Tempus AI, Inc. vs Guardant Health Inc. - IPR2025-01435

Patent Owner's Mandatory Notices

Patent Owner's Power of Attorney

U.S. Patent No. 10,793,916 (Corrected)

Prosecution history for the ’916 patent (1 of 3) (Corrected)

Prosecution history for the ’916 patent (2 of 3) (Corrected)

Prosecution history for the ’916 patent (3 of 3) (Corrected)

Declaration of Michael Metzker, Ph.D. (Corrected)

Curriculum Vitae of Michael Metzker, Ph.D. (Corrected)

U.S. Patent No. 9,752,188 (Corrected)

PCT Publication No. WO 2012/142213 A2 (Corrected)

U.S. Patent Application Publication No. 2011/0160078 (Corrected)

PCT Publication No. WO 2012/099832 A2 (Corrected)

U.S. Patent Application Publication No. 2014/0296081 (Corrected)

T. Forshew et al., Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA, SCIENCE TRANSLATIONAL MEDICINE, Vol. 4 Issue 136 (May 30, 2012) (Corrected)

U.S. Patent No. 9,404,156 (Corrected)

K. Shiroguchi et al., Digital RNA Sequencing Minimizes Sequence-Dependent Bias And Amplification Noise With Optimized Single-Molecule Barcodes, PNAS Vol. 109, No. 4 (Jan. 24, 2012) (Corrected)

U.S. Patent Publication No. 2012/0316074 A1 (Corrected)

Schwarzenbach et al., Cell-free nucleic acids as biomarkers in cancer patients, NATURE REVIEWS CANCER 11:426–437 (2011) (Corrected)

Human genome variation, fact sheet, National Human Genome Research Institute (NHGRI) (Corrected)

Guardant Health, Inc. v. Foundation Medicine, IPR2017- 01448, Paper 2 – Petition for Inter Partes Review of U.S. Patent No. 9,340,830 (Corrected)

Metzker, Sequencing technologies — the next generation, NATURE REVIEWS GENETICS 11:31 –46 (2010) (Corrected)

Guardant Health, Inc. v. University of Washington, IPR2022- 00816, Paper 3 – Petition for Inter Partes Review of U.S. Patent No. 10,760,127 (Corrected)

Metzker & Caskey, Polymerase Chain Reaction, In ENCYCLOPEDIA OF MEDICAL DEVICES AND INSTRUMENTATION, Second Edition, Volume 5 (2006) (Corrected)

Mamanova et al., Target-enrichment strategies for nextgeneration sequencing, NATURE METHODS 7:111–118 (2010) (Corrected)

Guardant Health, Inc. v. University of Washington, IPR2022- 00450, Paper 3 – Petition for Inter Partes Review of U.S. Patent No. 10,689,699 (Corrected)

Guardant Health, Inc. v. University of Washington, IPR2022- 01388, Paper 2 – Petition for Inter Partes Review of U.S. Patent No. 10,689,699 (Corrected)

Guardant Health, Inc. v. University of Washington, IPR2022- 00935, Paper 2 – Petition for Inter Partes Review of U.S. Patent No. 10,287,631 (Corrected)

U.S. Provisional Patent Application No. 61/600535 (Corrected)

Twinstrand Biosciences, Inc. v. Guardant Health, Inc., IPR2022-01400, Paper 2 – Petition for Inter Partes Review of U.S. Patent No. 11,149,306 (Corrected)

Twinstrand Biosciences, Inc. v. Guardant Health, Inc., IPR2022-01400, Paper 41 – Final Written Decision (Corrected)

Twinstrand Biosciences, Inc. v. Guardant Health, Inc., IPR2022-01400, Paper 9 – Institution Decision (Corrected)

Li et al., Structure-independent and quantitative ligation of single-stranded DNA, Analytical Biochemistry (2005) (Corrected)

U.S. Patent No. 9,085,798 (Corrected)

Thomas et al., Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing, NATURE MEDICINE 12:852–855 (2006) (Corrected)

Buckingham, Chromosomal structure and chromosomal mutations, In MOLECULAR DIAGNOSTIC FUNDAMENTAL, METHODS, & CLINICAL APPLICATIONS, Eds. Buckingham & Flaws, F.A. Davis Company, Chapter 8, pp. 155–172 (2007) (Corrected)

Gemayel et al., Variable tandem repeats accelerate evolution of coding and regulatory sequences, ANNUALS REVIEW OF GENETICS 44:445–477 (2010) (Corrected)

Tóth et al., Microsatellites in different eukaryotic genomes: Survey and analysis, GENOME RESEARCH 10:967–981 (2000) (Corrected)

Laghi et al., Differences and evolution of the methods for the assessment of microsatellite instability, ONCOGENE 27:6313– 6321 (2008) (Corrected)

Richard & Pâques, Mini- and microsatellite expansions: the recombination connection, EMBO REPORTS 1:122–126 (2000) (Corrected)

Hastings et al., Mechanisms of change in gene copy number, NATURE REVIEWS GENETICS 10:551–564 (2009) (Corrected)

Hiatt et al., Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation, GENOME RESEARCH 23:843–854 (2013) (Corrected)

Somatic & germline mutations, https://my.clevelandclinic.org/health/body/23067-somatic-- germline-mutations (last visited July 30, 2025) (Corrected)

Gene changes and cancer, https://www.cancer.org/cancer/understanding-cancer/genesand- cancer/gene-changes.html (last visited July 30, 2025) (Corrected)

International Human Genome Sequencing Consortium, Initial sequencing and analysis of the human genome, NATURE 409:860–921 (2001) (Corrected)

International Human Genome Sequencing Consortium, Finishing the euchromatic sequence of the human genome, NATURE 431:931–945 (2004) (Corrected)

Forbes, et al., COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer, NUCLEIC ACIDS RESEARCH 39:D945–D950 (2011) (Corrected)

Genomic Data Commons Data Portal, https://portal.gdc.cancer.gov/ ((last visited July 30, 2025) (Corrected)

Metzker, Emerging technologies in DNA sequencing, GENOME RESEARCH 15:1767–1776 (2005) (Corrected)

Rothberg et al., An integrated semiconductor device enabling non-optical genome sequencing, NATURE 475:348-352 (2011) (Corrected)

Jain et al., Improved data analysis for the MinION nanopore sequencer, NATURE METHODS 12:351-356 (2015) (Corrected)

Kinde et al., Detection and quantification of rare mutations with massively parallel sequencing, PNAS (June 7, 2011) (Corrected)

Turner et al., Methods for genomic partitioning, ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS 10:263-284 (Corrected)

Edwards & Gibbs, Multiplex PCR: Advantages, development, and applications, GENOME RESEARCH 3:S65-S75 (1994) (Corrected)

Sharma et al., (TG/CA)n repeats in human gene families: abundance and selective patterns of distribution according to function and gene length, BMC GENOMICS 6:83 pp. 1–12 (2005) (Corrected)

Gnirke et al., Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing, NATURE BIOTECHNOLOGY 27:182–189 (2009) (Corrected)

Meyerson et al., Advances in understanding cancer genomes through second-generation sequencing, NATURE REVIEWS GENETICS 11:685–696 (2010) (Corrected)

Preston et al., Innovation at Illumina: The road to the $600 human genome, NATURE PORTFOLIO (2023) at https://www.nature.com/articles/d42473-021-00030-9 (Corrected)

Bentley et al., Accurate whole human genome sequencing using reversible terminator chemistry, NATURE 456:53–59 (2008) (Corrected)

Kircher et al., Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform, NUCLEIC ACIDS RESEARCH 40:e3 pp. 1–8 (2012) (Corrected)

Pierce et al., A unique and universal molecular barcode array, NATURE METHODS 3:601–603 (2006) (Corrected)

Schmitt et al., Detection of ultra-rare mutations by nextgeneration sequencing, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES 109: 14508- 14513 (2012) (Corrected)

Glenn, Field guide to next-generation DNA sequencers, MOLECULAR ECOLOGY RESOURCES 11:759-769 (2011) (Corrected)

Cock et al., The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants, NUCLEIC ACIDS RESEARCH 38:1767–1771 (2010) (Corrected)

CASAVA 1.8: enhanced variant calling in whole-genome resequencing data (2011) (Corrected)

Li et al., Mapping short DNA sequencing reads and calling variants using mapping quality scores, Genome Research 18:1851–1858 (2008) (Corrected)

Li & Durbin, Fast and accurate short read alignment with Burrows–Wheeler transform, Bioinformatics 25:1754–1760 (2009) (Corrected)

Li & Durbin, Fast and accurate long-read alignment with Burrows–Wheeler transform, Bioinformatics 26: 589–595 (2010) (Corrected)

Langmead et al., Ultrafast and memory-efficient alignment of short DNA sequences to the human genome, Genome Biology 10:R25.1–R25.10 (2009) (Corrected)

Li et al., The sequence alignment/map format and SAMtools, BIOINFORMATICS 25:2078–2079 (2009) (Corrected)

DePristo et al., A framework for variation discovery and genotyping using next-generation DNA sequencing data, NATURE GENETICS 43:491–498 (2011) and Online Methods (Corrected)

McKenna et al., The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data, GENOME RESEARCH 20:1297-1303 (2010) (Corrected)

https://github.com/broadinstitute/gatk/releases (last visited Aug 11, 2025) (“GATK Updates”) (Corrected)

Koboldt et al., VarScan: variant detection in massively parallel sequencing of individual and pooled samples, BIOINFORMATICS 25:2283–2285 (2009) (Corrected)

Koboldt et al., VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing, GENOME RESEARCH 22:568–576 (2012) (Corrected)

Cibulskis et al., Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples, NATURE BIOTECHNOLOGY 31:213–219 (2013) (Corrected)

U.S. Patent No. 9,840,743 (Corrected)

U.S. Patent No. 9,834,822 (Corrected)

U.S. Patent Application Publication No. 2012/0165202 A1 (Corrected)

U.S. Patent Application Publication No. 2010/0264331 (Corrected)

M. van Lier, et al., A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory, J. CELL. MOL. MED. Vol. 13, No. 1-2 (2010) (Corrected)

C. Boland and A. Goel, Microsatellite Instability in Colorectal Cancer, GASTROENTEROLOGY, 138(6) (June 2010) (Corrected)

C. Boland, et al., A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer, CANCER RES, 58(22) (Nov. 15, 1998) (Corrected)

F. Sinicrope and D. Sargent, Clinical implications of microsatellite instability in sporadic colon cancers - PMC, CURR OPIN ONCOL., 21(4) (July 2009) (Corrected)

G. Li, Mechanisms and functions of DNA mismatch repair, CELL RESEARCH 18 (2008) (Corrected)

U.S. Provisional Application 61/613,413 (Corrected)

Foundation Medicine, Inc. v. Guardant Health, Inc., IPR2019- 00652, Paper 47 – Final Written Decision (Corrected)

Foundation Medicine, Inc. v. Guardant Health, Inc., IPR2019- 00652, Paper 54 – Termination (Corrected)

Foundation Medicine, Inc. v. Guardant Health, Inc., IPR2019- 00652, Paper 12 – Decision Granting Institution of Inter Partes Review (Corrected)

Declaration of Sylvia D. Hall-Ellis, Ph.D. (Corrected)

Notice: Notice filing date accorded

Updated Mandatory Notice

Updated Power of Attorney

Notice: Power of Attorney

U.S. Patent No. 10,793,916

Prosecution history for the ’916 patent (1 of 3)

Prosecution history for the ’916 patent (2 of 3)

Prosecution history for the ’916 patent (3 of 3)

Declaration of Michael Metzker, Ph.D.

Curriculum Vitae of Michael Metzker, Ph.D.

U.S. Patent No. 9,752,188 (“Schmitt”)

PCT Publication No. WO 2012142213 A2 (“Vogelstein”)

U.S. Patent Application Publication No. 2011/0160078 (“Fodor”)

PCT Publication No. WO 2012/099832 A2 (“Hendricks”)

T. Forshew et al., Noninvasive Identification and Monitoring of Cancer Muta

U.S. Patent No. 9,404,156 (“Hicks”)

K. Shiroguchi et al., Digital RNA Sequencing Minimizes Sequence-Dependent B

U.S. Patent Publication No. 2012/0316074 A1 (“Saxonov”)

Schwarzenbach et al., Cell-free nucleic acids as biomarkers in cancer patie

Human genome variation, fact sheet, National Human Genome Research Institut

Guardant Health, Inc. v. Foundation Medicine, IPR2017-01448, Paper 2 – Peti

Metzker, Sequencing technologies — the next generation, NATURE REVIEWS GENE

Guardant Health, Inc. v. University of Washington, IPR2022-00816, Paper 3 –

Metzker & Caskey, Polymerase Chain Reaction, In ENCYCLOPEDIA OF MEDICAL DEV

Mamanova et al., Target-enrichment strategies for next-generation sequencin

Guardant Health, Inc. v. University of Washington, IPR2022-00450, Paper 3 –

Guardant Health, Inc. v. University of Washington, IPR2022-01388, Paper 2 –

Guardant Health, Inc. v. University of Washington, IPR2022-00935, Paper 2 –

U.S. Provisional Patent Application No. 61/600535 (“Diehn Provisional”)

Twinstrand Biosciences, Inc. v. Guardant Health, Inc., IPR2022-01400, Paper

Twinstrand Biosciences, Inc. v. Guardant Health, Inc., IPR2022-01400, Paper

Twinstrand Biosciences, Inc. v. Guardant Health, Inc., IPR2022-01400, Paper

Li et al., Structure-independent and quantitative ligation of single-strand

U.S. Patent No. 9,085,798 (“Chee”)

Thomas et al., Sensitive mutation detection in heterogeneous cancer specime

Buckingham, Chromosomal structure and chromosomal mutations, In MOLECULAR D

Gemayel et al., Variable tandem repeats accelerate evolution of coding and

Tóth et al., Microsatellites in different eukaryotic genomes: Survey and an

Laghi et al., Differences and evolution of the methods for the assessment o

Richard & Pâques, Mini- and microsatellite expansions: the recombination co

Hastings et al., Mechanisms of change in gene copy number, NATURE REVIEWS G

Hiatt et al., Single molecule molecular inversion probes for targeted, high

Somatic & germline mutations, https://my.clevelandclinic.org/health/body/23

Gene changes and cancer, https://www.cancer.org/cancer/understanding-cancer

International Human Genome Sequencing Consortium, Initial sequencing and an

International Human Genome Sequencing Consortium, Finishing the euchromatic

Forbes, et al., COSMIC: mining complete cancer genomes in the Catalogue of

Genomic Data Commons Data Portal, https://portal.gdc.cancer.gov/ ((last vis

Metzker, Emerging technologies in DNA sequencing, GENOME RESEARCH 15:1767–1

Rothberg et al., An integrated semiconductor device enabling non-optical ge

Jain et al., Improved data analysis for the MinION nanopore sequencer, NATU

Kinde et al., Detection and quantification of rare mutations with massively

Turner et al., Methods for genomic partitioning, ANNUAL REVIEW OF GENOMICS

Edwards & Gibbs, Multiplex PCR: Advantages, development, and applications,

Sharma et al., (TG/CA)n repeats in human gene families: abundance and selec

Gnirke et al., Solution hybrid selection with ultra-long oligonucleotides f

Meyerson et al., Advances in understanding cancer genomes through second-ge

Preston et al., Innovation at Illumina: The road to the $600 human genome,

Bentley et al., Accurate whole human genome sequencing using reversible ter

Kircher et al., Double indexing overcomes inaccuracies in multiplex sequenc

Pierce et al., A unique and universal molecular barcode array, NATURE METHO

Schmitt et al., Detection of ultra-rare mutations by next-generation sequen

Glenn, Field guide to next-generation DNA sequencers, MOLECULAR ECOLOGY RES

Cock et al., The Sanger FASTQ file format for sequences with quality scores

CASAVA 1.8: enhanced variant calling in whole-genome resequencing data (201

Li et al., Mapping short DNA sequencing reads and calling variants using ma

Li & Durbin, Fast and accurate short read alignment with Burrows–Wheeler tr

Li & Durbin, Fast and accurate long-read alignment with Burrows–Wheeler tra

Langmead et al., Ultrafast and memory-efficient alignment of short DNA sequ

Li et al., The sequence alignment/map format and SAMtools, BIOINFORMATICS 2

DePristo et al., A framework for variation discovery and genotyping using n

McKenna et al., The Genome Analysis Toolkit: A MapReduce framework for anal

https://github.com/broadinstitute/gatk/releases (last visited Aug 11, 2025)

Koboldt et al., VarScan: variant detection in massively parallel sequencing

Koboldt et al., VarScan 2: Somatic mutation and copy number alteration disc

Cibulskis et al., Sensitive detection of somatic point mutations in impure

U.S. Patent No. 9,840,743

U.S. Patent No. 9,834,822

U.S. Patent Publication No. 2012/0165202 A1 (“Porreca”)

U.S. Patent Publication No. 2010/0264331 (“Sacko”)

M. van Lier, et al., A review on the molecular diagnostics of Lynch syndrom

C. Boland and A. Goel, Microsatellite Instability in Colorectal Cancer, GAS

C. Boland, et al., A National Cancer Institute Workshop on Microsatellite I

F. Sinicrope and D. Sargent, Clinical implications of microsatellite instab

G. Li, Mechanisms and functions of DNA mismatch repair, CELL RESEARCH 18 (2

U.S. Provisional Application 61/613,413 (“Schmitt '413 provisional”)

Foundation Medicine, Inc. v. Guardant Health, Inc., IPR2019-00652, Paper 47

Foundation Medicine, Inc. v. Guardant Health, Inc., IPR2019-00652, Paper 54

Foundation Medicine, Inc. v. Guardant Health, Inc., IPR2019-00652, Paper 12

Hall-Ellis Declaration

U.S. Patent Application Publication No. 2014/0296081 (“Diehn”)

Petition: as filed