Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 1 of 26 PageID #: 1
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`
`GUARDANT HEALTH, INC.,
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`
`
`
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`FOUNDATION MEDICINE, INC.,
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`Plaintiff
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`
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`v.
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`
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`C.A. No. _________________
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`JURY TRIAL DEMANDED
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`Defendant.
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`
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`COMPLAINT
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`Plaintiff Guardant Health, Inc. (“Guardant”), for its complaint against Defendant
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`Foundation Medicine, Inc. (“Foundation”) on behalf of itself, by Guardant’s attorneys, hereby
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`alleges as follows:
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`NATURE OF THE ACTION
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`1.
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`This is an action for patent infringement arising under the patent laws of the United
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`States, Title 35, United States Code, against Defendant Foundation.
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`2.
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`Guardant brings this action to halt Foundations’ infringement of Guardant’s rights
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`under the Patent Laws of the United States 35 U.S.C. § 1, et seq., which arise under U.S. Patent
`
`Nos. 10,501,810 (“the ’810 patent”) (attached as Exhibit 1), 10,704,085 (“the ’085 patent”)
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`(attached as Exhibit 2), and the 10,704,086 (“the ’086 patent”) (attached as Exhibit 3), 10,793,916
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`(“the ’916 patent”) (attached as Exhibit 4), 10,801,063 (“the ’063 patent”) (attached as Exhibit 5),
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`9,840,743 (“the ’743 patent”) (attached as Exhibit 6), and 9,834,822 (“the ’822 patent”) (attached
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`as Exhibit 7).
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`

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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 2 of 26 PageID #: 2
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`PARTIES
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`1.
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`Guardant is a corporation organized and existing under the laws of the state of
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`Delaware, having its principal place of business at 505 Penobscot Dr., Redwood City, CA 94063.
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`2.
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`Guardant was founded in 2012 by pioneers in DNA sequencing and cancer
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`diagnostics. Since its inception, Guardant has focused its expertise on the development of liquid
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`biopsy cancer assays. It was the first company to develop and commercialize a comprehensive
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`liquid biopsy assay to identify genomic biomarkers for advanced solid tumors using “cell-free
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`circulating tumor DNA,” or “ctDNA,” from simple, non-invasive blood draws.
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`3.
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`Today, Guardant markets and sells the Guardant360® ctDNA assay (“Guardant
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`360”). Guardant360 uses advanced DNA sequencing methods to identify targeted therapy
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`treatment options based on the specific changes—also known as somatic mutations—that occur
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`within the DNA of cancer cells. Guardant360 has helped thousands of oncologists find accurate
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`and actionable information about tens of thousands of cancer patients, while avoiding the high
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`costs and added risks of tissue biopsies.
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`4.
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`Guardant also markets and sells the GuardantOMNI ctDNA assay (“Guardant
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`OMNI). GuardantOMNI also uses DNA sequencing methods to provide a comprehensive
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`genomic profiling tool to help accelerate clinical development programs in immuno-oncology and
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`targeted therapy. Guardant OMNI has helped a number of partner biopharmaceutical companies
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`and research labs develop their cancer drug development pipelines.
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`5.
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`On information and belief, Foundation Medicine, Inc. (“Foundation”) is a
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`corporation organized and existing under the laws of the state of Delaware, having its principal
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`place of business at 150 Second Street, Cambridge, MA 02141. Foundation markets and sells
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`liquid biopsy products known as FoundationOne® Liquid and FoundationOne® Liquid CDx. On
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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 3 of 26 PageID #: 3
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`information and belief, Foundation performs the FoundationOne® Liquid and FoundationOne®
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`Liquid CDx tests at its facility in Cambridge, MA.
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`JURISDICTION AND VENUE
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`6.
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`This action arises under the patent laws of the United States, 35 U.S.C. §§ 100, et
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`seq., and this Court has jurisdiction over the subject matter of this action under 28 U.S.C. §§ 1331,
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`1338(a), 2201 and 2202.
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`7.
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`8.
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`Venue is proper in this Court under 28 U.S.C. §§ 1391 and 1400(b).
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`This Court has jurisdiction over Foundation because, upon information and belief,
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`Foundation Medicine is a Delaware corporation.
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`9.
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`This Court also has jurisdiction over Foundation because, upon information and
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`belief, Foundation, directly or indirectly, uses, offers for sale, and/or sells the FoundationOne®
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`Liquid and FoundationOne® Liquid CDx products throughout the United States and in this
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`judicial district.
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`10.
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`Further, the Court has jurisdiction over Foundation because, inter alia, this action
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`arises from actions of Foundation directed toward Delaware, and because Foundation has
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`purposefully availed itself of the rights and benefits of Delaware law by engaging in systematic
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`and continuous contacts with Delaware. Upon information and belief, Foundation regularly and
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`continuously transacts business within Delaware, including by selling the FoundationOne®
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`Liquid and FoundationOne® Liquid CDx products in Delaware, either on its own or through its
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`affiliates. Upon information and belief, Foundation derives substantial revenue from the sale of
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`FoundationOne® Liquid and FoundationOne® Liquid CDx in Delaware and has availed itself of
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`the privilege of conducting business within Delaware.
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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 4 of 26 PageID #: 4
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`11.
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`For these reasons and for other reasons that will be presented to the Court if
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`jurisdiction is challenged, the Court has personal jurisdiction over Foundation.
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`BACKGROUND
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`12.
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`Guardant repeats and re-alleges the foregoing paragraphs as if set forth specifically
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`herein.
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`13.
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`On information and belief, in the mid-2016 timeframe Foundation began
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`commercializing a liquid biopsy product termed FoundationACT. According to a Foundation
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`press release, FoundationACT is “an analytically validated and accurate blood-based circulating
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`tumor DNA (ctDNA) assay that provides patients and oncologists with a new option for
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`comprehensive genomic profiling when a tissue biopsy is not feasible or when tissue is not
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`available. By analyzing circulating tumor DNA isolated from a patient’s blood, FoundationACT
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`can identify clinically relevant genomic alterations, and like Foundation Medicine’s tissue-based
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`genomic profiles, FoundationOne® and FoundationOne Heme®, FoundationACT delivers this
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`comprehensive molecular information in a concise report that matches the findings with
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`potentially relevant targeted therapies and clinical trials.” Exhibit 8.
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`14.
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`In February 2017, scientists affiliated with Foundation presented the poster
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`“Genomic profiling of circulating tumor DNA (ctDNA) from patients with advanced cancers of
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`the GI tract and anus” (attached hereto as Exhibit 9) at the American Society of Clinical Oncology
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`meeting. On May 18, 2018, scientists associated with Foundation published a scientific paper
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`titled “Analytical Validation of a Hybrid Capture-Based Next-Generation Sequencing Clinical
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`Assay for Genomic Profiling of Cell-Free Circulating Tumor DNA” (attached hereto as Exhibit
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`10) in the Journal of Molecular Diagnostics. On information and belief, this paper describes the
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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 5 of 26 PageID #: 5
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`methodology that Foundation uses in its liquid biopsy tests, an overview of which is presented in
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`the figure below:
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`
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`Exhibit 10.
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`15.
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`On information and belief, in the 2018 timeframe, Foundation released a new
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`version of its liquid biopsy product, and renamed it “FoundationONE® Liquid.” According to a
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`Foundation press release, “FoundationOne Liquid is a hybrid capture-based, next-generation
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`sequencing in vitro diagnostic device for the detection of substitutions, insertion and deletion
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`alterations (indels), copy number alterations (CNAs) and select gene rearrangements using
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`circulating cell-free DNA (cfDNA) isolated from plasma derived from peripheral whole blood.
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`The FoundationOne Liquid test expands upon the previous version of the Company’s liquid biopsy
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`test, FoundationACT®, which has been analytically validated across the four main classes of
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`genomic alterations.”
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` Exhibit 11.
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` Foundation’s press release further explains that
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`FoundationONE Liquid “analyzes 70 genes known to drive cancer growth, including homologous
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`recombination deficiency (HRD) genes, and reports the genomic biomarker for microsatellite
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`instability (MSI).” Id.
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`16.
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`On information and belief, in the 2020 timeframe, Foundation released a
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`companion diagnostics version of its liquid biopsy product is called “FoundationONE® Liquid
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`CDx.” According to a press release, “FoundationOne Liquid CDx is a qualitative next generation
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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 6 of 26 PageID #: 6
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`sequencing based in vitro diagnostic test for prescription use only that uses targeted high
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`throughput hybridization-based capture technology to analyze 324 genes utilizing circulating
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`cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole
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`blood of advanced cancer patients.” Exhibit 12. Foundation’s press release explains that the
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`Foundation Platform detects “genomic signatures such as blood tumor mutational burden and high
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`microsatellite instability, as well as single gene alterations, including all NTRK fusions, for
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`patients with any solid tumor as an aid in patient care.” Id.
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`17.
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`On September 25, 2020, scientists associated with Foundation published a
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`scientific paper titled “Clinical and analytical validation of FoundationOne Liquid CDx, a novel
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`324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor
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`origin.” Exhibit 13. On information and belief, this paper further describes the methodology that
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`Foundation uses in the Foundation Platform, and in particular the FoundationOne® Liquid CDx
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`assay.
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`18.
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`On information and belief, FoundationACT, FoundationOne® Liquid and
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`FoundationOne® Liquid CDx operate in substantially similar manners, with the largest difference
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`being the numbers of genes targeted by each product. For instance, in a label accompanying the
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`FoundationOne® Liquid CDx’s submission to the FDA, Foundation states that “The
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`FoundationOne Liquid CDx assay was developed based on two versions of the FoundationOne
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`Liquid LDT assay, each of which targeted a subset of the genomic regions targeted by
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`FoundationOne Liquid CDx. FoundationACT (FACT) targeted 62 genes and FoundationOne
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`Liquid targeted 70 genes.” Exhibit 14.
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`19.
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`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’810
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`patent through its activities connected to its performance of the FoundationOne® Liquid and
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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 7 of 26 PageID #: 7
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`FoundationOne® Liquid CDx tests. For instance, representative claim 1 of the ’810 patent is listed
`
`below:
`
`for detecting somatic genetic variants of cell-free
`1. A method
`deoxyribonucleic acid (DNA) in a human subject, the method comprising:
`(a) obtaining 10 to 100 nanograms (ng) of double-stranded cell-free DNA
`from a blood sample from the human subject;
`(b) ligating adapters comprising molecular barcodes to ends of a plurality of
`molecules of the double-stranded cell-free DNA to produce tagged parent
`polynucleotides, wherein the molecular barcodes together constitute a set
`of 5-100 molecular barcodes from 5-20 nucleotides in length;
`(c) amplifying a plurality of the tagged parent polynucleotides to produce
`progeny polynucleotides with associated molecular barcodes;
`(d) selectively enriching the progeny polynucleotides for target regions
`associated with cancer, whereby enriched progeny polynucleotides are
`generated;
`(e) sequencing a portion of the enriched progeny polynucleotides to produce
`sequencing reads of the progeny polynucleotides with associated
`molecular barcodes;
`(f) aligning mappable portions of the sequencing reads to a human reference
`genome;
`(g) grouping a plurality of the sequencing reads into families based on the
`sequence information of the molecular barcodes and the beginning and end
`base positions of the mapped portion of the progeny polynucleotides; and
`(h) detecting, from among a plurality of the families, the presence or absence
`of one or more somatic genetic variants comprising a single nucleotide
`variant (SNV), a copy number variation (CNV), an insertion or deletion
`(indel), a gene fusion, or any combination thereof.
`
`20.
`
`Performance of Foundation’s liquid biopsy tests leads to infringement of claim 1 in
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`the following way. First, cfDNA is extracted from blood (step a). Next, barcodes are ligated to
`
`each end of cfDNA to produce tagged parent polynucleotides (step b). The tagged parent
`
`polynucleotides containing the ligated barcodes are then amplified (step c) and selectively
`
`enriched for target regions associated with cancer (step d). The amplified progeny polynucleotides
`
`are then sequenced (step e). Sequence reads are mapped to a human reference genome (step f) and
`
`are then grouped into families according to their barcode sequence and the beginning and end base
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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 8 of 26 PageID #: 8
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`positions of the mapped portion of the progeny (step g). Lastly, the tests detect the presence of
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`genetic mutations from the families (step h).
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`21.
`
`As an example, attached hereto as Exhibit 15 is a preliminary and exemplary claim
`
`chart detailing Foundation’s infringement of exemplary claims of the ’810 patent. This chart is not
`
`intended to limit Guardant’s right to modify this chart or any other claim chart or allege that other
`
`activities of Foundation infringe the identified claims or any other claims of the ’810 patent or any
`
`other patents.
`
`22.
`
`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’085
`
`patent through its activities connected to its performance of the FoundationOne® Liquid and
`
`FoundationOne® Liquid CDx tests. For instance, representative claim 1 of the ’085 patent is listed
`
`below:
`
`1. A method for generating a genetic profile of a tumor from a blood sample of
`double-stranded cell-free deoxyribonucleic acids (cfDNA) molecules from a
`subject having cancer or suspected of having a cancer, the method comprising:
`(a) obtaining a population comprising the double-stranded cfDNA molecules
`from the blood sample from the subject;
`(b) ligating a set of molecular barcodes to both ends of a plurality of the
`double-stranded cfDNA molecules using more than a 30x molar excess of
`molecular barcodes relative to the double-stranded cfDNA molecules to
`produce tagged parent polynucleotides, wherein a given molecular barcode
`is a member of a set of molecular barcodes comprising 2 to 1,000,000
`different molecular barcode sequences,
` wherein at least 20% of the double-stranded cfDNA molecules from the
`population of cfDNA molecules are attached to molecular barcodes
`(c) amplifying a plurality of the tagged parent polynucleotides to produce
`progeny polynucleotides with associated molecular barcodes;
`(d) selectively enriching a subset of the progeny polynucleotides for target
`regions associated with cancer, whereby enriched progeny polynucleotides
`are generated;
`(e) sequencing a portion of the enriched progeny polynucleotides to produce
`sequencing reads of the progeny polynucleotides with associated
`molecular barcodes;
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`(f) aligning a plurality of the sequencing reads to a reference sequence;
`(g) grouping a plurality of the sequencing reads into a plurality of families
`based at least on sequence information of the molecular barcodes, a start
`base position of a given sequencing read from among the sequencing reads
`at which the given sequencing read is determined to start aligning to the
`reference sequence, and a stop base position of the given sequencing read
`at which the given sequencing read is determined to stop aligning to the
`reference sequence, wherein a family of the plurality of families is
`representative of a cell-free nucleic acid molecule in the sample;
`(h) detecting, from among the families, the presence or absence of somatic
`genetic variants; and
`(i) quantifying a plurality of somatic genetic variants detected as present to
`generate the genetic profile of the tumor.
`
`
`
`23.
`
`Performance of Foundation’s liquid biopsy tests leads to infringement of claim 1 in
`
`the following way. First, cfDNA is extracted from blood (step a). Next, molecular barcodes are
`
`ligated to both ends of double-stranded cfDNA molecules (step b). The tagged parent
`
`polynucleotides containing the ligated barcodes are then amplified (step c) and selectively
`
`enriched (step d). Amplified progeny polynucleotides are sequenced to produce sequence reads
`
`(step e). Sequence reads are aligned to a reference genome (step f), and grouped based on
`
`sequence information of the barcodes, a start position, and a stop position of the sequencing read
`
`(step g). Lastly, the tests detect (step h) and quantified (step i) the genetic mutations of a tumor.
`
`24.
`
`As an example, attached hereto as Exhibit 16 is a preliminary and exemplary claim
`
`chart detailing Foundation’s infringement of exemplary claims of the ’085 patent. This chart is not
`
`intended to limit Guardant’s right to modify this chart or any other claim chart or allege that other
`
`activities of Foundation infringe the identified claims or any other claims of the ’085 patent or any
`
`other patents.
`
`25.
`
`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’086
`
`patent through its activities connected to its performance of the FoundationOne® Liquid and
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`- 9 -
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`

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`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 10 of 26 PageID #: 10
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`FoundationOne® Liquid CDx tests. For instance, representative claim 1 of the ’086 patent is listed
`
`below:
`
`1. A method for detecting a presence or absence of one or more somatic genetic
`variants in cell-free deoxyribonucleic acid (cfDNA) molecules from a bodily fluid
`sample of a subject, comprising:
`(a) non-uniquely tagging a plurality of cfDNA molecules from a population of
`cfDNA molecules obtained from the bodily fluid sample with molecular
`barcodes from a set of molecular barcodes to produce non-uniquely tagged
`parent polynucleotides;
` wherein the non-uniquely tagging comprises ligating molecular barcodes
`from the set of molecular barcodes to both ends of a cfDNA molecule from
`the plurality of cfDNA molecules using more than a 10x molar excess of
`molecular barcodes relative to the population of cfDNA molecules,
` wherein the cfDNA molecules that map to a mappable base position of a
`reference sequence are tagged with a number of diffrent[sic] molecular
`barcodes ranging from at least 2 and fewer than a number of cfDNA
`molecules that map to the mappable base position, and
` wherein at least 20% of the cfDNA molecules from the population of
`cfDNA molecules are attached to molecular barcodes;
`(b) amplifying a plurality of the non-uniquely tagged parent polynucleotides
`to produce progeny polynucleotides with associated molecular barcodes,
` (c) sequencing a plurality of the progeny polynucleotides to produce
`sequencing reads of the progeny polynucleotides with associated
`molecular barcodes;
`(d) mapping a plurality of the sequencing reads to the reference sequence to
`generate mapped sequencing reads;
`(e) grouping a plurality of the mapped sequencing reads into a plurality of
`families based on sequence information from the molecular barcodes and
`at least (1) a start base position of a given mapped sequencing read from
`among the mapped sequencing reads at which the given mapped
`sequencing read is determined to start mapping to the reference sequence
`and/or (2) a stop base position of the given mapped sequencing read at
`which the given mapped sequencing read is determined to stop mapping to
`the reference sequence; and
`(f) detecting, from among the mapped sequencing reads in a plurality of the
`families, the presence or absence of the one or more somatic genetic
`variants.
`
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`26.
`
`Performance of Foundation’s liquid biopsy tests leads to infringement of claim 1 in
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`the following way. First, cfDNA is non-uniquely tagged by ligating molecular barcodes to both
`
`ends of cfDNA molecules (step a). The tagged parent polynucleotides containing the ligated
`
`barcodes are then amplified (step b) and sequenced (step c). Sequence reads are mapped to a
`
`reference genome (step d) and grouped into a plurality of families based on sequence information
`
`of the barcodes and the start base position or stop base position (step e). Lastly, the tests detect the
`
`presence of genetic mutations some or all of the mapped sequence reads (step f).
`
`27.
`
`As an example, attached hereto as Exhibit 17 is a preliminary and exemplary claim
`
`chart detailing Foundation’s infringement of exemplary claims of the ’086 patent. This chart is not
`
`intended to limit Guardant’s right to modify this chart or any other claim chart or allege that other
`
`activities of Foundation infringe the identified claims or any other claims of the ’086 patent or any
`
`other patents.
`
`28.
`
`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’916
`
`patent through its activities connected to its performance of the FoundationOne® Liquid and
`
`FoundationOne® Liquid CDx tests. For instance, representative claim 13 of the ’916 patent is
`
`listed below:
`
`13. A method for detecting a genetic variation in one or more microsatellite
`regions in a sample of cell-free nucleic acid molecules from a subject having a
`cancer, the method comprising:
`(a) ligating molecular barcodes from a set of molecular barcodes having 2 to
`1,000,000 different molecular barcode sequences to a plurality of the
`cell-free nucleic acid molecules from the sample to produce tagged parent
`polynucleotides;
`(b) amplifying a plurality of the tagged parent polynucleotides to produce
`amplified tagged progeny polynucleotides;
`(c) sequencing a plurality of the amplified tagged progeny polynucleotides to
`produce a set of sequencing reads; and
`(d) determining, from among a plurality of sequencing reads in the set of
`sequencing reads, a quantitative measure of polymorphic forms
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`comprising microsatellite changes in the one or more microsatellite
`regions based at least on sequence information of the molecular barcodes,
`thereby detecting the genetic variation in the one or more microsatellite
`regions.
`
`29.
`
`Performance of Foundation’s liquid biopsy tests leads to infringement of claim 13
`
`in the following way. First, cfDNA is tagged with a set of molecular barcodes comprising 2 to
`
`1,000,000 different barcode sequences via ligation (step a). The tagged parent polynucleotides
`
`containing the ligated barcodes are then amplified (step b) and sequenced (step c). Sequence reads
`
`are grouped into families comprising sequence reads amplified from the same parent
`
`polynucleotide using at least sequence information of the molecular barcodes. Microsatellite
`
`changes are detected from among the families of sequence reads by quantifying sequence changes
`
`at repetitive loci regions (step d).
`
`30.
`
`As an example, attached hereto as Exhibit 18 is a preliminary and exemplary claim
`
`chart detailing Foundation’s infringement of exemplary claims of the ’916 patent. This chart is not
`
`intended to limit Guardant’s right to modify this chart or any other claim chart or allege that other
`
`activities of Foundation infringe the identified claims or any other claims of the ’916 patent or any
`
`other patents.
`
`31.
`
`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’063
`
`patent through its activities connected to its performance of the FoundationOne® Liquid and
`
`FoundationOne® Liquid CDx tests. For instance, representative claim 1 of the ’063 patent is listed
`
`below:
`
`1. A method for classifying consensus sequences generated from sequencing
`reads derived from double-stranded cell-free deoxyribonucleic acid (cfDNA)
`molecules from a sample of a human subject, the method comprising:
`(a) non-uniquely tagging a population of double-stranded cfDNA molecules
`from the sample with more than a 10× molar excess of adapters comprising
`molecular barcodes, relative to the double-stranded cfDNA molecules in
`the population, to generate non-uniquely tagged parent polynucleotides,
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`wherein the double-stranded cfDNA molecules that map to a mappable
`base position of a reference sequence are tagged with a number of different
`molecular barcodes ranging from at least 2 to fewer than a number of
`double-stranded cfDNA molecules that map to the mappable base position,
`and
`wherein at least 20% of the double-stranded cfDNA molecules are
`non-uniquely tagged with the adapters comprising the molecular barcodes
`at both ends of a molecule of the double-stranded cfDNA molecules;
`(b) amplifying a plurality of the non-uniquely tagged parent polynucleotides
`to produce progeny polynucleotides;
`(c) enriching a plurality of the progeny polynucleotides for target regions of
`interest to generate enriched progeny polynucleotides;
`(d) sequencing a plurality of the enriched progeny polynucleotides to produce
`a set of sequencing reads;
`(e) mapping a plurality of sequencing reads from the set of sequencing reads
`to the reference sequence;
`(f) grouping a plurality of the mapped sequencing reads into families of
`mapped sequencing reads based at least on (i) sequence information from
`the molecular barcodes and (ii) a beginning base position and an ending
`base position of the mapped sequencing reads;
`(g) generating a consensus sequence for each family from among one or more
`of the families to produce a set of consensus sequences; and
`(h) classifying one or more consensus sequences from among the set of
`consensus sequences as (1) paired consensus sequences generated from
`sequencing reads representing a Watson strand and a Crick strand of a
`non-uniquely tagged parent polynucleotide or (2) unpaired consensus
`sequences generated from sequencing reads representing only one of either
`a Watson strand or a Crick strand of a non-uniquely tagged parent
`polynucleotide.
` Performance of Foundation’s liquid biopsy tests leads to infringement of claim 1 in
`
`32.
`
`the following way. First, cfDNA is tagged with a set of molecular barcodes via ligation (step a).
`
`Upon information and belief, the ligation process involves utilizing at least 10 times molar excess
`
`of adapters, resulting in the tagging of at least 20% of cfDNA. The tagged parent polynucleotides
`
`containing the ligated barcodes are then amplified (step b). Amplified polynucleotides are
`
`enriched via a hybrid capture process using bait sets targeting desired sequence loci (step c).
`
`Enriched polynucleotides are sequenced on the Illumina high-throughput sequencing platform
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`(step d). Sequence reads are (i) mapped to reference sequences from databases such as the
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`COSMIC database (step e), and (ii) grouped into families based on the barcode and additional
`
`sequence information, thereby identifying sequence reads that arises from the same parent DNA
`
`molecule (step f). Foundation next identifies consensus sequences using the information
`
`contained in the set of sequence reads belonging to each family (step g). The combination of the
`
`sequence start position and barcode sequence allows Foundation to classify consensus sequences
`
`as either being paired consensus sequences or unpaired consensus sequences (step h). The identity
`
`of these base calls allow for detection of genetic aberrations including single base substitutions,
`
`copy number variations, and insertions/deletions (step h).
`
`33.
`
`As an example, attached hereto as Exhibit 19 is a preliminary and exemplary claim
`
`chart detailing Foundation’s infringement of exemplary claims of the ’063 patent. This chart is not
`
`intended to limit Guardant’s right to modify this chart or any other claim chart or allege that other
`
`activities of Foundation infringe the identified claims or any other claims of the ’063 patent or any
`
`other patents.
`
`34.
`
`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’743
`
`patent through its activities connected to its performance of the FoundationOne® Liquid CDX test.
`
`For instance, representative claim 10 of the ’743 patent is listed below:
`
`10. A method for detecting a rare mutation in a cell-free or substantially
`cell-free sample obtained from a subject, comprising:
`(a) sequencing extracellular polynucleotides from a bodily sample from the
`subject, wherein each of the extracellular polynucleotides generates a
`plurality of sequence reads;
`(b) filtering out reads that fail to meet a set accuracy, quality score, or mapping
`score threshold;
`(c) mapping sequence reads derived from the sequencing onto a reference
`sequence;
`(d) determining unique sequence reads corresponding to the extracellular
`polynucleotides from among the sequence reads; and
`
`- 14 -
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`

`

`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 15 of 26 PageID #: 15
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`(e) identifying a subset of mapped unique sequence reads that include a
`variant as compared to the reference sequence at each mappable base
`position;
`(f) for each mappable base position, calculating a ratio of (a) a number of
`mapped unique sequence reads that include a variant as compared to the
`reference sequence, to (b) a number of total unique sequence reads for each
`mappable base position; and
`(g) processing the ratio with a similarly derived number from a reference
`sample.
`Performance of Foundation’s liquid biopsy tests leads to infringement of this claim
`
`35.
`
`in the following way. First, cell free DNA is obtained from a patient blood draw (step a). After
`
`processing, the cell free DNA is sequenced, generating sequence reads (step a). Sequence reads
`
`are filtered using quality scores (step b). Sequence reads are (i) mapped to reference sequences
`
`from databases such as the COSMIC database (step c), (ii) grouped into families based on the
`
`barcode and additional sequence information, allowing one to determine unique sequence reads
`
`corresponding to the extracellular polynucleotides (step d). The subset of unique sequence reads
`
`containing a variant can be identified, by comparing the sequence read to the reference sequence
`
`(step e). That allows Foundation to calculate the ratio of unique sequence reads that include a
`
`variant versus total sequence reads, and compare that to a reference to identify rare mutations
`
`(steps f and g).
`
`36.
`
`As an example, attached hereto as Exhibit 20 is a preliminary and exemplary claim
`
`chart detailing Foundation’s infringement of exemplary claims of the ’743 patent. This chart is not
`
`intended to limit Guardant’s right to modify this chart or any other claim chart or allege that other
`
`activities of Foundation infringe the identified claims or any other claims of the ’743 patent or any
`
`other patents.
`
`37.
`
`On February 1, 2019, Foundation filed a Petition for Inter Partes Review of claims
`
`1-26 of the ’743 patent. On August 18, 2020, the US Patent Office ruled that claims 10-19 and 21
`
`- 15 -
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`

`

`Case 1:20-cv-01580-LPS Document 1 Filed 11/23/20 Page 16 of 26 PageID #: 16
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`were not unpatentable. Therefore, Foundation is estopped from further challenging the validity of
`
`claims 10-19 and 21 under 35 U.S.C. §§ 102, 103.
`
`38.
`
`Foundation infringes, literally or under the doctrine of equivalents, Guardant’s ’822
`
`patent through its activities connected to its performance of the FoundationOne® Liquid CDx test.
`
`For instance, representative claims 1 and 12 of the ’822 patent are listed below:
`
`1. A method, comprising:
`(a) providing a population of cell free DNA (“cfDNA”) molecules obtained
`from a bodily sample from a subject;
`(b) converting the population of cfDNA molecules into a population of
`non-uniquely tagged parent polynucleotides, wherein each of the
`non-uniquely tagged parent polynucleotides comprises (i) a sequence from
`a cfDNA molecu