetics 39(12) (2007) (IPR2022-00817 Ex. 1028.
[cited by applicant]
Illumina, Complete Secondary Analysis Workflow for the Genome Analyzer, Technical Note: Illumina Systems and Software (2009) (IPR2022-00816 Ex. 1011).
[cited by applicant]
Illumina, Preparing Samples for Sequencing Genomic DNA (2007) (IPR2022-00816 Ex. 1008).
[cited by applicant]
Illumina, TruSeq RNA and DNA Sample Preparation Kits, Data Sheet: Illumina Sequencing (2010) ((IPR2022-00816 Ex. 1012).
[cited by applicant]
Mattox et al., “Bisulfite-converted duplexes for the strand specific detection and quantification of rare mutations.” PNAS, 114; 4733-4738. Apr. 17, 2017.
[cited by applicant]
McCarthy, “Third Generation DNA Sequencing: Pacific Biosciences' Single Molecule Real Time Technology,” Chemistry & Biology 17 (2010) (IPR2022-00817 Ex. 1026).
[cited by applicant]
Minoche et al., “Evaluation of genomic high-throughput sequencing data generated on Illumina HiSeq and Genome Analyzer systems,” Genome Biology, 12, R112; 1-15. Nov. 8, 2011.
[cited by applicant]
NEB Expressions, New England BioLabs, https://web.archive.org/web/20080321144426/http://www.neb.com/nebecomm/tech_reference/neb_transcripts.asp (Feb. 23, 2022) (IPR2022-00816 Ex. 1015).
[cited by applicant]
Nisha et al., “Antioxidants and Their Protective Action Against DNA Damage,” International Journal of Pharmacology and Pharmaceutical Sciences 3 (2011) (IPR2022-00816 Ex. 1017).
[cited by applicant]
Perakis, S. et al., Advances in Circulating Tumor DNA Analysis, Advances in Clinical Chemistry, vol. 80, 2017.
[cited by applicant]
Song et al., “Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine,” Nature Methods 9(1) (2012) (IPR2022-00816 Ex. 1027).
[cited by applicant]
Guardant Health, Invalidity Contentions—
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,689,699, IPR2022-00449, Paper 3—Petition, Jan. 31, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,689,699, IPR2022-00449, Ex. 1002—Quackenbush Declaration, Jan. 31, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,689,699, IPR2022-00450, Paper 3—Petition, Jan. 31, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,689,699, IPR2022-00450, Ex. 1002—Quackenbush Declaration, Jan. 31, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,760,127, IPR2022-00816, Paper 3—Petition, Apr. 8, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,760,127, IPR2022-00816, Ex. 1002—Quackenbush Declaration, Apr. 8, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,760,127, IPR2022-00817, Paper 3—Petition, Apr. 8, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,760,127, IPR2022-00817, Ex. 1002—Quackenbush Declaration, Apr. 8, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,287,631, IPR2022-00935, Paper 2—Petition, May 6, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of U.S. Pat. No. 10,287,631, IPR2022-00935, Ex. 1002—Quackenbush Declaration, May 6, 2022.
[cited by applicant]
Withers & Rogers, Further Observations filed in Opposition against European Patent No. 2828218, dated Jan. 19, 2022, 8 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/361,245, Nonfinal Office Action, dated Nov. 3, 2021.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,175, Nonfinal Office Action, dated Dec. 9, 2021.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,193, Nonfinal Office Action, dated Dec. 13, 2021.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,398, Notice of Allowance, dated Jan. 18, 2022.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,180, Nonfinal Office Action, dated Feb. 3, 2022.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,207, Nonfinal Office Action, dated Feb. 18, 2022.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,185, Nonfinal Office Action, dated Feb. 22, 2022.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,175, Final Office Action, dated Apr. 13, 2022.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,180, Final Office Action, dated Jun. 6, 2022. 32 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,185, Notice of Allowance, dated Jun. 10, 2022. 24 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,207, Notice of Allowance, dated Jun. 14, 2022. 12 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,398, Nonfinal Office Action, dated Jun. 27, 2022. 24 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,175, Notice of Allowance, mail date: Oct. 12, 2022, 16 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,180, Notice of Allowance, mail date: Oct. 13, 2022, 15 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/503,398, Notice of Allowance, mail date: Nov. 16, 2022, 16 pages.
[cited by applicant]
Guardant Health, Inc., Response to Notice of Opposition, European Patent No. 2 893 040 (May 2020).
[cited by applicant]
Guardant Health, Petition for IPR of Patent No. 10,752,951, IPR2022-01158, Paper 3—Petition, Jul. 12, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of Patent No. 10,752,951, IPR2022-01158, Ex. 1002—Quackenbush Declaration, Jul. 12, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of Patent No. 10,752,951, IPR2022-01159, Paper 3—Petition, Jul. 12, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of Patent No. 10,752,951, IPR2022-01159, Ex. 1002—Quackenbush Declaration, Jul. 12, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of Patent No. 10,689,699, IPR2022-01388, Paper 2—Petition, Aug. 10, 2022.
[cited by applicant]
Guardant Health, Petition for IPR of Patent No. 10,689,699, IPR2022-01388, Ex. 1002—Quackenbush Declaration, Aug. 10, 2022.
[cited by applicant]
Guardant Health, Plaintiff's Opening Claim Construction Brief—
[cited by applicant]
Guardant Health, IPR2022-00449, Ex. 1008 - EP Application No. 13764186 Prosecution History through Sep. 7, 2020.
[cited by applicant]
Guardant Health, IPR2022-00449, Ex. 1031—U.S. Appl. No. 16/593,633 File History Excerpts, Jan. 31, 2022.
[cited by applicant]
Guardant Health, IPR2022-00449, Ex. 1032—U.S. Appl. No. 16/277,724 Notice of Allowance (Jun. 4, 2020).
[cited by applicant]
Guardant Health, IPR2022-00449, Ex. 1033—U.S. Appl. No. 14/712,754 Office Action (May 31, 2016).
[cited by applicant]
Guardant Health, IPR2022-00449, Ex. 1038—U.S. Appl. No. 16/672,267 Notice of Allowance (Jul. 21, 2021).
[cited by applicant]
COSMIC Data Analyses, Sanger Institute Catalogue of Somatic Mutations in Cancer, obtained from: https://cancer.sanger.ac.uk/cosmic/analyses, Last accessed Jun. 10, 2022.
[cited by applicant]
Krimmel et al., “Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues,” PNAS 113(21) (May 24, 2016).
[cited by applicant]
Wang et al., “Briefing in family characteristics of microRNAs and their applications in cancer research,” Biochimica et Biophysica Acta 1844 (2014).
[cited by applicant]
EPO, Application No. EP2828218, Summons to Attend Oral Proceedings and Preliminary, Non-Binding Opinion, Aug. 3, 2022.
[cited by applicant]
Withers & Rogers (01), Further Brief Comments filed in Opposition against European Patent No. 2828218, dated Jan. 20, 2023, 11 pages.
[cited by applicant]
Margaret Dixon (02), Further Comments filed in Opposition against European Patent No. 2828218, dated Jan. 19, 2023, 12 pages.
[cited by applicant]
Lewis Silkin (03), Further Comments filed in Opposition against European Patent No. 2828218, dated Jan. 20, 2023, 4 pages.
[cited by applicant]
Duncavage et al., “Targeted next generation sequencing of clinically significant gene mutations and translocations in leukemia,” Modern Pathology, 25:795-804 (2012).
[cited by applicant]
US District Court, Delaware, Report and Recommendation on Claim Construction by U.S. Magistrate Judge Sherry R. Fallon—
[cited by applicant]
EPO, Application No. EP13764186.6, Decision of Revocation Patent No. EP 2828218 with Written Opinion, dated May 24, 2023, 26 pages.
[cited by applicant]
EPO, Application No. EP20166917.3, Examination Report, dated Mar. 14, 2023, 4 pages.
[cited by applicant]
EPO, Application No. EP13764186.6, Notice of Revocation of Patent No. EP 2828218, dated Mar. 22, 2023, 2 pages.
[cited by applicant]
PTAB, IPR2022-01158, Paper 19, Decision Granting Institution of IPR, Jan. 13, 2023.
[cited by applicant]
PTAB, IPR2022-00817, Paper 14, Decision Granting Institution of IPR, Oct. 13, 2022.
[cited by applicant]
Guardant Health, IPR2022-00817, Paper 26, Petitioner's Reply re IPR of U.S. Pat. No. 10,760,127, Apr. 13, 2023.
[cited by applicant]
Guardant Health, IPR2022-00817, Ex. 1033 filed with Petitioner's Reply, Declaration of Dr. Andres Larrea, Apr. 13, 2023.
[cited by applicant]
Guardant Health, IPR2022-00817, Ex. 1037 filed with Petitioner's Reply, Deposition Transcript of Rahul Satija, D. Phil (Mar. 21, 2023).
[cited by applicant]
Guardant Health, IPR2022-00817, Ex. 1039 filed with Petitioner's Reply, Rebuttal Declaration of Dr. John Quackenbush, Apr. 13, 2023.
[cited by applicant]
Guardant Health, IPR2022-01158, Paper 13, Petitioner's Pre-Institution Reply re IPR of Patent No. 10,752,951, Nov. 22, 2022.
[cited by applicant]
Chin, Chen-Shan et al., “The Origin of the Haitian Cholera Outbreak Strain,” New England J Medicine, 364 (2011), 33-42, + supplemental information (290 pages) (IPR2022-00817 Ex. 1036).
[cited by applicant]
Pacific Biosciences Template Preparation and Sequencing Guide, 2010 (IPR2022-00817 Ex. 1035).
[cited by applicant]
Guardant Health, IPR2022-00817, Paper 45, Transcript of Oral Hearing held Jun. 15, 2023, Aug. 4, 2023.
[cited by applicant]
Guardant Health, IPR2022-01158, Paper 33, Petitioner's Reply re IPR of Patent No. 10,752,951, Jun. 30, 2023.
[cited by applicant]
Guardant Health, IPR2022-01158, Paper 33, Exhibit 1062 filed with Petitioner's Reply, Deep Sequence Data Analysis, Springer-Link, https://link.springer.com/book/10.1007/978-1-62703-514-9, (2013), Jun. 30, 2023.
[cited by applicant]
Guardant Health, IPR2022-01158, Paper 33, Exhibit 1063 filed with Petitioner's Reply, Stoler et al., “Family reunion via error correction: an efficient analysis of duplex sequencing data,” BMC Bioinformatics (2020), Jun…
[cited by applicant]
Guardant Health, IPR2022-01158, Paper 33, Exhibit 1064 filed with Petitioner's Reply, Stoler et al., “Streamlined analysis of duplex sequencing data with Du Novo,” Genome Biology (2016), Jun. 30, 2023.
[cited by applicant]
Guardant Health, IPR2022-01158, Paper 33, Exhibit 1066 filed with Petitioner's Reply, Declaration of Dr. Paul T. Spellman (IPR2022-01152), Jun. 30, 2023.
[cited by applicant]
Rusk, N “Uber-accurate sequencing,” Nature Methods, 9, 942-943, Jan. 2012.
[cited by applicant]
EPO, Application No. EP20166917.3, Examination Report, Mail Date: Jul. 20, 2023. 4 pages.
[cited by applicant]
EPO, Application No. EP23178659.1, Extended European Search Report, Sep. 22, 2023, 6 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 16/503,398, Nonfinal Office Action, mail date: Jun. 20, 2023, 26 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,175, Notice of Allowance, mail date: Aug. 4, 2023, 14 pages.
[cited by applicant]
USPTO, U.S. Appl. No. 17/392,180, Notice of Allowance, mail date: Aug. 30, 2023, 14 pages.
[cited by applicant]
PTAB, IPR2022-01158, Paper 47, Final Written Decision finding claims 1-28 of U.S. Pat. No. 10,752,951 unpatentable, Jan. 11, 2024.
[cited by applicant]
EPO Boards of Appeal, Communication Forwarding Submission to Parties—Withers & Rogers Comments in Response to Grounds of Appeal, dated Feb. 12, 2024, 153 pages with Annexes I and II.
[cited by applicant]
EPO Boards of Appeal, Communication Forwarding Submission to Parties—Margaret Dixon, Comments in Response to Ground of Appeal, dated Feb. 21, 2024, 50 pages.
[cited by applicant]
EPO Boards of Appeal, Communication Forwarding Submission to Parties—Lewis Silkin, Comments in Response to Grounds of Appeal, dated Feb. 27, 2024, 14 pages.
[cited by applicant]
Caldwell, Randolph B. et al., “Full-length cDNAs from chicken bursal lymphocytes to facilitate gene function analysis”, Genome Biology, Biomed Central Ltd, vol. 6, No. 1, Dec. 23, 2004, page R6.
[cited by applicant]
EPO, Application No. EP20166917.3, Examination Report, Mail Date: Jan. 23, 2024. 7 pages.
[cited by applicant]
Margaret Dixon, Further Observations filed in Opposition against European Patent No. 2828218, dated Feb. 27, 2023.
[cited by applicant]
Lewis Silkin (03), Further Observations filed in Opposition against European Patent No. 2828218, dated Mar. 14, 2023.
[cited by applicant]
EPO, Application No. EP20166917.3, Third Party Observations, Jun. 6, 2024, 3 pages.
[cited by applicant]
Guardant Health, Request for Ex Parte Reexam of U.S. Pat. No. 10,287,631, Jun. 21, 2024, 130 pages.
[cited by applicant]
Declaration of Dr. Peter A. Sims, Ex. G of Request for Ex Parte Reexam of U.S. Pat. No. 10,287,631, Jun. 21, 2024, 205 pages.
[cited by applicant]
Curriculum Vitae of Dr. Peter A Sims, Ex. X Accompanying Request for Exam Parte Reexam of U.S. Pat. No. 10,287,631, Jun. 21, 2024.
[cited by applicant]
Claim Chart CC-LI, Exhibit AA Accompanying Request for Ex Parte Reexam of U.S. Pat. No. 10,287,631, Jun. 21, 2024.
[cited by applicant]
Claim Chart CC-VI, Exhibit BB Accompanying Request for Ex Parte Reexam of U.S. Pat. No. 10,287,631, Jun. 21, 2024.
[cited by applicant]
Declaration of Nathaniel Frank-Wright regarding TruSeq Brochure, Exhibit CC Accompanying Request for Ex Parte Reexam of U.S. Pat. No. 10,287,631, Jun. 21, 2024.
[cited by applicant]
USPTO, Order Granting Request For Ex Parte Reexamination of 10,287,631; Control No. U.S. Appl. No. 90/019,551, Mail Date: Aug. 1, 2024, 19 pages.
[cited by applicant]
Jus District Court, Delaware, Claim Construction Order (Dkt. No. 324),
[cited by applicant]
Guardant Health, Appellant's Opening Brief—
[cited by applicant]
Reply Brief Filed by Appellant Guardant Health, Inc.—
[cited by applicant]
TwinStrand's Letter Brief (Dkt. No. 468),
[cited by applicant]